tbuckley/cabot-search huggingface dataset:
Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
Authors: Iago Gonzalez-Prada, Arthur Barcelos Ribeiro, Marine Dion, Beatriz Magariños, Clémentine Lapoujade, Audrey Rousseau, Angel Concheiro, Emmanuel Garcion, Carmen Alvarez-Lorenzo
Journal: Journal of Controlled Release (2025)

Glioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl2 enabled in situ formation of Cu(DDC)2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSF-loaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively.
Photopharmacological activation of adenosine A1 receptor signaling suppresses seizures in a mouse model for temporal lobe epilepsy
Authors: Jeroen Spanoghe, Evelien Wynendaele, Marijke Vergaelen, Maren De Colvenaer, Tina Mariman, Kristl Vonck, Evelien Carrette, Wytse Wadman, Erine Craey, Lars E Larsen, Mathieu Sprengers, Jeroen Missinne, Serge Van Calenbergh, Bart De Spiegeleer, Dimitri De Bundel, Ilse Smolders, Paul Boon, Robrecht Raedt
Journal: Journal of Controlled Release (2025)

Up to 30 % of epilepsy patients suffer from drug-resistant epilepsy (DRE). The search for innovative therapies is therefore important to close the existing treatment gap in these patients. The adenosinergic system possesses potent anticonvulsive effects, mainly through the adenosine A1 receptor (A1R). However, clinical application of A1R agonists is hindered by severe systemic side effects. To achieve local modulation of A1Rs, we employed a photopharmacological approach using a caged version of the A1R agonist N6-cyclopentyladenosine, termed cCPA. We performed the first in vivo study with intracerebroventricularly (ICV) administered cCPA to investigate the potential to photo-uncage and release sufficient amounts of cCPA in the hippocampus by local illumination in order to suppress hippocampal excitability and seizures in mice. We validated the presence of cCPA in the hippocampus after ICV injection and explored its pharmacokinetic profile and in vivo stability. Using hippocampal evoked potential recordings, we showed a reduction in hippocampal neurotransmission after photo-releasing CPA, similar to that obtained with ICV injection of CPA. Furthermore, in the intrahippocampal kainic acid mouse model for DRE, photo-release of CPA in the epileptic hippocampus resulted in a strong suppression of seizures. Finally, we demonstrated that intrahippocampal photo-release of CPA resulted in less impairment of motor performance in the rotarod test compared to ICV administration of CPA. These results provide a proof of concept for photopharmacological A1R modulation as an effective precision treatment for DRE.
Progress in skin gene therapy: from the inside and out
Authors: Mark J Osborn, Sidharth Panda, Theresa M Reineke, Jakub Tolar, Alexander Nyström
Journal: Molecular Therapy (2025)

The skin is the largest organ of the body and forms and serves as the barrier for preventing external material from accessing and damaging internal organs. As the outward interface to the environment, it is accessible for the application of therapeutic agents and cellular and gene therapy represent attractive and promising options to treat severe genetic conditions for which palliation has long been the main stay. However, because of its barrier function, transit across and to the sub-dermal compartment can be challenging. This commentary examines the current approaches of cell and gene therapies for genetic skin disorders. We write this from a local and systemic 'outside and inside' perspective. Delivery from the outside encompasses topical, intradermal, and transdermal strategies for cell and vector delivery and ex vivo cell expansion and grafting. The inside approach details systemic delivery via infusion of cells or agents toward providing benefit to the skin. We use recessive dystrophic epidermolysis bullosa (RDEB) as a representative and paradigmatic disease to showcase these approaches as a means to highlight potential broader applicability to other conditions.
AI explainability in oculomics: how it works, its role in establishing trust, and what still needs to be addressed
Authors: Songyang An, Kelvin Teo, Michael V McConnell, John Marshall, Christopher Galloway, David Squirrell
Journal: Progress in Retinal and Eye Research (2025)

