Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair.

Meniscus tissue is commonly injured due to sports-related injuries and age-related degeneration and approximately 50% of individuals with a meniscus tear will develop post-traumatic osteoarthritis (PTOA). Given that the meniscus has limited healing potential, new therapeutic strategies are required to enhance meniscus repair. Porcine meniscus-derived matrix (MDM) scaffolds improve meniscus integrative repair, but sources of human meniscus tissue have not been investigated.

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients.

Identification of 4'-Demethyl-3,9-dihydroeucomin as a Bitter-Masking Compound from the Resin of .

Masking the bitter taste of foods is one of the key strategies to improve their taste and palatability, particularly in the context of clean labeling, where natural compounds are preferred. Despite the demand, the availability of natural bitter-masking compounds remains limited. Here, we identified the bitter-masking compound 4'-demethyl-3,9-dihydroeucomin () isolated from the resin of by means of an activity-guided in vivo (sensory bitterness rating of quinine) and in vitro (cell-based bitter response assays) approach.

Comprehensive metabolome characterization of leaves, internodes, and aerial roots of Vanilla planifolia by untargeted LC-MS and GC × GC-MS.

Introduction: Untargeted metabolomics is a powerful tool that provides strategies for gaining a systematic understanding of quantitative changes in the levels of metabolites, especially when combining different metabolomic platforms. Vanilla is one of the world's most popular flavors originating from cured pods of the orchid Vanilla planifolia. However, only a few studies have investigated the metabolome of V.

Ramucirumab in combination with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma: a single-centre, phase 1/2 trial.

Background: VEGF, a key mediator of angiogenesis and resistance to immunotherapy, is overexpressed in head and neck squamous cell carcinoma (HNSCC). We aimed to determine the recommended phase 2 dose of ramucirumab, a selective VEGFR2 inhibitor, given with pembrolizumab and the objective response rate of this combination as first-line treatment for recurrent or metastatic HNSCC.

Methods: In this single-centre, phase 1/2 trial, which was done at Washington University (St Louis, MO, USA), eligible patients were aged 18 years or older with incurable recurrent or metastatic HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2.

Novel Catechol -methyltransferases from Catalyze the Generation of Taste-Active Flavonoids.

Due to the increasing demand for natural food ingredients, including taste-active compounds, enzyme-catalyzed conversions of natural substrates, such as flavonoids, are promising tools to align with the principles of Green Chemistry. In this study, a novel -methyltransferase activity was identified in the mycelium of , which was successfully applied to generate the taste-active flavonoids hesperetin, hesperetin dihydrochalcone, homoeriodictyol, and homoeriodictyol dihydrochalcone. Furthermore, the mycelium-mediated OMT activity allowed for the conversion of various catecholic substrates, yielding their respective (iso-)vanilloids, while monohydroxylated compounds were not converted.

Privacy by Projection: Federated Population Density Estimation by Projecting on Random Features.

We consider the problem of population density estimation based on location data crowdsourced from mobile devices, using kernel density estimation (KDE). In a conventional, centralized setting, KDE requires mobile users to upload their location data to a server, thus raising privacy concerns. Here, we propose a Federated KDE framework for estimating the user population density, which not only keeps location data on the devices but also provides probabilistic privacy guarantees against a server that tries to infer users' location.

How Well Do Dogs Cope with Air Travel? An Owner-Reported Survey Study.

It is estimated that 2 million domestic animals travel on commercial flights every year in the US alone and that dogs make up 58% of pets travelling worldwide. There has been little research on the welfare effects of air travel on dogs. The purpose of this owner-reported study was to understand how well dogs cope with and recover from air travel from a physical, mental, and emotional health perspective.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking.

Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma.

Purpose: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

Chemical identification and optimization of the 4-aminophenol colorimetric test for the differentiation between hemp-type and marijuana-type cannabis plant samples.

The 4- Aminophenol (4-AP) colorimetric test is a fast, easy-to-use, and cost-effective presumptive assay of cannabis plant material producing different chromophores with THC-rich cannabis (blue color) and with CBD-rich cannabis (pink color). The main drawback of the 4-AP test is a brief observation window where the color rapidly changes to black, limiting the utility of the test. We now report for the first time, the identification of the product chromophores between 4-AP and CBD/THC as well as propose an explanation and a solution for the color degradation of the chromophores.

Technical note: Consistency of IAEA's TRS-483 and AAPM's extended TG-51 protocols for clinical reference dosimetry of the CyberKnife M6 machine.

Background: While IAEA's TRS-483 code of practice is adapted for the calibration of CyberKnife machines, AAPM's TG-51 is still the protocol recommended by the manufacturer for their calibration. The differences between both protocols could lead to differences in absorbed dose to water during the calibration process.

Purpose: The aims of this work are to evaluate the difference resulting from the application of TG-51 (including the manufacturer's adaptations) and TRS-483 in terms of absorbed dose to water for a CyberKnife M6, and to evaluate the consistency of TRS-483.

Human Gingival Fibroblasts as a Novel Cell Model Describing the Association between Bitter Taste Thresholds and Interleukin-6 Release.

