tbuckley/cabot-search huggingface dataset:
Haemophilus influenzae remains the predominant otitis media pathogen in Australian children undergoing ventilation tube insertion in the PCV13 era
Authors: Elke J Seppanen, Josephine Bayliss, Sharon L Clark, Cristina Gamez, Danielle Headland, Caitlyn M Granland, Shyan Vijayasekaran, Hayley Herbert, Peter Friedland, Peter C Richmond, Ruth B Thornton, Lea-Ann S Kirkham
Journal: Journal of Infection (2025)

Understanding patterns of bacterial carriage and otitis media (OM) microbiology are crucial for assessing vaccine impact and informing policy. The microbiology of OM can vary with geography, time, and interventions like pneumococcal conjugate vaccines (PCVs). We evaluated the microbiology of nasopharyngeal and middle ear effusions in children living in Western Australia, 11 years following the introduction of PCV13. Children undergoing surgery for recurrent acute OM and/or chronic OM with effusion (cases), and children undergoing surgery for non-infectious reasons (controls), were recruited. Nasopharyngeal swabs and middle ear effusions (MEE - cases only) were collected, and quantitative PCR applied for detection of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes. S. pneumoniae-positive MEE were serotyped by culture. Nasopharyngeal swabs from 166 children under 5 years of age (123 cases, 43 controls) and MEE from 103 cases (93 with bilateral effusion - 196 MEE samples) were collected between September 2022 to December 2023. Nasopharyngeal carriage of H. influenzae was more common and density 10 times higher in cases compared to controls (84.2% H. influenzae carriage-positive cases versus 48.9% of controls, p=0.024; mean DNA concentration of 1.8pg/µL versus 0.13pg/µL, p=0.037). S. pneumoniae was more commonly carried in cases (not significant), and carriage density was higher in cases compared to controls (mean pneumococcal DNA concentration of 0.4pg/µL versus 0.09pg/µL, p=0.049). M. catarrhalis carriage and carriage density were similar between cases and controls (82.1% versus 76.7%). Carriage of 2 or more otopathogen species was common (80% of swabs). In the MEE, H. influenzae predominated (53% PCR-positive) followed by M. catarrhalis (31%), S. pneumoniae (22%), S. aureus (6%), S. pyogenes (2%) and P. aeruginosa (2%). Polymicrobial infection was identified in 26% of effusions. Of the S. pneumoniae PCR-positive MEE, 14 specimens from 11 children were culturable and all serotypes were non-PCV13 types. The aetiology of recurrent and/or chronic OM in children continues to be primarily associated with H. influenzae. These data highlight the need for a concerted effort to develop effective preventative strategies for H. influenzae, most notably, nontypeable (NTHi). Higher valency PCVs may impact on pneumococcal OM.
Mitophagy in Alzheimer's disease and other metabolic disorders: a focus on mitochondrial-targeted therapeutics
Authors: Shadt Skawratananond, Daniel X Xiong, Charlie Zhang, Sahil Tonk, Aljon Pinili, Brad Delacruz, Patrick Pham, Shane C Smith, Rahul Navab, P Hemachandra Reddy
Journal: Ageing Research Reviews (2025)
HER2-targeted star polymer conjugates for improved tumor distribution and efficacy
Authors: Silvia Sonzini, Richard M England, Alexander N Kapustin, Jennifer I Moss, Daniel Sutton, Aaron Smith, Soumya Sharma, Elise Siouve, Mariarosa Mazza, Peter Ravn, Sanya Puri, Marianne Ashford
Journal: Journal of Controlled Release (2025)

Actively targeted nanoparticle systems have the potential to improve delivery to tumors over untargeted systems however the design rules to achieve this have not been fully elucidated. A HER2-targeted polymer drug delivery system composed of a 32-arm star polymer (SD) conjugated with the TOP1 inhibitor molecule SN-38, with a trastuzumab antigen binding fragment (HER2-Fab), has been used to target cancer cells overexpressing this receptor. The HER2-Fab was attached to the SD at two different densities (average of 1 or 3 Fabs per star polymer) and compared to the native star polymer without Fab. In vitro experimentation showed that both the targeted star polymers (HER2-SDs) had better binding and uptake in HER2-positive cell lines (SK-BR3 and HEK293) compared to the non-targeted SD. In vivo biodistribution studies showed enhanced accumulation of HER2-targeted SDs in tumors, but not normal tissues, particularly at the later (96 h post-dose) timepoint. The HER2-SDs demonstrated increased localization with tumor cells rather than in stromal regions, greater penetration into the tumor core and a more homogenous distribution in the tumor section than the untargeted SD. The targeted star polymer conjugated to SN-38 was tested for anti-tumor activity in a HER2-positive gastric cancer xenograft in mice and showed significantly greater efficacy compared to untargeted SDs.