Recent developments in artificial intelligence (AI) have seen a proliferation of algorithms that are now capable of predicting a range of systemic diseases from retinal images. Unlike traditional retinal disease detection AI models which are trained on well-recognised retinal biomarkers, systemic disease detection or "oculomics" models use a range of often poorly characterised retinal biomarkers to arrive at their predictions. As the retinal phenotype that oculomics models use may not be intuitive, clinicians have to rely on the developers' explanations of how these algorithms work in order to understand them. The discipline of understanding how AI algorithms work employs two similar but distinct terms: Explainable AI and Interpretable AI (iAI). Explainable AI describes the holistic functioning of an AI system, including its impact and potential biases. Interpretable AI concentrates solely on examining and understanding the workings of the AI algorithm itself. iAI tools are, therefore, what the clinician must rely on if they are to understand how the algorithm works and whether its predictions are reliable. The iAI tools that developers use can be delineated into two broad categories: Intrinsic methods that improve transparency through architectural changes, and post-hoc methods that explain trained models via external algorithms. Currently, post-hoc methods, class activation maps in particular, are far more widely used than other techniques but they have their limitations especially when applied to oculomics AI models. Aimed at clinicians, we examine how the key iAI methods work, what they are designed to do, and what their limitations are when applied to oculomics AI. We conclude by discussing how combining existing iAI techniques with novel approaches could allow AI developers to better explain how their oculomics models work and reassure clinicians that the results issued are reliable.
Mesoporou Carbon Nanosphere Derived from MOF for Sono-Immunotherapy Against Pancreatic Cancer
Authors: Libin Chen, Haiwei Li, Jing Liu, Yunzhong Wang, Shengmin Zhang
Journal: Cyborg and Bionic Systems (2025)

Sono-immunotherapy is expected to effectively enhance treatment efficacy and reduce mortality in patients with pancreatic cancer. Hence, efficient applicable sono-immunotherapy systems are urgently needed for the treatment of this condition. In this study, hollow mesoporous carbon (HMC) nanoparticles were prepared using the sacrificial template method. These nanoparticles had a porphyrin-like structure and could generate singlet oxygen more efficiently than commercial TiO 2 . Cellular assays showed that HMC killed tumor cells in the presence of ultrasonication, primarily by inducing apoptosis. HMC could also accelerate the release of immune factors by tumor cells, thereby activating dendritic cells and enhancing the efficacy of immunotherapy. Experiments in tumor-bearing mice and in situ pancreatic cancer tests showed that HMC, in combination with the small-molecule inhibitors of programmed cell death ligand 1, could reduce tumor growth via the generation of reactive oxygen species following ultrasonication. HMC could enhance the efficacy of immunotherapy by disrupting the immunosuppressive tumor microenvironment and promoting the accumulation of immune cells. Accordingly, in vivo sono-immunotherapy was achieved, and the growth of transplanted tumors and in situ tumors could be reduced. In conclusion, this study proposes a novel method for the preparation of HMC nanoparticles and demonstrates their potential in tumor treatment. Additionally, owing to their unique structure, these HMC nanoparticles could be used for different combination therapies tailored based on specific clinical requirements.
Efficacy and safety of preoperative biliary drainage in patients with Hilar Cholangiocarcinoma: a systematic review and meta-analysis
Authors: Xiuwen Chen, Xueyi Wei, Liqing Yue, Yao Xiao
Journal: International Journal of Surgery (2025)

