Featured
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Article
| Open AccesscircCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models
Aberrant circRNAs expression in repair cells is intricately linked to deficits in wound healing. Here, the authors engineered extracellular vesicles enriched with circCDK13 and demonstrate their ability to facilitate diabetic wound repair.
- Qilin Huang
- , Ziqiang Chu
- & Cuiping Zhang
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Article
| Open AccessPopulation pharmacokinetic modelling of primaquine exposures in lactating women and breastfed infants
Primaquine treatment for breastfeeding mothers is currently not recommended. Here, the authors develop a pharmacokinetic model to predict drug exposure of infants and show that ingesting breastmilk from mothers treated with primaquine results in <1% of maternal drug exposure. This suggests that primaquine should not be restricted in post-neonatal breastfeeding women as standard doses are unlikely to cause adverse events in infants.
- Thanaporn Wattanakul
- , Mary Ellen Gilder
- & Richard M. Hoglund
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Article
| Open AccessIntrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial
In the CELLTOP Phase I trial, stem cells were harvested from patients with spinal cord injury and injected into their central nervous system after processing. The procedure was safe, with no reported serious adverse events during the 2-year follow-up period.
- Mohamad Bydon
- , Wenchun Qu
- & Allan B. Dietz
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Review Article
| Open AccessArtificial cells for in vivo biomedical applications through red blood cell biomimicry
Despite the enormous progress in the field of giant lipid vesicles, their use for in vivo biomedical applications is limited. Here, the authors discuss red blood cells as inspiration for enhancing those vesicles, investigating the required cellular features and the corresponding technical hurdles.
- Jorik Waeterschoot
- , Willemien Gosselé
- & Xavier Casadevall i Solvas
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Article
| Open AccessSpeaking without vocal folds using a machine-learning-assisted wearable sensing-actuation system
Addressing challenges in voice disorders, the authors present a self-powered, wearable sensor-actuator system based on magnetoelasticity. This innovation enables assisted speaking by capturing laryngeal movements and translating them into voice signals, bypassing the vocal folds.
- Ziyuan Che
- , Xiao Wan
- & Jun Chen
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Article
| Open AccessA phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss
Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss.
- Anne G. M. Schilder
- , Stephan Wolpert
- & Athanasios G. Bibas
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Article
| Open AccessDimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.
- Peter Sandercock
- , Janet Darbyshire
- & Martin J. Landray
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Article
| Open AccessMyeloid-derived grancalcin instigates obesity-induced insulin resistance and metabolic inflammation in male mice
The mechanism by which the cross-talk between bone and adipose tissue regulates metabolic homeostasis is unknown. Here, the authors show a mechanism whereby bone marrow factor GCA initiates adipose tissue inflammation and insulin resistance, showing how GCA targeting could potentially treat metainflammation.
- Tian Su
- , Yue He
- & Xianghang Luo
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Article
| Open AccessA deep unrolled neural network for real-time MRI-guided brain intervention
Real-time MRI provides accurate navigation and targeting for neurological interventions. Here, the authors propose a deep unrolled neural network for MRI reconstruction that enables real-time monitoring of remote-controlled brain interventions and can be integrated into diagnostic scanners.
- Zhao He
- , Ya-Nan Zhu
- & Yuan Feng
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Article
| Open AccessHigh-throughput target trial emulation for Alzheimer’s disease drug repurposing with real-world data
Target trial emulation (TTE) simulates randomized controlled trials using real world data (RWD). Here, authors show the effectiveness of different TTE strategies to identify drug candidates that could be potentially repurposed to Alzheimer’s disease using two large scale RWD warehouses.
- Chengxi Zang
- , Hao Zhang
- & Fei Wang
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Article
| Open AccessAAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa
Base editing technology has great potential in treating pathogenic single-nucleotide variations. Using a dual-AAV base editing system, Wu et al. restored visual functions in a mouse model of retinitis pigmentosa.
- Yidong Wu
- , Xiaoling Wan
- & Xueli Zhang
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Article
| Open AccessIdentification of scaffold proteins for improved endogenous engineering of extracellular vesicles
Extracellular vesicles are naturally occurring nanoparticles that are gaining ground as delivery modalities for therapeutics. Here, the authors conducted a large-scale screening programme to identify potential scaffold proteins for cargo loading into extracellular vesicles.
- Wenyi Zheng
- , Julia Rädler
- & Samir EL Andaloussi
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Article
| Open AccessMolecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Nirsevimab binds the respiratory syncytial virus (RSV) fusion protein and has been tested for RSV prevention in clinical trials. Here, the authors analyse RSV from infections and show that binding site substitutions are rare and that over 99% of isolates remain susceptible to nirsevimab.
