tbuckley/cabot-search huggingface dataset:
Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis
Authors: Jinwang Ye, Suyue Zhong, Huali Wan, Xing Guo, Xuanbao Yao, Qiong Liu, Liming Chen, Jian-Zhi Wang, Shifeng Xiao
Journal: Molecular Neurodegeneration (2025)

Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear. We investigated the expression of class IIa HDAC7 in astrocytes from AD patients and PS19 mice. PS19 mice were treated with AAVs expressing shRNA for HDAC7 with astrocyte-specific promoter and with a selective class IIa HDAC inhibitor, TMP195, and the effects on tau pathology, gliosis, synaptic plasticity and cognition-related behavioral performance were measured. Tau uptake and degradation assays in cultured astrocytes were utilized to investigate the role of HDAC7 on astrocyte-mediated tau clearance. Immunoprecipitation, immunofluorescence, western blotting, RT-qPCR, mass spectrometric, and luciferase reporter assay were used to identify HDAC7 substrates, modification site and related signaling pathways in astrocyte-tau clearance. We generated a new antibody to clarify the role of HDAC7-mediated signaling in AD patients and PS19 mice. Here, we found that the level of histone deacetylase 7 (HDAC7) was remarkably increased in the astrocytes of AD patients and P301S tau transgenic (PS19) mice. Genetic or pharmacological inhibition of HDAC7 effectively enhanced astrocytic clearance of tau with improved cognitive functions in PS19 mice. HDAC7 could modulate astrocytic uptake and lysosomal degradation of tau proteins through a transcriptional factor EB (TFEB) acetylation-dependent manner. Specifically, deacetylation of TFEB at K310 site by HDAC7 prevented TFEB nuclear translocation with reduced lysosomal biogenesis and tau clearance in astrocytes, whereas inhibiting HDAC7 restored astrocytic TFEB acetylation level at K310 with improved tau pathology and cognitive functions in PS19 mice. Our findings suggest that upregulation of HDAC7 induces AD-like tau pathologies via deacetylating TFEB and inhibiting lysosomal biogenesis in astrocytes, and downregulating HDAC7-TFEB signaling is promising for arresting AD and other tauopathies.
An engineered adeno-associated virus mediates efficient blood-brain barrier penetration with enhanced neurotropism and reduced hepatotropism
Authors: Nengsong Luo, Kunzhang Lin, Yuxiang Cai, Zilian Zhang, Xiaokai Sui, Zengpeng Han, Wenjia Yuan, Jiayong Xing, Zhu Gui, Gangning Liu, Jie Wang, Fuqiang Xu
Journal: Journal of Controlled Release (2025)

The blood-brain barrier (BBB) is a formidable barrier that restricts the entry of substances into the brain, complicating the study of brain function and the treatment of neurological conditions. Traditional methods of delivering genes from the periphery to the central nervous system (CNS) using adeno-associated viruses (AAVs) often require high doses, which can trigger immune responses and hepatotoxicity. Here, we developed a new AAV variant named AAVhu.32-PLUS based on a rational strategy. Following intravenous injection, AAVhu.32-PLUS can cross the BBB and exhibits higher efficiency and specificity in transducing neurons and significantly reduced hepatotropism compared to the extensively used AAV-PHP.eB. Furthermore, through in vitro cell experiments, we identified that AAVhu.32-PLUS may rely on the LY6A receptor for crossing the BBB. Finally, our research indicates that AAVhu.32-PLUS, while having lower transduction efficiency in astrocytes compared to AAV-PHP.eB, is still capable of efficiently transducing glioblastoma after intravenous injection. These properties make AAVhu.32-PLUS a promising tool for neuroscience research and targeted therapies of brain disease.
Structural Optimization of Microfluidic Chips for Enhancing Droplet Manipulation and Observation
Authors: Yanfeng Zhao, Zhiqiang Zheng, Jiaxin Liu, Xinyi Dong, Haotian Yang, Anping Wu, Qing Shi, Huaping Wang
Journal: Cyborg and Bionic Systems (2025)

