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Kelp forests provide key habitat on the Pacific Coast of Canada; however, the long-term changes in their distribution and abundance remain poorly understood. With advances in satellite technology, floating kelp forests can now be monitored across large-scale areas. We present a methodological framework using an object-based image analysis approach that enables the combination of imagery from multiple satellites at different spatial resolutions and temporal coverage, to map kelp forests with floating canopy through time. The framework comprises four steps: (1) compilation and quality assessment; (2) preprocessing; (3) an object-oriented classification; and (4) an accuracy assessment. Additionally, the impact of spatial resolution on the detectability of floating kelp forests is described. Overall, this workflow was successful in producing accurate maps of floating kelp forests, with global accuracy scores of between 88% and 94%. When comparing the impact of resolution on detectability, lower resolutions were less reliable at detecting small kelp forests in high slope areas. Based on the analysis, we suggest removing high slope areas (11.4%) from time series analyses using high- to medium-resolution satellite imagery and that error, in this case up to 7%, be considered when comparing imagery at different resolutions in low–mid slope areas through time.

T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOF IMS ) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOF IMS -based immunopeptidomics, a novel extensive benign TOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development. MS-based immunopeptidomics provides direct evidence for HLA peptide-antigen presentation, which is indispensable for therapeutic use. Here the authors present an ion mobility MS-based immunopeptidome workflow, largely expand benign reference databases and enables next generation tumor antigen discovery.

Redo cardiac surgery outcomes, including increased transfusions and risk of reoperation, worsen with post-operative bleeding. This study aimed to directly compare the use of an absorbable polysaccharide powder to no hemostatic agent use during planned non-emergent redo cardiac surgery. Fifty-one participants in two cohorts underwent planned non-emergent redo cardiac surgery. The retrospective cohort (n = 26) was chosen from redo cardiac surgeries completed between 2019 and 2020, while the prospective cohort (n = 25) included sequential redo cardiac surgeries with the use of an absorbable polysaccharide powder. Patient operative characteristics, along with first 24-hour transfusion use (packed red blood cells (pRBC), fresh frozen plasma (FFP) and platelets (Plts), chest tube outputs (CTO) at 12, 24 and 48 hours, and reoperation rates were compared. There was a higher non-statistical average of intraoperative pRBC and FFP rates in the retrospective cohort, compared to cases where absorbable polysaccharide powder was used (2 ± 2.9 vs 1.1 ± 1.4 units pRBC, p = 0.414; and 1.4 ± 1.8 vs 0.6 ± 1 units FFP, p = 0.070) while there were statistical differences in Plts use in the retrospective cohort compared to when absorbable polysaccharide powder was used (1 ± 1.3 vs 0.4 ± 0.7 units plts, p = 0.028). Statistically significant lower amounts of CTO in the first 12 hours and the 12-24-hour intervals were found when absorbable polysaccharide powder was used (817 ± 520 vs 558 ± 352 milliliters, p = 0.028; and 1144 ± 704 vs 830 ± 474 milliliters, p = 0.044, respectively). There were three reoperations in the retrospective cohort due to suspected bleeding, compared to no reoperations in the absorbable polysaccharide powder cohort. This study highlights fewer transfusions, lower CTO, and decreased need for reoperation when using absorbable polysaccharide powder in redo cardiac surgeries. Further randomized trials are needed to more accurately define benefits of absorbable polysaccharide powder in redo cardiac surgeries. Word count: 302.

The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease lacking specific therapies. This study reports on the identification, characterization, and immunotherapeutic application of HLA-presented neoantigens specific for the DNAJB1-PRKACA fusion transcript in fibrolamellar hepatocellular carcinoma. DNAJB1-PRKACA-derived HLA class I and HLA class II ligands induce multifunctional cytotoxic CD8 + and T-helper 1 CD4 + T cells, and their cellular processing and presentation in DNAJB1-PRKACA expressing tumor cells is demonstrated by mass spectrometry-based immunopeptidome analysis. Single-cell RNA sequencing further identifies multiple T cell receptors from DNAJB1-PRKACA-specific T cells. Vaccination of a fibrolamellar hepatocellular carcinoma patient, suffering from recurrent short interval disease relapses, with DNAJB1-PRKACA-derived peptides under continued Poly (ADP-ribose) polymerase inhibitor therapy induces multifunctional CD4 + T cells, with an activated T-helper 1 phenotype and high T cell receptor clonality. Vaccine-induced DNAJB1-PRKACA-specific T cell responses persist over time and, in contrast to various previous treatments, are accompanied by durable relapse free survival of the patient for more than 21 months post vaccination. Our preclinical and clinical findings identify the DNAJB1-PRKACA protein as source for immunogenic neoepitopes and corresponding T cell receptors and provide efficacy in a single-patient study of T cell-based immunotherapy specifically targeting this oncogenic fusion. The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease with limited therapeutic options. Here, the authors identify the DNAJB1-PRKACA protein as a source for immunogenic neoepitopes and a potential target of T cell-based immunotherapy.