Background: Preoperative biliary drainage (PBD) has been proposed as a strategy to manage the complications associated with biliary obstruction in hilar cholangiocarcinoma patients. However, the efficacy and safety of PBD in remain controversial, even in clinical guidelines. This meta-analysis aimed to provide a comprehensive evaluation of the efficacy and safety of PBD in patients with hilar cholangiocarcinoma. Methods: PubMed, Medline, Embase, Cochrane Library and registers were screened to investigated the efficacy and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma. The search timeframe was set before December 2024. Mortality, morbidity and postoperative infection served as the primary outcomes, while the secondary outcomes included transfusion, operative time, operative bloody loss, intraabdominal abscess, intraabdominal bleeding, leakage (bile leake or anastomotic leakage), hepatic insufficiency, renal insufficiency, second laparotomy, total hospital stay, cholangitis. Studies were evaluated for quality by Newcastle-Ottawa scale. Data were pooled as odds ratio ( OR ) or standard mean difference ( SMD ). Results: Our meta-analysis of 21 studies (3,059 patients) showed that PBD reduced hepatic insufficiency( OR = 0.38, 95% CI = 0.16–0.90, P = 0.03, I2 = 69%) but increased risks of long term follow up mortality ( OR = 1.90, 95% CI = 1.02-3.56, P = 0.04, I2 = 0%), morbidity ( OR = 1.47, 95% CI = 1.12-1.92, P = 0.01, I2 = 52%), postoperative infection( OR = 2.46, 95% CI = 1.17-5.18, P = 0.02, I2 = 69%), transfusion( OR = 1.39, 95% CI = 1.06–1.81, P = 0.02, I2 = 49%), leakage( OR = 1.67, 95% CI = 1.08–2.60, P = 0.02, I2 = 44%), cholangitis ( OR = 6.40, 95% CI = 1.75–23.48, P = 0.01, I2 = 51%), and prolonged hospital stay( SMD = 0.53, 95% CI = 0.06-0.99, P = 0.03, I2 = 87%). There was no difference in overall mortality, operative time, blood loss, or other complications ( P &gt; 0.05). Subgroup analysis showed that differences in some outcomes lost significance with higher bilirubin levels, fewer PBD cases, studies published after 2010, and strictly select PBD patients ( P &lt; 0.05). Conclusions: Routine PBD cannot be recommended but it tends to be a better choice in patients with average initial bilirubin above 218.75 μmol/l, portal vein embolization and malnutrition. Further multicenter randomized studies should address the potential advantages of PBD over NPBD, identify clear patient selection criteria, and determine the optimal bilirubin threshold for PBD.
Effect of chewing gum on clinical outcomes and postoperative recovery in adult patients after gastrointestinal surgery: an umbrella review
Authors: Shu Ling Lew, Ling Jie Cheng, Siat Yee Yap, Yi Qi Liaw, Jiyoung Park, Siew Tiang Lau
Journal: International Journal of Surgery (2025)

Background: Gastrointestinal surgery is crucial for many medical conditions but can lead to difficult recoveries. Chewing gum is proposed as a remedy, yet existing reviews offer conflicting results. This umbrella review aims to synthesize the effectiveness of chewing gum on time to first flatus, time to first bowel movement, length of stay and complication rates in adult patients. Methods: We conducted an umbrella review, searching seven databases up to 17 November 2023, with an updated search extending to 1 January 2025. The focus was on post-surgery chewing gum interventions. The quality and certainty of evidence were assessed using the AMSTAR-2 tool and umbrella review criteria. Results: Seventeen reviews, encompassing 26,672 participants from 264 primary studies, were included. Meta-analyses indicated reductions in time to first flatus by −0.36 days (95% CI = − 0.61, − 0.1) or −12.26 hours (95% CI = − 14.73, − 9.78), time to first bowel movement by −0.59 days (95% CI = − 0.94, − 0.23) or −19.29 hours (95% CI = − 23.79, − 14.79), and length of stay by −0.85 days (95% CI = − 1.22, − 0.48) or −20.08 hours (95% CI = − 28.62, − 11.54). Additionally, chewing gum was associated with fewer postoperative complications. Conclusion: Chewing gum may significantly aid postoperative care by reducing time to first flatus, time to first bowel movement, and length of stay. However, many included reviews were of low quality with weak evidence, highlighting the need for more rigorous studies to confirm these benefits. Integrating chewing gum into clinical practice could enhance recovery and optimise hospital bed turnover, making it a valuable addition to postoperative care protocols. Registration: PROSPERO Number: CRD4202451XXXX
Higher life’s essential 8 score is associated with reduced risk of related surgery and all-cause mortality among 3,232 individuals with inflammatory bowel disease in a longitudinal cohort study
Authors: Fangmin Jing, Yuxuan Cao, Qijia Gong, Lintao Dan, Yuexin Zhu, Fernando Magro, Tian Fu, Jie Chen, Xiaoyan Wang
Journal: International Journal of Surgery (2025)

