tbuckley/cabot-search huggingface dataset:
The impact of antimicrobial stewardship ward rounds on antimicrobial use and predictors of advice, uptake, and outcomes
Authors: David W Eyre, Gemma Pill, Bee Yean Ng, Caroline Herin, Bernadette O'Riordan, Douglas Izzard, Louise Dunsmure, Stephane Paulus, Katie Jeffery, Nicola Jones
Journal: Journal of Infection (2025)

To identify the impact of introducing antimicrobial stewardship (AMS) ward rounds. We used an interrupted time-series approach to investigate the impact of implementing AMS ward rounds with in-person feedback from a multi-disciplinary team in Hospital-1, also comparing to Hospital-2 in the same city where AMS ward rounds were not yet implemented. Regression models were used to identify predictors of advice given, whether advice was followed, and associations between advice uptake and length of stay. Introducing AMS ward rounds was followed by new or accelerated declines in ceftriaxone, ciprofloxacin, amoxicillin-clavulanate, meropenem and piperacillin-tazobactam use at Hospital-1. Except for ceftriaxone, similar declines were not seen at Hospital-2. Half of reviews (3471/6878; 50%) recommended an intervention; 2003/2726 (73%) subsequently evaluated recommendations were implemented. Senior doctors were more likely than pharmacists or specialist doctors in training to recommend de-escalation/stopping antibiotics and to have their advice followed. The more prior AMS reviews completed, the more likely advice was to be followed. Following advice to de-escalate/stop antimicrobials was associated with a 0.58 day [95%CI 0.22-0.94] reduction in hospital stay. Multidisciplinary AMS ward rounds reduced antibiotic use and likely reduced length of hospital stay. Senior clinician input and more AMS experience increased advice uptake. The datasets analysed during the current study are not publicly available as they contain personal data but are available from the Infections in Oxfordshire Research Database (https://oxfordbrc.nihr.ac.uk/ research-themes-overview/antimicrobial- resistance-and-modernising-microbiology/ infections-in-oxfordshire-research-database-iord/), subject to an application and research proposal meeting the ethical and governance requirements of the Database. For further details on how to apply for access to the data and for a research proposal template please email iord@ndm.ox.ac.uk.
Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation
Authors: Haihan Zhang, Matthew T Patrick, Jingyu Zhao, Xintong Zhai, Jialin Liu, Zheng Li, Yiqian Gu, Joshua Welch, Xiang Zhou, Robert L Modlin, Lam C Tsoi, Johann E Gudjonsson
Journal: Journal of Allergy and Clinical Immunology (2025)
Switching to Besifovir in Patients with Chronic Hepatitis B Receiving Tenofovir Disoproxil Fumarate: A Randomized Trial
Authors: Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Woong Lee, Jung Hyun Kwon, Moon Young Kim, Do Seon Song, Jung Gil Park, Yoon Seok Lee, Eileen L. Yoon, Han Ah Lee, Seong Hee Kang, Jin Mo Yang
Journal: Clinical and Molecular Hepatology (2025)

Background/AimsBesifovir (BSV) showed comparable antiviral activity superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB).However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV.This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment. MethodsIn this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks. ResultsThe per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66).The median duration of TDF use before enrollment was 4.14 years.After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% CI -0.01 to 0.04; P=1.000), with a predefined margin of -0.18.The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%)than in the TDF group (-1.24±11.02%).The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group. ConclusionsIn patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with noninferior antiviral efficacy compared to that of maintaining TDF.ClinicalTrials.
Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects
Authors: Ada Alice Dona, Theophilus Tandoh, Lokesh Nigam, Mahmoud Singer, Enrico Caserta, Mariam Murtadha, Yinghui Zhu, Milad Moloudizargari, Preeti Sharma, Ottavio Napolitano, Janet Winchester, Arnab Chowdhury, Alex Pozhitkov, James F. Sanchez, Hawa Vahed, Guido Marcucci, Matt Coffey, Gerard Nuovo, Douglas W. Sborov, Flavia Pichiorri, Craig C Hofmeister
Journal: Journal of Hematology & Oncology (2025)

Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated. Electron microscopy, q-RT-PCR, single-cell mass cytometry (CyTOF), flow cytometry, plaque assays, immunohistochemistry, and Western blot analysis were used to assess RV infection of both myeloma and immune cells. Immune fluorescence, flow cytometry, and luciferase reporter assays were used to assess NF-κB pathway activation upon RV treatments. Immune profiling changes, both ex vivo and in MM patients, were analyzed by flow cytometry and CyTOF analysis. T-cell receptor (TCR) sequencing was also conducted both in immune competent MM mice and in patients enrolled in a phase 1b trial per a standard 3 + 3 dose escalation schedule. Here we show ex vivo and in vivo that proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on NF-κB activation and that this effect is impaired by the addition of PIs. Conversely, the addition of PIs to RV therapy supports immune activation and killing of MM, independently of direct PI sensitivity. To validate the importance of PIs in enhancing oncolytic viral therapy independently of their killing activity on cancer cells, we then conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated PI-resistant MM patients. Objective responses, which were associated with active reovirus replication in MM cells, T cell activation, and monocytic expansion, were noted in 70% of patients. Although characterized as immunosuppressive drugs, PIs improved RV delivery to MM cells but also enhanced anti-MM efficacy through immune-mediated killing of myeloma cells, independently of their PI sensitivity. These results highlight a more generalizable use of PIs as therapeutic companions to support oncolytic-based therapies in cancers. clinicaltrials.gov, NCT 02101944.
Targeting intracellular cancer proteins with tumor‐microenvironment‐responsive bispecific nanobody‐PROTACs for enhanced therapeutic efficacy
Authors: Changping Deng, Jiacheng Ma, Yuping Liu, Xikui Tong, Lei Wang, Jiayi Dong, Ping Shi, Meiyan Wang, Wenyun Zheng, Xingyuan Ma
Journal: MedComm (2025)

Abstract Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non‐specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity. In this study, we engineered BumPeD, a novel bispecific nanobody‐targeted PROTACs‐like platform, by fusing two nanobodies with a Furin protease cleavage site (RVRR) and a degron sequence (ALAPYIP or KIGLGRQKPPKATK), enabling the tumor microenvironment to direct the degradation of intracellular proteins. We utilized KN035 and Nb4A to target PD‐L1 (programmed death ligand 1) on the cell surface and intracellular Survivin, respectively. In vitro experiments showed that BumPeD triggers Survivin degradation via the ubiquitin‐proteasome pathway, inducing tumor apoptosis and suppressing bladder tumor cell proliferation and migration. In vivo experiments further confirmed BumPeD's robust anti‐tumor efficacy, underscoring its potential as a precise protein degradation strategy for cancer therapy. Our platform provides a systematic approach to developing effective and practical protein degraders, offering a targeted theoretical basis and experimental support for the development of novel degradative drugs, as well as new directions for cancer therapy.
Liquid Crystalline Networks Hamper the Malignancy of Cancer Cells
Authors: Daniele Martella, Ignazia Tusa, Alessandro Tubita, Alessia Negri, Marco Turriani, Marta Rojas‐Rodríguez, Martina Salzano de Luna, Alessio Menconi, Camilla Parmeggiani, Elisabetta Rovida
Journal: Advanced Healthcare Materials (2025)

Abstract Mimicking compositions and structures of extracellular matrix is widely studied to create in vitro tumor models, to deepen the understanding of the pathogenesis of the different types of cancer, and to identify new therapies. On the other hand, the use of synthetic materials to modulate cancer cell biology and, possibly, to reduce the malignancy of cancer cells through their exploitation is far less explored. Here, the study evaluates the effects of Liquid Crystalline Networks (LCNs) based scaffolds on the growth of A375 metastatic melanoma cells. Interestingly, cells grown on such materials show reduced cell proliferation and colony‐forming capacity with respect to those cultivated on standard plates. These effects are associated with a higher percentage of senescent cells and a shift to a more epithelial phenotype, pointing to the occurrence of a mesenchymal to epithelial transition. All these biological outcomes are affected by the amount of crosslinker in the material and have been induced only thanks to the interactions with the polymeric substrate without the need of further chemical (e.g., specific growth factor) or physical (e.g., irradiation) stimuli, opening to the possible development of anti‐cancer coatings.
Trojan Horse‐Like Biohybrid Nanozyme for Ameliorating Liver Ischemia‐Reperfusion Injury
Authors: Dao‐Feng Zheng, Xiang‐Jun Zha, En‐Lai Jiang, Yuan Qiu, Wei Yang, Wei‐Dong Xiao
Journal: Advanced Healthcare Materials (2025)