Biological effects of rapid short pulses of focused ultrasound for drug delivery to the brain
Authors: Sophie V Morse, Sarah Rimer, Grainne Geoghegan, Manaal Shah, Nicholas Chan, Ceren Yalcin, Maria Afonso Mota Cruz Pereira, Lucia Rohfleisch, Neema Nkontchou, Samuel Winiarski, Jamie Ee, Aurna Maitra, Tiffany G Chan, Magdalena Sastre, James J Choi
Journal: Journal of Controlled Release (2025)

Focused ultrasound in combination with intravenously injected microbubbles offers a non-invasive and localised method to deliver drugs across the blood-brain barrier, enabling targeted treatment of brain disorders. Recently, we have shown that applying sequences of Rapid Short-Pulses (RaSP; 5 μs pulses emitted at 1.25 kHz grouped into 10 ms bursts) of ultrasound can deliver drugs with an improved efficacy and safety profile compared with traditionally-used longer pulses (> 10 ms). In this study, we examined the extent to which RaSP sequences allowed the extravasation of endogenous blood proteins, including albumin and immunoglobulin, as well as T cells, into the brain parenchyma. We also investigated the effect of RaSP ultrasound treatments on synaptic connectivity, and the distribution and excretion of fluorescently-labelled 3 kDa dextran delivered to the brain with RaSP. The left hippocampus of mice was sonicated with either a RaSP sequence (5 μs at 1.25 kHz in groups of 10 ms at 0.5 Hz) or a long pulse sequence (10 ms at 0.5 Hz), at 0.35, 0.53 and 0.71 MPa with a 1-MHz center frequency. Significantly less albumin was detected in RaSP-treated brains immediately after treatment and was cleared within 10 min compared to those treated with long pulses, while immunoglobulin was hardly detected in RaSP-treated brains at 0, 10 or 20 min after treatment. No T cells were detected in RaSP-treated brains at 0.35, 0.53 or 0.71 MPa after 0 or 2 h. In long pulse samples, however, T cells did extravasate when using the two higher acoustic pressures, 0.53 and 0.71 MPa, immediately after treatment. Quantification of dendritic spine area revealed no differences between RaSP-treated hippocampi compared to untreated contralateral hippocampi and control mice following three weekly ultrasound treatments. Finally, fluorescently-labelled dextran increasingly moved towards blood vessels and away from the parenchyma once delivered to the brain with both RaSP and long pulse sequences. Uptake of dextran within cells decreased over time with both sequences, and long pulses lead to a larger number of vessels with dextran uptake. This study highlights that RaSP ultrasound sequences can deliver molecules across the blood-brain barrier with minimal extravasation of endogenous proteins and no T cell infiltration, while preserving dendritic spine integrity, thus offering an improved safety profile.
Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model.