Background: Previous studies indicated discrete lifestyle health metrics that benefit cardiovascular health are associated with better prognosis in inflammatory bowel disease (IBD), while evidence regarding the comprehensive impact of cardiovascular health remains limited. This study aimed to investigate the association between the overall cardiovascular health indicator, Life’s Essential 8 (LE8), and the adverse outcomes of IBD. Materials and methods: We included 3,232 IBD participants recruited from the UK Biobank between 2006 and 2010. LE8 encompasses 8 metrics, including physical activity, diet, sleep health, nicotine exposure, body mass index, blood glucose, blood lipids, and blood pressure. The adverse outcomes studied in our study included IBD-related surgery and all-cause mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) for the strength of the associations between LE8 score and IBD-related surgery as well as all-cause mortality were calculated using Cox proportional hazard models. Results: Over a mean (standard deviation) follow-up of 12.60 (2.74) years and 13.17 (1.89) years, 282 IBD-related surgery and 259 death events were recorded. UC patients with a high LE8 score showed decreased risk of IBD-related surgery (HR 0.47, 95% CI 0.26, 0.87) and all-cause mortality (HR 0.47, 95% CI 0.25, 0.87), in comparison to those with a low LE8 score. No significant associations were observed between LE8 score and the risk of IBD-related surgery and all-cause mortality among CD in the primary analyses. Conclusion: Participants with a higher LE8 score showed decreased risk of IBD-related surgery and all-cause mortality among UC, but not CD, underscoring the significance of implementing LE8 as a management approach in improving the prognosis of UC.
Effectiveness of ERAS program on postoperative recovery after gastric cancer surgery: a randomized clinical trial
Authors: Ho-Jin Lee, Jeesun Kim, Soo-Hyuk Yoon, Seong-Ho Kong, Won Ho Kim, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang
Journal: International Journal of Surgery (2025)

Background: Previous studies have reported the effectiveness of the “enhanced recovery after surgery” program in patients who underwent gastric cancer surgery, mostly based on the 2014 gastrectomy guidelines. Therefore, based on subsequent advancements in perioperative management, this randomized, controlled, open-label, single-center study aimed to assess the impact of a recent evidence-based multimodal enhanced recovery after surgery program on the quality of early recovery after gastric cancer surgery. Materials and methods: This study included adult patients scheduled to undergo elective laparoscopic or robotic distal gastrectomy for gastric cancer. Patients were randomly assigned to the enhanced recovery after surgery or conventional group. The primary outcome was the total Quality of Recovery-15 score assessed 24, 48, and 72 h postoperatively. Differences between both groups were evaluated using a linear mixed-effects model. We hypothesized that an increase of at least 8 points in the Korean version of Quality of Recovery-15 scores would indicate a clinically significant improvement, consistent with the minimal clinically important difference (≥8) for Quality of Recovery-15. Secondary outcomes included pain scores at rest and during coughing, cumulative fentanyl consumption through intravenous patient-controlled analgesia, postoperative nausea/vomiting incidence, and gastrointestinal dysfunction as measured using the I-FEED score – all assessed 24, 48, and 72 h postoperatively. Results: For the 92 patients examined (enhanced recovery after surgery, n = 45; conventional, n = 47), the estimated difference in the postoperative Quality of Recovery-15 total scores between the two groups during the first days was significantly larger than the minimal clinically important difference of Quality of Recovery-15 (mean difference: 16.0, 95% confidence interval: 8.9–23.0, P &lt; 0.001). Therefore, excluding the incidence of postoperative nausea/vomiting, the enhanced recovery after surgery group demonstrated significant improvements in other secondary outcomes. Conclusions: Our evidence-based multimodal enhanced recovery after surgery program significantly improved the quality of early postoperative recovery after minimally invasive distal gastrectomy.
Breast neurotization along with breast reconstruction after nipple sparing mastectomy enhances quality of life and reduces denervation symptoms in patient reported outcome: a prospective cohort study
Authors: Shiuan Shyu, Tommy Nai-Jen Chang, JohnnyChuieng-Yi Lu, Chia-Fang Chen, David Chon-Fok Cheong, Shu-Wei Kao, Wen-Ling Kuo, Jung-Ju Huang
Journal: International Journal of Surgery (2025)

