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1.
Sensors (Basel) ; 24(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38732910

ABSTRACT

IoT has seen remarkable growth, particularly in healthcare, leading to the rise of IoMT. IoMT integrates medical devices for real-time data analysis and transmission but faces challenges in data security and interoperability. This research identifies a significant gap in the existing literature regarding a comprehensive ontology for vulnerabilities in medical IoT devices. This paper proposes a fundamental domain ontology named MIoT (Medical Internet of Things) ontology, focusing on cybersecurity in IoMT (Internet of Medical Things), particularly in remote patient monitoring settings. This research will refer to similar-looking acronyms, IoMT and MIoT ontology. It is important to distinguish between the two. IoMT is a collection of various medical devices and their applications within the research domain. On the other hand, MIoT ontology refers to the proposed ontology that defines various concepts, roles, and individuals. MIoT ontology utilizes the knowledge engineering methodology outlined in Ontology Development 101, along with the structured life cycle, and establishes semantic interoperability among medical devices to secure IoMT assets from vulnerabilities and cyberattacks. By defining key concepts and relationships, it becomes easier to understand and analyze the complex network of information within the IoMT. The MIoT ontology captures essential key terms and security-related entities for future extensions. A conceptual model is derived from the MIoT ontology and validated through a case study. Furthermore, this paper outlines a roadmap for future research, highlighting potential impacts on security automation in healthcare applications.


Subject(s)
Computer Security , Internet of Things , Humans , Monitoring, Physiologic/methods , Monitoring, Physiologic/instrumentation , Telemedicine/methods
2.
Med Teach ; : 1-15, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627020

ABSTRACT

PURPOSE: Management reasoning is a distinct subset of clinical reasoning. We sought to explore features to be considered when designing assessments of management reasoning. METHODS: This is a hybrid empirical research study, narrative review, and expert perspective. In 2021, we reviewed and discussed 10 videos of simulated (staged) physician-patient encounters, actively seeking actions that offered insights into assessment of management reasoning. We analyzed our own observations in conjunction with literature on clinical reasoning assessment, using a constant comparative qualitative approach. RESULTS: Distinguishing features of management reasoning that will influence its assessment include management scripts, shared decision-making, process knowledge, illness-specific knowledge, and tailoring of the encounter and management plan. Performance domains that merit special consideration include communication, integration of patient preferences, adherence to the management script, and prognostication. Additional facets of encounter variation include the clinical problem, clinical and nonclinical patient characteristics (including preferences, values, and resources), team/system characteristics, and encounter features. We cataloged several relevant assessment approaches including written/computer-based, simulation-based, and workplace-based modalities, and a variety of novel response formats. CONCLUSIONS: Assessment of management reasoning could be improved with attention to the performance domains, facets of variation, and variety of approaches herein identified.

3.
Acad Med ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38683885

ABSTRACT

PURPOSE: Learner engagement is the energy learners exert to remain focused and motivated to learn. The Learner Engagement Instrument (LEI) was developed to measure learner engagement in a short continuing professional development (CPD) activity. The authors validated LEI scores using validity evidence of internal structure and relationships with other variables. METHOD: Participants attended 1 of 4 CPD courses (1 in-person, 2 online livestreamed, and 1 either in-person or online) in 2018, 2020, 2021, and 2022. Confirmatory factor analysis was used to examine model fit for several alternative structural models, separately for each course. The authors also conducted a generalizability study to estimate score reliability. Associations were evaluated between LEI scores and Continuing Medical Education Teaching Effectiveness (CMETE) scores and participant demographics. All statistical methods accounted for repeated measures by participants. RESULTS: 415 unique participants attended 203 different CPD presentations and completed the LEI 11,567 times. The originally hypothesized 4-domain model of learner engagement (domains: emotional, behavioral, cognitive in-class, cognitive out-of-class) demonstrated best model fit in all 4 courses, with Comparative Fit Index ≥0.99, Standardized Root Mean Square Residual ≤0.031, and Root Mean Square Error of Approximation ≤0.047. The reliability for overall scores and domain scores were all acceptable (50-rater G-coefficient ≥ 0.74) except for the cognitive-in-class domain (50-rater G-coefficient 0.55 to 0.66). All findings were similar for both in-person and online delivery modalities. Correlation of LEI scores with teaching effectiveness was confirmed (rho 0.58), and a small correlation was found with participant age (rho 0.19); other associations were small and not statistically significant. Using these findings, we generated a shortened 4-item instrument, the LEI Short Form. CONCLUSIONS: This study confirms a 4-domain model of learner engagement, and provides validity evidence that supports using LEI scores to measure learner engagement in both in-person and livestreamed CPD activities.

