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Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis

Eur J Microbiol Immunol (Bp). 2024 Mar 12. doi: 10.1556/1886.2024.00015. Online ahead of print.

ABSTRACT

INTRODUCTION: APC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment.

METHODS: Clinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan-Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman’s correlation analysis.

RESULTS: APC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman’s analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+.

CONCLUSIONS: APC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.

PMID:38470482 | DOI:10.1556/1886.2024.00015

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Improving Quality of ICD-10 (International Statistical Classification of Diseases, Tenth Revision) Coding Using AI: Protocol for a Crossover Randomized Controlled Trial

JMIR Res Protoc. 2024 Mar 12;13:e54593. doi: 10.2196/54593.

ABSTRACT

BACKGROUND: Computer-assisted clinical coding (CAC) tools are designed to help clinical coders assign standardized codes, such as the ICD-10 (International Statistical Classification of Diseases, Tenth Revision), to clinical texts, such as discharge summaries. Maintaining the integrity of these standardized codes is important both for the functioning of health systems and for ensuring data used for secondary purposes are of high quality. Clinical coding is an error-prone cumbersome task, and the complexity of modern classification systems such as the ICD-11 (International Classification of Diseases, Eleventh Revision) presents significant barriers to implementation. To date, there have only been a few user studies; therefore, our understanding is still limited regarding the role CAC systems can play in reducing the burden of coding and improving the overall quality of coding.

OBJECTIVE: The objective of the user study is to generate both qualitative and quantitative data for measuring the usefulness of a CAC system, Easy-ICD, that was developed for recommending ICD-10 codes. Specifically, our goal is to assess whether our tool can reduce the burden on clinical coders and also improve coding quality.

METHODS: The user study is based on a crossover randomized controlled trial study design, where we measure the performance of clinical coders when they use our CAC tool versus when they do not. Performance is measured by the time it takes them to assign codes to both simple and complex clinical texts as well as the coding quality, that is, the accuracy of code assignment.

RESULTS: We expect the study to provide us with a measurement of the effectiveness of the CAC system compared to manual coding processes, both in terms of time use and coding quality. Positive outcomes from this study will imply that CAC tools hold the potential to reduce the burden on health care staff and will have major implications for the adoption of artificial intelligence-based CAC innovations to improve coding practice. Expected results to be published summer 2024.

CONCLUSIONS: The planned user study promises a greater understanding of the impact CAC systems might have on clinical coding in real-life settings, especially with regard to coding time and quality. Further, the study may add new insights on how to meaningfully exploit current clinical text mining capabilities, with a view to reducing the burden on clinical coders, thus lowering the barriers and paving a more sustainable path to the adoption of modern coding systems, such as the new ICD-11.

TRIAL REGISTRATION: clinicaltrials.gov NCT06286865; https://clinicaltrials.gov/study/NCT06286865.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54593.

PMID:38470476 | DOI:10.2196/54593

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Feasibility Study on Menstrual Cycles With Fitbit Device (FEMFIT): Prospective Observational Cohort Study

JMIR Mhealth Uhealth. 2024 Mar 12;12:e50135. doi: 10.2196/50135.

ABSTRACT

BACKGROUND: Despite its importance to women’s reproductive health and its impact on women’s daily lives, the menstrual cycle, its regulation, and its impact on health remain poorly understood. As conventional clinical trials rely on infrequent in-person assessments, digital studies with wearable devices enable the collection of longitudinal subjective and objective measures.

OBJECTIVE: The study aims to explore the technical feasibility of collecting combined wearable and digital questionnaire data and its potential for gaining biological insights into the menstrual cycle.

METHODS: This prospective observational cohort study was conducted online over 12 weeks. A total of 42 cisgender women were recruited by their local gynecologist in Berlin, Germany, and given a Fitbit Inspire 2 device and access to a study app with digital questionnaires. Statistical analysis included descriptive statistics on user behavior and retention, as well as a comparative analysis of symptoms from the digital questionnaires with metrics from the sensor devices at different phases of the menstrual cycle.