Authors: Samuel Mon-Wei Yu, John Yongjoon Choi, Jamie Kady, Marina De Cos, Jenny S Wong, Emily King, Nour Younis, Nadim Al Rahy, Soltan Al Chaar, Houda Djebli, Siawosh Eskandari, Stephen Samuel, Tamara Merhej, Nivedha Sukumar, Jia-Ren Lin, Jia-Yun Chen, Yilin Xu, Sandro Santagata, Astrid Weins, Melissa Yeung, Paolo Cravedi, Kirk N Campbell, Dario Lemos, Joseph V Bonventre, Michael Brehm, Jamil Azzi
Journal: Kidney International (2025)
Quercetin liposomes conjugated with hyaluronidase: An efficient drug delivery system to block pancreatic cancer
Authors: Ge Sun, Ying Wu, Jiekai Li, Mingjie Yang, Hang Xu, Yiping Li, Peilin Tong, Rong Shao, Yingbin Liu, Xianming Kong
Journal: Journal of Controlled Release (2025)
Neutrophil serine proteases NE and PR3 controlled by the miR-223/STAT3 axis potentiate MASH and liver fibrosis
Authors: Pengfei Zhang, Dongyang Liu, Lihong Wu, Xiaoqin Wu, Kaixuan Yan, Mengqi Fan, Danqi Zou, Erfei Song, Yumeng Jiang, Ying Xu, Xiaoping Wu, Shufei Zang, Fei Zhu, Yuqi Chen, Zhikang Cen, Mengqiao Bi, Yuying Zhang, Xicheng Wang, Wei Liu, Rongxin Zhang, Cunchuan Wang, Ruby Lai Chong Hoo, Aimin Xu, Dewei Ye
Journal: Hepatology (2025)

Background &amp; Aims: Metabolic dysfunction-associated steatohepatitis (MASH) and its related liver fibrosis represent a substantial public health burden with limited treatment options. Although MASH is associated with enhanced neutrophil infiltration in the liver, the mediators and mechanisms underlying neutrophil-driven progression of MASH and fibrosis remain largely unknown. This study aimed to investigate the role of neutrophil serine proteases neutrophil elastase (NE) and proteinase 3 (PR3) in the development of MASH and fibrosis. Approach: Liver biopsies from 121 morbidly obese patients were recruited for analysis. NE -/- , PR3 -/- , microRNA-223 (miR-223) -/- mice and their wild type controls were fed a choline-deficient, L-amino acid-defined, high-fat diet to induce MASH fibrosis. Bone marrow transplantation was performed to generate mice with miR-223 chimerism in bone marrow-derived cells. Results: NE and PR3 content in human liver with MASH and fibrosis was markedly increased in close association with histological features. Genetic ablation or AAV-mediated inhibition of NE and PR3 substantially alleviated MASH and liver fibrosis in mice. Mechanistic study revealed that miR-223 suppressed neutrophilic NE and PR3 by targeting STAT3. MiR-223 deficiency augmented inflammation and fibrosis in mouse liver. Bone marrow transplantation-induced miR-223 chimerism significantly affected hepatic NE/PR3 content and the progression of MASH fibrosis in mice. Conclusions: Our findings reveal that NE and PR3 are key factors triggering liver inflammation to potentiate the development of MASH and liver fibrosis, offering insight into the development of new therapeutic approaches that target NE and PR3.
