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BACKGROUND: The context of practice is often not explicit in the discourse around the personal and professional resilience of nurses. The unique factors related to providing nursing care in home and community care may provide novel insight into the resilience of this health workforce. Therefore, this research addressed how nurses build and maintain resilience working in the home and community care sector. METHOD: A qualitative study was conducted between November 2022 to August 2023 using 36 in-depth interviews (29 registered practical nurses [RPNs], five supervisors of RPNs, two family/care partners (FCPs) of clients receiving home and community care services). Analysis was consistent with a grounded theory approach including coding and comparative methods. RESULTS: The factors of personal and professional resilience were not distinct but rather mixed together in the experience of nurses having resilience working in the home and community care sector. The process of building and maintaining resilience as home and community care nurses was informed by three categories: (1) The conditions of working in HCC; (2) The rapport RPNs held with FCPs; and (3) The nurses' ability for supporting the 'self'. Multiple components to inform these categories were identified and illustrated by the words of the nurse participants. CONCLUSION: The process of building and maintaining resilience by RPNs working in the home and community care sector was guided by the day-to-day experiences of providing care for clients and the conditions of being a mobile health care provider. However, nurses may sense when they need to support their 'self' and must be empowered to request and receive support to do so.

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Early indicators of healing provide valuable information on the potential benefit of treatment. In patients with hard-to-heal (chronic) diabetic foot ulcers (DFUs), timely intervention is critical. Ulcers that fail to show measurable progress within four weeks of treatment are considered recalcitrant. These ulcers increase the risk of soft tissue infection, osteomyelitis and lower extremity amputation. A prognostic indicator or surrogate marker allows for rapid evaluation of treatment efficacy and safety. An inverse correlation between a percentage area reduction (PAR) of ≤50% at week 4 and complete healing by week 12 has been previously established; however, the data were derived from a standard of care (SoC) arm of clinical trials that are over a decade old. In this post hoc analysis, data from a large multicentre prospective randomised controlled trial were reviewed to assess PAR at week 4 as a prognostic indicator in patients treated with SoC. Overall, 65.4% (17/26) of patients with PAR >50% at week 4 achieved complete closure at week 12. The receiver operating characteristic (ROC) curve for area reduction by week 4 showed strong discrimination for predicting non-healing (area under the ROC curve: 0.92; p<0.001; positive predictive value: 70.6%; negative predictive value: 87.2%). These findings are consistent with previous studies and support the use of four-week PAR as a prognostic indicator.

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INTRODUCTION: As the treatment of breast cancer advances, the focus has shifted from solely improving oncological endpoints to a greater weight being placed on cosmetic and psychological outcomes. The advent of advanced oncoplastic techniques allows for successful breast-conserving surgery (BCS) to patients who otherwise would have required a mastectomy. The aim of this study is to ascertain if the adoption of these procedures has assisted in the reduction of mastectomies performed. METHODS: A dataset of all breast cancer procedures based upon coding between April 2016 and July 2023 was evaluated, categorising procedures into: BCS, mastectomy, oncoplastic BCS and total reconstructions. R-Studio Software 4.3.1 (®) was used to explore statistical analysis and data visualisation. Registered as a clinical services evaluation study (Project ID: 14649). RESULTS: During the period stated, 3875 index breast cancer procedures were recorded (sample size = 3638 patients). The BCS rate increased from 66.2 % in 2016 to 80.7 % in 2023. Using a linear regression model, the BCS rate demonstrates an increase of 2.1 % each year (coefficient = 2.12, p-value = 0.0069). Concurrently, the rate of oncoplastic BCS increased from 10.5 % to 22.9 % (coefficient = 2.14, p-value = 0.00017). Using Pearson's product-moment, a positive correlation between these two variables is seen (coefficient = 0.86, p-value = 0.0056). CONCLUSION: Having reviewed 3875 index breast cancer procedures over the past eight years, the BCS rate has shown a statistically significant increase and a positive correlation with the oncoplastic BCS rate. This suggests oncoplastic surgery has helped to reduce the rates of mastectomy at the centre.

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Most phenotype-associated genetic variants map to non-coding regulatory regions of the human genome. Moreover, variants associated with blood cell phenotypes are enriched in regulatory regions active during hematopoiesis. To systematically explore the nature of these regions, we developed a highly efficient strategy, Perturb-multiome, that makes it possible to simultaneously profile both chromatin accessibility and gene expression in single cells with CRISPR-mediated perturbation of a range of master transcription factors (TFs). This approach allowed us to examine the connection between TFs, accessible regions, and gene expression across the genome throughout hematopoietic differentiation. We discovered that variants within the TF-sensitive accessible chromatin regions, while representing less than 0.3% of the genome, show a ~100-fold enrichment in heritability across certain blood cell phenotypes; this enrichment is strikingly higher than for other accessible chromatin regions. Our approach facilitates large-scale mechanistic understanding of phenotype-associated genetic variants by connecting key cis-regulatory elements and their target genes within gene regulatory networks.