RESULTS: The average time spent in the study was 63.3 (SD 33.0) days with 9 of the 42 individuals dropping out within 2 weeks of the start of the study. We collected partial data from 114 ovulatory cycles, encompassing 33 participants, and obtained complete data from a total of 50 cycles. Participants reported a total of 2468 symptoms in the daily questionnaires administered during the luteal phase and menses. Despite difficulties with data completeness, the combined questionnaire and sensor data collection was technically feasible and provided interesting biological insights. We observed an increased heart rate in the mid and end luteal phase compared with menses and participants with severe premenstrual syndrome walked substantially fewer steps (average daily steps 10,283, SD 6277) during the luteal phase and menses compared with participants with no or low premenstrual syndrome (mean 11,694, SD 6458).

CONCLUSIONS: We demonstrate the feasibility of using an app-based approach to collect combined wearable device and questionnaire data on menstrual cycles. Dropouts in the early weeks of the study indicated that engagement efforts would need to be improved for larger studies. Despite the challenges of collecting wearable data on consecutive days, the data collected provided valuable biological insights, suggesting that the use of questionnaires in conjunction with wearable data may provide a more complete understanding of the menstrual cycle and its impact on daily life. The biological findings should motivate further research into understanding the relationship between the menstrual cycle and objective physiological measurements from sensor devices.

PMID:38470472 | DOI:10.2196/50135

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Effects of a Social Media Intervention on Vaping Intentions: Randomized Dose-Response Experiment

J Med Internet Res. 2024 Mar 12;26:e50741. doi: 10.2196/50741.

ABSTRACT

BACKGROUND: e-Cigarette use, especially by young adults, is at unacceptably high levels and represents a public health risk factor. Digital media are increasingly being used to deliver antivaping campaigns, but little is known about their effectiveness or the dose-response effects of content delivery.

OBJECTIVE: The objectives of this study were to evaluate (1) the effectiveness of a 60-day antivaping social media intervention in changing vaping use intentions and beliefs related to the stimulus content and (2) the dose-response effects of varying levels of exposure to the intervention on vaping outcomes, including anti-industry beliefs, vaping intentions, and other attitudes and beliefs related to vaping.

METHODS: Participants were adults aged 18 to 24 years in the United States. They were recruited into the study through Facebook (Meta Platforms) and Instagram (Meta Platforms), completed a baseline survey, and then randomized to 1 of the 5 conditions: 0 (control), 4, 8, 16, and 32 exposures over a 15-day period between each survey wave. Follow-up data were collected 30 and 60 days after randomization. We conducted stratified analyses of the full sample and in subsamples defined by the baseline vaping status (never, former, and current). Stimulus was delivered through Facebook and Instagram in four 15-second social media videos focused on anti-industry beliefs about vaping. The main outcome measures reported in this study were self-reported exposure to social media intervention content, attitudes and beliefs about vaping, and vaping intentions. We estimated a series of multivariate linear regressions in Stata 17 (StataCorp). To capture the dose-response effect, we assigned each study arm a numerical value corresponding to the number of advertisements (exposures) delivered to participants in each arm and used this number as our focal independent variable. In each model, the predictor was the treatment arm to which each participant was assigned.

RESULTS: The baseline sample consisted of 1491 participants, and the final analysis sample consisted of 57.28% (854/1491) of the participants retained at the 60-day follow-up. We compared the retained participants with those lost to follow-up and found no statistically significant differences across demographic variables. We found a significant effect of the social media treatment on vaping intentions (β=-0.138, 95% CI -0.266 to -0.010; P=.04) and anti-industry beliefs (β=-0.122, 95% CI 0.008-0.237; P=.04) targeted by the intervention content among current vapers but not among the full sample or other strata. We found no significant effects of self-reported exposure to the stimulus.

CONCLUSIONS: Social media interventions are a promising approach to preventing vaping among young adults. More research is needed on how to optimize the dosage of such interventions and the extent to which long-term exposure may affect vaping use over time.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04867668; https://clinicaltrials.gov/study/NCT04867668.