Associations between metabolic syndrome and cholangiocarcinoma risk: A large-scale population-based cohort study
Authors: Tzu-I Chen, Ming-Huang Chen, Szu-Ching Yin, Chih-Jo Lin, Tram Kim Lam, Chia-Wei Huang, Yi-Ting Chen, Xia-Rong Liu, Yun-Zheng Gao, Wan-Lun Hsu, Hsuan-Yu Chen, Ta-Sen Yeh, Jill Koshiol, Mei-Hsuan Lee
Journal: Hepatology (2025)

Background and Aims: This large-scale, population-based cohort study examined the associations between metabolic syndrome and cholangiocarcinoma risk, including its intra- and extra-hepatic forms. Approach and Results: A total of 4,932,211 adults aged ≥40 years participated in a government-initiated health checkup program (2012–2017), which collected lifestyle data, anthropometric measurements, and biochemical tests. Follow-up continued until 2021, with data linkage to National Cancer and Death Registries to ascertain the occurrence of cholangiocarcinoma and obtain vital status information. Fine and Gray models accounted for competing risks. During 35,879,371 person-years of follow-up, 6,117 cholangiocarcinoma cases were identified, with an incidence rate of 17.05 (95% CI: 15.90-18.20) per 100,000 person-years. Individuals with metabolic syndrome had significantly higher incidences of both intra- and extra-hepatic cholangiocarcinoma ( p &lt;0.0001). The multivariate-adjusted hazard ratio (HR) for cholangiocarcinoma among those with metabolic syndrome was 1.20 (1.14-1.27). Stratification analyses by age, sex, liver enzyme levels, and comorbidities consistently demonstrated an increased cholangiocarcinoma risk among individuals with metabolic syndrome. A dose-response relationship was observed, with a higher number of metabolic components correlating with an elevated cholangiocarcinoma risk, even after accounting for all-cause mortality as a competing risk. The adjusted subdistribution HRs ranged from 1.16 (95% CI: 1.02–1.32) for individuals with one metabolic component to 1.67 (95% CI: 1.45–1.94) for those with five ( p for trend &lt;0.0001). Conclusions: The positive association between metabolic syndrome and cholangiocarcinoma risk suggests that managing metabolic risk factors might reduce the occurrence of both intra- and extra-hepatic cholangiocarcinoma.
Early screening, diagnosis and recurrence monitoring of hepatocellular carcinoma in chronic hepatitis B patients based on serum N-glycomics analysis: A cohort study
Authors: Rui Su, Xuemei Tao, Lihua Yan, Yonggang Liu, Cuiying Chitty Chen, Ping Li, Jia Li, Jing Miao, Feng Liu, Wentao Kuai, Jiancun Hou, Mei Liu, Yuqiang Mi, Liang Xu
Journal: Hepatology (2025)

Background and Aims: Hepatocellular carcinoma (HCC) poses a significant global health burden, with hepatitis B virus (HBV) being the predominant etiology in China. However, current diagnostic markers lack the requisite sensitivity and specificity. This study aims to develop and validate serum N-glycomics-based models for the diagnosis and prognosis of HCC in patients with chronic hepatitis B (CHB)-related cirrhosis. Approach and Results: This study enrolled a total of 397 patients with CHB-related cirrhosis and HCC for clinical management. N-glycomics profiling was conducted on all participants and clinical data were collected. First, machine learning-based models, HCC-GRF and HCC-GSVM, were established for early screening and diagnosis of HCC using N-glycomics. The AUC values in the validation set were 0.967 (95% CI: 0.930-1.000) and 0.908 (0.840-0.976) for HCC-GRF and HCC-GSVM, respectively, outperforming AFP [0.687 (0.575-0.765)] and PIVKA-II [0.665 (0.507-0.823)]. It also showed superiority in subgroups analysis and external validation. Calibration and decision curve analysis also showed good predictive performance. Additionally, we developed a prognostic model, the prog-G model, based on N-glycans to monitor recurrence in HCC patients after curative treatment. During the follow-up period, it was observed that this model correlated with the clinical condition of the patients and could identify all recurrent HCC cases (n=12) prior to imaging findings, outperforming AFP (n=7) and PIVKA-II (n=9), while also detecting recurrent lesions earlier than imaging. Conclusions: N-glycomics models can effectively predict the occurrence and recurrence of HCC to improving the efficiency of clinical decision-making and promoting the precision treatment of HCC.
