Spin Waves and Three Dimensionality in the High-Pressure Antiferromagnetic Phase of SrCu_{2}(BO_{3})_{2}.

Quantum magnetic materials can provide explicit realizations of paradigm models in quantum many-body physics. In this context, SrCu_{2}(BO_{3})_{2} is a faithful realization of the Shastry-Sutherland model for ideally frustrated spin dimers, even displaying several of its quantum magnetic phases as a function of pressure. We perform inelastic neutron scattering measurements on SrCu_{2}(BO_{3})_{2} at 5.

Fibroblast integrin α11β1 is a collagen assembly receptor in mechanoregulated fibrillar adhesions.

Solid epithelial cancers with significant desmoplasia are characterized by an excessive deposition of collagen-based matrix, which often supports tumor progression. However, the mechanism of how collagen receptors mediate collagen fibrillogenesis still remains mostly unclear. We show that the collagen-binding integrin α11β1 can co-localize with tensin-1 and deposited collagen I in human pancreatic ductal adenocarcinoma (PDAC) stroma.

Binding kinetics of quaternary ammonium ions in Kcv potassium channels.

Kcv channels from plant viruses represent the autonomous pore module of potassium channels, devoid of any regulatory domains. These small proteins show very reproducible single-channel behavior in planar lipid bilayers. Thus, they are an optimum system for the study of the biophysics of ion transport and gating.

A novel multitargeted self-assembling peptide-siRNA complex for simultaneous inhibition of SARS-CoV-2-host cell interaction and replication.

Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors.

Engineered SPIONs functionalized with endothelin a receptor antagonist ameliorate liver fibrosis by inhibiting hepatic stellate cell activation.

Endothelin-1/endothelin A receptor (ET-1/ETAR) pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells (HSCs) - a key cell type involved in the pathogenesis of liver fibrosis. Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist (ERA) represents a promising therapeutic approach for liver fibrosis. Unfortunately, small-molecule ERAs possess limited clinical potential due to poor bioavailability, short half-life, and rapid renal clearance.

IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition.

Background: Mutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition.

Method: To address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy.

T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer primarily induced by Merkel cell polyomavirus, which is driven by the expression of the oncogenic T antigens (T-Ags). Blockade of the programmed cell death protein-1 (PD-1) pathway has shown remarkable response rates, but evidence for therapy-associated T-Ag-specific immune response and therapeutic strategies for the nonresponding fraction are both limited. We tracked T-Ag-reactive CD8+ T cells in peripheral blood of 26 MCC patients under anti-PD1 therapy, using DNA-barcoded pMHC multimers, displaying all peptides from the predicted HLA ligandome of the oncoproteins, covering 33 class I haplotypes.

Simultaneous analysis of pMHC binding and reactivity unveils virus-specific CD8 T cell immunity to a concise epitope set.

CD8 T cells provide immunity to virus infection through recognition of epitopes presented by peptide major histocompatibility complexes (pMHCs). To establish a concise panel of widely recognized T cell epitopes from common viruses, we combined analysis of TCR down-regulation upon stimulation with epitope-specific enumeration based on barcode-labeled pMHC multimers. We assess CD8 T cell binding and reactivity for 929 previously reported epitopes in the context of 1 of 25 HLA alleles representing 29 viruses.

Hem1 is essential for ruffled border formation in osteoclasts and efficient bone resorption.

Bone resorption is highly dependent on the dynamic rearrangement of the osteoclast actin cytoskeleton to allow formation of actin rings and a functional ruffled border. Hem1 is a hematopoietic-specific subunit of the WAVE-complex which regulates actin polymerization and is crucial for lamellipodia formation in hematopoietic cell types. However, its role in osteoclast differentiation and function is still unknown.

Unveiling the efficacy of a bulk Raman spectra-based model in predicting single cell Raman spectra of microorganisms.

In a previous publication, we trained predictive models based on Raman bulk spectra of microorganisms placed on a silicon dioxide protected silver mirror slide to make predictions for new Raman spectra, unknown to the models, of microorganisms placed on a different substrate, namely stainless steel. Now we have combined large sections of this data and trained a convolutional neural network (CNN) to make predictions for single cell Raman spectra. We show that a database based on microbial bulk material is conditionally suited to make predictions for the same species in terms of single cells.

A novel method to efficiently differentiate human osteoclasts from blood-derived monocytes.

Background: Osteoclasts are the tissue-specific macrophage population of the bone and unique in their bone-resorbing activity. Hence, they are fundamental for bone physiology in health and disease. However, efficient protocols for the isolation and study of primary human osteoclasts are scarce.

