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Recent work in single-cell imaging has allowed unprecedented insight into single-cell interactions that control disease progression. However, approaches to understanding the combined extracellular and cellular microenvironment are limited. In the current protocol, we describe an approach that allows single-cell type imaging using matrix-assisted laser desorption/ionization immunohistochemistry (MALDI-IHC) of UV (ultraviolet) photocleavable mass tags combined with N-glycomic and ECM-targeted proteomic imaging from the same formalin-fixed paraffin-embedded tissue section. These approaches use the same imaging mass spectrometry platform to provide a comprehensive view of both the cellular and extracellular tissue microenvironment., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To conduct the first known comprehensive examination of loneliness and its correlates in a diverse sample of people with spinal cord injury (SCI)., Methods: A cross-sectional sample of 343 people with SCI provided responses to the 20-item UCLA Loneliness Scale-Version 3. We examined the relation of loneliness to measures of demographic, disability, physical health, and social characteristics., Results: The majority (56%) of respondents had scores indicating high levels of loneliness. At least a quarter of respondents indicated that they often felt alone, left out, isolated, and lacking in companionship. At least a quarter rarely or never felt there were people who really understood them, with whom they could talk, and with whom they had a lot in common. In univariate analyses, loneliness was associated with several demographic, disability, and health characteristics suggesting potential risk factors. In multiple regression analyses, social characteristics (social integration, social support, satisfaction with social roles) were the most strongly associated with loneliness., Conclusions: Our findings underscore the high prevalence of loneliness among people with SCI. Given the adverse health consequences of loneliness documented in the general literature, there is an urgent need for researchers, healthcare providers, and policy makers to address the loneliness crisis in this population.

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; n = 12) and better outcome (Subtype 3; S3; n = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.

Purpose/objective: This study aims to explore the perspectives of rehabilitation professionals regarding the barriers to spinal cord injury (SCI) rehabilitation services in Nepal., Research Method/design: A qualitative study involved 15 rehabilitation professionals working in the Spinal Injury Rehabilitation Center in Nepal. After obtaining informed consent, in-depth semistructured interviews were conducted using Zoom and phone calls between June and July 2023. Braun and Clarke's thematic analysis approach was utilized to analyze the interviews and generate themes from the participants' responses., Results: The participants represented nine different rehabilitation professions. Over half of them were female (53.33%), and 86.67% had one to 10 years of experience in SCI rehabilitation. From in-depth interviews, four themes depicting barriers to rehabilitation were identified: (a) resource constraints within the rehabilitation centers, (b) concerns related to finance, awareness, and support mechanisms, (c) systemic problems coupled with geographical and physical barriers, and (d) beliefs and practices influencing access and adherence to rehabilitation., Conclusions and Implications: Delivering effective rehabilitation services for people with SCI presents a range of barriers. Considering the critical importance of rehabilitation for this population, the findings underscore the necessity of engaging stakeholders at multiple levels, individuals, communities, and government agencies to address the identified barriers and improve rehabilitation services in Nepal. The implications of the findings are further discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Design: Cross-sectional survey., Objective: To evaluate the perceived helpfulness of pharmacological and non-pharmacological interventions and their combinations for neuropathic pain (NeuP) and subcategories of NeuP after spinal cord injury (SCI)., Setting: Six Spinal Cord Injury Model System Centers., Methods: Three hundred ninety one individuals at least one year post traumatic SCI were enrolled. A telephone survey was conducted to determine the pharmacologic and non-pharmacologic treatments used in the last 12 months for each participant's three worst pains, whether these treatments were "helpful", and if currently used, each treatments' effectiveness., Results: Two hundred twenty participants (56%) reported 354 distinct NeuPs. Pharmacological treatments rated helpful for NeuP were non-tramadol opioids (opioids were helpful for 86% of opioid treated NeuPs), cannabinoids (83%), and anti-epileptics (79%). Non-pharmacological treatments rated helpful for NeuP were massage (76%), body position adjustment (74%), and relaxation therapy (70%). Those who used both opioids and exercise reported greater NeuP treatment helpfulness compared to participants using opioids without exercise (P = 0.03)., Conclusions: Opioids, cannabinoids, and massage were reported more commonly as helpful than treatments recommended as first-line therapies by current clinical practice guidelines (CPGs) for NeuP after SCI (antiepileptics and antidepressants). Individuals with SCI likely value the modulating effects of pharmacological and non-pharmacological treatments on the affective components of pain in addition to the sensory components of pain when appraising treatment helpfulness.

Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4 + T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4 + and CD8 + T cell epitopes to maximize vaccine effectiveness., Competing Interests: Declaration of interests S.W.-G., D.-Y.C., S.S., K.R.C., N.H., S.A.C., J.G.A., M.S., and P.C.S. are named co-inventors on a patent application related to this work, filed by The Broad Institute, that is being made available in accordance with the COVID-19 technology licensing framework to maximize access to university innovations. N.H. is a founder of Neon Therapeutics (now BioNTech US), was a member of its scientific advisory board, and holds shares. N.H. is also an advisor for IFM Therapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer, and PrognomIQ. J.G.A. is a past employee of Neon Therapeutics (now BioNTech US). P.C.S. is a cofounder of and consultant to Sherlock Biosciences and Delve Biosciences and a board member of Danaher Corporation and holds equity in the companies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mounting empirical evidence suggests that, compared to women without disabilities, women with disabilities are more likely to experience interpersonal violence (IPV). However, there is extremely limited research attention on IPV against women with spinal cord injury (SCI), a particularly understudied and underserved population., Objectives: To conduct the first known examination of lifetime IPV experience in women with SCI, to explore demographic and disability-related correlates of IPV, and to examine the health impacts of IPV., Methods: The sample included 175 women with traumatic SCI from across the United States who enrolled in a randomized controlled trial of an online psychological health promotion intervention. The data, which included a brief measure of lifetime abuse, were collected as part of the baseline survey administered prior to randomization to the intervention or control conditions., Results: The majority (55%) of the women described experiencing some abuse in their lifetime, with 43% reporting physical abuse, 32% reporting sexual abuse, and 23% reporting disability-related abuse. Sixteen percent of the women indicated that they had experienced all three (physical, sexual, disability) types of abuse. Few demographic and disability characteristics were related to overall lifetime IPV experience; however, disability characteristics were associated with disability-related IPV victimization. In addition, those with a history of IPV had poorer self-reported health and greater depression., Conclusion: This study suggests that IPV is common among women with SCI. More research is needed to understand the prevalence, risk factors, and consequences of IPV against women with SCI to help inform policy and practice., Competing Interests: Conflicts of Interest The authors report no conflicts of interest., (©2023 American Spinal Injury Association.)

This study represents the first known research addressing the impact of the COVID-19 pandemic on women with spinal cord injury (SCI) in the United States. Women in this population face unique barriers that put them at elevated risk for compromised quality of life, risk that was magnified by physical and social restrictions imposed during the pandemic. This qualitative study examined the perceptions of women with SCI and the effect of the pandemic on their lives. The predominantly White and relatively well-educated sample of 105 women with traumatic SCI was diverse in age, injury characteristics, and geographic representation. Recruited across the USA, participants in an online psychological health intervention trial were asked to respond to the item, "Please tell us how COVID-19 has affected you and your life", administered May-October, 2020. An overall sentiment rating of impact was coded as well as the impact of COVID-19 on eight individual themes: Physical Health, Mental Health, Social Health, Activities of Daily Living, Exercise, Work, Activities Outside the Home, and Activities at Home. Sentiment responses were rated as positive, negative, a mixture of positive and negative impacts, or neutral impact. Participants described the overall impact of COVID-19 as negative (54%), positive (10%), mixed (21%) or neutral (15%). Sentiment ratings to individual themes were also described. Our findings highlight the importance of providing access to disability-sensitive and affordable support, resources, and interventions for women with SCI, especially during a public health crisis.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies., Competing Interests: Declaration of interests R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the Scientific Advisory Board at Nestle, and a member of the Board of Directors at Moonlake Immunotherapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer, and PrognomIQ., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Serial multi-omic analysis of proteome, phosphoproteome, and acetylome provides insights into changes in protein expression, cell signaling, cross-talk and epigenetic pathways involved in disease pathology and treatment. However, ubiquitylome and HLA peptidome data collection used to understand protein degradation and antigen presentation have not together been serialized, and instead require separate samples for parallel processing using distinct protocols. Here we present MONTE, a highly sensitive multi-omic native tissue enrichment workflow, that enables serial, deep-scale analysis of HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome from the same tissue sample. We demonstrate that the depth of coverage and quantitative precision of each 'ome is not compromised by serialization, and the addition of HLA immunopeptidomics enables the identification of peptides derived from cancer/testis antigens and patient specific neoantigens. We evaluate the technical feasibility of the MONTE workflow using a small cohort of patient lung adenocarcinoma tumors., (© 2023. The Author(s).)