T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4 + T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469. Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.

Bull kelp Nereocystis luetkeana is an important foundation species, providing structural habitat and nutrients to the nearshore ecosystems of temperate coastal regions in the Northeast Pacific. Sensitive to environmental conditions, this species thrives in cool, nutrient‐rich water. Reported declines in the extent and distribution of bull kelp may reflect changing oceanic conditions and result in breakdown of important food chains and ecosystem services. This study uses satellite remote sensing to map kelp bed extent from 2004 to 2017 in the Salish Sea on the West Coast of British Columbia, Canada and examines the relationship between trends in kelp persistence with local and global scale environmental conditions. In our study area, we found limited evidence of kelp decline. Local scale effects of current speed, temperature and substrate type may play a role in the spatial and temporal patterns of persistence. Kelp persistence was higher in sites with rocky substrate and lower in areas with low current and gravel or sand substrate. A decline in kelp was recorded from a high in 2015 to a low in 2017; however, a longer and more complete record is needed to distinguish declining trends from natural variability. This work highlights the importance of continued collection of long‐term data for use in time series of kelp abundance as multiple factors can influence the reliability of image interpretation and kelp classification. A time series of high‐resolution satellite imagery was used to detect floating kelp (Nereocystis luetkeana) in the nearshore region of coastal British Columbia. Kelp persistence over time was calculated and the spatial trends relating to environmental conditions of substrate, temperature and currents were examined. Areas with both high currents and rocky substrate had the highest kelp extent and greatest persistence, while those regions with either low currents or gravel substrate had higher variability and lower kelp presence. A decline in kelp extent was measured from a high in 2015 to a low in 2017.

Self-management is a health behavior known to predict treatment outcomes in patients with multiple co-morbidities and/or chronic conditions. However, the self-management process and outcomes in the left-ventricular assist device (LVAD) population are understudied. This pilot randomized control trial (RCT) evaluated the feasibility of a novel “smartphone app-directed and nurse-supported self-management intervention” in patients implanted with durable LVADs. Assessments included behavioral (self-efficacy and adherence), clinical (complications), and healthcare utilization (unplanned clinic, emergency room (ER) visits, and re-hospitalization) outcomes, completed at baseline (pre-hospital discharge) and months 1, 3, and 6 post-hospital discharge. Intervention patients (n = 14) had favorable patterns/trends of results across study outcomes than control patients (n = 16). Notably, intervention patients had much lower complications and healthcare utilization rates than controls. For example, intervention patients had 2 (14.3%) driveline infections in 6 months while control patients had 3 (19.0%). Additionally, at month 3, intervention patients had 0% ER visits versus 36% of control patients. At month 6, the mean cumulative number of re-hospitalizations for the control group was higher (0.9 ± 0.93) than intervention (0.3 ± 0.61) group. Despite the small sample size and limitations of feasibility/pilot studies, our outcomes data appeared to favor the novel intervention. Lessons learned from this study suggest the intervention should be implemented for 6 months post-hospital discharge. Further research is needed including large and rigorous multi-center RCTs to generate knowledge explaining the mechanism of the effect of self-management on LVAD treatment outcomes.