Digital microfluidic chips (DMCs) have shown huge potential for biochemical analysis applications due to their excellent droplet manipulation capabilities. The driving force is a critical factor for characterizing and optimizing the performance of droplet manipulation. Conducting numerical analysis of the driving force is essential for DMC design, as it helps optimize the structural parameters. Despite advances in numerical analysis, evaluating driving forces in partially filled electrodes remains challenging. Here, we propose a versatile electrodynamics simulation model designed to analyze the driving forces of partially filled electrodes to optimize the structural parameters of DMCs. This model utilizes finite element analysis to determine the voltage distribution within the DMC and calculates the driving force acting on the droplets using the principles of virtual work. Using this electrodynamics simulation model, we evaluated the effects of various structural parameters, including the dielectric constant and thickness of the dielectric layer, the dielectric constant and conductivity of the droplet, and substrate spacing, on the droplet driving force. This evaluation helps to optimize the structural parameters and enhances the droplet manipulation of DMCs. Measurements of droplet acceleration demonstrated that the droplet acceleration on the partially filled electrode aligns with the simulated driving force trend, which verified the effectiveness of the proposed electrodynamics simulation model. We anticipate that the electrodynamics simulation model is capable of evaluating the driving force in partially filled electrodes within complex DMCs, offering unprecedented possibilities for future structural designs of DMCs.
Baricitinib in early polymyalgia rheumatica (BACHELOR): a randomised, double-blind, placebo-controlled, parallel-group trial
Authors: Alain Saraux, Guillermo Carvajal Alegria, Emmanuelle Dernis, Christian Roux, Christophe Richez, Alice Tison, Baptiste Quere, Sandrine Jousse-Joulin, Dewi Guellec, Thierry Marhadour, Patrice Kervarrec, Divi Cornec, Catherine Le Henaff, Sandra Lesven, Emmanuel Nowak, Aghiles Souki, Valérie Devauchelle-Pensec
Journal: The Lancet Rheumatology (2025)
Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics
Authors: Constanze Ciavarella, Chris Drakeley, Ric N Price, Ivo Mueller, Michael White
Journal: The Lancet Infectious Diseases (2025)

Plasmodium vivax forms dormant liver stages (hypnozoites) that can reactivate weeks to months after primary infection. Radical cure requires a combination of antimalarial drugs to kill both the blood-stage and liver-stage parasites. Hypnozoiticidal efficacy of the liver-stage drugs primaquine and tafenoquine cannot be estimated directly because hypnozoites are undetectable. We aimed to estimate hypnozoiticidal efficacy from clinical trial data, and quantify the community-level impact of implementing case management with radical cure. We calibrated a novel P vivax Recurrence Model to publicly available data from prospective clinical trials to estimate the hypnozoiticidal efficacy of different supervised primaquine (3·5 mg/kg or 7 mg/kg over 7 or 14 days) and tafenoquine (5 mg/kg or 7·5 mg/kg single dose) regimens in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. We used an existing P vivax Individual-Based Model to quantify the 5-year impact of case management with unsupervised primaquine or tafenoquine regimens across various transmission settings. We estimated median hypnozoiticidal efficacies of 99·1% (95% credible interval 96·0-100) for primaquine 7 mg/kg over 14 days; 96·3% (90·8-99·7) for primaquine 7 mg/kg over 7 days; 72·3% (68·1-76·3) for primaquine 3·5 mg/kg over 7 or 14 days; 62·4% (49·1-76·3) for tafenoquine 5 mg/kg single dose; and 87·5% (62·1-99·3) for tafenoquine 7·5 mg/kg single dose. 5 years of community-level tafenoquine case management was estimated to reduce P vivax transmission by 74-79% where pre-intervention prevalence as measured by PCR was low (<2%) and by 17-20% where prevalence as measured by PCR was high (around 35%). Similar 5-year reductions were estimated with primaquine case management only when adherence to the primaquine regimen was above 50%. Substantial reductions in prevalence as measured by PCR were predicted with primaquine and tafenoquine regimens if these could be implemented with high coverage and adherence. The benefits of preventing P vivax relapses need to be balanced against the risks of inducing severe haemolysis in patients with G6PD deficiency. Bill & Melinda Gates Foundation and Horizon Europe.
Psychosocial impact associated with a multicancer early detection test (PATHFINDER): a prospective, multicentre, cohort study
Authors: Lincoln Nadauld, Charles H McDonnell, Christina A Dilaveri, Eric A Klein, Robert Reid, Catherine R Marinac, Karen C Chung, Margarita Lopatin, Eric T Fung, Deborah Schrag, Donald L Patrick
Journal: The Lancet Oncology (2025)
Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study
Authors: Lotta Plomp, Hortense Chassepot, Dimitri Psimaras, Thierry Maisonobe, Eric Mensi, Sarah Leonard-Louis, Isabelle Plu, Antoine Rozes, Florence Tubach, Mehdi Touat, Celine Anquetil, Nadege Wesner, Nicolas Champtiaux, Aude Rigolet, Sophie Demeret, Nicolas Weiss, Marie-Alexandra Alyanakian, Rozen Le Panse, Frédérique Truffault, Marie-Agnès Dragon-Durey, Lucienne Chatenoud, Baptiste Abbar, Marie-Claire Bretagne, Adrien Procureur, Thomas Similowski, Capucine Morelot-Panzini, Martin Dres, Stephane Ederhy, Olivier Benveniste, Joe-Elie Salem, Yves Allenbach
Journal: The Lancet Regional Health - Europe (2025)
Exploring Methylation Signatures for High De Novo Recurrence Risk in Hepatocellular carcinoma
Authors: Da-Won Kim, Jin Hyun Park, Suk Kyun Hong, Min-Hyeok Jung, Ji-One Pyeon, Jin-Young Lee, Kyung-Suk Suh, Nam-Joon Yi, YoungRok Choi, Kwang-Woong Lee, Young-Joon Kim
Journal: Clinical and Molecular Hepatology (2025)

Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69-0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14-0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy
Authors: Shaida Ouladan, Elias Orouji
Journal: Journal of Clinical Oncology (2025)

Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients with metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful in hematologic malignancies, presents a promising avenue for treating solid tumors, including CRC. This review explores the potential of CAR-T cell therapy in CRC by analyzing clinical trials and highlighting prominent CRC-specific targets. We discuss the challenges such as immunosuppressive microenvironment, tumor heterogeneity, and physical barriers that limit CAR-T efficacy. Emerging strategies, such as logic-gated and dual-targeting CAR-T cells, offer practical solutions to overcome these hurdles. Furthermore, we explore the combination of CAR-T cell therapy with immune checkpoint inhibitors to enhance T-cell persistence and tumor infiltration. As the field continues to evolve, CAR-T cell therapies hold significant potential for revolutionizing the treatment landscape of CRC.
A Carrier-Free Ultrasound-Responsive Polyphenol Nanonetworks with Enhanced Sonodynamic-Immunotherapy for Synergistic Therapy of Breast Cancer
Authors: Shenzhen Ren, Mingzhe Zhang, Chunxiu Cai, Ning Zhang, Zijia Wang, Gen Li, Quan Liu, Hailiang Zhu, Hailong An, Yafei Chen
Journal: Biomaterials (2025)
Hierarchical skin lesion image classification with prototypical decision tree
Authors: Zhen Yu, Toan D. Nguyen, Lie Ju, Yaniv Gal, Maithili Sashindranath, Paul Bonnington, Lei Zhang, Victoria Mar, Zongyuan Ge
Journal: npj Digital Medicine (2025)

Traditional disease classification models often disregard the clinical significance of misclassifications and lack interpretability. To overcome these challenges, we propose a hierarchical prototypical decision tree (HPDT) for skin lesion classification. HPDT combines prototypical networks and decision trees, leveraging a class hierarchy to guide interpretable predictions from general to specific categories. By incorporating a hierarchy-based distance matrix, the model prioritizes less severe misclassifications while maintaining diagnostic accuracy. Evaluated on a dataset of 235,268 dermoscopic images across 65 conditions, HPDT outperforms flat classifiers and existing hierarchical methods in accuracy, error severity reduction, and interpretability. It also generalizes effectively to unseen classes. These results highlight the value of integrating clinical hierarchies into model design and training to improve diagnostic reliability and decision transparency, demonstrating HPDT's potential for clinical decision support.
Tongue squamous cell carcinoma-targeting Au-HN-1 nanosystem for CT imaging and photothermal therapy
Authors: Ming Hao, Xingchen Li, Xinxin Zhang, Boqiang Tao, He Shi, Jianing Wu, Yuyang Li, Xiang Li, Shuangji Li, Han Wu, Jingcheng Xiang, Dongxu Wang, Weiwei Liu, Guoqing Wang
Journal: International Journal of Oral Science (2025)

