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JMIR Human Factors May 2024Studies evaluating the usability of mobile-phone assessments in older adults are limited.
BACKGROUND
Studies evaluating the usability of mobile-phone assessments in older adults are limited.
OBJECTIVE
This study aims to identify design-based barriers and facilitators to mobile app survey completion among 2 samples of older adults; those in the Framingham Heart Study and a more diverse sample from a hospital-based setting.
METHODS
We used mixed methods to identify challenging and beneficial features of the mobile app in participants from the electronic Framingham Heart Study (n=15; mean age of 72 years; 6/15, 40% women; 15/15, 100% non-Hispanic and White) and among participants recruited from a hospital-based setting (n=15; mean age of 71 years; 7/15, 47% women; 3/15, 20% Hispanic; and 8/15, 53% non-White). A variety of app-based measures with different response formats were tested, including self-reported surveys, pictorial assessments (to indicate body pain sites), and cognitive testing tasks (eg, Trail Making Test and Stroop). Participants completed each measure using a think-aloud protocol, while being audio- and video-recorded with a qualitative interview conducted at the end of the session. Recordings were coded for participant usability errors by 2 pairs of coders. Participants completed the Mobile App Rating Scale to assess the app (response range 1=inadequate to 5=excellent).
RESULTS
In electronic Framingham Heart Study participants, the average total Mobile App Rating Scale score was 7.6 (SD 1.1), with no significant differences in the hospital-based sample. In general, participants were pleased with the app and found it easy to use. A large minority had at least 1 navigational issue, most committed only once. Most older adults did not have difficulty completing the self-reported multiple-choice measures unless it included lengthy instructions but participants had usability issues with the Stroop and Trail Making Test.
CONCLUSIONS
Our methods and results help guide app development and app-based survey construction for older adults, while also giving consideration to sociodemographic differences.
Topics: Humans; Mobile Applications; Aged; Female; Male; Smartphone; Surveys and Questionnaires; Aged, 80 and over
PubMed: 38815261
DOI: 10.2196/56653 -
Frontiers in Pharmacology 2024Chronic pain is a major socioeconomic burden in the Mediterranean region. However, we noticed an under-representation of these populations in the pharmacogenetics of...
BACKGROUND
Chronic pain is a major socioeconomic burden in the Mediterranean region. However, we noticed an under-representation of these populations in the pharmacogenetics of pain management studies. In this context, we aimed 1) to decipher the pharmacogenetic variant landscape among Mediterranean populations compared to worldwide populations in order to identify therapeutic biomarkers for personalized pain management and 2) to better understand the biological process of pain management through investigation of pharmacogenes pathways.
MATERIALS AND METHODS
We collected genes and variants implicated in pain response using the Prisma guidelines from literature and PharmGK database. Next, we extracted these genes from genotyping data of 829 individuals. Then, we determined the variant distribution among the studied populations using multivariate (MDS) and admixture analysis with R and STRUCTURE software. We conducted a Chi2 test to compare the interethnic frequencies of the identified variants. We used SNPinfo web server, miRdSNP database to identify miRNA-binding sites. In addition, we investigated the functions of the identified genes and variants using pathway enrichment analysis and annotation tools. Finally, we performed docking analysis to assess the impact of variations on drug interactions.
RESULTS
We identified 63 variants implicated in pain management. MDS analysis revealed that Mediterranean populations are genetically similar to Mexican populations and divergent from other populations. STRUCTURE analysis showed that Mediterranean populations are mainly composed of European ancestry. We highlighted differences in the minor allele frequencies of three variants (rs633, rs4680, and rs165728) located in the gene. Moreover, variant annotation revealed ten variants with potential miRNA-binding sites. Finally, protein structure and docking analysis revealed that two missense variants (rs4680 and rs6267) induced a decrease in COMT protein activity and affinity for dopamine.
CONCLUSION
Our findings revealed that Mediterranean populations diverge from other ethnic groups. Furthermore, we emphasize the importance of pain-related pathways and miRNAs to better implement these markers as predictors of analgesic responses in the Mediterranean region.
PubMed: 38813106
DOI: 10.3389/fphar.2024.1380613 -
IScience Jun 2024Interactions within the tumor microenvironment (TME) significantly influence tumor progression and treatment responses. While single-cell RNA sequencing (scRNA-seq) and...