4.
Article in English | MEDLINE | ID: mdl-38564376

ABSTRACT

RATIONALE: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. Results of clinical trials with MSCs for many disorders do not yet match the promising preclinical studies. A lack of specific criteria to define functionally distinct MSCs persists. OBJECTIVES: To determine and correlate single-cell UC-MSC transcriptomic profile with therapeutic potential. METHODS: UC-MSCs from five term donors and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin) transcriptomes were investigated by single-cell RNA sequencing analysis (scRNA-seq). The lung-protective effect of UC-MSCs with a distinct transcriptome and control HNDFs was tested in vivo in hyperoxia-induced neonatal lung injury in rats. MEASUREMENTS AND MAIN RESULTS: UC-MSCs showed limited transcriptomic heterogeneity, but were different from HNDFs. Gene ontology enrichment analysis revealed distinct - progenitor-like and fibroblast-like - UC-MSC subpopulations. Only the treatment with progenitor-like UC-MSCs improved lung function and structure and attenuated pulmonary hypertension in hyperoxia-exposed rat pups. Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of non-therapeutic cells and associated with decreased lung retention. CONCLUSIONS: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.

5.
Science ; 384(6692): 178-184, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38603511

ABSTRACT

Single-phase body-centered cubic (bcc) refractory medium- or high-entropy alloys can retain compressive strength at elevated temperatures but suffer from extremely low tensile ductility and fracture toughness. We examined the strength and fracture toughness of a bcc refractory alloy, NbTaTiHf, from 77 to 1473 kelvin. This alloy's behavior differed from that of comparable systems by having fracture toughness over 253 MPa·m1/2, which we attribute to a dynamic competition between screw and edge dislocations in controlling the plasticity at a crack tip. Whereas the glide and intersection of screw and mixed dislocations promotes strain hardening controlling uniform deformation, the coordinated slip of <111> edge dislocations with {110} and {112} glide planes prolongs nonuniform strain through formation of kink bands. These bands suppress strain hardening by reorienting microscale bands of the crystal along directions of higher resolved shear stress and continually nucleate to accommodate localized strain and distribute damage away from a crack tip.

6.
Int J Circumpolar Health ; 83(1): 2336284, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38573784

ABSTRACT

This paper outlines the methodological approaches to a multi-site Circumpolar case study exploring the impacts of COVID-19 on Indigenous and remote communities in 7 of 8 Arctic countries. Researchers involved with the project implemented a three-phase multi-site case study to assess the positive and negative societal outcomes associated with the COVID-19 pandemic in Arctic communities from 2020 to 2023. The goal of the multi-site case study was to identify community-driven models and evidence-based promising practices and recommendations that can help inform cohesive and coordinated public health responses and protocols related to future public health emergencies in the Arctic. Research sites included a minimum of 1 one community each from Canada (Nunavut,) United States of America (Alaska), Greenland, Iceland, Norway, Sweden, Finland. The approaches used for our multi-site case study provide a comprehensive, evidence-based account of the complex health challenges facing Arctic communities, offering insights into the effectiveness of interventions, while also privileging Indigenous local knowledge and voices. The mixed method multi-site case study approach enriched the understanding of unique regional health disparities and strengths during the pandemic. These methodological approaches serve as a valuable resource for policymakers, researchers, and healthcare professionals, informing future strategies and interventions.