Abstract Liver ischemia and reperfusion (I/R) injury is a reactive oxygen species (ROS)‐related disease that occurs during liver transplantation and resection and hinders postoperative liver function recovery. Current approaches to alleviate liver I/R injury have limited effectiveness due to the short circulation time, poor solubility, and severe side effects of conventional antioxidants and anti‐inflammatory drugs. Herein, a universal strategy is proposed to fabricate a Trojan horse‐like biohybrid nanozyme (THBN) with hepatic‐targeting capabilities. Tannic acid (TA) mediates adeno‐associated virus (AAV8) decoration onto 2D Ti 3 C 2 nanosheets, resulting in THBN with a size of 116.2 ± 9.5 nm. Remarkably, THBN exhibits catalase (CAT)‐like activity, broad‐spectrum ROS scavenging activity and targeted delivery to liver tissue owing to the presence of AAV8. Both in vivo and in vitro experiments confirmed the efficacy of THBN in attenuating liver I/R injury by mitigating inflammation and oxidative stress and inhibiting hepatocellular apoptosis. RNA‐seq analysis suggests that THBN may alleviate liver I/R injury by activating the PKC pathway. The effective targeting and therapeutic capabilities of THBN represent an advancement in nanotherapeutics for hepatic ischemia‒reperfusion injury, shedding light on the promising potential of this next‐generation nanotherapeutic approach.
Dexamethasone Delivery via Amphiphilic, Low‐swelling Hydrogels Treats Postoperative Inflammation in Cervical Spine Applications
Authors: Stephen W. Linderman, Graham F. Barber, S'Dravious A. DeVeaux, Edward A. Botchwey, Daniel Refai, Adam M. Klein, Andrés J. García
Journal: Advanced Healthcare Materials (2025)

Abstract Anterior cervical spine surgeries are often complicated by difficulty swallowing due to local postoperative swelling, pain, scarring, and tissue dysfunction. These postoperative events lead to systemic steroid and narcotic use. Local, sustained drug delivery may address these problems, but current materials are unsafe for tight surgical spaces due to high biomaterial swelling, especially upon degradation. To address these shortcomings, a low‐swelling, amphiphilic hydrogel system termed DexaPatch is developed containing dexamethasone‐poly(lactic‐co‐glycolic acid) (PLGA) microparticles for sustained release upon local implantation in the surgical site. The bulk amphiphilic hydrogel, comprised of 4‐arm poly(ethylene glycol) (PEG)‐maleimide macromer cross‐linked with triblock dithiolated PEG‐poly(propylene glycol)‐PEG (poloxamer a.k.a. Pluronic), achieves consistent and tunable mechanical and low‐swelling properties. Dexamethasone is released in a burst, followed by a sustained release over 40 days, similar to the release from microparticles alone. The DexaPatch system is lyophilized for shelf stability and surgical handling properties, sterilized, and briefly rehydrated in the operating room prior to surgical implantation in a rabbit model of anterior spinal surgery. DexaPatch results in significantly reduced prevertebral edema radiographically and decreased fibrosis in prevertebral muscles compared to sham surgery. This implantable biomaterial platform reduces local postoperative inflammation with potential surgical applications throughout the body.
A Modified Polydopamine Nanoparticle Loaded with Melatonin for Synergistic ROS Scavenging and Anti‐Inflammatory Effects in the Treatment of Dry Eye Disease
Authors: Xue Yang, Bowen Wang, Hao Zeng, Lihong Liang, Runze Zhang, Wenrui Deng, Xuan Zhao, Jin Yuan
Journal: Advanced Healthcare Materials (2025)

