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Phenotypic plasticity represents the most relevant hallmark of the carcinoma cell as it bestows it with the capacity of transiently altering its morphological and functional features while en route to the metastatic site. However, the study of phenotypic plasticity is hindered by the rarity of these events within primary lesions and by the lack of experimental models. Here, we identified a subpopulation of phenotypic plastic colon cancer cells: EpCAM lo cells are motile, invasive, chemo-resistant, and highly metastatic. EpCAM lo bulk and single-cell RNAseq analysis indicated (1) enhanced Wnt/β-catenin signaling, (2) a broad spectrum of degrees of epithelial to mesenchymal transition (EMT) activation including hybrid E/M states (partial EMT) with highly plastic features, and (3) high correlation with the CMS4 subtype, accounting for colon cancer cases with poor prognosis and a pronounced stromal component. Of note, a signature of genes specifically expressed in EpCAM lo cancer cells is highly predictive of overall survival in tumors other than CMS4, thus highlighting the relevance of quasi-mesenchymal tumor cells across the spectrum of colon cancers. Enhanced Wnt and the downstream EMT activation represent key events in eliciting phenotypic plasticity along the invasive front of primary colon carcinomas. Distinct sets of epithelial and mesenchymal genes define transcriptional trajectories through which state transitions arise. pEMT cells, often earmarked by the extracellular matrix glycoprotein SPARC together with nuclear ZEB1 and β-catenin along the invasive front of primary colon carcinomas, are predicted to represent the origin of these (de)differentiation routes through biologically distinct cellular states and to underlie the phenotypic plasticity of colon cancer cells.

Cyclin-dependent kinase 2-associated protein 1 ( CDK2AP1 ; also known as deleted in oral cancer or DOC1 ) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much CDK2AP1 mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1–3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity.

Phenotypic plasticity and inflammation, two well-established hallmarks of cancer, play key roles in local invasion and distant metastasis by enabling rapid adaptation of tumor cells to dynamic micro- environmental changes. Here, we show that in oral squamous carcinoma cell carcinoma (OSCC), the competition between the NuRD and SWI/SNF chromatin remodeling complexes plays a pivotal role in regulating both epithelial-mesenchymal plasticity (EMP) and inflammation. By perturbing these complexes, we demonstrate their opposing downstream effects on inflammatory pathways and EMP regulation. In particular, downregulation of the BRG1-specific SWI/SNF complex deregulates key inflammatory genes such as TNF-α and IL6 in opposite ways when compared with loss of CDK2AP1, a key member of the NuRD complex. We show that CDK2AP1 genetic ablation triggers a pro-inflammatory secretome encompassing several chemo- and cytokines thus promoting the recruitment of monocytes into the tumor microenvironment (TME). Furthermore, CDK2AP1 deletion stimulates their differentiation into M2-like macrophages, as also validated on tumor microarrays from OSCC patient- derived tumor samples. Further analysis of the inverse correlation between CDK2AP1 expression and TME immune infiltration revealed specific downstream effects on CD68+ macrophage abundance and localization. Our study sheds light on the role of chromatin remodeling complexes in OSCC locoregional invasion and points at the potential of CDK2AP1 and other members of the NuRD and SWI/SNF chromatin remodeling complexes as prognostic markers and therapeutic targets.