Subject(s)
COVID-19 , Pandemics , Humans , Arctic Regions , Alaska/epidemiology , Canada , Greenland
7.
J Econ Entomol ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38518379

ABSTRACT

This study determined a cost-effective larval diet for rearing Calliphora dubia Macquart for use as a potential managed pollinator in Australia. This fly has potential as a pollination species to support honey bees (Apis mellifera). Larvae of C. dubia were reared mostly in meat meals with varying amounts of either whole egg powder, whole eggs (+ shell), bran flakes, skimmed milk powder, brewer's yeast, or poultry oil. This was done from an economic and production perspective to support commercial rearing. Several laboratory-based studies determined the growth and output from various ingredient combinations. Larvae fed 90% meat meal and 10% whole egg powder developed rapidly through to pupation with a high pupation rate, adult size, and percent adult emergence. Given the high cost and difficulty in sourcing whole egg powder, media comprising mostly meat meals with the addition of bran flakes and whole eggs also supported rapid larval development, pupation rate, and adult emergence. The ideal amount of media/larvae was 0.5 g/larvae to support high pupation rates and adult emergence. Adult eclosion occurred over 4-5 days, even when larvae were laid and fed within 1 h on ample media. Commercial mass rearing would then require daily cohorts of larvae to ensure peak adult fly emergence over 1-2 days for release into a crop. Mass-rearing C. dubia should use meat meal as the base ingredient with bran flakes and whole eggs added and fed at 0.5 g of media/larvae. Based on the current media ingredient costs, rearing 1-m adult C. dubia would cost just over $500 (US$342).

8.
Sci Rep ; 14(1): 5760, 2024 03 08.
Article in English | MEDLINE | ID: mdl-38459073

ABSTRACT

Stroke is a leading cause of death and disability worldwide, and early diagnosis and prompt medical intervention are thus crucial. Frequent monitoring of stroke patients is also essential to assess treatment efficacy and detect complications earlier. While computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used for stroke diagnosis, they cannot be easily used onsite, nor for frequent monitoring purposes. To meet those requirements, an electromagnetic imaging (EMI) device, which is portable, non-invasive, and non-ionizing, has been developed. It uses a headset with an antenna array that irradiates the head with a safe low-frequency EM field and captures scattered fields to map the brain using a complementary set of physics-based and data-driven algorithms, enabling quasi-real-time detection, two-dimensional localization, and classification of strokes. This study reports clinical findings from the first time the device was used on stroke patients. The clinical results on 50 patients indicate achieving an overall accuracy of 98% in classification and 80% in two-dimensional quadrant localization. With its lightweight design and potential for use by a single para-medical staff at the point of care, the device can be used in intensive care units, emergency departments, and by paramedics for onsite diagnosis.


Subject(s)
Brain , Stroke , Humans , Brain/diagnostic imaging , Electromagnetic Phenomena , Head , Stroke/diagnostic imaging , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging
9.
Neurology ; 102(7): e209197, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38478804

ABSTRACT

BACKGROUND AND OBJECTIVES: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aß40 and Aß42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aß42 and Aß40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aß42 (p ≤ 0.05) in older participants. DISCUSSION: CSF Aß levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.


Subject(s)
Alzheimer Disease , Brain Concussion , Brain Injuries, Traumatic , Veterans , Middle Aged , Humans , Male , Aged , Female , Brain Concussion/complications , Case-Control Studies , Cross-Sectional Studies , Amyloid beta-Peptides , Alzheimer Disease/pathology , tau Proteins , Brain Injuries, Traumatic/complications , Biomarkers , Memory Disorders/complications
10.
Am J Trop Med Hyg ; 110(5): 1021-1028, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38531104

ABSTRACT

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels. Based on manufacturers' reference range values, which are currently used in Malian clinical laboratories, abnormal values were common in this healthy population. In fact, 30.4% of adult participants had abnormal neutrophil levels and 19.8% had abnormal hemoglobin levels. Differences by sex were observed in those who were older, but not in those younger than 10 years, for several parameters, including hemoglobin, platelet, and absolute neutrophil counts in hematology, and creatinine in biochemistry. The site-specific reference intervals we report can be used in malaria vaccine clinical trials and other interventional studies, as well as in routine clinical care, to identify abnormalities in hematological and biochemical parameters among healthy Malian trial participants.