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Melanoma is the most common malignant oral tumor in dogs. It frequently presents a diagnostic challenge as many melanomas lack or contain scant melanin and may have a variable microscopic phenotype. Previous studies evaluating immunohistochemical markers for diagnosing melanoma have shown limited sensitivity and/or specificity for S-100, PNL2, melan A, TRP-1, TRP-2, and HMB-45. Sry-related HMG-box gene 10 (SOX-10) is a transcription factor associated with melanocytic, peripheral neural crest, and peripheral nervous system development. In humans, SOX-10 expression has been demonstrated in melanoma, breast carcinoma, glioma, and schwannoma, but has only recently been explored in veterinary species. In this study, 198 tumors comprised of 147 melanocytic neoplasms and 51 non-melanocytic neoplasms were evaluated by immunohistochemistry using a tissue microarray for SOX-10, PNL2, melan A, TRP-1, and TRP-2 expressions. The SOX-10 had the highest diagnostic sensitivity (96.7%) in melanomas. In addition, SOX-10 had the highest percentage (91.5%; 130/142) of melanomas label at least 75% of neoplastic cells. Of the 51 selected non-melanocytic tumors examined, SOX-10 labeling was observed in mammary carcinomas (6/6), gliomas (4/4), and oral soft tissue sarcomas (4/18). Of the 41 non-melanocytic oral neoplasms evaluated, SOX-10 had a specificity of 92.7%. Therefore, SOX-10 represents a useful immunohistochemical screening marker for the diagnosis of canine melanoma given its extremely high sensitivity and robust labeling intensity. The SOX-10 may have utility in diagnosing some non-melanocytic neoplasms in the dog, although this requires further investigation.

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Home care rehabilitation professionals (hcRPs) provide health services for clients with a broad range of medical conditions. During the COVID-19 pandemic, home care rehabilitation professionals experienced exacerbations of pre-existing work-related stressors, increased risk of transmission of the COVID-19 virus, reduced resource availability, greater workloads, and staffing shortages. The primary aim of this study was to examine the experience and impact of occupational and mental stress on hcRPs working during the COVID-19 pandemic. Semi-structured interviews were conducted with 24 hcRPs working in Ontario, Canada during the COVID-19 pandemic. Inductive thematic analysis was used to interpret and organize the data into conceptualized themes. Interview data was organized into three themes: (a) unique challenges of a home care rehabilitation professional, (b) COVID-19 exacerbations of home care occupational and mental stress, and (c) personal and workplace coping strategies. Many participants reported reducing their hours or taking on adjunctive roles in different clinical settings outside of home care due to work-related stress exacerbated by the COVID-19 pandemic. With a focus on the effects of COVID-19 on the practice of home care, this study provides a unique perspective on the challenges experienced by hcRPs during an emergent and evolving global public health concern. The exploratory nature of this research works towards providing a framework of factors to be addressed when creating sustainable healthcare interventions, as well as recommendations to support hcRPs to benefit both the community and health-care providers.

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Osteoarthritis is a common cause of morbidity and mortality in geriatric gazelles. Propionibacterium australiense has been reported as a cause of systemic granulomas in cattle, but there are no descriptions of this bacteria infecting other species nor causing osteoarthritis, to our knowledge. An 8-y-old, castrated male, sand gazelle (Gazella leptoceros leptoceros) was managed for chronic, intermittent, progressive osteoarthritis of the right tarsus. Serial biopsies revealed pyogranulomatous dermatitis with intralesional bacteria. Serial diagnostic imaging identified osseous and soft tissue proliferation with draining tracts. Treatments over 1 y included broad-spectrum antibiotics, anti-inflammatories, joint debridement, and infusion with platelet-rich plasma and stem cells. Despite therapy, lameness persisted, azotemia developed, and subsequently, the animal was euthanized. On postmortem examination, the periarticular tissue of the right tarsus was markedly expanded by pyogranulomas and fibrosis. Histologically, the synovium, joint capsule, and overlying soft tissues were markedly expanded by pyogranulomas and numerous gram-positive and acid-fast-negative filamentous bacteria surrounded by Splendore-Hoeppli material. Within the joint, there was regionally extensive cartilage ulceration, osteonecrosis, osteolysis, and pannus formation. PCR assay of affected formalin-fixed, paraffin-embedded tissue amplified segments of 16S rRNA and ß subunit of bacterial RNA polymerase (rpoB) genes with 99.7% and 95.6% identity to P. australiense. This bacterium should be considered a differential for chronic pyogranulomatous osteoarthritis in gazelles.