Interactions within the tumor microenvironment (TME) significantly influence tumor progression and treatment responses. While single-cell RNA sequencing (scRNA-seq) and spatial genomics facilitate TME exploration, many clinical cohorts are assessed at the bulk tissue level. Integrating scRNA-seq and bulk tissue RNA-seq data through computational deconvolution is essential for obtaining clinically relevant insights. Our method, ProM, enables the examination of major and minor cell types. Through evaluation against existing methods using paired single-cell and bulk RNA sequencing of human urothelial cancer (UC) samples, ProM demonstrates superiority. Application to UC cohorts treated with immune checkpoint inhibitors reveals pre-treatment cellular features associated with poor outcomes, such as elevated SPP1 expression in macrophage/monocytes (MM). Our deconvolution method and paired single-cell and bulk tissue RNA-seq dataset contribute novel insights into TME heterogeneity and resistance to immune checkpoint blockade.
PubMed: 38812546
DOI: 10.1016/j.isci.2024.109928 -
Epidemiology and Health May 2024Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract...
OBJECTIVES
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to observe the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest versus lowest tertile [T3 vs. T1]=2.02; 95% CI, 1.41-2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR=0.62; 95% CI, 0.46-0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers=2.93; 95% CI, 1.77-4.87; and OR for the T3 of methylmercury and AC/CC genotype=1.30; 95% CI, 0.76-2.21; p-interaction=0.013).
CONCLUSION
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
PubMed: 38810984
DOI: 10.4178/epih.e2024051 -
Science Advances May 2024Increasing ethnic and racial diversity often fuels feelings of threat among ethnic-racial majorities (e.g., self-identified white Americans and European nationals). We...
Increasing ethnic and racial diversity often fuels feelings of threat among ethnic-racial majorities (e.g., self-identified white Americans and European nationals). We contend that these threat perceptions depend on the policy context. Across four studies, we test whether more inclusive immigrant integration policies attenuate ethnic-racial majorities' threat reactions. Studies 1 to 3 ( = 469, 733, and 1745, respectively) used experimental methods with white American participants in the United States. Study 4 ( = 499,075) used secondary analysis of survey data comparing attitudes of nationals in 30 European countries and measured the impact of actual changes in diversity and policies over 10 years. Our results show that integration policies shape threat reactions even in those situations when increasing diversity could be seen as the most threatening: when narratives highlight the majority's impending minority position or when diversity suddenly increases. When policies are more inclusive toward immigrants, ethnic-racial majority participants report less threat (or no threat) in response to increasing diversity.
Topics: Humans; Cultural Diversity; Ethnicity; United States; Male; Female; Emigrants and Immigrants; Adult; Attitude; White People; Racial Groups
PubMed: 38809972
DOI: 10.1126/sciadv.adk8556 -
Acta Dermatovenerologica Alpina,... May 2024Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the type VII collagen gene (COL7A1; 3p21.31). Mutations in this...
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the type VII collagen gene (COL7A1; 3p21.31). Mutations in this gene lead to an alteration in function or reduced amounts of collagen VII. This alteration of collagen VII leads to skin fragility and lesions at minor injuries with difficult healing. Cutaneous squamous cell carcinoma (cSCC) is more frequent in patients with RDEB than in the general population because of chronic wound formation; it constitutes a major cause of morbidity and is often cited as a cause of death for these patients. There is little experience with the treatment of cSCC in patients with RDEB. We report the case of a 19-year-old female patient with RDBE and inoperable locally advanced cSCC of the left arm. Because of the lack of therapy options, therapy with cemiplimab was started at a dose of 350 mg administered intravenously every 3 weeks. A confirmed clinical response was observed after the second cycle of treatment with no toxicity. During follow-up, the patient had a notable clinical response with no auto-immune adverse reactions. This shows that cemiplimab has a good safety profile for cSCC in patients with RDEB and is a valuable therapy option.
Topics: Humans; Epidermolysis Bullosa Dystrophica; Female; Skin Neoplasms; Carcinoma, Squamous Cell; Antibodies, Monoclonal, Humanized; Young Adult; Treatment Outcome; Antineoplastic Agents, Immunological
PubMed: 38808531
DOI: No ID Found -
Frontiers in Immunology 2024Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical...
BACKGROUND
Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors.
METHODS
Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.
RESULTS
GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of was distributed in endothelial cells. Cellular experiments demonstrated that facilitated the proliferation of GC cells.
CONCLUSION
This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.