Bioprinting of Alginate-Norbornene bioinks to create a versatile platform for kidney in vitro modeling
Authors: Francesca Perin, Anna Ricci, Sveva Fagiolino, Aleksandra Rak-Raszewska, Helen Kearney, Jopeth Ramis, Ivo Bereen, Matthew Baker, Devid Maniglio, Antonella Motta, Lorenzo Moroni, Carlos Mota
Journal: Bioactive Materials (2025)
A systematic review and meta-analysis of diagnostic performance comparison between generative AI and physicians
Authors: Hirotaka Takita, Daijiro Kabata, Shannon L. Walston, Hiroyuki Tatekawa, Kenichi Saito, Yasushi Tsujimoto, Yukio Miki, Daiju Ueda
Journal: npj Digital Medicine (2025)

Abstract While generative artificial intelligence (AI) has shown potential in medical diagnostics, comprehensive evaluation of its diagnostic performance and comparison with physicians has not been extensively explored. We conducted a systematic review and meta-analysis of studies validating generative AI models for diagnostic tasks published between June 2018 and June 2024. Analysis of 83 studies revealed an overall diagnostic accuracy of 52.1%. No significant performance difference was found between AI models and physicians overall ( p = 0.10) or non-expert physicians ( p = 0.93). However, AI models performed significantly worse than expert physicians ( p = 0.007). Several models demonstrated slightly higher performance compared to non-experts, although the differences were not significant. Generative AI demonstrates promising diagnostic capabilities with accuracy varying by model. Although it has not yet achieved expert-level reliability, these findings suggest potential for enhancing healthcare delivery and medical education when implemented with appropriate understanding of its limitations.
Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning
Authors: Zilong Bai, Mohamed Osman, Matthew Brendel, Catherine M. Tangen, Thomas W. Flaig, Ian M. Thompson, Melissa Plets, M. Scott Lucia, Dan Theodorescu, Daniel Gustafson, Siamak Daneshmand, Joshua J. Meeks, Woonyoung Choi, Colin P. N. Dinney, Olivier Elemento, Seth P. Lerner, David J. McConkey, Bishoy M. Faltas, Fei Wang
Journal: npj Digital Medicine (2025)

Building accurate prediction models and identifying predictive biomarkers for treatment response in Muscle-Invasive Bladder Cancer (MIBC) are essential for improving patient survival but remain challenging due to tumor heterogeneity, despite numerous related studies. To address this unmet need, we developed an interpretable Graph-based Multimodal Late Fusion (GMLF) deep learning framework. Integrating histopathology and cell type data from standard H&E images with gene expression profiles derived from RNA sequencing from the SWOG S1314-COXEN clinical trial (ClinicalTrials.gov NCT02177695 2014-06-25), GMLF uncovered new histopathological, cellular, and molecular determinants of response to neoadjuvant chemotherapy. Specifically, we identified key gene signatures that drive the predictive power of our model, including alterations in TP63, CCL5, and DCN. Our discovery can optimize treatment strategies for patients with MIBC, e.g., improving clinical outcomes, avoiding unnecessary treatment, and ultimately, bladder preservation. Additionally, our approach could be used to uncover predictors for other cancers.
ORCHESTRA Delphi Consensus: diagnostic and therapeutic management of SARS-CoV-2 infection in haematological patients
Authors: Lorenzo Maria Canziani, Anna Maria Azzini, Jon Salmanton-García, Alessia Savoldi, Maria Giulia Caponcello, Zeno Pasquini, Livio Pagano, Oliver A Cornely, Antonella Cingolani, Valentina Mazzotta, Federica Cosentino, Jesús Rodríguez Baño, Mauro Krampera, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2025)
A synthetic opsin restores vision in patients with severe retinal degeneration
Authors: Samarendra K Mohanty, Santosh Mahapatra, Subrata Batabyal, Michael Carlson, Gayatri Kanungo, Ananta Ayyagari, Kissaou Tchedre, Joel A Franco, Michael Singer, Samuel Barone, Sai Chavala, Vinit B Mahajan