Phenotypic plasticity represents the most relevant hallmark of the carcinoma cell as it bestows it with the capacity of transiently altering its morphologic and functional features while en route to the metastatic site. However, the study of phenotypic plasticity is hindered by the rarity of these events within primary lesions and by the lack of experimental models. Here, we identified a subpopulation of phenotypic plastic colon cancer cells: EpCAMlo cells are motile, invasive, chemo-resistant, and highly metastatic. EpCAMlo bulk and single-cell RNAseq analysis indicated 1. enhanced Wnt/β-catenin signaling, 2. a broad spectrum of degrees of EMT activation including hybrid E/M states (partial EMT) with highly plastic features, and 3. high correlation with the CMS4 subtype, accounting for colon cancer cases with poor prognosis and a pronounced stromal component. Of note, a signature of genes specifically expressed in EpCAMlo cancer cells is highly predictive of overall survival in tumors other than CMS4, thus highlighting the relevance of quasi-mesenchymal tumor cells across the spectrum of colon cancers. Enhanced Wnt and the downstream EMT activation represent key events in eliciting phenotypic plasticity along the invasive front of primary colon carcinomas. Distinct sets of epithelial and mesenchymal genes define transcriptional trajectories through which state transitions arise. pEMT cells, often earmarked by the extracellular matrix glycoprotein SPARC together with nuclear ZEB1 and β-catenin along the invasive front of primary colon carcinomas, are predicted to represent the origin of these (de)differentiation routes through biologically distinct cellular states, and to underlie the phenotypic plasticity of colon cancer cells. Competing Interest Statement The authors have declared no competing interest. Footnotes * We have substantially revised the manuscript both in its overall structure, data presentation, and focus on the more novel aspects. By responding to the reviewers' criticisms and suggestions, we have implemented additional and state-of-the-art computational analysis pointing to the key role of pEMT in underlying phenotypic plasticity in colon cancer. Mining of bulk and scRNAseq data sets from colon cancer patients, we validated the relevance of our study by developing classifiers that outperform existing ones in predicting overall relapse-free survival.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients’ quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm 2 , 30 mW, illuminated area 0.04 cm 2 , 7.5 J/cm 2 , 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p  = 0.0012; stimulated: p  < 0.0001), mean pH values ( p  = 0.0002 and p  = 0.0004), and mean score from the quality of life questionnaire ( p  < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

Ancient Herculaneum papyrus scrolls, hopelessly charred in the 79 A.D. Vesuvius eruption, contain valuable writings of the Greek philosophers of the day, including works of the Epicurean Philodemus. X-ray phase contrast tomography has recently begun unlocking their secrets. However, only small portions of the text hidden inside the scroll have been recover. One of the challenging tasks in Herculaneum papyri investigation is their virtual unfolding because of their highly complicated structure and three-dimensional arrangement. Although this procedure is feasible, problems in segmentation and flattening hinder the unrolling of a large portion of papyrus. We propose a computational platform for the virtual unfolding procedure, and we show the results of its application on two Herculaneum papyrus fragments. This work paves the way to a comprehensive survey and to further interpretation of larger portions of text hidden inside the carbonized Herculaneum papyri.

The solar wind plasma is a fully ionized and turbulent gas ejected by the outer layers of the solar corona at very high speed, mainly composed by protons and electrons, with a small percentage of helium nuclei and a significantly lower abundance of heavier ions. Since particle collisions are practically negligible, the solar wind is typically not in a state of thermodynamic equilibrium. Such a complex system must be described through self-consistent and fully nonlinear models, taking into account its multi-species composition and turbulence. We use a kinetic hybrid Vlasov-Maxwell numerical code to reproduce the turbulent energy cascade down to ion kinetic scales, in typical conditions of the uncontaminated solar wind plasma, with the aim of exploring the differential kinetic dynamics of the dominant ion species, namely protons and alpha particles. We show that the response of different species to the fluctuating electromagnetic fields is different. In particular, a significant differential heating of alphas with respect to protons is observed. Interestingly, the preferential heating process occurs in spatial regions nearby the peaks of ion vorticity and where strong deviations from thermodynamic equilibrium are recovered. Moreover, by feeding a simulator of a top-hat ion spectrometer with the output of the kinetic simulations, we show that measurements by such spectrometer planned on board the Turbulence Heating ObserveR (THOR mission), a candidate for the next M4 space mission of the European Space Agency, can provide detailed three-dimensional ion velocity distributions, highlighting important non-Maxwellian features. These results support the idea that future space missions will allow a deeper understanding of the physics of the interplanetary medium.

