tbuckley/cabot-search huggingface dataset:
Dynamic versus static testing and in vivo mechanical performance of poly(glycolide-trimethylene carbonate-ε-caprolactone) delayed release implants
Authors: Norman L Ilich, Siamak Saifzadeh, Dietmar W Hutmacher, Tim R Dargaville
Journal: Journal of Controlled Release (2025)

The manufacturing of millimeter-sized implants for delayed drug release presents several challenges. However, it allows for the encapsulation of a therapeutic agent within a single device, enabling precise control over factors such as geometry, polymer composition, and drug formulation. The relatively large size, however, means that when inserted into subcutaneous tissue the implants experience mechanical stresses that are not predicted by current in vitro methods consisting of incubation under static conditions. The absence of a suitable in vitro assay complicates the device development process, often resulting in unsuccessful preclinical testing. This study presents the fabrication of flexible implants of poly(glycolide-co-trimethylene carbonate-co-ε-caprolactone), in vitro degradation, and performance when implanted subcutenously in rats. Predicting the in vivo behaviour is addressed by the development of a scalable, high-throughput, cyclic flexural testing system. Flexural loading of the implant demonstrates a clear impact on loss in mechanical properties compared to static conditions in lipoprotein lipase. Under static conditions, a lag time of 60 days is observed before sustained release of the model dye. Conversely, the flexural loading assay results in early fracture by 20 days consistent with what is observed in the animal model. Decisively, this study emphasizes the importance of tailoring in vitro assays according to the dosage form and intended mode of administration. Implementation of a dynamic in vitro assay is invaluable to efficiently evaluate device viability and release kinetics and will, in turn, allow a more streamlined workflow for translation into preclinical models.
Biosensors and Biomarkers for the Detection of Motion Sickness
Authors: Yanbing Wang, Chen Liu, Wenjie Zhao, Qingfeng Wang, Xu Sun, Sheng Zhang
Journal: Advanced Healthcare Materials (2025)

Motion sickness (MS) is a prevalent syndrome that predominantly occurs during transportation and virtual reality (VR). The absence of reliable indicators and detection methods makes precise diagnosis difficult. Biomarker concentrations and trends may imply individual susceptibility, symptom classification, and the specific progression of MS. It is therefore essential to explore biosensors capable of providing sensitive, accurate, and real-time monitoring of biomarkers. This review provides a summary of the pathogenesis and biological pathways underlying MS, followed by an examination of biomarkers and their research progress. The most recent electrochemical biosensors developed for the non-invasive detection of representative biomarkers (e.g., cortisol, α-amylase, and estrogen) are comprehensively summarized. The effectiveness of these biosensors in practical application is discussed. It is anticipated that electrochemical biosensors can be gradually improved from the sampling methods, multimodal combinations, and data processing, which can facilitate the detection of MS toward individuation, refinement, and intelligence.
A step forwarded on the in vitro and in vivo validation of rifabutin-loaded liposomes for the management of highly virulent MRSA infections
Authors: Mariana P Coelho, Jacinta O Pinho, Sandra N Pinto, Maria Manuela Gaspar
Journal: Journal of Controlled Release (2025)