Purpose: Few studies have examined the impacts of the COVID-19 pandemic on the lives of people with spinal cord injury (SCI), a population uniquely vulnerable to pandemic-related stressors. This study examines the impact of the pandemic on three life domains (psychosocial health, health and health behavior, and social participation) and identifies risk factors for adverse psychosocial health impacts in a sample of people with SCI., Method: A diverse sample of 346 adults with SCI completed a survey assessing demographic, disability, health, and social characteristics, and perceived impacts of the pandemic., Results: Many respondents reported no change on items reflecting psychosocial health, health and health behavior, and social participation; however, among those reporting change, more reported negative than positive impacts. Negative impacts were most striking with regard to psychosocial health and social engagement, with approximately half reporting a worsening of stress, depression, anxiety, and loneliness and a reduction in face-to-face interactions and participation in life roles. Regression analyses revealed that those at greater risk of adverse psychosocial impacts were women, were non-Black, were in poorer health, had greater unmet care needs, and were less satisfied with their social roles and activities., Conclusions: Although not universal, negative impacts were reported by many respondents 9-15 months into the pandemic. Future research should examine the impacts of the pandemic over time and on a wider range of outcomes. Such research could generate substantial benefits in understanding, preventing, or minimizing the adverse effects of the evolving pandemic and future public health emergencies in people with SCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort., Methods: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves., Results: Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY., Conclusions: The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research., (© 2023. The Author(s).)

Context/objective: Spinal cord injury (SCI) often results in a significant loss of mobility and independence coinciding with reports of decreased quality of life (QOL), community participation, and medical complications often requiring re-hospitalization. Locomotor training (LT), the repetition of stepping-like patterning has shown beneficial effects for improving walking ability after motor incomplete SCI, but the potential impact of LT on psychosocial outcomes has not been well-established. The purpose of this study was to evaluate one year QOL, community participation and re-hospitalization outcomes between individuals who participated in a standardized LT program and those who received usual care (UC)., Design/setting/participants: A retrospective (nested case/control) analysis was completed using SCI Model Systems (SCIMS) data comparing one year post-injury outcomes between individuals with traumatic motor incomplete SCI who participated in standardized LT to those who received UC., Outcome Measures: Outcomes compared include the following: Satisfaction with Life Scale (SWLS™), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF™), and whether or not an individual was re-hospitalized during the first year of injury., Results: Statistically significant improvements for the LT group were found in the following outcomes: SWLS (P = 0.019); and CHART subscales [mobility (P = <0.001)]; occupation (P = 0.028); with small to medium effects sizes., Conclusion: Individuals who completed a standardized LT intervention reported greater improvements in satisfaction with life, community participation, and fewer re-hospitalizations at one year post-injury in comparison to those who received UC. Future randomized controlled trials are needed to verify these findings.