- Bahar Ahani
- , Kevin M. Tuffy
- & Tonya Villafana
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Article
| Open AccessA randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease
Different classes of biologic therapeutics have been assessed in the context of Vogt-Koyanagi-Harada disease. Here the authors compared cyclosporine immunosuppression or adalimumab in a randomised clinical trial for the treatment of patients with Vogt-Koyanagi-Harada disease and found non-inferiority upon treatment with cyclosporine.
- Zhenyu Zhong
- , Lingyu Dai
- & Peizeng Yang
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Article
| Open AccessNanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy
Targeting the TGF-β signaling pathway has been exploited to relieve immunosuppression in the tumor microenvironment. Here the authors describe the design of a nanoplatform integrating the TGF-β receptor 1 inhibitor LY2157299 and the ROS-responsive JQ1 pro-drug, promoting anti-tumor immune responses in preclinical cancer models.
- Mengxue Zhou
- , Jiaxin Wang
- & Haijun Yu
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Article
| Open AccessScarless wound healing programmed by core-shell microneedles
Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Here, the authors report a core-shell structured microneedle array patch with programmed functions which dynamically modulates the wound immune microenvironment according to the varied healing phases
- Ying Zhang
- , Shenqiang Wang
- & Zhen Gu
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Article
| Open AccessVitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model
The possibility of banking cryopreserved organs could make transplantation medicine much more accessible. Here, the authors show that vitrification and nanowarming—cooling organs to an ice-free state followed by rapid rewarming using nanoparticles and magnetic fields—enables organ cryopreservation, long-term banking, and recovery of full function in a rat kidney transplant model.
- Zonghu Han
- , Joseph Sushil Rao
- & Erik B. Finger
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Article
| Open AccessAn aptamer-based depot system for sustained release of small molecule therapeutics
Controlled delivery of small molecule therapeutics is challenging. Here the authors report a simple and effective aptamer-based depot system where the formation of aptamer/drug complexes leads to sustained release, and using this approach demonstrate improved in vivo delivery of channel blockers.
- Dali Wang
- , Yang Li
- & Christopher B. Weldon
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Article
| Open AccessAcoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease
Treating acute disease like anaphylaxis is challenging due to the inability to administer therapeutics in a timely manner and regulate pharmacokinetics precisely within a short time window. Here the authors develop active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management.
- Junhua Xu
- , Hongwei Cai
- & Feng Guo
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Article
| Open AccessEfficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer
Immune checkpoint inhibitors with or without chemotherapy are now standard of care for non-small cell lung cancer. However, the benefits of combination vs sequential therapy have not been fully explored. Here, the authors analysed 1,133 patient records and show combination therapy showed increased protection against early progression, but similar overall survival.
- Lingzhi Hong
- , Muhammad Aminu
- & Natalie I. Vokes
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Article
| Open AccessAdipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects
Although thyroid hormone (TH) has anti-obesity potential, systemic administration of TH causes severe adverse effects without obvious weight loss. Here, the authors show that adipose tissue-targeted delivery of TH with liposomes is a safe and efficient strategy to treat obesity and its related complications in mice.
- Kang Chen
- , Lai Yee Cheong
- & Aimin Xu
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Article
| Open AccessA multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer
Neoadjuvant therapy is recommended for patients with locally advanced breast cancer. Here the authors report the results of a phase 2 clinical trial of oral neoadjuvant therapy with pyrotinib (pan-HER tyrosine kinase inhibitor), letrozole (aromatase inhibitor) and dalpiciclib (CDK4/6 inhibitor) in patients with treatment-naïve and stage II-III triple positive breast cancer.
- Nan Niu
- , Fang Qiu
- & Caigang Liu
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Article
| Open AccessWireless theranostic smart contact lens for monitoring and control of intraocular pressure in glaucoma
Glaucoma is an irreversible ocular disease that may lead to vision loss. Here the authors develop a theranostic smart contact lens with an intraocular pressure sensor, a flexible drug delivery system, wireless power and communication systems and an application specific integrated circuit chip for both monitoring and control of intraocular pressure in glaucoma induced rabbits.
- Tae Yeon Kim
- , Jee Won Mok
- & Sei Kwang Hahn
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Article
| Open AccessAnalysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources
Although COVID-19 convalescent plasma is commonly used for the treatment of immunosuppressed patients, this approach has yielded mixed results. Here, the authors present a systematic review of Omicron-neutralization data in convalescent plasma from vaccinated and unvaccinated individuals.
- David J. Sullivan
- , Massimo Franchini
- & Daniele Focosi
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Article
| Open AccessSynthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
An effective delivery system and imaging method for 5-Aminolevulinic acid (5-ALA)-based photodynamic therapy facilitated by the conversion of 5-ALA to protoporphyrin IX (PpIX) are lacking. Here, reversing the hypoxic tumour microenvironment can increase the in vivo biosynthesis of PpIX through the regulation of PpIX-related synthetases for traceable photodynamic therapy.