Subject(s)
Rural Population , Humans , Mali/epidemiology , Male , Female , Adolescent , Adult , Child , Child, Preschool , Reference Values , Middle Aged , Infant , Rural Population/statistics & numerical data , Young Adult , Aged , Aged, 80 and over , Age Factors , Sex Factors , Hemoglobins/analysis , Creatinine/blood , Laboratories, Clinical , Blood Cell Count
11.
Acad Med ; 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38412483

ABSTRACT

PURPOSE: Supervisors may be prone to implicit (unintentional) bias when granting procedural autonomy to trainees due to the subjectivity of autonomy decisions. The authors aimed to conduct a systematic review and meta-analysis to assess the differences in perceptions of procedural autonomy granted to physician trainees based on gender and/or race. METHOD: MEDLINE, Embase, CENTRAL, Scopus, and Web of Science were searched (search date: January 5, 2022) for studies reporting quantitative gender- or race-based differences in perceptions of procedural autonomy of physician trainees. Reviewers worked in duplicate for article selection and data abstraction. Primary measures of interest were self-reported and observer-rated procedural autonomy. Meta-analysis pooled differences in perceptions of procedural autonomy based on trainee gender. RESULTS: The search returned 2,714 articles, of which 16 were eligible for inclusion. These reported data for 6,109 trainees (median 90 per study) and 2,763 supervisors (median 54 per study). No studies investigated differences in perceptions of autonomy based on race. In meta-analysis of disparities between genders in autonomy ratings (positive number favoring female trainees), pooled standardized mean differences were -0.12 (95% confidence interval [CI] = -0.19, -0.04; P = .003; n = 10 studies) for trainee self-rated autonomy and -0.05 (95% CI = -0.11, 0.01; P = .07; n = 9 studies) for supervisor ratings of autonomy. CONCLUSIONS: Limited evidence suggests that female trainees perceived that they received less procedural autonomy than did males. Further research exploring the degree of gender- and race-based differences in procedural autonomy, and factors that influence these differences, is warranted.

12.
Nat Commun ; 15(1): 1701, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402218

ABSTRACT

The spatial organization of eukaryotic genomes is linked to their biological functions, although it is not clear how this impacts the overall evolution of a genome. Here, we uncover the three-dimensional (3D) genome organization of the phytopathogen Verticillium dahliae, known to possess distinct genomic regions, designated adaptive genomic regions (AGRs), enriched in transposable elements and genes that mediate host infection. Short-range DNA interactions form clear topologically associating domains (TADs) with gene-rich boundaries that show reduced levels of gene expression and reduced genomic variation. Intriguingly, TADs are less clearly insulated in AGRs than in the core genome. At a global scale, the genome contains bipartite long-range interactions, particularly enriched for AGRs and more generally containing segmental duplications. Notably, the patterns observed for V. dahliae are also present in other Verticillium species. Thus, our analysis links 3D genome organization to evolutionary features conserved throughout the Verticillium genus.


Subject(s)
Genomics , Plants , Plants/genetics , DNA Transposable Elements/genetics , Chromatin/genetics , Evolution, Molecular , Genome, Fungal/genetics
13.
Int J Circumpolar Health ; 83(1): 2311966, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38324668

