Steinmetz

Implantable polymeric hydrogels loaded with immunostimulatory cowpea mosaic virus (CPMV) were fabricated using digital light processing (DLP) printing technology. The CPMV-laden hydrogels were surgically implanted into the peritoneal cavity to serve as depots for cancer slow-release immunotherapy. Sustained release of CPMV within the intraperitoneal space alleviates the need for repeated dosing and we demonstrated efficacy against ovarian cancer in a metastatic mouse model.

We have developed nanoparticle formulations targeting M2 macrophages for cancer immunotherapy by conjugating high-affinity binding peptides to cowpea mosaic virus as an immunostimulatory adjuvant. We confirmed the targeting of and uptake by M2 macrophages in vitro and the therapeutic efficacy of the nanoparticles against murine melanoma in vivo .

In the era of (re)legalisation of medicinal and recreational cannabis, accidental and intentional exposure to edibles, cannabis-infused food products, has increased substantially. However, there is particular concern regarding younger age groups. Most concerning is the increase in hospitalisations. According to a study by Myran et al. (1), provinces in Canada, where the sale of edibles is permitted, saw an increase in paediatric poisonings due to unintentional consumption of edibles. Similar trends have been observed in "legalised states" in the US, such as Colorado (2)...

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"- a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity were created...

BACKGROUND: Smoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the antidiabetic drug glucagon-like peptide-1 (GLP-1) analogue to modulate addictive behaviours and nicotine craving. Previously, we reported the short-term results of a randomised, double-blind, placebo-controlled trial. Herein we report long-term abstinence rates and weight developments after 24 and 52 weeks. METHODS: This single-centre, randomised, double-blind, placebo-controlled, parallel group trial was done at the University Hospital Basel in Switzerland...

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. METHODS: We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers...

Due to the increasing incidence of cancer, there is a need to develop new platforms that can combat this disease. Cancer immunotherapy is a platform that takes advantage of the immune system to recognize and eradicate tumors and metastases. Our lab has identified a plant virus nanoparticle, cowpea mosaic virus (CPMV) as a promising approach for cancer immunotherapy. When administered intratumorally, CPMV relieves the immune system of tumor-induced immunosuppression and reprograms the tumor microenvironment into an activated state to launch systemic antitumor immunity...

Extracellular vesicles (EVs) are important players in melanoma progression, but their use as clinical biomarkers has been limited by the difficulty of profiling blood-derived EV proteins with high depth of coverage, the requirement for large input amounts, and complex protocols. Here, we provide a streamlined and reproducible experimental workflow to identify plasma- and serum- derived EV proteins of healthy donors and melanoma patients using minimal amounts of sample input. SEC-DIA-MS couples size-exclusion chromatography to EV concentration and deep-proteomic profiling using data-independent acquisition...

Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly...

To fulfill their actual cellular role, individual microtubules become functionally specialized through a broad range of mechanisms. The 'search and capture' model posits that microtubule dynamics and functions are specified by cellular targets that they capture (i.e., a posteriori), independently of the microtubule-organizing center (MTOC) they emerge from. However, work in budding yeast indicates that MTOCs may impart a functional identity to the microtubules they nucleate, a priori. Key effectors in this process are microtubule plus-end tracking proteins (+TIPs), which track microtubule tips to regulate their dynamics and facilitate their targeted interactions...

Immune checkpoint therapy (ICT) for cancer can yield dramatic clinical responses; however, these may only be observed in a minority of patients. These responses can be further limited by subsequent disease recurrence and resistance. Combination immunotherapy strategies are being developed to overcome these limitations. We have previously reported enhanced efficacy of combined intratumoral cowpea mosaic virus immunotherapy (CPMV IIT) and ICT approaches. Lymphocyte-activation gene-3 (LAG-3) is a next-generation inhibitory immune checkpoint with broad expression across multiple immune cell subsets...

PEGylation has been the 'gold standard' in bioconjugation due to its ability to improve the pharmacokinetics and pharmacodynamics of native proteins. However, growing clinical evidence of hypersensitivity reactions to PEG due to pre-existing anti-PEG antibodies in healthy humans have raised concerns. Advancements in controlled polymerization techniques and conjugation chemistries have paved the way for the development of protein-polymer conjugates that can circumvent these adverse reactions while retaining the benefits of such modifications...

Attention can be deployed in multiple forms and facilitates behavior by influencing perceptual sensitivity and choice bias. Attention is also associated with a myriad of changes in sensory neural activity. Yet, the relationship between the behavioral components of attention and the accompanying changes in neural activity remains largely unresolved. We examined this relationship by quantifying sensitivity and bias in monkeys performing a task that dissociated eye movement responses from the focus of covert attention...

Many virus-like particles (VLPs) have good chemical, thermal, and mechanical stabilities compared to those of other biologics. However, their stability needs to be improved for the commercialization and use in translation of VLP-based materials. We developed an endoskeleton-armored strategy for enhancing VLP stability. Specifically, the VLPs of physalis mottle virus (PhMV) and Qβ were used to demonstrate this concept. We built an internal polymer "backbone" using a maleimide-PEG15 -maleimide cross-linker to covalently interlink viral coat proteins inside the capsid cavity, while the native VLPs are held together by only noncovalent bonding between subunits...

Interactions between genetic perturbations and segregating loci can cause perturbations to show different phenotypic effects across genetically distinct individuals. To study these interactions on a genome scale in many individuals, we used combinatorial DNA barcode sequencing to measure the fitness effects of 7,700 CRISPRi perturbations targeting 1,712 distinct genes in 169 yeast cross progeny (or segregants). We identified 460 genes whose perturbation has different effects across segregants. Several factors caused perturbations to show variable effects, including baseline segregant fitness, the mean effect of a perturbation across segregants, and interacting loci...

IMPORTANCE: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive. OBJECTIVE: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery. DATA SOURCES: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials...

Ecosystem functions and services are severely threatened by unprecedented global loss in biodiversity. To counteract these trends, it is essential to develop systems to monitor changes in biodiversity for planning, evaluating, and implementing conservation and mitigation actions. However, the implementation of monitoring systems suffers from a trade-off between grain (i.e., the level of detail), extent (i.e., the number of study sites), and temporal repetition. Here, we present an applied and realized networked sensor system for integrated biodiversity monitoring in the Nature 4...

IMPORTANCE: Standard treatment for patients with medullary thyroid cancer (MTC) consists of total thyroidectomy with central neck dissection, but the rationale for bilateral surgery in patients with unilateral disease on ultrasonography remains unclear. OBJECTIVE: To determine the presence of occult contralateral disease (lesions not seen on preoperative ultrasonography) in patients with MTC as a rationale for total thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS: This multi-institutional, retrospective cohort study was conducted from September 1998 to April 2022 in academic medical centers and included patients with MTC who underwent thyroidectomy with preoperative imaging...

BACKGROUND: The prevalence of sarcopenia and its impact in older patients undergoing inpatient cardiac rehabilitation (iCR) after cardiac procedure has been insufficiently studied. The main aim of this study was to evaluate the prevalence of sarcopenia and quantify the functional capacity of older sarcopenic and non-sarcopenic patients participating in iCR. METHODS: Prospective, observational cohort study within the framework of the ongoing multicenter prehabilitation study "PRECOVERY"...

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