Merkel cell polyomavirus-specific and CD39CLA CD8 T cells as blood-based predictive biomarkers for PD-1 blockade in Merkel cell carcinoma.

Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti-PD-1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti-PD-1-associated immune responses and provide a means to directly study tumor-specific T cell responses to treatment. Using mass cytometry and combinatorial tetramer staining, we find that baseline frequencies of blood MCPyV-specific cells correlated with response and survival.

PALS1 is a key regulator of the lateral distribution of tight junction proteins in renal epithelial cells.

The evolutionarily conserved apical Crumbs (CRB) complex, consisting of the core components CRB3a (an isoform of CRB3), PALS1 and PATJ, plays a key role in epithelial cell-cell contact formation and cell polarization. Recently, we observed that deletion of one Pals1 allele in mice results in functional haploinsufficiency characterized by renal cysts. Here, to address the role of PALS1 at the cellular level, we generated CRISPR/Cas9-mediated PALS1-knockout MDCKII cell lines.

[Are the assessments of individual out-of-pocket health services of the IGeL-Monitor in line with clinical guidelines?].

Objectives: The IGeL-Monitor of the Federal Medical Advisory Service in Germany evaluates the benefits and harms of individual out-of-pocket health services (in German: Individuelle Gesundheitsleistungen / IGeL). The aim of the analysis was to systematically compare IGeL-assessements with the recommendations from evidence-based guidelines.

Method: To identify guidelines, we conducted searches in guidelines databases (AWMF, Guidelines International Network and Trip database) and the websites of guideline organisations (February/March 2022).

TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy.

Background: Adoptive cell therapy (ACT) has shown promising results for the treatment of cancer and viral infections. Successful ACT relies on ex vivo expansion of large numbers of desired T-cells with strong cytotoxic capacity and in vivo persistence, which constitutes the greatest challenge to current ACT strategies. Here, in this study, we present a novel technology for ex vivo expansion of antigen-specific T-cells; artificial antigen-presenting scaffolds (Ag-scaffolds) consisting of a dextran-polysaccharide backbone, decorated with combinations of peptide-Major Histocompatibility Complex (pMHC), cytokines and co-stimulatory molecules, enabling coordinated stimulation of antigen-specific T-cells.

Adherence to support pessary in the treatment of pelvic organ prolapse: a retrospective study conducted among 1,371 women.

Introduction And Hypothesis: The objective was to investigate the adherence to pessary treatment in women with pelvic organ prolapse (POP) who were found eligible for this treatment by the urogynecologist, at the first visit at the Department of Gynecology and Obstetrics, Odense University Hospital.

Methods: Data were extracted from the women's medical records. Frequency tabulations were performed to describe the women's reasons for pessary discontinuation by age group.

A Cross-Sectional Study of Bone Nanomechanics in Hip Fracture and Aging.

Bone mechanics is well understood at every length scale except the nano-level. We aimed to investigate the relationship between bone nanoscale and tissue-level mechanics experimentally. We tested two hypotheses: (1) nanoscale strains were lower in hip fracture patients versus controls, and (2) nanoscale mineral and fibril strains were inversely correlated with aging and fracture.

In vivo evaluation of ankle kinematics and tibiotalar joint contact strains using digital volume correlation and 3 T clinical MRI.

Background: In vivo evaluation of ankle joint biomechanics is key to investigating the effect of injuries on the mechanics of the joint and evaluating the effectiveness of treatments. The objectives of this study were to 1) investigate the kinematics and contact strains of the ankle joint and 2) to investigate the correlation between the tibiotalar joint contact strains and the prevalence of osteochondral lesions of the talus distribution.

Methods: Eight healthy human ankle joints were subjected to compressive load and 3 T MRIs were obtained before and after applying load.

CD11b Deficiency Favors Cartilage Calcification via Increased Matrix Vesicles, Apoptosis, and Lysyl Oxidase Activity.

Pathological cartilage calcification is a hallmark feature of osteoarthritis, a common degenerative joint disease, characterized by cartilage damage, progressively causing pain and loss of movement. The integrin subunit CD11b was shown to play a protective role against cartilage calcification in a mouse model of surgery-induced OA. Here, we investigated the possible mechanism by which CD11b deficiency could favor cartilage calcification by using naïve mice.

Preoperative planning to preserve glenoid subchondral bone in anatomical total shoulder replacement.

Background: Glenoid loosening remains a concern in anatomical total shoulder replacement. Preoperative planning software allows optimization of the component positioning, but the target orientation remains unclear due to conflicting optimization priorities. Commonly, the component is aligned to the prescribed version and inclination that reflect the population's average anatomy.

Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy.

Background: Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.