- Gang He
- , Yashi Li
- & Peng Huang
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Article
| Open AccessEffect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial
Many survivors of COVID-19 experience persistent symptoms, continuing beyond three months from the onset of infection. In this study, authors investigate the effect of remdesivir on recovery and long-COVID-19 symptoms, as well as quality of life and other symptom outcomes, in the 1-year follow-up of a randomised trial.
- Olli P. O. Nevalainen
- , Saana Horstia
- & Kari A. O. Tikkinen
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Article
| Open AccessComprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study
Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs.
- Xianghua Ye
- , Dazhou Guo
- & Tsung-Ying Ho
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Article
| Open AccessMacromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
Amyloid fibrils of β2-microglobulin (β2m) can cause dialysis-related amyloidosis. Here, the authors show that a decrease in serum albumin levels in long-term dialysis deteriorates the inhibitory effects of serum milieux on supersaturation-limited amyloid formation of β2m, suggesting that macromolecular crowding protects the onset of amyloidosis.
- Kichitaro Nakajima
- , Keiichi Yamaguchi
- & Yuji Goto
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Article
| Open AccessA pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma
In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.
- Wu-tong Ju
- , Rong-hui Xia
- & Lai-ping Zhong
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Article
| Open AccessCAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies
The success rate of chimeric antigen receptor T cell therapy is high in blood cancers, yet individual patient characteristics might reduce therapeutic benefit. Here authors show that therapeutic response in multiple myeloma, acute lymphoblastic leukemia and non-Hodgkin lymphoma, and occurrence of severe cytokine release syndrome in multiple myeloma are associated with specific gut microbiome alterations.
- Yongxian Hu
- , Jingjing Li
- & He Huang
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Article
| Open AccessOrganic phosphorescent nanoscintillator for low-dose X-ray-induced photodynamic therapy
Conventional X-ray-induced photodynamic therapy usually requires heavy-metal-containing inorganic scintillators and organic photosensitizers to generate singlet oxygen. Here, the authors develop an organic phosphorescent nanoscintillator for low-dose X-ray-induced photodynamic therapy of deep tumours.
- Xiao Wang
- , Wenjing Sun
- & Wei Huang
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Article
| Open AccessIn vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions
Hereditary tyrosinemia type 1 (HT1) is an inborn error of metabolism caused by a deficiency in fumarylacetoacetate hydrolase (FAH). Here, the authors show in an animal model that HT1 can be treated via in vivo portal vein administration of a lentiviral vector carrying the human FAH transgene.
- Clara T. Nicolas
- , Caitlin J. VanLith
- & Joseph B. Lillegard
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Article
| Open AccessMultifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade
Radiotherapy can activate an in situ vaccine response and promote response to immune checkpoint inhibitors. Here the authors design a multifunctional nanoparticle to enhance tumor antigen presentation and modulate the tumor immune microenvironment following radiotherapy, showing improved anti-tumor immune responses in radiotherapy-treated tumors when combined with immune checkpoint inhibitors.
- Ying Zhang
- , Raghava N. Sriramaneni
- & Zachary S. Morris
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Article
| Open AccessDynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform
Drug delivery implants suffer from diminished release profiles due to fibrous capsule formation over time. Here, the authors use soft robotic actuation to modulate the immune response of the host to maintain drug delivery over the longer-term and to perform controlled release in vivo.
- William Whyte
- , Debkalpa Goswami
- & Ellen T. Roche
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Article
| Open AccessReduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
Lung transplantation is hindered by the scarcity of organs and by mortality following primary graft dysfunction. Here, the authors show that cytokine absorption can be used in donor lungs during ex vivo lung perfusion and post-transplant, and leads to restored lung function and reduced primary graft dysfunction in animal models.
- Haider Ghaidan
- , Martin Stenlo
- & Sandra Lindstedt
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Article
| Open AccessTPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia
Overproduction of efflux pumps represents an important mechanism of Klebsiella pneumonia resistance to tigecycline. Here, the authors design TPGS- and S-thanatin functionalized nanorods loaded with tigecycline to increase drug accumulation inside bacteria and overcome bacterial resistance.
- Xiaojuan Wang
- , Xiaoling Xu
- & Saiping Jiang
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Article
| Open AccessAge and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines
There have been reports of myocarditis and pericarditis following mRNA COVID-9 vaccination. Here, the authors use nationwide data from France and find increased risks of these outcomes in the first week following vaccination, for both the first and second dose, and present age- and sex-specific rates.