Staphylococcus aureus (S. aureus) infections, especially methicillin resistant (MRSA), constitute an alarming public health issue due to its association with high mortality, morbidity, and hospitalization costs. The increasing antibiotic resistance and biofilm-associated infections of MRSA prompted the discovery of novel and more effective therapeutic strategies. Our team has been working on alternative therapies against S. aureus infections. For this, we have been repurposing an existing antibacterial drug, rifabutin (RFB), through its association to a nanotechnological platform, liposomes, aiming to promote a preferential targeting to infected sites and maximizing its potential antibacterial effect. The therapeutic potential of RFB formulations against a MRSA commercial strain (MRSA ATCC®-33592), either in planktonic or biofilm forms, was assessed. RFB displayed higher antibacterial effects towards biofilm than vancomycin (VCM), the gold standard treatment against MRSA infections, with MBIC50 values of 103 and > 800 μg/ml, respectively. Moreover, the antimicrobial effect of RFB-loaded liposomes demonstrated to be lipid composition-dependent based on MIC50 and MBIC50 values, which was also confirmed by confocal laser scanning microscopy. These studies supported that for positively charged RFB liposomes an electrostatic interaction at biofilm surface occurs without internalization. On the other hand, for RFB-loaded liposomes with neutral surface charge a high internalization within the biofilm was observed. Moreover, this RFB liposomal formulation has also demonstrated to be stable in human plasma, as more than 83 % of RFB was still associated to liposomes 24 h after incubation at 37 °C. The proof of concept of RFB formulations was assessed in MRSA systemic murine models of infection. Therapeutic effect and survival rates were evaluated for animals induced and treated with RFB in free and liposomal forms and compared with negative and positive controls. For the lower infection murine model, 100 % survival was achieved for all groups under study. However, in a higher infection model only for the group of animals treated with RFB incorporated in liposomes a 100 % survival was attained. In terms of bacterial burden, RFB formulations exhibited lower levels when compared to VCM, even using a lower therapeutic dose: 20 vs 40 mg/kg of body weight, respectively. Overall, RFB constitutes an alternative and effective therapeutic strategy towards MRSA infections, being this effect potentiated through its association to a lipid nanoplatform.
Reactive oxygen species regulate early development of the intestinal macrophage-microbiome interface
Authors: Zohreh Mansoori Moghadam, Bei Zhao, Candice Raynaud, Valentina Strohmeier, Jana Neuber, Anne Kathrin Lösslein, Sabrina Qureshi, Vitka Gres, Tara Ziegelbauer, Sebastian Baasch, Christoph Schell, Klaus Warnatz, Naohiro Inohara, Gabriel Nuñez, Thomas Clavel, Stephan P. Rosshart, Julia Kolter, Philipp Henneke
Journal: Blood (2025)
Outcomes of Pembrolizumab plus chemotherapy for patients with metastatic non-squamous NSCLC: Real-world evidence
Authors: Irina Surovtsova, Felix J. F. Herth, Daria B. Kokh, Philipp Morakis
Journal: Pulmonology (2025)

Background Pembrolizumab with chemotherapy (immunochemotherapy) has shown encouraging overall survival (OS) benefits in non-squamous mNSCLC, as demonstrated by the KEYNOTE-189 trial. However, randomised controlled trials may not fully capture the diversity of real-world patients. This study aims to evaluate immunochemotherapy outcomes in a real-world setting, including subgroups underrepresented in the KEYNOTE-189 trial.
SETD2 loss-of-function uniquely sensitizes cells to epigenetic targeting of NSD1-directed H3K36 methylation
Authors: Ryan T. Wagner, Ryan A. Hlady, Xiaoyu Pan, Liguo Wang, Sungho Kim, Xia Zhao, Louis Y. El Khoury, Shafiq Shaikh, Jian Zhong, Jeong-Heon Lee, Jolanta Grembecka, Tomasz Cierpicki, Thai H. Ho, Keith D. Robertson
Journal: Genome biology (2025)
An institutional framework to support ethical fair and equitable artificial intelligence augmented care
Authors: Steven Dykstra, Matthew MacDonald, Rhys Beaudry, Dina Labib, Melanie King, Yuanchao Feng, Jacqueline Flewitt, Jeff Bakal, Bing Lee, Stafford Dean, Marina Gavrilova, Paul W. M. Fedak, James A. White
Journal: npj Digital Medicine (2025)

Coordinated access to multi-domain health data can facilitate the development and implementation of artificial intelligence-augmented clinical decision support (AI-CDS). However, scalable institutional frameworks supporting these activities are lacking. We present the PULSE framework, aimed to establish an integrative and ethically governed ecosystem for the patient-guided, patient-contextualized use of multi-domain health data for AI-augmented care. We describe deliverables related to stakeholder engagement and infrastructure development to support routine engagement of patients for consent-guided data abstraction, pre-processing, and cloud migration to support AI-CDS model development and surveillance. Central focus is placed on the routine collection of social determinants of health and patient self-reported health status to contextualize and evaluate models for fair and equitable use. Inaugural feasibility is reported for over 30,000 consecutively engaged patients. The described framework, conceptually developed to support a multi-site cardiovascular institute, is translatable to other disease domains, offering a validated architecture for use by large-scale tertiary care institutions.
Efficacy and safety of CAR-T cell therapy in B-ALL patients previously treated with blinatumomab
Authors: Yurou Chu, Biqi Zhou, Rui Gao, Miao Miao, Huiying Qiu, Xiaowen Tang, Ying Wang, Suning Chen, Liqing Kang, Depei Wu, Yang Xu
Journal: Blood Cancer Journal (2025)
Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer
Authors: Seungyeul Yoo, Ayushi S. Patel, Sarah Karam, Yi Zhong, Li Wang, Feng Jiang, Ranran Kong, Sharon Bikvan, Wenhui Wang, Abhilasha Sinha, Charles A. Powell, Jun Zhu, Hideo Watanabe
Journal: Journal of Hematology & Oncology (2025)
Luspatercept for the treatment of anemia in allo-HSCT for patients with hematological diseases
Authors: Xiangke Xin, Wenli Zhang, Zhen Li, Ruirui Gui, Juan Wang, Liyun Ji, Yanli Zhang, Baijun Fang, Yongping Song, Yingling Zu, Jian Zhou
Journal: Blood Cancer Journal (2025)
Ribosomal RNA Biosynthesis Functionally Programs Tumor-Associated Macrophages to Support Breast Cancer Progression
Authors: Brandon J. Metge, Li'an Williams, Courtney A. Swain, Dominique C. Hinshaw, Amr R. Elhamamsy, Dongquan Chen, Rajeev S. Samant, Lalita A. Shevde
Journal: Cancer Research (2025)