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Introduction: The COVID-19 pandemic has had an unprecedented impact on nurses' well-being and desire to practice; however, the experience of Canadian home and community care nurses remains less well understood. As the health human resources crisis in this sector persists, understanding these nurses' experiences may be vital in creating more effective retention strategies. Objective: The aim of this study was to explore how the COVID-19 pandemic shaped the working experiences, motivations, and attitudes of home and community care nurses in the Greater Toronto Area. Methods: Using an exploratory, descriptive, qualitative approach, 16 home and community care nurses participated in semistructured interviews. Data were analyzed using collaborative thematic analysis. Participants shared their reflections on work by detailing their experiences prepandemic, during crisis, transitioning out of crisis, and regarding pandemic recovery. Results: During the COVID-19 pandemic inadequate staffing resources during and beyond the crisis period disrupted many desirable facets of work for home and community care nurses such as stable, balanced, and flexible work conditions, and exacerbated the unfavorable aspects such as isolation and inconsistent support. Many nurses were reevaluating their careers: for some, this meant stronger professional attachment and for others, it meant intentions to leave. Improved sector preparedness, wages, and workplace support were identified as strategies to sustain this workforce beyond the pandemic. Conclusion: Home care organizations must consider ways to address the root cause of concerns expressed by nurses who wish to practice in a supportive environment that is sufficiently staffed and sensitive to workload expectations.

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Genome editing technologies based on DNA-dependent polymerases (DDPs) could offer several benefits compared with other types of editors to install diverse edits. Here, we develop click editing, a genome writing platform that couples the advantageous properties of DDPs with RNA-programmable nickases to permit the installation of a range of edits, including substitutions, insertions and deletions. Click editors (CEs) leverage the 'click'-like bioconjugation ability of HUH endonucleases with single-stranded DNA substrates to covalently tether 'click DNA' (clkDNA) templates encoding user-specifiable edits at targeted genomic loci. Through iterative optimization of the modular components of CEs and their clkDNAs, we demonstrate the ability to install precise genome edits with minimal indels in diverse immortalized human cell types and primary fibroblasts with precise editing efficiencies of up to ~30%. Editing efficiency can be improved by rapidly screening clkDNA oligonucleotides with various modifications, including repair-evading substitutions. Click editing is a precise and versatile genome editing approach for diverse biological applications.

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BACKGROUND: Facial-protective equipment (FPE) use increased during the SARS-CoV-2 pandemic. This study explored factors influencing home care personal support workers' (PSWs) and nurses' self-reported adherence to FPE. METHODS: A cross-sectional, electronic, survey was distributed to PSWs and nurses (1,108 complete responses) at 3 home care agencies in Ontario, Canada, in May to June 2022. Descriptive, bivariate, and multivariable analysis were used to assess individual, environmental, and organizational factors influencing adherence. RESULTS: Among participants (786 PSWs, 322 nurses), 64% reported being adherent to both respiratory and eye FPE (Respiratory: 96%, Eye: 64%). Higher adherence was associated with facility-based work; better knowledge of FPE; prepandemic FPE use; good availability and convenient access; strong organizational support for health and safety; and Caribbean identity. Lower adherence was found for men; nurses with 2-year diplomas; shorter length of employment; communal transportation; and experiencing negative mental health effects from workplace infectious disease exposure. DISCUSSION: Agencies should prioritize increasing providers' knowledge of FPE, supporting mental well-being, fostering a supportive culture, and ensuring availability of FPE. The influences of gender, ethnicity, and role require further exploration. CONCLUSIONS: FPE adherence may be improved by addressing modifiable factors and developing population-specific strategies.

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Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.