Topics: Humans; Stomach Neoplasms; Manganese; Prognosis; Tumor Microenvironment; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Transcriptome; Gene Expression Profiling; Immunotherapy; Male; Female; Databases, Genetic
PubMed: 38807601
DOI: 10.3389/fimmu.2024.1377472 -
Frontiers in Immunology 2024L-carnitine, available as feed additive, is essential for the beta-oxidation of free fatty acids in the mitochondrial matrix. It provides energy to immune cells and may...
L-carnitine, available as feed additive, is essential for the beta-oxidation of free fatty acids in the mitochondrial matrix. It provides energy to immune cells and may positively impact the functionality of leukocytes during the acute phase response, a situation of high energy demand. To test this hypothesis, German Holstein cows were assigned to a control group (CON, n = 26) and an L-carnitine supplemented group (CAR, n = 27, rumen-protected L-carnitine product: 125 g/cow/d, corresponded to total L-carnitine intake: 25 g/cow/d, supplied with concentrate) and received an intravenous bolus injection of lipopolysaccharides (LPS, 0.5 µg/kg body weight, ) on day 111 as a model of standardized systemic inflammation. Blood samples were collected from day 1 until day 14 , with frequent sampling through an indwelling venous catheter from 0.5 h to 12 h . All parameters of the white blood cell count responded significantly to LPS, while only a few parameters were affected by L-carnitine supplementation. The mean eosinophil count, as well as the percentage of basophils were significantly higher in CAR than in CON over time, which may be due to an increased membrane stability. However, phagocytosis and production of reactive oxygen species by leukocytes remained unchanged following L-carnitine supplementation. In conclusion, although supplementation with 25 g L-carnitine per cow and day resulted in increased proportions of specific leukocyte populations, it had only minor effects on the functional parameters studied in mid-lactating dairy cows during LPS-induced inflammation, and there was no evidence of direct improvement of immune functionality.
Topics: Animals; Cattle; Lipopolysaccharides; Carnitine; Dietary Supplements; Female; Lactation; Inflammation; Leukocyte Count
PubMed: 38807585
DOI: 10.3389/fimmu.2024.1390137 -
Scientific Reports May 2024Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of...
Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Biomarkers, Tumor; Ligands; Male; Female; Middle Aged; Gene Expression Regulation, Neoplastic; Receptors, Immunologic; Interleukin-10; Macrophages; Multiomics
PubMed: 38806553
DOI: 10.1038/s41598-024-62668-x -
PLoS Genetics May 2024APOBEC-induced mutations occur in 50% of sequenced human tumors, with APOBEC3A (A3A) being a major contributor to mutagenesis in breast cancer cells. The mechanisms that...
APOBEC-induced mutations occur in 50% of sequenced human tumors, with APOBEC3A (A3A) being a major contributor to mutagenesis in breast cancer cells. The mechanisms that cause A3A activation and mutagenesis in breast cancers are still unknown. Here, we describe factors that influence basal A3A mRNA transcript levels in breast cancer cells. We found that basal A3A mRNA correlates with A3A protein levels and predicts the amount of APOBEC signature mutations in a panel of breast cancer cell lines, indicating that increased basal transcription may be one mechanism leading to breast cancer mutagenesis. We also show that alteration of ERBB2 expression can drive A3A mRNA levels, suggesting the enrichment of the APOBEC mutation signature in Her2-enriched breast cancer could in part result from elevated A3A transcription. Hierarchical clustering of transcripts in primary breast cancers determined that A3A mRNA was co-expressed with other genes functioning in viral restriction and interferon responses. However, reduction of STAT signaling via inhibitors or shRNA in breast cancer cell lines had only minor impact on A3A abundance. Analysis of single cell RNA-seq from primary tumors indicated that A3A mRNA was highest in infiltrating immune cells within the tumor, indicating that correlations of A3A with STAT signaling in primary tumors may be result from higher immune infiltrates and are not reflective of STAT signaling controlling A3A expression in breast cancer cells. Analysis of ATAC-seq data in multiple breast cancer cell lines identified two transcription factor sites in the APOBEC3A promoter region that could promote A3A transcription. We determined that Rel-A, and Bach1, which have binding sites in these peaks, elevated basal A3A expression. Our findings highlight a complex and variable set of transcriptional activators for A3A in breast cancer cells.
PubMed: 38805570
DOI: 10.1371/journal.pgen.1011293