Abstract Macrophages are important cellular components of the innate immune system, serving as the first line of immune defense. They are also among the first immune cells to be reprogrammed by the evolving tumor milieu into tumor-supportive macrophages that facilitate tumor progression and promote therapeutic evasion. Here, we uncovered that macrophages from preneoplastic breast lesions were enriched for ribosome biosynthesis genes, indicating that this is an early event that is maintained in the tumor tissue. Furthermore, following treatment with irradiation or chemotherapy, breast tumors featured an abundance of tumor-supporting macrophages that displayed an enrichment of signatures of ribosomal RNA expression and ribosome biosynthesis. Consistently, rRNA synthesis was increased in tumor-supportive macrophages. In preclinical models of mammary cancer, a low dose of the RNA biogenesis inhibitor BMH-21 converted pro-tumor macrophages to tumor-suppressive macrophages and supported an inflammatory tumor microenvironment. Inhibition of rRNA transcription stimulated a nucleolar stress response that activated the p53 and NF-κB pathways, which orchestrated impaired ribosome biogenesis checkpoint signaling that induced an inflammatory program in macrophages. Finally, inhibiting ribosome biogenesis augmented the effectiveness of neoadjuvant therapy. Together, these findings provide evidence that ribosome biogenesis is a targetable dependency to reprogram the tumor immune microenvironment.
Antithrombotic Therapy to Minimize Total Events After ACS or PCI in Atrial Fibrillation
Authors: Manasi Tannu, Renato D Lopes, Daniel M Wojdyla, Shaun G Goodman, Ronald Aronson, Roxana Mehran, Christopher B Granger, Stephan Windecker, John H Alexander, W Schuyler Jones
Journal: Journal of the American College of Cardiology (2025)
Long-Term Outcomes of Contemporary Surgical Repair for Degenerative Mitral Regurgitation
Authors: Benedetto Del Forno, Guido Ascione, Davide Carino, Mariangela D'Ovidio, Elisabetta Lapenna, Alessandro Verzini, Paolo Denti, Andrea Blasio, Nicolò Azzola Guicciardi, Anna Mara Scandroglio, Fabrizio Monaco, Eustachio Agricola, Marina Davoli, Giorgia Duranti, Giovanni Baglio, Enrico Coscioni, Alessandro Castiglioni, Ottavio Alfieri, Michele De Bonis, Francesco Maisano
Journal: Journal of the American College of Cardiology (2025)
Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER
Authors: Siyan Liu, Marisa C. Hamilton, Thomas Cowart, Alejandro Barrera, Lexi R. Bounds, Alexander C. Nelson, Sophie F. Dornbaum, Julia W. Riley, Richard W. Doty, Andrew S. Allen, Gregory E. Crawford, William H. Majoros, Charles A. Gersbach
Journal: Cell Genomics (2025)

