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•Photochromic and photoluminescent colorless composite adhesive was prepared.•Polylactic acid grafted gum was integrated with lanthanide aluminate (5–11 nm).•Photochromic colorless ...adhesive changed color to green under UV lamp.•Emission ban was monitored at 518 nm upon excitation at 365 nm.•Smart luminous adhesive provided high superhydrophobicity and photostability.
An intelligent nanocomposite adhesive was developed to streamline the manufacturing process for long-lasting photoluminescent and hydrophobic consumer goods. The photoluminescent adhesive composite continued to emit light for up to 120 min after being exposed to darkness. Using lanthanide-activated strontium aluminate (LaSA) nanoparticles (NPs; 5–11 nm) homogeneously immobilized in the eco-friendly polylactic acid oligomer grafted Arabic gum (PLA/AG), a light-transmitting nanocomposite adhesive agent was created. The produced adhesives at various LaSA NPs concentrations exhibited excitation intensity at 365 nm and an emission wavelength at 518 nm. Afterglow phosphorescence or fluorescence was seen in the emission spectra, depending on the LaSA ratio. The photochromic effect was observed as the adhesive film switch color from translucent to green in the presence of ultraviolet light and greenish-yellow in the absence of light. The LaSA nanoparticles embedded in the polylactic acid oligomer grafted Arabic gum matrix improved the nanocomposite hydrophobicity and scratch resistance. Both of durability and photostability of the LaSA@PLA/AG nanocomposite were found to be exceptional. This work verified the viability of mass producing photoluminescent adhesive for a variety of smart uses such as smart windows, smart packaging, and safety directional signs in buildings.
Summary Background Treatment with doxorubicin is a present standard of care for patients with metastatic soft-tissue sarcoma and median overall survival for those treated is 12–16 months, but few, if ...any, novel treatments or chemotherapy combinations have been able to improve these poor outcomes. Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody that has antitumour activity in human sarcoma xenografts. We aimed to assess the efficacy of olaratumab plus doxorubicin in patients with advanced or metastatic soft-tissue sarcoma. Methods We did an open-label phase 1b and randomised phase 2 study of doxorubicin plus olaratumab treatment in patients with unresectable or metastatic soft-tissue sarcoma at 16 clinical sites in the USA. For both the phase 1b and phase 2 parts of the study, eligible patients were aged 18 years or older and had a histologically confirmed diagnosis of locally advanced or metastatic soft-tissue sarcoma not previously treated with an anthracycline, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and available tumour tissue to determine PDGFRα expression by immunohistochemistry. In the phase 2 part of the study, patients were randomly assigned in a 1:1 ratio to receive either olaratumab (15 mg/kg) intravenously on day 1 and day 8 plus doxorubicin (75 mg/m2 ) or doxorubicin alone (75 mg/m2 ) on day 1 of each 21-day cycle for up to eight cycles. Randomisation was dynamic and used the minimisation randomisation technique. The phase 1b primary endpoint was safety and the phase 2 primary endpoint was progression-free survival using a two-sided α level of 0·2 and statistical power of 0·8. This study was registered with ClinicalTrials.gov , number NCT01185964. Findings 15 patients were enrolled and treated with olaratumab plus doxorubicin in the phase 1b study, and 133 patients were randomised (66 to olaratumab plus doxorubicin; 67 to doxorubicin alone) in the phase 2 trial, 129 (97%) of whom received at least one dose of study treatment (64 received olaratumab plus doxorubicin, 65 received doxorubicin). Median progression-free survival in phase 2 was 6·6 months (95% CI 4·1–8·3) with olaratumab plus doxorubicin and 4·1 months (2·8–5·4) with doxorubicin (stratified hazard ratio HR 0·67; 0·44–1·02, p=0·0615). Median overall survival was 26·5 months (20·9–31·7) with olaratumab plus doxorubicin and 14·7 months (9·2–17·1) with doxorubicin (stratified HR 0·46, 0·30–0·71, p=0·0003). The objective response rate was 18·2% (9·8–29·6) with olaratumab plus doxorubicin and 11·9% (5·3–22·2) with doxorubicin (p=0·3421). Steady state olaratumab serum concentrations were reached during cycle 3 with mean maximum and trough concentrations ranging from 419 μg/mL (geometric coefficient of variation in percentage CV% 26·2) to 487 μg/mL (CV% 33·0) and from 123 μg/mL (CV% 31·2) to 156 μg/mL (CV% 38·0), respectively. Adverse events that were more frequent with olaratumab plus doxorubicin versus doxorubicin alone included neutropenia (37 58% vs 23 35%), mucositis (34 53% vs 23 35%), nausea (47 73% vs 34 52%), vomiting (29 45% vs 12 18%), and diarrhoea (22 34% vs 15 23%). Febrile neutropenia of grade 3 or higher was similar in both groups (olaratumab plus doxorubicin: eight 13% of 64 patients vs doxorubicin: nine 14% of 65 patients). Interpretation This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11·8 months in median overall survival, suggesting a potential shift in the treatment of soft-tissue sarcoma. Funding Eli Lilly and Company.