Abstract Dry eye disease (DED) is a multifaceted ocular surface disorder that significantly impacts patients’ daily lives and imposes a substantial economic burden on society. Oxidative stress, induced by the overproduction of reactive oxygen species (ROS), is a critical factor perpetuating the inflammatory cycle in DED. Effectively scavenging ROS is essential to impede the progression of DED. In this study, boronophenylalanine‐ containing polydopamine (PDA‐PBA) nanoparticles are developed loaded with melatonin (MT), which are blended with poly(vinyl alcohol) (PVA) to create eye drops PVA/ PDA‐PBA@MT (PPP@MT). In vitro and in vivo studies demonstrate that PPP@MT exhibits dual functionalities in reducing ROS production and downregulating inflammatory pathways, thereby preserving mitochondrial integrity and further inhibiting programmed cell death. Following PPP@MT treatment, tear secretion, corneal structure, and the number of goblet cells are markedly restored in a mouse model of dry eye, indicating the therapeutic efficacy of this agent. Collectively, PPP@MT, characterized by minimal side effects and favorable bioavailability, offers promising therapeutic insights for the management of DED and other ROS‐mediated disorders.
Advanced Carriers for Precise Delivery and Therapeutic Mechanisms of Traditional Chinese Medicines: Integrating Spatial Multi‐Omics and Delivery Visualization
Authors: Yusheng Zhang, Zhiguo Lu, Jing Guo, Qing Wang, Xin Zhang, Hongjun Yang, Xianyu Li
Journal: Advanced Healthcare Materials (2025)

Abstract The complex composition of traditional Chinese medicines (TCMs) has posed challenges for in‐depth study and global application, despite their abundance of bioactive compounds that make them valuable resources for disease treatment. To overcome these obstacles, it is essential to modernize TCMs by focusing on precise disease treatment. This involves elucidating the structure‐activity relationships within their complex compositions, ensuring accurate in vivo delivery, and monitoring the delivery process. This review discusses the research progress of TCMs in precision disease treatment from three perspectives: spatial multi‐omics technology for precision therapeutic activity, carrier systems for precise in vivo delivery, and medical imaging technology for visualizing the delivery process. The aim is to establish a novel research paradigm that advances the precision therapy of TCMs.
A treatable cause of bilateral leg edema and pleural effusion: yellow nail syndrome with <scp>IgG4</scp>‐related disease
Authors: Seiya Oba, Yusuke Matsuo
Journal: Arthritis & Rheumatology (2025)

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Computer‐Aided Design of Self‐Assembled Nanoparticles to Enhance Cancer Chemoimmunotherapy via Dual‐Modulation Strategy
Authors: Xiaoting Shan, Ying Cai, Binyu Zhu, Xujie Sun, Lingli Zhou, Zhiwen Zhao, Yaping Li, Dangge Wang
Journal: Advanced Healthcare Materials (2025)

Abstract The rational design of self‐assembled compounds is crucial for the highly efficient development of carrier‐free nanomedicines. Herein, based on computer‐aided strategies, important physicochemical properties are identified to guide the rational design of self‐assembled compounds. Then, the pharmacophore hybridization strategy is used to design self‐assemble nanoparticles by preparing new chemical structures by combining pharmacophore groups of different bioactive compounds. Hydroxychloroquine is grafted with the lipophilic vitamin E succinate and then co‐assembled with bortezomib to fabricate the nanoparticle. The nanoparticle can reduce M2‐type tumor‐associated macrophages (TAMs) through lysosomal alkalization and induce immunogenic cell death (ICD) and nuclear factor‐κB (NF‐κB) inhibition in tumor cells. In mouse models, the nanoparticles induce decreased levels of M2‐type TAMs, regulatory T cells, and transforming growth factor‐β (TGF‐β), and increase the proportion of cytotoxicity T lymphocytes. Additionally, the nanoparticles reduce the secretion of Interleukin‐6 (IL‐6) by inhibiting NF‐κB and enhance the programmed death ligand‐1 (PD‐L1) checkpoint blockade therapy. The pharmacophore hybridization‐derived nanoparticle provides a dual‐modulation strategy to reprogram the tumor microenvironment, which will efficiently enhance the chemoimmunotherapy against triple‐negative breast cancer.
Acceptor Elongation Boosted Intersystem Crossing Affords Efficient NIR Type‐I and AIE‐Active Photosensitizers for Targeting Ferroptosis‐Based Cancer Therapy
Authors: Yilin Zhu, Rongyuan Zhang, Xu‐Min Cai, Liping Zhang, Bo Wu, Haozhe Tan, Kun Zhou, Haoran Wang, Yong Liu, Yumei Luo, Ryan T. K. Kwok, Jacky W. Y. Lam, Zheng Zhao, Cuiping Yao, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2025)