- Stéphane Le Vu
- , Marion Bertrand
- & Mahmoud Zureik
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Article
| Open AccessTherapeutic homology-independent targeted integration in retina and liver
Limits of AAV-mediated gene therapy include targeting dominant mutations and inducing long-term transgene expression. Here, the authors show that AAV-HITI results in efficient allele-independent integration of a donor DNA in both retina and liver providing therapeutic benefit in mouse models of either a genetic form of blindness or a lysosomal storage disease, respectively.
- Patrizia Tornabene
- , Rita Ferla
- & Alberto Auricchio
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Comment
| Open AccessImmune-related adverse events and the balancing act of immunotherapy
The benefit from immune checkpoint inhibitors is tempered by immunologic toxicities, which involve diverse organs, have varying biology, onset time, and severity. Herein, we identify important areas of controversy and open research questions in the field of immune-related toxicity.
- Michael Conroy
- & Jarushka Naidoo
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Article
| Open AccessCombination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae
In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.
- Anaïs Eskenazi
- , Cédric Lood
- & Jean-Paul Pirnay
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Article
| Open AccessSystematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database
Multiple drugs have been in the past associated with myocarditis. Here the authors perform a pharmacovigilance study and analyze 5108 reports of drug-induced myocarditis reporting temporal trends and overall mortality and identifying emerging drug classes among the treatments associated with myocarditis.
- Lee S. Nguyen
- , Leslie T. Cooper
- & Joe-Elie Salem
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Article
| Open AccessHepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates
Pompe disease is currently treated with enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (GAA). Here, the authors show hepatic-directed gene therapy with AAV vectors enhances GAA bioavailability compared with ERT, resulting in improved rescue of the disease phenotype in mice and broad enzyme distribution in mice and non-human primates.
- Helena Costa-Verdera
- , Fanny Collaud
- & Federico Mingozzi
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Article
| Open AccessA randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes
Community pharmacists are accessible healthcare providers with expertise in medication management. Here the authors show that a low-carbohydrate, low-energy diet implemented by community pharmacists reduced diabetes medication use and improved glucose control in people with type 2 diabetes.
- Cody Durrer
- , Sean McKelvey
- & Jonathan P. Little
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Matters Arising
| Open AccessTransplantation of discarded livers: the complementary role of normothermic regional perfusion
- Chris J. C. Johnston
- , Ahmed E. Sherif
- & Gabriel C. Oniscu
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Article
| Open AccessSelf-healing polyurethane-elastomer with mechanical tunability for multiple biomedical applications in vivo
The unique properties of self-healing materials hold great potential in the field of biomedical engineering. Here, the authors designed a series of biodegradable and biocompatible self-healing elastomers with tunable mechanical properties, and apply them to various disease models in vivo, including aortic aneurism, bone fracture and nerve amputation.
- Chenyu Jiang
- , Luzhi Zhang
- & Xiaofeng Ye
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Comment
| Open AccessBreaking new ground in antimicrobial stewardship in companion animal veterinary practice
Singleton and colleagues publish in Nature Communications an intervention study to reduce antimicrobial usage in companion animal practice. They identify significant reductions in antimicrobial usage with their more active intervention group over approximately a 6-month period. The study offers an exciting way forward to explore further the trial interventions and assess alternative methods to improve antimicrobial stewardship in veterinary practice.
- David Brodbelt
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Article
| Open AccessFavipiravir antiviral efficacy against SARS-CoV-2 in a hamster model
Favipiravir has broad-spectrum antiviral activity against a variety of RNA viruses. Here the authors investigate the safety, pharmacokinetics and anti-SARS-CoV-2 efficacy of different drug dosage in the a Syrian hamster model of infection and, combined with genetic analyses, they show that Favipiravir at high doses decrease viral infectivity while inducing the emergence of mutations in viral genomes, decreasing fitness.
- Jean-Sélim Driouich
- , Maxime Cochin
- & Antoine Nougairède
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Article
| Open AccessA randomised controlled trial to reduce highest priority critically important antimicrobial prescription in companion animals
Effective use of antimicrobials in both humans and animals is essential to help slow the emergence of antimicrobial resistance. Here, Singleton et al. present a randomised controlled trial demonstrating the efficacy of social norm messaging to reduce antibiotic prescription frequency in veterinary surgeries.
- David A. Singleton
- , Angela Rayner
- & Gina L. Pinchbeck
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Perspective
| Open AccessDegradable polymeric vehicles for postoperative pain management
Pain management is an extremely important topic both medically and socio-economically. Here the authors offer an overview of the use of degrading polymeric materials for delivery of pharmaceutical agents for pain management and offer a perspective of the future directions of the field.
- Natasha C. Brigham
- , Ru-Rong Ji
- & Matthew L. Becker
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