ABSTRACT

Remote Arctic communities have often been depicted as being particularly vulnerable to the challenges of disasters, with their location and lack of infrastructure exacerbating risk. This study explores the characteristics of local resilience in the Arctic using the case study of the communities of the north-western Westfjords. A total of 42 semi-structured interviews were carried out with various community members, seeking to uncover the features of inbuilt resilience that contribute to successes and vulnerabilities. These were transcribed, coded, and categorised in relation to an integrated framework for assessing community resilience in disaster management, which groups topics via the themes of environmental, social, governance, economic, and infrastructure. All themes played a role in the success of local coping strategies, with easy access to the natural environment central to physical and mental well-being. Despite this, vulnerabilities of the community were evident, including insufficient local healthcare workers during a severe COVID-19 outbreak in a care home, the absence of a local quarantine hotel, and insufficient information in foreign languages for non-natives of Iceland. The general trend of following rules and expert advice was demonstrative of strong social capital, with locals trusting those in charge, nationally and locally, to manage the pandemic.


Subject(s)
COVID-19 , Disaster Planning , Disasters , Resilience, Psychological , Humans , Iceland/epidemiology
14.
Int J Mol Sci ; 25(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38256223

ABSTRACT

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.


Subject(s)
Blast Injuries , Brain Concussion , Vascular System Injuries , Animals , Humans , Endothelial Cells , Astrocytes , Inflammation
15.
Stud Health Technol Inform ; 310: 865-869, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38269932

ABSTRACT

The lack of transparency and explainability hinders the clinical adoption of Machine learning (ML) algorithms. While explainable artificial intelligence (XAI) methods have been proposed, little research has focused on the agreement between these methods and expert clinical knowledge. This study applies current state-of-the-art explainability methods to clinical decision support algorithms developed for Electronic Medical Records (EMR) data to analyse the concordance between these factors and discusses causes for identified discrepancies from a clinical and technical perspective. Important factors for achieving trustworthy XAI solutions for clinical decision support are also discussed.


Subject(s)
Artificial Intelligence , Electronic Health Records , Algorithms , Knowledge , Machine Learning
16.
Simul Healthc ; 19(1S): S4-S22, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38240614

ABSTRACT

BACKGROUND: Simulation has become a staple in the training of healthcare professionals with accumulating evidence on its effectiveness. However, guidelines for optimal methods of simulation training do not currently exist. METHODS: Systematic reviews of the literature on 16 identified key questions were conducted and expert panel consensus recommendations determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. OBJECTIVE: These evidence-based guidelines from the Society for Simulation in Healthcare intend to support healthcare professionals in decisions on the most effective methods for simulation training in healthcare. RESULTS: Twenty recommendations on 16 questions were determined using GRADE. Four expert recommendations were also provided. CONCLUSIONS: The first evidence-based guidelines for simulation training are provided to guide instructors and learners on the most effective use of simulation in healthcare.


Subject(s)
Health Personnel , Simulation Training , Humans , Delivery of Health Care
17.
Simul Healthc ; 19(1S): S23-S31, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38240615

ABSTRACT

ABSTRACT: This systematic review was performed to assess the effectiveness of in situ simulation education. We searched databases including MEDLINE and Embase for studies comparing in situ simulation with other educational approaches. Two reviewers screened articles and extracted information. Sixty-two articles met inclusion criteria, of which 24 were synthesized quantitatively using random effects meta-analysis. When compared with current educational practices alone, the addition of in situ simulation to these practices was associated with small improvements in clinical outcomes, including mortality [odds ratio, 0.66; 95% confidence interval (CI), 0.55 to 0.78], care metrics (standardized mean difference, -0.34; 95% CI, -0.45 to -0.21), and nontechnical skills (standardized mean difference, -0.52; 95% CI, -0.99 to -0.05). Comparisons between in situ and traditional simulation showed mixed learner preference and knowledge improvement between groups, while technical skills showed improvement attributable to in situ simulation. In summary, available evidence suggests that adding in situ simulation to current educational practices may improve patient mortality and morbidity.