Journal: Molecular Therapy (2025)
Molybdoenzymes-Emulating Bio-Heterojunction Hydrogel with Rapid Disinfection and Macrophage Reprogramming for Wound Regeneration
Authors: Xiong Zhou, Peiqi Wang, Lu Xie, Yau Kei Chan, Zheng Jiao, Rui Shu, Ding Bai, Shuangquan Lai, Yi Deng
Journal: Biomaterials (2025)
Design of NanoBiT-Nanobody-based FGL1 biosensors for early assisted diagnosis of esophageal cancer
Authors: Lingyun Li, Zhongyun Lan, Huarui Qiao, Xiangjing Meng, Ziyang Shi, Wanting Zhang, Yi'ang Wang, Zengchao Sun, Qianqian Cui, Lu Wang, Siyu Zhou, Fangzheng Hu, Daizhou Zhang, Yuanyuan Dai, Hao Chen, Yong Geng
Journal: Biomaterials (2025)
Co-infection dynamics of SARS-CoV-2 and respiratory viruses in the 2022/2023 respiratory season in the Netherlands
Authors: Gesa Carstens, Eva Kozanli, Kirsten Bulsink, Scott McDonald, Mansoer Elahi, Jordy de Bakker, Maarten Schipper, Rianne van Gageldonk-Lafeber, Susan van den Hof, Albert Jan van Hoek, Dirk Eggink
Journal: Journal of Infection (2025)
EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer
Authors: Jiefu Zhou, Min He, Qiong Zhao, Enxian Shi, Hairong Wang, Vaidehi Ponkshe, Jiahang Song, Zhengquan Wu, Dongmei Ji, Gisela Kranz, Anna Tscherne, Sabina Schwenk-Zieger, Nilofer Abdul Razak, Julia Hess, Claus Belka, Horst Zitzelsberger, Iordanis Ourailidis, Fabian Stögbauer, Melanie Boxberg, Jan Budczies, Christoph A. Reichel, Martin Canis, Philipp Baumeister, Hongxia Wang, Kristian Unger, Andreas Mock, Olivier Gires
Journal: Molecular Cancer (2025)

Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) is a severe, frequently lethal condition. Oncogene addiction to epidermal growth factor receptor (EGFR) is a hallmark of HNSCC, but the clinical efficacy of EGFR-targeted therapies remains low. Understanding molecular networks governing EGFR-driven progression is paramount to the exploration of (co)-treatment targets and predictive markers. Methods We performed function-based mapping of differentially expressed genes in EGFR-mediated local invasion (fDEGs) using photoconvertible tracers and RNA-sequencing (RNA-seq) in a cellular 3D-model. Results Upon alignment with public single-cell RNA-seq (scRNA-seq) datasets and HNSCC-specific regulons, a gene regulatory network of local invasion (invGRN) was inferred from gene expression data, which was overrepresented in budding tumors. InvGRN comprises the central hubs inhibin subunit beta alpha ( INHBA ) and snail family transcriptional repressor 2 ( SNAI2 ), and druggable fDEGs integrin subunit beta 4 ( ITGB4 ), laminin 5 ( LAMB3 / LAMC2 ), and sphingosine kinase 1 ( SPHK1 ). Blockade of INHBA repressed local invasion and was reverted by activin A, laminin 5, and sphingosine-1-phosphate, demonstrating a functional interconnectivity of the invGRN. Epithelial-to-mesenchymal transition (EMT) of malignant cells and the invGRN are induced by newly defined EGFR-activity subtypes with prognostic value that are promoted by amphiregulin ( AREG ) and epiregulin ( EREG ). Importantly, co-inhibition of SPHK1 showed synthetic effects on Cetuximab-mediated invasion blockade and high expression of selected fDEGs was associated with response to Cetuximab in patient-derived xenotransplantation (PDX) and R/M-HNSCC patients. Conclusions We describe an actionable network of EGFR-mediated local invasion and define druggable effectors with predictive potential regarding the response of R/M-HNSCC to Cetuximab.
Preoxygenation strategies for intubation of patients who are critically ill: a systematic review and network meta-analysis of randomised trials
Authors: Tyler Pitre, Winnie Liu, Dena Zeraatkar, Jonathan D Casey, Joanna C Dionne, Kevin W Gibbs, Adit A Ginde, Natalie Needham-Nethercott, Todd W Rice, Matthew W Semler, Bram Rochwerg
Journal: The Lancet Respiratory Medicine (2025)