Immunopeptidome profiling of infected cells is a powerful technique for detecting viral peptides that are naturally processed and loaded onto class I human leukocyte antigens (HLAs-I). Here, we provide a protocol for preparing samples for immunopeptidome profiling that can inactivate enveloped viruses while still preserving the integrity of the HLA-I complex. We detail steps for lysate preparation of infected cells followed by HLA-I immunoprecipitation and virus inactivation. We further describe peptide purification for mass spectrometry outside a high-containment facility. For complete details on the use and execution of this protocol, please refer to Weingarten-Gabbay et al. (2021). 1 ., Competing Interests: Declaration of interests S.W.-G., S.K., S.A.C., J.G.A., M.S., and P.C.S. are named co-inventors on a patent application related to this manuscript filed by The Broad Institute that is being made available in accordance with the COVID-19 technology licensing framework to maximize access to university innovations. N.L.W. is a consultant for Carver Biosciences. D.B.K. own equity in Affimed N.V., Agenus, Armata Pharmaceuticals, Breakbio, BioMarin Pharmaceutical, Celldex Therapeutics, Clovis Oncology, Editas Medicine, Exelixis, Gilead Sciences, Immunitybio, ImmunoGen, IMV, Lexicon Pharmaceuticals, Moderna, Neoleukin Therapeutics, Regeneron Pharmaceuticals, and Sesen Bio. BeiGene, a Chinese biotech company, supported unrelated SARS COV-2 research at TIGL. S.A.C. is a member of the scientific advisory boards of Kymera, PrognomIQ, PTM BioLabs, and Seer and an ad hoc scientific advisor to Pfizer and Biogen. J.G.A. is a past employee and shareholder of Neon Therapeutics, Inc. (now BioNTech US). P.C.S. is a co-founder of and consultant to Sherlock Biosciences and Delve Biosciences and a board member of Danaher Corporation and holds equity in the companies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This systematic review aims to gain a comprehensive understanding of the feasibility, acceptability, and efficacy of mindfulness-based interventions (MBIs) on depression, anxiety, fatigue, and health-related quality of life among individuals with upper motor neuron disorders (UMNDs)., Data Sources: PubMed, PsycINFO, Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature were searched for relevant studies published between January 2001 and June 2021., Study Selection: Clinical trials published in English evaluating MBIs in adults with the 4 most common UMNDs (multiple sclerosis, brain injury including stroke, spinal cord injury, amyotrophic lateral sclerosis) were included., Data Extraction: Two reviewers independently performed the risk of bias assessment using standardized tools and extracted desired data electronically., Data Synthesis: A total of 44 studies were included: 26 randomized controlled trials, 10 nonrandomized controlled trials, and 8 pre-post intervention studies. The average ± SD duration of MBIs was 8±2 weeks. On average, 85%±14% of participants completed the MBI, and the retention rate at follow-up was 80%±16%. Only 14% of the studies delivered MBIs virtually, and feasibility metrics were similar to in-person studies. Among studies reporting acceptability data, most participants reported satisfaction with the MBI. Randomized controlled trials that evaluated the effects of MBI on depression, anxiety, fatigue, and quality of life revealed greater relative improvement in these outcomes among MBI participants compared with controls, with differences greater when compared with passive control than active control participants. None of the studies included in this review studied dose response., Conclusions: Based on current data, MBIs are feasible and offer a promising approach to address the biopsychosocial needs of individuals with UMNDs. MBIs are associated with a high acceptance rate among participants, with notable improvements in depression, anxiety, fatigue, and quality of life post intervention. Future studies are needed to evaluate alternate models of delivery of MBIs and the dose-response relationship., (Published by Elsevier Inc.)

Objective: To characterize individuals with spinal cord injuries (SCI) who use outpatient physical therapy or community wellness services for locomotor training and predict the duration of services, controlling for demographic, injury, quality of life, and service and financial characteristics. We explore how the duration of services is related to locomotor strategy., Design: Observational study of participants at 4 SCI Model Systems centers with survival. Weibull regression model to predict the duration of services., Setting: Rehabilitation and community wellness facilities at 4 SCI Model Systems centers., Participants: Eligibility criteria were SCI or dysfunction resulting in motor impairment and the use of physical therapy or community wellness programs for locomotor/gait training. We excluded those who did not complete training or who experienced a disruption in training greater than 45 days. Our sample included 62 participants in conventional therapy and 37 participants in robotic exoskeleton training., Interventions: Outpatient physical therapy or community wellness services for locomotor/gait training., Main Outcome Measures: SCI characteristics (level and completeness of injury) and the duration of services from medical records. Self-reported perceptions of SCI consequences using the SCI-Functional Index for basic mobility and SCI-Quality of Life measurement system for bowel difficulties, bladder difficulties, and pain interference., Results: After controlling for predictors, the duration of services for the conventional therapy group was an average of 63% longer than for the robotic exoskeleton group, however each visit was 50% shorter in total time. Men had an 11% longer duration of services than women had. Participants with complete injuries had a duration of services that was approximately 1.72 times longer than participants with incomplete injuries. Perceived improvement was larger in the conventional group., Conclusions: Locomotor/gait training strategies are distinctive for individuals with SCI using a robotic exoskeleton in a community wellness facility as episodes are shorter but individual sessions are longer. Participants' preferences and the ability to pay for ongoing services may be critical factors associated with the duration of outpatient services., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)