Highlights•CRISPR barnyard screens characterize the distribution of ambient gRNAs•CRISPR barnyard screens identify factors influencing the abundance of ambient gRNAs•CLEANSER is open-source software that assigns gRNAs to cells in perturb-seq screens•CLEANSER demonstrates increased accuracy in calling hits in published datasetsSummarySingle-cell RNA sequencing CRISPR (perturb-seq) screens enable high-throughput investigation of the genome, allowing for characterization of thousands of genomic perturbations on gene expression. Ambient gRNAs, which are contaminating gRNAs, are a major source of noise in perturb-seq experiments because they result in an excess of false-positive gRNA assignments. Here, we utilize CRISPR barnyard assays to characterize ambient gRNAs in perturb-seq screens. We use these datasets to develop CRISPR Library Evaluation and Ambient Noise Suppression for Enhanced single-cell RNA-seq (CLEANSER), a mixture model that filters ambient gRNAs. CLEANSER includes both gRNA and cell-specific normalization parameters, correcting for confounding technical factors that affect individual gRNAs and cells. The output of CLEANSER is the probability that a gRNA-cell assignment is in the native distribution over the ambient distribution. We find that ambient gRNA filtering methods impact differential gene expression analysis outcomes and that CLEANSER outperforms alternate approaches by increasing gRNA-cell assignment accuracy across multiple screen formats.Graphical abstract
Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence
Authors: Sara Arce-Gallego, Pablo Cresta Morgado, Luisa Delgado-Serrano, Sara Simonetti, Macarena Gonzalez, Paula Romero-Lozano, David Marmolejo, Rafael Morales-Barrera, Gisela Mir Arnau, Maria Eugenia Semidey, Daniel Aguilar, Sarai Cordoba-Terreros, Richard Mast, Matias de Albert, Jacques Planas, Mercè Cuadras, Xavier Maldonado, Cristina Suarez, Irene Casanova-Salas, Mariona Figols, Sara Cros, Alba Mas, Lara Nonell, Rodrigo Dienstmann, Paolo Nuciforo, Ana Vivancos, Alba Llop-Guevara, Joan Carles, Violeta Serra, Joaquin Mateo
Journal: Cell Reports Medicine (2025)

Highlights•RAD51-IF is feasible in FFPE clinical biopsies from patients with advanced prostate cancer•Low RAD51 scores associate with alterations in BRCA1/2•Low RAD51 scores associate with improved outcomes from PARPi or platinum chemotherapy•RAD51-IF captures HRR restoration of function upon drug resistanceSummaryMetastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and RAD51 immunofluorescence (RAD51-IF) in 219 primary or metastatic biopsies from 187 patients with stage IV prostate cancer. NGS showed frequent genomic alterations in TP53 (40%), AR (15%), PTEN (14%), FOXA1 (12%), MYC (10%), BRCA2 (9%), ATM (8%), and BRCA1 (2%). We pursued RAD51-IF in 206 samples; of those, 139/206 (67%) were evaluable. 21% of samples had RAD51-low score compatible with HRR deficiency (HRD). RAD51-IF showed high sensitivity (71%) and specificity (86%) for BRCA1/2 alterations. Patients with RAD51-low scores experienced longer progression-free survival (PFS) on poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum chemotherapy. RAD51-IF is feasible in routine clinical samples from patients with mPC and is associated with clinically relevant HRR gene alterations.Graphical abstract
The metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system
Authors: Stephanie E. Simonds, Jack T. Pryor, Brian Y.H. Lam, Georgina K. Dowsett, Tomris Mustafa, Astrid Munder, Kayla Elysee, Eglantine Balland, Lachlan O. Cowley, Giles S.H. Yeo, Andrew Lawrence, David C. Spanswick, Michael A. Cowley
Journal: Cell Reports Medicine (2025)

Highlights•Amphetamine indirectly depolarizes a subpopulation of POMC neurons via the activation of excitatory serotonergic inputs and the suppression of inhibitory noradrenergic inputs•Amphetamine activates POMC neurons, via MC4R, to reduce food intake and body weight•The tachycardic and hypertensive effects of amphetamine are partially dependent on the melanocortin system•Antagonism of the melanocortin system prevents AMPH-induced hypertension and tachycardiaSummaryAmphetamine (AMPH) exerts metabolic and cardiovascular effects. The central melanocortin system is a key regulator of both metabolic and cardiovascular functions. Here, we show that the melanocortin system partially mediates AMPH-induced anorexia, energy expenditure, tachycardia, and hypertension. AMPH increased α-melanocyte stimulating hormone (αMSH) secretion from the hypothalamus, elevated blood pressure and heart rate (HR), increased brown adipose tissue (BAT) thermogenesis, and reduced both food intake (FI) and body weight (BW). In melanocortin 4 receptor-deficient (MC4R knockout [KO]) mice, metabolic and cardiovascular effects of AMPH were significantly attenuated. Antagonism of serotonergic and noradrenergic neurotransmitter systems attenuated AMPH-induced αMSH secretion as well as AMPH-induced metabolic and cardiovascular effects. We propose that AMPH increases serotonergic activation of proopiomelanocortin (POMC) neurons and reduces the noradrenergic inhibition of POMC neurons, thereby disinhibiting them. Together, these presynaptic mechanisms result in increased POMC activity, increased αMSH secretion, and increased activation of MC4R pathways that regulate both the metabolic and cardiovascular systems.Graphical abstract
Single-cell delineation of the microbiota-gut-brain axis: Probiotic intervention in Chd8 haploinsufficient mice
Authors: Peifeng Ji, Ning Wang, You Yu, Junjie Zhu, Zhenqiang Zuo, Bing Zhang, Fangqing Zhao
Journal: Cell Genomics (2025)