Subject(s)
Delivery of Health Care , Simulation Training , Humans , Patient Care
18.
Toxics ; 12(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38250996

ABSTRACT

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically relevant chemicals in the aerosols and characterize any related toxicology. Herein, we present a proposed framework for characterizing novel ENDS products (i.e., devices and formulations) and determining the reduced risk potential utilizing analytical chemistry and in vitro toxicological studies with a qualitative risk assessment. To demonstrate this proposed framework, long-term stability studies (12 months) analyzing relevant toxicant emissions from six formulations of a next-generation product, JUUL2, were conducted and compared to reference combustible cigarette (CC) smoke under both non-intense and intense puffing regimes. In addition, in vitro cytotoxicity, mutagenicity, and genotoxicity assays were conducted on aerosol and smoke condensates. In all samples, relevant toxicants under both non-intense and intense puffing regimes were substantially lower than those observed in reference CC smoke. Furthermore, neither cytotoxicity, mutagenicity, nor genotoxicity was observed in aerosol condensates generated under both intense and non-intense puffing regimes, in contrast to results observed for reference cigarettes. Following the proposed framework, the results demonstrate that the ENDS products studied in this work generate significantly lower levels of toxicants relative to reference cigarettes and were not cytotoxic, mutagenic, or genotoxic under these in vitro assay conditions.

19.
Nat Commun ; 15(1): 841, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38286856

ABSTRACT

Strengthening materials via conventional "top-down" processes generally involves restricting dislocation movement by precipitation or grain refinement, which invariably restricts the movement of dislocations away from, or towards, a crack tip, thereby severely compromising their fracture resistance. In the present study, a high-entropy alloy Al0.5CrCoFeNi is produced by the laser powder-bed fusion process, a "bottom-up" additive manufacturing process similar to how nature builds structures, with the microstructure resembling a nano-bridged honeycomb structure consisting of a face-centered cubic (fcc) matrix and an interwoven hexagonal net of an ordered body-centered cubic B2 phase. While the B2 phase, combined with high-dislocation density and solid-solution strengthening, provides strength to the material, the nano-bridges of dislocations connecting the fcc cells, i.e., the channels between the B2 phase on the cell boundaries, provide highways for dislocation movement away from the crack tip. Consequently, the nature-inspired microstructure imparts the material with an excellent combination of strength and toughness.

20.
Sci Rep ; 14(1): 787, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191799

ABSTRACT

The tumour microenvironment is infiltrated by immunosuppressive cells, such as regulatory T cells (Tregs), which contribute to tumour escape and impede immunotherapy outcomes. Soluble fibrinogen-like protein 2 (sFGL2), a Treg effector protein, inhibits immune cell populations, via receptors FcγRIIB and FcγRIII, leading to downregulation of CD86 in antigen presenting cells and limiting T cell activation. Increased FGL2 expression is associated with tumour progression and poor survival in several different cancers, such as glioblastoma multiforme, lung, renal, liver, colorectal, and prostate cancer. Querying scRNA-seq human cancer data shows FGL2 is produced by cells in the tumour microenvironment (TME), particularly monocytes and macrophages as well as T cells and dendritic cells (DCs), while cancer cells have minimal expression of FGL2. We studied the role of FGL2 exclusively produced by cells in the TME, by leveraging Fgl2 knockout mice. We tested two murine models of cancer in which the role of FGL2 has not been previously studied: epithelial ovarian cancer and melanoma. We show that absence of FGL2 leads to a more activated TME, including activated DCs (CD86+, CD40+) and T cells (CD25+, TIGIT+), as well as demonstrating for the first time that the absence of FGL2 leads to more activated natural killer cells (DNAM-1+, NKG2D+) in the TME. Furthermore, the absence of FGL2 leads to prolonged survival in the B16F10 melanoma model, while the absence of FGL2 synergizes with oncolytic virus to prolong survival in the ID8-p53-/-Brca2-/- ovarian cancer model. In conclusion, targeting FGL2 is a promising cancer treatment strategy alone and in combination immunotherapies.


Subject(s)
Fibrinogen , Melanoma , Ovarian Neoplasms , Animals , Female , Humans , Mice , Antigen-Presenting Cells , Carcinoma, Ovarian Epithelial , Melanoma/genetics , Melanoma/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Tumor Microenvironment
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