High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

<p>Abstract</p> <p>Background</p> <p>Human Leukocyte Antigen (HLA)-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C) and non-classical (HLA-G) family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs), Natural killer (NK) cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition) of the different HLA-E receptors, the preferred role (if any) of HLA-E expressed <it>in vivo </it>on tumor cells remains to be established.</p> <p>Methods</p> <p>Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded) of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A.</p> <p>Results</p> <p>High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A). Thus, combination phenotypes (HLA-E^lo-int/HLA-AE and HLA-E^hi/HLA-AE) of classical and non-classical class I HLA molecules mark two graded levels of good prognosis.</p> <p>Conclusions</p> <p>These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted 'immunoediting' model.</p

Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives

Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics

Novel technologies to characterize and engineer the microbiome in inflammatory bowel disease

We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, myco - biome and virome data, co-occurrence networks, and compositional data analysis. In addition, we review novel techniques to therapeutically manipulate the microbiome in IBD. We discuss the benefits and drawbacks of these technologies to increase awareness of specific biases, and to facilitate a more rigorous interpretation of results and their potential clinical application. Finally, we present future lines of research to better characterize the relation between microbial communities and IBD pathogenesis and progression

Embodied semantics in a second language: critical review and clinical implications

The role of the sensorimotor system in second language (L2) semantic processing as well as its clinical implications for bilingual patients has hitherto been neglected. We offer an overview of the issues at stake in this under-investigated field, presenting the theoretical and clinical relevance of studying L2 embodiment and reviewing the few studies on this topic. We highlight that (a) the sensorimotor network is involved in L2 processing, and that (b) in most studies, L2 is differently embodied than L1, reflected in a lower degree or in a different pattern of L2 embodiment. Importantly, we outline critical issues to be addressed in order to guide future research. We also delineate the subsequent steps needed to confirm or dismiss the value of language therapeutic approaches based on embodiment theories as a complement of speech and language therapies in adult bilinguals

Ticks from migratory birds as possible route to spread Crimean-Congo Hemorrhagic fever virus : preliminary data about species composition from three Italian islands

Migratory birds have been known to be passive carriers of arthropod vectors of various pathogens. A study to assess the potential role of migratory birds, which are tick-carriers, as a possible route to spread the Crimean-Congo Hemorrhagic Fever Virus (CCHFV) into Europe was initiated in 2017 by the Italian Ministry of Health. Ticks were collected from birds during seasonal bird ringing activities in Mediterranean islands known to be stop-over sites for migratory birds from Africa or from East Europe and Turkey.peer-reviewe

Ecological Meanings: A Consensus Paper on Individual Differences and Contextual Influences in Embodied Language

Embodied theories of cognition consider many aspects of language and other cognitive domains as the result of sensory and motor processes. In this view, the appraisal and the use of concepts are based on mechanisms of simulation grounded on prior sensorimotor experiences. Even though these theories continue receiving attention and support, increasing evidence indicates the need to consider the flexible nature of the simulation process, and to accordingly refine embodied accounts. In this consensus paper, we discuss two potential sources of variability in experimental studies on embodiment of language: individual differences and context. Specifically, we show how factors contributing to individual differences may explain inconsistent findings in embodied language phenomena. These factors include sensorimotor or cultural experiences, imagery, context-related factors, and cognitive strategies. We also analyze the different contextual modulations, from single words to sentences and narratives, as well as the top-down and bottom-up influences. Similarly, we review recent efforts to include cultural and language diversity, aging, neurodegenerative diseases, and brain disorders, as well as bilingual evidence into the embodiment framework. We address the importance of considering individual differences and context in clinical studies to drive translational research more efficiently, and we indicate recommendations on how to correctly address these issues in future research. Systematically investigating individual differences and context may contribute to understanding the dynamic nature of simulation in language processes, refining embodied theories of cognition, and ultimately filling the gap between cognition in artificial experimental settings and cognition in the wild (i.e., in everyday life)

Survey of transfemoral amputee experience and priorities for the user-centered design of powered robotic transfemoral prostheses

BACKGROUND: Transfemoral amputees experience a complex host of physical, psychological, and social challenges, compounded by the functional limitations of current transfemoral prostheses. However, the specific relationships between human factors and prosthesis design and performance characteristics have not yet been adequately investigated. The present study aims to address this knowledge gap. METHODS: A comprehensive single-cohort survey of 114 unilateral transfemoral amputees addressed a broad range of demographic and clinical characteristics, functional autonomy, satisfaction and attitudes towards their current prostheses, and design priorities for an ideal transfemoral prosthesis, including the possibility of active assistance from a robotic knee unit. The survey was custom-developed based on several standard questionnaires used to assess motor abilities and autonomy in activities of daily living, prosthesis satisfaction, and quality of life in lower-limb amputees. Survey data were analyzed to compare the experience (including autonomy and satisfaction) and design priorities of users of transfemoral prostheses with versus without microprocessor-controlled knee units (MPKs and NMPKs, respectively), with a subsequent analyses of cross-category correlation, principal component analysis (PCA), cost-sensitivity segmentation, and unsupervised K-means clustering applied within the most cost-sensitive participants, to identify functional groupings of users with respect to their design priorities. RESULTS: The cohort featured predominantly younger (< 50 years) traumatic male amputees with respect to the general transfemoral amputee population, with pronounced differences in age distribution and amputation etiology (traumatic vs. non-traumatic) between MPK and NMPK groups. These differences were further reflected in user experience, with MPK users reporting significantly greater overall functional autonomy, satisfaction, and sense of prosthesis ownership than those with NMPKs, in conjunction with a decreased incidence of instability and falls. Across all participants, the leading functional priorities for an ideal transfemoral prosthesis were overall stability, adaptability to variable walking velocity, and lifestyle-related functionality, while the highest-prioritized general characteristics were reliability, comfort, and weight, with highly variable prioritization of cost according to reimbursement status. PCA and user clustering analyses revealed the possibility for functionally relevant groupings of prosthesis features and users, based on their differential prioritization of these features—with implications towards prosthesis design tradeoffs. CONCLUSIONS: This study’s findings support the understanding that when appropriately prescribed according to patient characteristics and needs in the context of a proactive rehabilitation program, advanced transfemoral prostheses promote patient mobility, autonomy, and overall health. Survey data indicate overall stability, modularity, and versatility as key design priorities for the continued development of transfemoral prosthesis technology. Finally, observed associations between prosthesis type, user experience, and attitudes concerning prosthesis ownership suggest both that prosthesis characteristics influence device acceptance and functional outcomes, and that psychosocial factors should be specifically and proactively addressed during the rehabilitation process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12984-021-00944-x