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BACKGROUND: Facial protective equipment (FPE) adherence is necessary for the health and safety of nursing professionals. This review was conducted to synthesize predisposing, enabling, and reinforcing factors that influence FPE adherence, and thus inform efforts to promote adherence. METHODS: Articles were collected using Cumulated Index to Nursing and Allied Health Literature and MEDLINE and screened for inclusion. Included articles were original studies focused on FPE adherence by nurses to prevent respiratory infection which contained occupation-specific data from at least 10 individuals and were published in English between January 2005 and February 2022. RESULTS: Thirty articles were included, 21 of which reported adherence rates. Adherence ranged from 33% to 100% for respiratory protection and 22% to 100% for eye protection. Predisposing demographic factors influencing adherence included tenure and occupation, while modifiable predisposing factors included knowledge and perception of FPE, infection transmission, and risk. Enabling factors included geography, care settings, and FPE availability. Reinforcing factors included organizational support for health and safety, clear policies, and training. CONCLUSIONS: The identified demographic factors suggest populations that may benefit from targeted interventions, while modifiable factors suggest opportunities to enhance education as well as operational processes and supports. Interventions that target these areas have the potential to promote adherence and thereby improve the occupational safety of nurses.

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BACKGROUND: Each year, millions of Americans develop truncal pressure ulcers (PUs) which can persist for months, years, or until the end of life. Despite the negative impact on quality of life and escalating costs associated with PUs, there is sparse evidence supporting validated and efficacious treatment options. As a result, treatment is based on opinion and extrapolation from other wound etiologies. The ideal reconstructive plan maximizes the patient's nutritional status, incorporates the basic tenets of wound bed preparation (debridement, offloading, proper moisture balance, reduction of bacterial burden), and employs diagnostics to guide therapeutic intervention. The use of combination therapies can potentially overcome several of the barriers to wound healing. Negative pressure wound therapy (NPWT), a commonly used modality in the management of PUs, facilitates healing by stimulating the formation of granulation tissue and promoting wound contraction; however, NPWT alone is not always effective. Clinical studies examining microbial bioburden in PUs determined that most ulcers contain bacteria at levels that impede wound healing (>104 CFU/g). OBJECTIVE: Thus, we hypothesized that adding an anti-microbial agent to decrease both planktonic and biofilm bacteria in the wound would increase the efficacy of NPWT. METHOD: In this prospective study, twenty patients with recalcitrant PUs that previously failed NPWT were treated with a biofilm-disrupting agent (Blast-X, Next Science, Jacksonville, FL, USA) in combination with NPWT. Fluorescence imaging was used to follow bacterial burden and guide therapy. RESULTS: In total, 45% of the PUs reduced in size over the course of the four-week study, with a resolution of bacterial fluorescence in the NPWT dressing and wound bed seen in an average of three weeks. CONCLUSION: The combination of an antibiofilm agent and NPWT reduced bacterial levels and improved wound healing in recalcitrant PUs.

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BACKGROUND: Workplace violence and harassment are commonplace for healthcare workers and most incidents are unreported. Normalization of these experiences, lack of confidence in reporting systems, and fear of the consequences of reporting contribute to the invisibility of these experiences. Challenges are exacerbated in homecare settings and for precarious workforces including Personal Support Workers (PSWs). We created, piloted, and evaluated an intervention to enhance safety culture and encourage reporting of workplace violence and harassment. METHODS: A multi-stakeholder steering committee designed an intervention combining policy changes, a pre-visit screening tool, education, and brief end-of-visit reporting. This was piloted with a PSW care team which provided >55,000 client visits during the 32-week intervention. Operational metrics characterized screening, education, and reporting uptake. Pre- and post-intervention surveys characterized PSWs' experiences with workplace violence and harassment, reporting experiences, training history and intervention feedback. FINDINGS: PSWs reported increased comfort discussing workplace violence and harassment, and increased confidence managing client-to-worker incidents. The screening went smoothly with most clients in private homes. Most PSWs (75%) engaged at least once with end-of-visit reporting and nearly half submitted reports regularly. During the pilot, 21% of PSWs reported incidents and 52% of reports shared client-specific strategies for managing these situations. APPLICATION TO PRACTICE: Changes in comfort and behavior with reporting indicated a shift toward a more open culture surrounding workplace violence and harassment. Tools created for this intervention and lessons for implementation are shared for consideration by occupational health practitioners throughout the homecare sector.

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Grab bars facilitate bathing and reduce the risk of falls during bathing. Suction cup handholds and rim-mounted tub rails are an alternative to grab bars. The objective of this study was to determine whether older adults could install handholds and tub rails effectively to support bathing transfers. Participants installed rim-mounted tub rails and suction cup handholds in a simulated bathroom environment. Installation location and mechanical loading performance were evaluated. Participant perceptions during device installation and a bathing transfer were characterized. While 85% of suction cup handholds met loading requirements, more than half of participants installed the suction cup handhold in an unexpected location based on existing guidance documents. No rim-mounted tub rails were successfully installed. Participants were confident that the devices had been installed effectively. Suction cup handholds and rim mounted tub rails are easy to install, but clients may need additional guidance regarding where, and how to install them.