Hydrogels are versatile materials with numerous applications; however, their potential in water treatment is hindered by their tendency to exhibit high swelling, degradation, and excessive water ...absorption. In this study, a hydrogel composed of natural clay, polyacrylic acid (PAA), and tannic acid (TA) was prepared with varying ratios of TA to control swelling ratio, reduce degradation and enhance adsorption efficiency for removal of cationic dye-contaminated wastewater. The effect of the TA ratio on the physical, chemical, and adsorption properties of prepared hydrogel (clay/PAA-TA) was studied by preparing a series of hydrogel composites and characterizing them using various techniques. The swelling ratio of pure PAA hydrogels was 7061%, but by incorporating TA into the polymer mixture, the swelling ratio decreased to less than 500%, with the lowest observed swelling of 250% occurring at a 5% tannic acid. In adsorption studies, the target pollutant was crystal violet dye (CV) and the pH effect, time effect, temperature and initial dye concentration for the adsorption CV dye were investigated using batch adsorption parameters. Adsorption studies showed that using 5% of TA is the optimal ratio to achieve the highest adsorption capacity of the prepared clay/PAA-TA to uptake CV dye. With an adsorption capacity of 444.5 mg/g, the Langmuir-Freundlich model suited the adsorption isotherm. The adsorption kinetics were best explained by the pseudo-first-order model. The results of thermodynamic studies indicated that the adsorption was spontaneous, favorable, and endothermic.
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•A series of hydrogel composite was prepared using clay, polyacrylic acid, and tannic acid.•The hydrogel grafted with 5% tannic acid showed less swelling and higher adsorption capacity than the PAA.•The adsorption capacity for removal of the CV dye was 444.5 mg/g at 35 °C.•The equilibrium kinetic adsorption data agreed well with the Langmuir-Freundlich isotherm model.•The adsorption process was spontaneous and favorable.
Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of sarcomas. We have validated and implemented a ...clinical molecular diagnostic assay, MSK- Fusion Solid, for detection of gene fusions in solid tumors, including sarcomas. Starting with RNA extracted from formalin-fixed paraffin-embedded tumor material, this targeted RNA sequencing assay utilizes anchored multiplex PCR to detect oncogenic fusion transcripts involving 62 genes known to be recurrently rearranged in solid tumors including sarcomas without prior knowledge of fusion partners. From 1/2016 to 1/2018, 192 bone and soft tissue tumors were submitted for MSK- Fusion Solid analysis and 96% (184/192) successfully passed all the pre-sequencing quality control parameters and sequencing steps. These sarcomas encompass 24 major tumor types, including 175 soft tissue tumors and 9 osteosarcomas. Ewing and Ewing-like sarcomas, rhabdomyosarcoma, and sarcoma-not otherwise specified were the three most common tumor types. Diagnostic in-frame fusion transcripts were detected in 43% of cases, including 3% (6/184) with novel fusion partners, specifically TRPS1-PLAG1, VCP-TFE3, MYLK-BRAF, FUS-TFCP2, and ACTB-FOSB, the latter in two cases of pseudomyogenic hemangioendothelioma, representing a novel observation in this sarcoma. Our experience shows that this targeted RNA sequencing assay performs in a robust and sensitive fashion on RNA extracted from most routine clinical specimens of sarcomas thereby facilitating precise diagnosis and providing opportunities for novel fusion partner discovery.
Sarcomas are rare and heterogeneous neoplasms of mesenchymal tissues with diverse morphologies and clinical behavior. In the last few years, the discovery of specific genetic aberrations in these ...tumors has allowed better classification and understanding of mechanisms driving their pathogenesis. While the majority of sarcomas are still treated by traditional modalities, molecular markers driving the pathogenesis have paved the way for more accurate diagnosis and opportunity to explore other therapeutic strategies. This review discusses the available molecular tools in sarcoma diagnostics and highlight some of the biological significance of the recent discoveries and their clinical applications.
