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Introduction: Identification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases. Methods: Here, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I presentation and positive/negative immune response (ITSNdb), sixteen metrics were evaluated as immunogenicity predictors. In addition, by using a dataset emulating patient derived TSNs and immunotherapy cohorts containing predicted TSNs for tumor neoantigen burden (TNB) with outcome association, the metrics were evaluated as TSNs prioritizers and as immunotherapy response biomarkers. Results: Our results show high performance variability among methods, highlighting the need for substantial improvement. Deep learning predictors were top ranked on ITSNdb but show discrepancy on validation databases. In overall, current predicted TNB did not outperform existing biomarkers. Conclusion: Recommendations for their clinical application and the ITSNdb are presented to promote development and comparison of computational TSNs immunogenicity predictors. [ABSTRACT FROM AUTHOR]

Becoming an informal caregiver for an adult living with dementia has been shown to have a significant impact upon the conception of identity. This study aimed to identify how identity is constructed online amongst caregivers of individuals living with dementia and how healthcare interactions can influence identity development through the analysis of online web blogs. Sixteen online blogs (172 entries) were selected through purposive and snowball sampling, and discourse analysis was used to analyse online identity construction for informal caregivers of adults living with dementia. Six areas of online identity construction were identified: changing family role; powerful expert social campaigner; being an advocate; guardian of their relative's selfhood; sustaining creative and spiritual individuality and wider community member in online and real life. Further to this, the importance of health and social care service interactions in the development of caregiver identity revealed that professionals must ensure person‐centred service contacts for caregivers. This is a challenging task in the pandemic climate where interactions between health and social care professionals and caregivers are limited due to isolation measures. It is evident that the blog format can provide a forum through which the identity of the caregiver of an adult living with dementia can evolve. The six areas of identity construction reveal the multifaceted nature of identity for the caregiver and the value of belonging to an online community both in relation to identity construction and support. This finding is especially applicable in the current pandemic when accessing a face‐to‐face community is challenging for caregivers who may be shielding or living in isolation. The findings of this research can aid health and social care professionals in understanding the development of caregiver identity and in providing appropriate support during service interactions, on accessing virtual and face to face community support. [ABSTRACT FROM AUTHOR]

It is acknowledged that there are many challenges to ensuring a positive hospital experience for patients with cognitive impairment. The study ('Improving hospital care for adults with cognitive impairment') aimed to explore the positive and negative experiences of older adults with cognitive impairment (dementia and delirium) and their relatives and/or carers, during an acute hospital stay, from admission to discharge, using a qualitative, case study methodology. Six participants with cognitive impairment, eight relatives and 59 members of the health care team were recruited. Data was collected via ethnographic, observational periods at each stage of the hospital journey and through the use of semi-structured interviews with relatives, carers and health care staff including: medical staff; nursing staff; physiotherapists and ward managers. Interpretive phenomenological analysis was used to facilitate data analysis. 52 hours 55 minutes of ethnographic observations and 18 interviews with ward staff and relatives were undertaken. Three superordinate themes emerged from the data as crucial in determining the quality of the hospital experience: valuing the person; activities of empowerment and disempowerment and the interaction of environment with patient well-being. Whether the patient's hospital experience was positive or negative was powerfully influenced by family involvement and ward staff actions and communication. Participants identified a requirement for a ward based activity service for patients with cognitive impairment. Further research must be undertaken focusing on the development of ward based activities for patients with cognitive impairment, alongside a move towards care which explores measures to improve and expand relative involvement in hospital care. [ABSTRACT FROM AUTHOR]

Studying tissue-independent components of cancer and defining pan-cancer subtypes could be addressed using tissue-specific molecular signatures if classification errors are controlled. Since PAM50 is a well-known, United States Food and Drug Administration (FDA)-approved and commercially available breast cancer signature, we applied it with uncertainty assessment to classify tumor samples from over 33 cancer types, discarded unassigned samples, and studied the emerging tumor-agnostic molecular patterns. The percentage of unassigned samples ranged between 55.5% and 86.9% in non-breast tissues, and gene set analysis suggested that the remaining samples could be grouped into two classes (named C1 and C2) regardless of the tissue. The C2 class was more dedifferentiated, more proliferative, with higher centrosome amplification, and potentially more TP53 and RB1 mutations. We identified 28 gene sets and 95 genes mainly associated with cell-cycle progression, cell-cycle checkpoints, and DNA damage that were consistently exacerbated in the C2 class. In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications. [ABSTRACT FROM AUTHOR]

Objective: Some salivary proteins seem to be differently abundant among caries-free (CF) and caries-affected (CA) individuals, but previous results are contradictory precluding that definitive conclusion be drawn. A pooled analysis of the available evidence may provide more robust data on identifying oral cavity protein patterns among CF and CA individuals. This systematic review and meta-analysis (PROSPERO CRD42021269079) aimed to compare the oral cavity protein abundance among caries-free and caries-affected individuals., Methods: This study was conducted following PRISMA guidelines. PubMed, Embase, and Web of Science databases were systematically assessed (up to February 2023) to retrieve clinical studies written in English, German, or in Latin-based languages that compared the oral cavity protein abundance among CF and CA individuals. Data extraction and methodological quality assessment (NIH guidelines) were independently performed by two investigators. Qualitative synthesis was performed from all included studies and meta-analysis was performed using a random-effects model with inverse variance for studies that reported the concentration of proteins or enzymatic activity. Standardized mean difference (SMD) with respective 95% confidence interval (CI) were calculated for each outcome., Results: A total of 90 studies (two cohort and 88 cross-sectional designs) of more than 6,000 participants were selected for data extraction, being the quality of evidence graded as "fair" for most of them. The oral cavity of CF individuals presented lower total protein concentration [SMD = 0.37 (95% CI: 0.07-0.68; 18 studies)], lower total antioxidant capacity [SMD = 1.29 (95% CI: 0.74-1.85); 17 studies], and lower carbonic anhydrase activity [SMD = 0.83 (95% CI: 0.58-1.09); three studies], whereas CA individuals presented lower carbonic anhydrase concentration [SMD = -0.66 (95% CI: -1.00 to -0.32); three studies], urease [SMD = -0.95 (IC 95%: -1.72 to -0.17); four studies], and arginine deiminase system [SMD = -2.07 (95% CI: -3.53 to -0.62); three studies] activities. Antimicrobial peptides, secretory immunoglobulin-A concentrations and alpha-amylase activity were similar among individuals., Conclusion: Differences on oral cavity protein abundance were observed among CF and CA individuals. These data indicate some protein patterns for the oral health and dental caries conditions. Even when statistically significant, some of the results were not very consistent. Cohort studies need to be conducted to validate these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Silveira, Prato, Pilati and Arthur.)