Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies.

Introduction: Severe respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host's response to SARS-CoV-2.

Methods: To gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.

Older Adults' Use of and Interest in Technology and Applications for Health Management: A Survey Study.

Background: Older adults face challenges with managing their medications, obtaining health education, and accessing health services. Mobile health (mHealth), defined as any medical or public health practice facilitated through mobile devices, could help to overcome these difficulties.

Objectives: To determine what technologies and apps are in current use by older adults, to explore the types of technologies and apps that may be of interest to people in this age group, to explore concerns about technologies, and to examine any age-related differences.

Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation.

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation.

Density functional theory investigation of mechanisms of degradation reactions of sulfonated PEEK membranes with OH radicals in fuel cells: addition-elimination reactions and acid catalyzed water elimination.

Unlabelled: Sulfonated polyether (ether) ketone or sulfonated PEEK (sPEEK) membranes are one possible candidate for proton-transfer membranes in hydrogen fuel cells. Reaction with hydroxy radicals is expected to be a significant source of degradation of these membranes during fuel cell operation. In this work, the reactivity of the sPEEK polymer molecule with OH radicals is studied by M062X hybrid density functional calculations of the energetics of several reaction paths in a water environment as modeled by polarized continuum model calculations.

Density functional theory investigation of mechanisms of degradation reactions of sulfonated PEEK membranes with OH radicals in fuel cells: Addition-elimination reactions and acid catalyzed water elimination.

Sulfonated polyether (ether) ketone, or sulfonated PEEK (sPEEK) membranes are one possible candidate for proton-transfer membranes in hydrogen fuel cells. Reaction with hydroxy radicals is expected to be a significant source of degradation of these membranes during fuel cell operation. In this work, the reactivity of the sPEEK polymer molecule with OH radicals is studied by M062X hybrid density functional calculations of the energetics of several reaction paths in a water environment as modeled by polarized continuum model (PCM) calculations.

Evaluation and clinical impact of a pharmacist-led, interdisciplinary service focusing on education, monitoring and toxicity management of immune checkpoint inhibitors.

Introduction: Immune-related adverse events are complications of immune checkpoint inhibitors which require robust patient education and proactive follow-up to ensure timely identification and management. Oncology pharmacist practice models with other anticancer modalities have been well documented, but there is limited evidence assessing the spectrum of pharmacist interventions in patients receiving immune checkpoint inhibitor(s) and the impact of these interventions on patient outcomes.

Methods: Patients initiated on immune checkpoint inhibitor(s) from 1 January 2016 to 31 August 2019 were included for data collection and analysis.

Ectopic extramammary Paget disease in thoracic location.

Extramammary Paget disease (EMPD) is a rare skin cancer that affects areas with a high concentration of apocrine glands including genital, axillary, and anal skin. When it affects other locations it is called ectopic extramammary Paget disease (E-EMPD) and is uncommon. To date, there are only 45 case reports to the best of our knowledge.

Mechanism of EBV inducing anti-tumour immunity and its therapeutic use.

Tumour-associated antigens (TAAs) comprise a large set of non-mutated cellular antigens recognized by T cells in human and murine cancers. Their potential as targets for immunotherapy has been explored for more than two decades, yet the origins of TAA-specific T cells remain unclear. While tumour cells may be an important source of TAAs for T cell priming, several recent studies suggest that infection with some viruses, including Epstein-Barr virus and influenza virus can elicit T cell responses against abnormally expressed cellular antigens that function as TAAs.

A large peptidome dataset improves HLA class I epitope prediction across most of the human population.

Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines.

Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation.

Immune evasion is a hallmark of cancer and a central mechanism underlying acquired resistance to immune therapy. In allogeneic hematopoietic cell transplantation (alloHCT), late relapses can arise after prolonged alloreactive T-cell control, but the molecular mechanisms of immune escape remain unclear. To identify mechanisms of immune evasion, we performed a genetic analysis of serial samples from 25 patients with myeloid malignancies who relapsed ≥1 year after alloHCT.

Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade.

Expression of inhibitors of apoptosis protein (IAP) family members is associated with poor prognosis in cancer patients. Immunity to ML-IAP (livin) and survivin has been well studied in patients with a variety of tumors. XIAP, the most potent inhibitor of apoptosis, is widely expressed in melanoma.

Effects of Age Discrimination on Self-perceptions of Aging and Cancer Risk Behaviors.

Background And Objectives: Almost one-third of older adults report experiencing age discrimination. We hypothesized sequential links between older adults' everyday experiences of age discrimination and future health behaviors related to cancer risk through self-perceptions of aging (SPA).

Research Design And Methods: Participants were community-dwelling respondents (age: 51-96 years) from the 2008, 2012, and 2014 waves of the Health and Retirement Study (N = 4,467).

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically 'cold' tumour microenvironment. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study.

A cloning and expression system to probe T-cell receptor specificity and assess functional avidity to neoantigens.

Recent studies have highlighted the promise of targeting tumor neoantigens to generate potent antitumor immune responses and provide strong motivation for improving our understanding of antigen-T-cell receptor (TCR) interactions. Advances in single-cell sequencing technologies have opened the door for detailed investigation of the TCR repertoire, providing paired information from TCRα and TCRβ, which together determine specificity. However, a need remains for efficient methods to assess the specificity of discovered TCRs.

Corrigendum: An immunogenic personal neoantigen vaccine for patients with melanoma.

This corrects the article DOI: 10.1038/nature22991.

Clinical Barriers to Effective Treatment of Eating Disorders and Co-occurring Psychiatric Disorders in Transgendered Individuals.

Eating disorders (EDs) are complex and difficult to treat illnesses that are often chronic and disabling on their own accord or due to comorbidity with other psychiatric conditions. Historically, EDs have been viewed as illnesses of heterosexual, affluent white females. This stereotype increases the likelihood that these disorders will be underrecognized in the lesbian, gay, bisexual, and transgender community, as well as in different gender, socioeconomic, and ethnic populations.

An immunogenic personal neoantigen vaccine for patients with melanoma.

Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules.

Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction.

Identification of human leukocyte antigen (HLA)-bound peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is poised to provide a deep understanding of rules underlying antigen presentation. However, a key obstacle is the ambiguity that arises from the co-expression of multiple HLA alleles. Here, we have implemented a scalable mono-allelic strategy for profiling the HLA peptidome.