Emerging research underscores the gut microbiome's impact on the nervous system via the microbiota-gut-brain axis, yet comprehensive insights remain limited. Using a CHD8-haploinsufficient model for autism spectrum disorder (ASD), we explored host-gut microbiota interactions by constructing a single-cell transcriptome atlas of brain and intestinal tissues in wild-type and mutant mice across three developmental stages. CHD8 haploinsufficiency caused delayed development of radial glial precursors and excitatory neural progenitors in the E14.5 brain, inflammation in the adult brain, immunodeficiency, and abnormal intestinal development. Selective CHD8 knockdown in intestinal epithelial cells generated Chd8ΔIEC mice, which exhibited normal sociability but impaired social novelty recognition. Probiotic intervention with Lactobacillus murinus selectively rescued social deficits in Chd8ΔIEC mice, with single-cell transcriptome analysis revealing underlying mechanisms. This study provides a detailed single-cell transcriptomic dataset of ASD-related neural and intestinal changes, advancing our understanding of the gut-brain axis and offering potential therapeutic strategies for ASD.
Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling
Authors: Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco
Journal: Cell Genomics (2025)
Return on Investment of Enhanced Behavioral Health Services
Authors: Matt Hawrilenko, Casey Smolka, Emily Ward, Geetu Ambwani, Millard Brown, Anita Mohandas, Martin Paulus, John Krystal, Adam Chekroud
Journal: JAMA Network Open (2025)

Importance Employer-sponsored benefit programs aim to increase access to behavioral health care, which may help contain health care costs. However, research has either focused solely on clinical outcomes or demonstrated reductions in medical claims without accounting for the costs of behavioral health services, leaving the financial return on investment unknown. Objective To determine whether a clinically effective employer-sponsored behavioral health benefit is associated with net medical cost savings. Design, Setting, and Participants This retrospective cohort study included participants eligible for an employer-sponsored behavioral health benefit between November 1, 2019, and May 31, 2023. Eligibility criteria included having a behavioral health diagnosis and, in the program group, attending at least 1 behavioral health appointment. Program users were matched to nonusers on medical risk scores, behavioral health diagnoses, date of diagnosis, age, sex, and employer. Participants were followed up for 1 year before and after the benefit launch. Exposure A digital platform screened individuals for common behavioral health conditions and provided access to video and in-person psychotherapy, medication management, care navigation, and self-guided digital content. Main Outcomes and Measures Primary outcomes were per member per month (PMPM) medical spending, inclusive of all medical claims and program costs. A difference-in-differences analysis was used to compare changes in net medical spending between groups from the year before and up to 1 year after an index mental health diagnosis. Results This study included 13 990 participants: 4907 of 4949 (99.1%) eligible program group members were matched to 9083 control participants. Their mean (SD) age was 37 (13.2) years, and most participants (65.5%) were female. Costs decreased in the program group relative to the control group, with a net difference-in-differences of −$164 PMPM (95% CI, −$228 to −$100 PMPM), corresponding to savings of $1070 per participant in the first program year and a return on investment of 1.9 times the costs (ie, every $100 invested reduced medical claims costs by $190). Behavioral health costs in the program group increased relative to the control group but were more than offset by decreases in physical health care costs. Savings were larger for participants with higher medical risk. Conclusions and Relevance In this cohort study, every $100 invested in an employer-sponsored behavioral health program with fast access to psychotherapy and medication management was associated with a reduction in medical claims costs by $190. These findings suggest that expanding access to behavioral health care may be a financially viable cost-reduction strategy for health care buyers.