Erdheim-Chester disease is a rare, non-Langerhans cell histiocytosis histologically characterized by multi-systemic proliferation of mature histiocytes in a background of inflammatory stroma. The ...disease can involve virtually any organ system; most commonly the bones, skin, retroperitoneum, heart, orbit, lung, and brain are affected. Although a histiocytic proliferation is the histological hallmark of the disease, a wide range of morphological appearances have been described as part of case studies or small series. A comprehensive review of histopathological features in clinically and molecularly defined Erdheim-Chester disease has yet to be characterized. To address this issue and help guide clinical practice, we comprehensively analyzed the pathological spectrum of Erdheim-Chester disease in a clinically and molecularly defined cohort. We reviewed 73 biopsies from 42 patients showing involvement by histiocytosis from a variety of organ systems, including bone (16), retroperitoneum (11), skin (19), orbit (6), brain (5), lung (6), cardiac structures (2), epidural soft tissue (3), oral cavity (2), subcutaneous soft tissue (2), and testis (2). In eight patients, one or more bone marrow biopsies were performed due to clinical indication and an accompanying myeloid neoplasm was detected in six of them. Thirty-eight cases were investigated for genetic abnormalities. Somatic mutations involving BRAF (25/38), MAP2K1 (6/38), ARAF (2/38), MAP2K2 (1/38), KRAS (1/38), and NRAS (1/38) genes were detected. One of the cases with a MAP2K1 mutation also harbored a PIK3CA mutation. We have observed marked heterogeneity in histology and immunophenotype, identified site-specific features, overlap with other histiocytic and myeloid disorders and potential diagnostic pitfalls. We hope that broadening the spectrum of recognized pathologic manifestations of Erdheim-Chester disease will help practicing clinicians and pathologists to diagnose Erdheim-Chester disease early in the disease course and manage these patients effectively.
The field of anatomic pathology has been evolving in the last few decades and the advancements have been largely fostered by innovative technology. Immunohistochemistry enabled a paradigm shift in ...discovery and diagnostic evaluation, followed by booming genomic advancements which allowed for submicroscopic pathologic characterization, and now the field of digital pathology coupled with machine learning and big data acquisition is paving the way to revolutionize the pathology medical domain. Whole slide imaging (WSI) is a disruptive technology where glass slides are digitized to produce on-screen whole slide images. Specifically, in the past decade, there have been significant advances in digital pathology systems that have allowed this technology to promote integration into clinical practice. Whole slide images (WSI), or digital slides, can be viewed and navigated comparable to glass slides on a microscope, as digital files. Whole slide imaging has increased in adoption among pathologists, pathology departments, and scientists for clinical, educational, and research initiatives. Integration of digital pathology systems requires a coordinated effort with numerous stakeholders, not only within the pathology department, but across the entire enterprise. Each pathology department has distinct needs, use cases and blueprints, however the framework components and variables for successful clinical integration can be generalized across any organization seeking to undergo a digital transformation at any scale. This article will review those components and considerations for integrating digital pathology systems into clinical practice.
Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical ...separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear
. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway
, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.
Biomarkers that guide therapy selection are gaining unprecedented importance as targeted therapy options increase in scope and complexity. In conjunction with high-throughput molecular techniques, ...therapy-guiding biomarker assays based upon immunohistochemistry (IHC) have a critical role in cancer care in that they inform about the expression status of a protein target. Here, we describe the validation procedures for four clinical IHC biomarker assays-PTEN, RB, MLH1, and MSH2-for use as integral biomarkers in the nationwide NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) EAY131 clinical trial. Validation procedures were developed through an iterative process based on collective experience and adaptation of broad guidelines from the FDA. The steps included primary antibody selection; assay optimization; development of assay interpretation criteria incorporating biological considerations; and expected staining patterns, including indeterminate results, orthogonal validation, and tissue validation. Following assay lockdown, patient samples and cell lines were used for analytic and clinical validation. The assays were then approved as laboratory-developed tests and used for clinical trial decisions for treatment selection. Calculations of sensitivity and specificity were undertaken using various definitions of gold-standard references, and external validation was required for the PTEN IHC assay. In conclusion, validation of IHC biomarker assays critical for guiding therapy in clinical trials is feasible using comprehensive preanalytic, analytic, and postanalytic steps. Implementation of standardized guidelines provides a useful framework for validating IHC biomarker assays that allow for reproducibility across institutions for routine clinical use.
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