Coastal foundation species such as kelps, corals, and seagrasses play vital roles in supporting marine biodiversity and ecosystem services globally, but are increasingly threatened by climate change. In particular, kelp forests are highly dynamic ecosystems experiencing natural fluctuations across seasons and climate cycles, e.g., El Niño Southern Oscillation, Pacific Decadal Oscillation. As climate change increases variability in these cycles and extreme events such as marine heatwaves become more frequent, long term data are essential to understand deviations from the norm and to better estimate trends of change. This study uses a century-long dataset to examine kelp forest responses to regional drivers in Haida Gwaii, British Columbia, by combining remote sensing data from 1973-2021 with a snapshot of kelp distribution derived from historical records from 1867-1945. We reveal complex patterns of change, with kelp losses and resilience varying at different spatial scales. Kelp forests that had likely persisted for over a century exhibited an overall declining trend of 5 ± 2% per decade starting in the 1970s. Throughout the time series kelp area was driven by multi-year impacts of the Pacific Decadal Oscillation, El Nino Southern Oscillation, sea surface temperature anomalies and marine heatwaves, such as the 1998 El Niño and the 2014-2016 marine heatwave known as the ‘Blob’. In the warmest areas, kelp forests completely disappeared during the 1977 Pacific Decadal Oscillation shift. Cooler areas showed greater resilience, buffering the loss at the region wide scale, highlighting the importance of local gradients in understanding areas vulnerable to climate change. Lastly, local in situ surveys showed a lack of urchin barrens, and the presence of turf algae in the study region, further supporting the hypothesis that temperature, not herbivory, drove kelp forest loss in this region.

The impacts of local-scale temperatures and winds on bull kelp ( Nereocystis luetkeana ) vary along a coastal gradient, while also being influenced by corresponding global-scale oceanic conditions. Around Vancouver Island and the Gulf Islands, BC, Canada, bull kelp floating canopies were mapped using high-resolution imagery from 2005 to 2022, whereas the largest kelp bed of the area was mapped with medium-resolution imagery spanning from 1972 to 2022. In order to understand spatial patterns of kelp resilience, the abiotic characteristics were used to organize the coastline into four clusters, ranging from the coldest and most exposed coast to a more sheltered and warmer location. Additionally, local-scale sea surface temperatures, winds, and marine heatwaves were categorized by global-scale temporal conditions defined by the positive/negative oceanic oscillations of the Oceanic Niño Index (ONI) and Pacific Decadal Oscillation (PDO). Comparing spatial and temporal categories, we observed that years with positive ONI and PDO, in particular the 2014–2019 period, concentrated most of the marine heatwaves and the spring temperature peaks. However, there are some indications of an underlying long-term trend. During the period 2020–2022, when ONI and PDO were negative, summer temperatures kept increasing and wind displayed a higher frequency of extreme events. Mapped kelp showed different trends to these stressors: the coldest and most exposed area showed a constant presence of kelp during the entire period, even dating back to 1972. Warmer and semi-sheltered coasts increased in kelp percentage cover after the positive ONI+PDO period of 2014–2019, and the coasts facing the Strait of Georgia displayed a lower kelp percentage cover than the other clusters. In summary, bull kelp was resilient in the study area, but for different reasons: colder and more exposed coasts had the most favorable conditions for kelp, but warmer and more sheltered coastal kelp beds may have benefited from wind-wave forcing.

The Salish Sea, a dynamic system of straits, fjords, and channels in southwestern British Columbia, is home to ecologically and culturally important bull kelp ( Nereocystis luetkeana ) forests. Yet the long-term fluctuations in the area and the persistence of this pivotal coastal marine habitat are unknown. Using very high-resolution satellite imagery to map kelp forests over two decades, we present the spatial changes in kelp forest area within the Salish Sea, before (2002 to 2013) and after (2014 to 2022) the ‘Blob,’ an anomalously warm period in the Northeast Pacific. This analysis was spatially constrained by local environmental conditions. Based on nearshore sea surface temperatures (SSTs) from four decades (1984–2022), we found two periods of distinct increases in SST, one starting in 2000 and another in 2014. Further, the highest SST anomalies occurred on warmer coastlines in the enclosed inlets and the Strait of Georgia, while smaller anomalies were found on colder coastlines near the Strait of Juan de Fuca and the Discovery Passage. The total area of bull kelp forests from 2014 to 2022 has decreased compared to 2002 to 2013, particularly in the northern sector of the Salish Sea. Using the satellite-derived kelp data, we also present an analysis of kelp persistence compared with historical distribution of kelp forests depicted on British Admiralty Nautical Charts from 1858 to 1956. This analysis shows that warm, sheltered areas experienced a considerable decrease in persistence of kelp beds when compared to satellite-derived distribution of modern kelp, confirming a century-scale loss. In particular, the presence of kelp forests in the Strait of Georgia and on the warmest coasts has decreased considerably over the century, likely due to warming temperatures. While the coldest coasts to the south have maintained their centennial persistence, the northern Salish Sea requires further research to understand its current dynamics. This research contributes to a wider understanding of temporal and spatial factors for kelp from the regional perspective of the Salish Sea.