Objective: Persistent postoperative sensory loss significantly limits breast reconstruction following mastectomy. In addition, the absence of sensation profoundly impacts patients’ physical well-being and overall quality of life. New surgical techniques involving nerve autograft intercostal nerve elongation have been introduced to neurotize reconstructed breasts. However, patient quality of life after neurotization has not been well evaluated. This study aimed to investigate improvements in patient quality of life in association with breast neurotization. Methods: A prospective cohort study of 132 patients treated at (blinded for review) between January 2018 and December 2022 was conducted. Two groups of patients who underwent nipple-sparing mastectomy (NSM) and breast reconstruction were compared: those with (n = 67) and without (n = 65) breast neurotization. Patient-reported outcomes were assessed via the BREAST-Q reconstruction module questionnaire and an additional questionnaire measuring sensation, nipple satisfaction, and breast symptoms. Objective measurements were conducted via the Semmes–Weinstein monofilaments test. Results: With respect to patient-reported outcomes, the innervated group had significantly higher scores for nipple sensation and on the BREAST-Q domains of psychosocial well-being (71.6 ± 18.1 vs. 62.8 ± 18.6, P = 0.006), sexual well-being (56.9 ± 22.1 vs. 47.3 ± 20.7, P = 0.015), satisfaction with the medical team, as well as less frequent post-operative breast symptoms. In the subgroup analysis, the innervated group demonstrated higher scores in both autologous flap and implant-based reconstruction. Linear regression revealed a statistically significant relationship between objectively measured monofilament value and subjectively examined patient-reported outcomes: nipple sensation, breast sensation, and BREAST-Q score for the psychosocial well-being domain (coefficient: − 4.922, P = 0.033). Conclusion: Breast reconstruction with autologous nerve graft neurotization yields improved sensory outcomes and has a statistically significant positive impact on the quality of life of breast reconstruction patients.
The risks of autoimmune inflammatory outcomes in patients infected with SARS-CoV-2: a longitudinal, population-based cohort study
Authors: Lijun Zhang, Dong Chen, Yu Long, Lingyi Li, Yanlin Lyu, Meijun Meng, Yuying Ma, Yanjun Wu, Felix W Leung, Weihong Sha, Hao Chen, Yufeng Liu
Journal: International Journal of Surgery (2025)

Zhang, Lijun MD; Chen, Dong BS; Long, Yu MD; Li, Lingyi MD; Lyu, Yanlin MD; Meng, Meijun MD; Ma, Yuying MD; Wu, Yanjun MD; Leung, Felix W MD; Sha, Weihong MD; Chen, Hao PhD; Liu, Yufeng MD, PhD Author Information
Update on the Treatment of Chronic Spontaneous Urticaria
Authors: Pavel Kolkhir, Jie Shen Fok, Emek Kocatürk, Philip H. Li, Tiia-Linda Okas, Joao Marcelino, Martin Metz
Journal: Drugs (2025)

Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin disease that presents with wheals, angioedema, or both for more than 6 weeks. Less than 10% of patients have complete control of their CSU (the main goal of CSU treatment) with second generation H1-antihistamines, the first-line treatment. About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment. Novel therapies are especially needed for patients with mast cell-activating immunoglobulin (Ig)G autoantibodies (autoimmune CSU) associated with nonresponse or late response to omalizumab. Furthermore, there is a lack of disease-modifying treatments that induce long-term CSU remission after drug withdrawal. Several emerging treatments can address these unmet needs including Bruton tyrosine kinase inhibitors, e.g., remibrutinib and rilzabrutinib; anti-KIT monoclonal antibodies, e.g., barzolvolimab; and anti-cytokine therapies, e.g., dupilumab. In clinical trials, 30–31%, 28–32%, and 38–51% of patients with CSU showed complete response to treatment with dupilumab (phase 3, week 24), remibrutinib (phase 3, week 24), and barzolvolimab (phase 2, week 12), respectively. The most common adverse events were injection site reactions for dupilumab (12%), respiratory tract infections (11%), headache (6%), and petechiae (4%) for remibrutinib and changes in hair color (14%), neutropenia / decreased neutrophil count (9%) and skin hypopigmentation (1%) for barzolvolimab. This review provides an update on the current state of development of treatments for CSU.