Human gingival fibroblast cells (HGF-1 cells) present an important cell model to investigate the gingiva's response to inflammatory stimuli such as lipopolysaccharides from (LPS). Recently, we demonstrated -resveratrol to repress the -LPS evoked release of the pro-inflammatory cytokine interleukin-6 (IL-6) via involvement of bitter taste sensing receptor TAS2R50 in HGF-1 cells. Since HGF-1 cells express most of the known 25 TAS2Rs, we hypothesized an association between a compound's bitter taste threshold and its repressing effect on the -LPS evoked IL-6 release by HGF-1 cells.

Hearing Outcomes in a Deintensification Trial of Adjuvant Therapy for HPV-Related Oropharyngeal Squamous Cell Carcinoma.

Objective: To explore whether deintensification of adjuvant therapy reduces ototoxicity among patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC).

Study Design: Retrospective cohort study.

Setting: Single academic center.

Novel α-glycosyl compounds from glycosylation of rubusoside.

In this work we investigated mixtures from α-glycosylation of rubusoside with cyclodextrin glycosyltransferases. In addition to the previously known α-1,4 glycosylated derivatives, nine new compounds with rare α-1,3-glycosidic bonds were identified based on nuclear magnetic resonance spectroscopy and mass spectrometric analysis. Furthermore, sensory properties of monoglycosylated rubusoside derivatives were investigated and compared to previously described monoglycosylated compounds.

Impact of lactisole on the time-intensity profile of selected sweeteners in dependence of the binding site.

Currently, there is limited insight into the influence of the different binding sites of agonists and antagonists of the sweet taste receptor TAS1R2/TAS1R3 on temporal sensory properties of sweet tasting compounds. We investigated whether the binding site and a competitive or allosteric inhibition of TAS1R2/TAS1R3 influence the time-dependent sensory perception and in vitro TAS1R2/TAS1R3-activation profiles. We compared time-intensity ratings of cyclamate, NHDC, acesulfame K, and aspartame with and without lactisole with the corresponding TAS1R2/TAS1R3-activation in transfected HEK293 cells.

The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma.

Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC.

Comprehensive Metabolite Profiling of ssp. Extracts Using Liquid Chromatography Coupled with Electrospray Ionization Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry.

A wide range of secondary metabolites has been described for various species, including the sweet-tasting phenyldihydroisocoumarin phyllodulcin, which is found in the leaves of ssp. . This work aims at the development and validation of an analytical workflow for comprehensive semi-polar metabolite profiling using liquid chromatography coupled with electrospray ionization ion mobility quadrupole time-of-flight mass spectrometry (UPLC-ESI-IMS-QToF-MS) to complement existing analytical studies.

An enzymatic tandem reaction to produce odor-active fatty aldehydes.

Aldehydes represent a versatile and favored class of flavoring substances. A biocatalytic access to odor-active aldehydes was developed by conversion of fatty acids with two enzymes of the α-dioxygenase pathway. The recombinant enzymes α-dioxygenase (α-DOX) originating from Crocosphaera subtropica and fatty aldehyde dehydrogenase (FALDH) from Vibrio harveyi were heterologously expressed in E.

Individual Sweet Taste Perception Influences Salivary Characteristics After Orosensory Stimulation With Sucrose and Noncaloric Sweeteners.

Emerging evidence points to a major role of salivary flow and viscoelastic properties in taste perception and mouthfeel. It has been proposed that sweet-tasting compounds influence salivary characteristics. However, whether perceived differences in the sensory properties of structurally diverse sweet-tasting compounds contribute to salivary flow and saliva viscoelasticity as part of mouthfeel and overall sweet taste perception remains to be clarified.

Reducing the Bitter Taste of Pharmaceuticals Using Cell-Based Identification of Bitter-Masking Compounds.

The palatability of a pharmaceutical preparation is a significant obstacle in developing a patient-friendly dosage form. Bitter taste is an important factor for patients in (i) selecting a certain drug from generic products available in the market and (ii) adhering to a therapeutic regimen. The various methods developed for identification of bitter tasting and bitter-taste modulating compounds present a number of limitations, ranging from limited sensitivity to lack of close correlations with sensory data.

T cell subtype profiling measures exhaustion and predicts anti-PD-1 response.

Anti-PD-1 therapy can provide long, durable benefit to a fraction of patients. The on-label PD-L1 test, however, does not accurately predict response. To build a better biomarker, we created a method called T Cell Subtype Profiling (TCSP) that characterizes the abundance of T cell subtypes (TCSs) in FFPE specimens using five RNA models.

Electrostatic flocking of salt-treated microfibers and nanofiber yarns for regenerative engineering.

Electrostatic flocking is a textile technology that employs a Coulombic driving force to launch short fibers from a charging source towards an adhesive-covered substrate, resulting in a dense array of aligned fibers perpendicular to the substrate. However, electrostatic flocking of insulative polymeric fibers remains a challenge due to their insufficient charge accumulation. We report a facile method to flock electrostatically insulative poly(ε-caprolactone) (PCL) microfibers (MFs) and electrospun PCL nanofiber yarns (NFYs) by incorporating NaCl during pre-flock processing.