The demand for wearable devices to measure respiratory activity is constantly growing, finding applications in a wide range of scenarios (e.g., clinical environments and workplaces, outdoors for monitoring sports activities, etc.). Particularly, the respiration rate (RR) is a vital parameter since it indicates serious illness (e.g., pneumonia, emphysema, pulmonary embolism, etc.). Therefore, several solutions have been presented in the scientific literature and on the market to make RR monitoring simple, accurate, reliable and noninvasive. Among the different transduction methods, the piezoresistive and inertial ones satisfactorily meet the requirements for smart wearable devices since unobtrusive, lightweight and easy to integrate. Hence, this review paper focuses on innovative wearable devices, detection strategies and algorithms that exploit piezoresistive or inertial sensors to monitor the breathing parameters. At first, this paper presents a comprehensive overview of innovative piezoresistive wearable devices for measuring user’s respiratory variables. Later, a survey of novel piezoresistive textiles to develop wearable devices for detecting breathing movements is reported. Afterwards, the state-of-art about wearable devices to monitor the respiratory parameters, based on inertial sensors (i.e., accelerometers and gyroscopes), is presented for detecting dysfunctions or pathologies in a non-invasive and accurate way. In this field, several processing tools are employed to extract the respiratory parameters from inertial data; therefore, an overview of algorithms and methods to determine the respiratory rate from acceleration data is provided. Finally, comparative analysis for all the covered topics are reported, providing useful insights to develop the next generation of wearable sensors for monitoring respiratory parameters.

Organic materials have revolutionized optoelectronics by their processability, flexibility and low cost, with application to light-emitting devices for full-colour screens 1 , solar cells 2 and lasers 3 , 4 . Some low-dimensional organic semiconductor structures exhibit properties resembling those of inorganics, such as polarized emission 5 and enhanced electroluminescence 6 . One-dimensional metallic, III–V and II–VI nanostructures have also been the subject of intense investigation 7 , 8 as building blocks for nanoelectronics and photonics. Given that one-dimensional polymer nanostructures, such as polymer nanofibres, are compatible with sub-micrometre patterning capability 9 and electromagnetic confinement within subwavelength volumes 8 , they can offer the benefits of organic light sources to nanoscale optics. Here we report on the optical properties of fully conjugated, electrospun polymer nanofibres. We assess their waveguiding performance and emission tuneability in the whole visible range. We demonstrate the enhancement of the fibre forward emission through imprinting periodic nanostructures using room-temperature nanoimprint lithography, and investigate the angular dispersion of differently polarized emitted light. Conjugated polymer fibres offer many advantages over other photonic materials, such as tunable properties and easy processability, making them attractive for optoelectronic applications. The waveguiding performance and emission tunability of fully conjugated, electrospun polymer nanofibres have been assessed and their forward emission shown to improve after periodic structures are imprinted using nanoimprint lithography.

Aim of the present study is to evaluate the relationship between genetic and phenotypic data in a series of patients affected by grade I and II of foveal hypoplasia with stable fixation and good visual acuity using multimodal imaging techniques. All patients underwent complete clinical and instrumental assessment including structural Optical Coherence Tomography (OCT), OCT Angiography and Adaptive Optics (AO) imaging. Central macular thickness (CMT), inner nuclear layer (INL), vessel density in superficial capillary plexus were the main variables evaluated with OCT technology. Cone density, cone spacing, cone regularity, cone dispersion and angular density were the parameters evaluated with AO. Genetic evaluation and trio exome sequencing were performed in all affected individuals. Eight patients (3 males and 5 females) with a mean age of 12.62 years (range 8–18) were enrolled. The mean best corrected visual acuity (BCVA) was 0.18 ± 0.13 logMAR, mean CMT was 291.9 ± 16.6 µm and INL was 26.2 ± 4.6 µm. The absence of a foveal avascular zone (FAZ) was documented by examination of OCT-A in seven patients in the superficial capillary plexus. However, there was a partial FAZ in the deep plexus in patients P5 and P8. Of note, all the patients presented with major retinal vessels clearly crossing the foveal center. All individuals exhibited a grade I or II of foveal hypoplasia. In 5 patients molecular analyses showed an extremely mild form of albinism caused by compound heterozygosity of a TYR pathogenic variant and the hypomorphic p.[Ser192Tyr;Arg402Gln] haplotype. One patient had Waardenburg syndrome type 2A caused by a de novo variant in MITF. Two patients had inconclusive molecular analyses. All the patients displayed abnormalities on OCT-A. Photoreceptor count did not differ from normal subjects according to the current literature, but qualitative analysis of AO imaging showed distinctive features likely related to an abnormal pigment distribution in this subset of individuals. In patients with foveal hypoplasia, genetic and multimodal imaging data, including AO findings, can help understand the physiopathology of the foveal hypoplasia phenotype. This study confirms that cone density and visual function can both be preserved despite the absence of a pit.