Abstract Photosensitizers (PSs) featuring type I reactive oxygen species (ROS) generation and aggregation‐induced emission (AIE) activity offer a promising solution to achieve non‐invasive and precise theranostics. However, the reported AIE luminogens (AIEgens) with both AIE characteristic and strong type‐I ROS generation are still scarce and the structure‐property relationship is still unclear. Herein, an innovative acceptor elongation boosted intersystem crossing (AEBIC) design strategy has been proposed to endow the AIEgen strong type‐I ROS producibility. The results indicate that the obtained AIEgen exhibit type‐I ROS and aggregation‐enhanced ROS efficacy, which has been verified by both experimental and theoretical results. Mechanistic study reveal that the acceptor elongation has promoted a dual‐channel intersystem crossing pathway to enhance the intersystem crossing (ISC) process due to the differences in triplet configurations, which can be further amplified by aggregation. The afforded type‐I AIE‐PS show lipid droplet‐anchored characteristic and can induce the ferroptosis through destroying the cellular redox homeostasis and increasing lethal levels of lipid peroxidation. Finally, targeting ferroptosis‐based cancer therapy can be realized with excellent anti‐tumor effect.
Patient‐derived xenograft model in cancer: establishment and applications
Authors: Ao Gu, Jiatong Li, Meng‐Yao Li, Yingbin Liu
Journal: MedComm (2025)

Abstract The patient‐derived xenograft (PDX) model is a crucial in vivo model extensively employed in cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, and diverse treatment histories. Various treatment strategies utilized in PDX models can offer valuable insights into the mechanisms of tumor progression, drug resistance, and the development of novel therapies. This review provides a comprehensive overview of the establishment and applications of PDX models. We present an overview of the history and current status of PDX models, elucidate the diverse construction methodologies employed for different tumors, and conduct a comparative analysis to highlight the distinct advantages and limitations of this model in relation to other in vivo models. The applications are elucidated in the domain of comprehending the mechanisms underlying tumor development and cancer therapy, which highlights broad applications in the fields of chemotherapy, targeted therapy, delivery systems, combination therapy, antibody–drug conjugates and radiotherapy. Furthermore, the combination of the PDX model with multiomics and single‐cell analyses for cancer research has also been emphasized. The application of the PDX model in clinical treatment and personalized medicine is additionally emphasized.
Circulating tumor DNA analysis for prediction of prognosis and molecular insights in patients with resectable gastric cancer: results from a prospective study
Authors: Zheng Liu, Zhongyi Shi, Wenchao Jiang, Zhenbin Shen, Weidong Chen, Kuntang Shen, Yihong Sun, Zhaoqing Tang, Xuefei Wang
Journal: MedComm (2025)

Abstract This study aimed to evaluate the prognostic value of plasma circulating tumor DNA (ctDNA) level in patients with resectable gastric cancer (GC). A total of 59 patients were prospectively enrolled, with their ctDNA detected and paired tumor tissue collected at various peri‐operative time points. Patients with higher 1‐month post‐operative ctDNA levels demonstrated shorter overall survival status (hazard ratio [HR] = 5.30, p = 0.0022) and a higher risk of recurrence (HR = 3.85, p = 0.011). The model combining ctDNA with conventional serum tumor markers for GC, including carcinoembryonic antigen, carbohydrate antigen 19‐9, and CA72‐4, shows high predictive effectiveness for GC prognosis with an area under the curve of 0.940 ( p = 0.002), which is higher than net ctDNA and other models without ctDNA. Patients with lower ctDNA levels were more likely to have positive stromal programmed cell death ligand 1 expression ( p = 0.046). Additionally, DCAF4L2 mutation was identified as the crucial gene mutation in ctDNA suggesting poor prognosis of patients with GC. Overall, this study highlights that post‐operative ctDNA can serve as an effective biomarker for prognostic prediction and recurrence surveillance in resectable GC.