Abstract Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Effects of digital-based interventions on the outcomes of the eligibility criteria for sarcopenia in healthy older adults: a systematic review and meta-analysis
Authors: Hyuma Makizako, Daijo Shiratsuchi, Shoma Akaida, Mana Tateishi, Keisuke Maeda, Katsuya Iijima, Hiroyuki Shimada, Tatsuro Inoue, Minoru Yamada, Ryo Momosaki, Hidetaka Wakabayashi, Koichi Yamamoto, Hidenori Arai
Journal: Ageing Research Reviews (2025)
Progress in enzyme-powered micro/nanomotors in diagnostics and therapeutics
Authors: Jinpeng Zhao, Banghui Wang, Mingzhe Yan, Yuxin Liu, Ruizhe Zhao, Xuezhe Wang, Tianyi Shao, Yifei Li, Muhammad Imran, Mingze Ji, Hong Zhao, Carlos F Guimarães, Guotai Li, Qihui Zhou, Rui L Reis
Journal: Bioactive Materials (2025)
Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study
Authors: Pedro D Wendel-Garcia, Adrian Ceccato, Ana Motos, Diego Franch-Llasat, Mar O Pérez-Moreno, Marie F Domenech-Spanedda, Elena Chamarro-Martí, Ricard Ferrer, Laia Fernández-Barat, Jordi Riera, Sergio Álvarez-Napagao, Oscar Peñuelas, Jose A Lorente, Raquel Almansa, Albert Gabarrús, David de Gonzalo-Calvo, Jessica González, Jose M Añon, Carme Barberà, José Barberán, Aaron Blandino-Ortiz, Elena Bustamante-Munguira, Jesús Caballero, Cristina Carbajales-Pérez, Nieves Carbonell, Mercedes Catalán-González, Patricia Barral-Segade, Rafael Mañez, Mari C de la Torre, Emili Díaz, Ángel Estella, Elena Gallego, José L García-Garmendia, José Garnacho-Montero, Rosario Amaya-Villar, José M Gómez, Arturo Huerta, Ruth N Jorge-García, Ana Loza-Vázquez, Judith Marin-Corral, María Cruz Martin-Delgado, Amalia Martínez de la Gándara, Ignacio Y Martínez-Varela, Juan López-Messa, Guillermo Muñiz-Albaiceta, Mariana A Novo, Yhivian Peñasco, Juan C Pozo-Laderas, Pilar Ricart, Ángel Sánchez-Miralles, Susana Sancho, Lorenzo Socias, Jordi Solé-Violan, Fernando Suárez-Sipmann, Luis Tamayo, José Trenado, Ferran Barbé, Antoni Torres, Ferran Roche-Campo
Journal: Journal of Infection (2025)
Real-World Evidence on Digital Therapeutics in Pediatric Amblyopia: Insights into Rapid Axial Elongation Risk
Authors: Ying Yao, Yunsi He, Yun Wen, Lei Feng, Qingqing Ye, Zixuan Xu, Yusong Zhou, Yangfei Pang, Wentong Yu, Yudan Zhong, Qiuying Li, Junpeng Yuan, Jing Liu, Jinrong Li
Journal: Ophthalmology (2025)
Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers
Authors: Karen M Tuesley, Katrina Spilsbury, Sallie-Anne Pearson, Peter Donovan, Andreas Obermair, Michael D Coory, Sitwat Ali, Nirmala Pandeya, Louise Stewart, Susan J Jordan, Penelope M Webb
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited. Methods We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk (OR = 1.26, 95% CI = 1.21 to 1.31, and OR = 1.24, 95% CI = 1.17 to 1.32, respectively), but depot-medroxyprogesterone acetate was not, except when used for 5 or more years (OR = 1.23, 95% CI = 0.95 to 1.59). Reduced risks were seen for levonorgestrel intrauterine system (≥1 years of use) in endometrial cancer (OR = 0.80, 95% CI = 0.65 to 0.99), ovarian cancer (OR = 0.71, 95% CI = 0.57 to 0.88), and cervical cancer (OR = 0.62, 95% CI = 0.51 to 0.75); for etonogestrel implant in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34) and ovarian cancer (OR = 0.76, 95% CI = 0.57 to 1.02); and for depot-medroxyprogesterone acetate in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34). Although levonorgestrel intrauterine system, etonogestrel implant and depot-medroxyprogesterone acetate were all associated with increased cancer risk overall, for etonogestrel implant, the risk returned to baseline after cessation, similar to the oral contraceptive pill. We were unable to adjust for all potential confounders, but sensitivity analyses suggested that adjusting for parity, smoking, and obesity would not have materially changed our findings. Conclusion Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). This information may be helpful to women and their physicians when discussing contraception options.
Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia
Authors: Levi B. Wood, Annabelle C. Singer
Journal: Annual Review of Biomedical Engineering (2025)

Regulation of the brain's neuroimmune system is central to development, normal function, and disease. Neuronal communication to microglia, the primary immune cells of the brain, is well known to involve purinergic signaling mediated via ATP secretion and the cytokine fractalkine. Recent evidence shows that neurons release multiple cytokines beyond fractalkine, yet these are less studied and poorly understood. In contrast to ATP, cytokines are a class of signaling molecule that are much larger, with longer signaling and farther diffusion. We posit that neuron-expressed cytokines are an essential mechanism of neuron-microglia communication that arises as part of both normal learning and memory and in response to tissue pathology. Thus, neurons are underappreciated immunomodulatory cells that express diverse immunomodulatory signals. While neuronally sourced cytokines have been understudied, new technical advances make this a timely topic. The goal of this review is to define what is known about the cytokines expressed from neurons, how they are regulated, and the effects of these cytokines on microglia. We delineate key knowledge gaps and needs for new tools to define and analyze neuronal roles in immunomodulation. Given that cytokines are central regulators of microglial function, a broad new body of work is required to illuminate functional links between these neuronally expressed cytokines and sustained and transient microglial function.