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DECLARATION OF INTEREST: TS is a consultant for Inotec AMD Ltd., UK. The authors have no other conflicts of interest to declare.

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PURPOSE: This study describes how an employer-based tuition-assistance program for homecare workers at one Canadian homecare organization enabled nursing career advancement and retention. DESIGN: A convergent parallel mixed-methods design. METHODS: We reviewed existing administrative data and concurrently conducted semi-structured interviews. Descriptive statistics were used on quantitative data and qualitative data was analyzed using thematic analysis. A joint data display was developed to integrate findings from both quantitative and qualitative data together. FINDINGS: Tuition assistance reduced financial barriers to career advancement; 83% of recipients remained with their employer for at least 1-year post-studies but only 29% experienced career advancement. Psychosocial supports, career navigation and coaching to ease the licensing and role transition processes were identified as opportunities to support learners. CONCLUSION: Employer-based tuition assistance programs are impactful in helping to develop skilled employees. Practical enhancements to further support career transitions may maximize retention to address urgent homecare staffing challenges. CLINICAL EVIDENCE: Employer-based tuition assistance can be a useful strategy to support nursing career growth and staff retention.

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OBJECTIVE: Excessive numbers of bacteria in hard-to-heal wounds impede wound healing. Numerous topical antiseptics have demonstrated effectiveness in benchtop studies; however, few clinical studies have demonstrated efficacy in the target population: patients with hard-to-heal wounds. This study addressed the clinical efficacy of a novel antibiofilm cleanser and gel in reducing bacterial load and improving wound outcomes. METHOD: Hard-to-heal wounds were photographed, measured and evaluated for bacterial load using fluorescence imaging weekly for four weeks. The target ulcers were randomised to be cleaned and treated with either a synergistic antibiofilm cleanser and antibiofilm gel with standard of care (AMC-AMG + SoC) or normal saline wash and an amorphous gel with standard of care (NSS-HG + SoC). RESULTS: A Chi-squared test of independence determined that the relationship between the treatment and the patient reaching 40% percentage area reduction (PAR) in four weeks was not significant (χ2(1, n=54)=0.73; p=0.39 at a significance level of 0.05); however, there was a strong trend favouring the antibiofilm cleanser and gel. A significant reduction (p<0.05) in bacterial load was observed in the antibiofilm group. CONCLUSION: This randomised controlled double-blind proof-of-concept study suggests that the performance of antibiofilm agents in vivo is comparable to that in vitro studies.

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Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited. In this study, we designed and synthesized a codon optimized HTLV-1 envelope (Env) mRNA encapsulated in a lipid nanoparticle (LNP) and evaluated its efficacy as a vaccine candidate in an established rabbit model of HTLV-1 infection and persistence. Immunization regimens included a prime/boost protocol using Env mRNA-LNP or control green fluorescent protein (GFP) mRNA-LNP. After immunization, rabbits were challenged by intravenous injection with irradiated HTLV-1 producing cells. Three rabbits were partially protected and three rabbits were completely protected against HTLV-1 challenge. These rabbits were then rechallenged 15 weeks later, and two rabbits maintained sterilizing immunity. In Env mRNA-LNP immunized rabbits, proviral load and viral gene expression were significantly lower. After viral challenge in the Env mRNA-LNP vaccinated rabbits, an increase in both CD4+/IFN-γ+ and CD8+/IFN-γ+ T-cells was detected when stimulating with overlapping Env peptides. Env mRNA-LNP elicited a detectable anti-Env antibody response after prime/boost vaccination in all animals and significantly higher levels of neutralizing antibody activity. Neutralizing antibody activity was correlated with a reduction in proviral load. These findings hold promise for the development of preventive strategies and therapeutic interventions against HTLV-1 infection and its associated diseases.IMPORTANCEmRNA vaccine technology has proven to be a viable approach for effectively triggering immune responses that protect against or limit viral infections and disease. In our study, we synthesized a codon optimized human T-cell leukemia virus type 1 (HTLV-1) envelope (Env) mRNA that can be delivered in a lipid nanoparticle (LNP) vaccine approach. The HTLV-1 Env mRNA-LNP produced protective immune responses against viral challenge in a preclinical rabbit model. HTLV-1 is primarily transmitted through direct cell-to-cell contact, and the protection offered by mRNA vaccines in our rabbit model could have significant implications for optimizing the development of other viral vaccine candidates. This is particularly important in addressing the challenge of enhancing protection against infections that rely on cell-to-cell transmission.

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