PMID:38470468 | DOI:10.2196/50741

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Usability and Acceptability of a Conversational Agent Health Education App (Nthabi) for Young Women in Lesotho: Quantitative Study

JMIR Hum Factors. 2024 Mar 12;11:e52048. doi: 10.2196/52048.

ABSTRACT

BACKGROUND: Young women in Lesotho face myriad sexual and reproductive health problems. There is little time to provide health education to women in low-resource settings with critical shortages of human resources for health.

OBJECTIVE: This study aims to determine the acceptability and usability of a conversational agent system, the Nthabi health promotion app, which was culturally adapted for use in Lesotho.

METHODS: We conducted a descriptive quantitative study, using a 22-item Likert scale survey to assess the perceptions of the usability and acceptability of 172 young women aged 18-28 years in rural districts of Lesotho, who used the system on either smartphones or tablets for up to 6 weeks. Descriptive statistics were used to calculate the averages and frequencies of the variables. χ2 tests were used to determine any associations among variables.

RESULTS: A total of 138 participants were enrolled and completed the survey. The mean age was 22 years, most were unmarried, 56 (40.6%) participants had completed high school, 39 (28.3%) participants were unemployed, and 88 (63.8%) participants were students. Respondents believed the app was helpful, with 134 (97.1%) participants strongly agreeing or agreeing that the app was “effective in helping them make decisions” and “could quickly improve health education and counselling.” In addition, 136 (98.5%) participants strongly agreed or agreed that the app was “simple to use,” 130 (94.2 %) participants reported that Nthabi could “easily repeat words that were not well understood,” and 128 (92.7%) participants reported that the app “could quickly load the information on the screen.” Respondents were generally satisfied with the app, with 132 (95.6%) participants strongly agreeing or agreeing that the health education content delivered by the app was “well organised and delivered in a timely way,” while 133 (96.4%) participants “enjoyed using the interface.” They were satisfied with the cultural adaptation, with 133 (96.4%) participants strongly agreeing or agreeing that the app was “culturally appropriate and that it could be easily shared with a family or community members.” They also reported that Nthabi was worthwhile, with 127 (92%) participants reporting that they strongly agreed or agreed that they were “satisfied with the application and intended to continue using it,” while 135 (97.8%) participants would “encourage others to use it.” Participants aged 18-24 years (vs those aged 25-28 years) agreed that the “Nthabi app was simple to use” (106/106, 100% vs 30/32, 98.8%; P=.01), and agreed that “the educational content was well organised and delivered in a timely way” (104/106, 98.1% vs 28/32, 87.5%; P=.01).

CONCLUSIONS: These results support further study of conversational agent systems as alternatives to traditional face-to-face provision of health education services in Lesotho, where there are critical shortages of human resources for health.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04354168; https://www.clinicaltrials.gov/study/NCT04354168.

PMID:38470460 | DOI:10.2196/52048

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The changing landscape of small cell lung cancer

Cancer. 2024 Mar 12. doi: 10.1002/cncr.35281. Online ahead of print.

ABSTRACT

BACKGROUND: Small-cell lung cancer (SCLC) is characterized by rapid proliferation and early dissemination. The objective of this study was to examine the demographic trends and outcomes in SCLC.

METHODS: The authors queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results database to assess the trends in incidence, demographics, staging, and survival for SCLC from 1975 to 2019. Trends were determined using joinpoint analysis according to the year of diagnosis.

RESULTS: Among the 530,198 patients with lung cancer, there were 73,362 (13.8%) with SCLC. The incidence per 100,000 population peaked at 15.3 in 1986 followed by a decline to 6.5 in 2019. The percentage of SCLC among all lung tumors increased from 13.3% in 1975 to a peak of 17.5% in 1986, declining to 11.1% by 2019. There was an increased median age at diagnosis from 63 to 69 years and an increased percentage of women from 31.4% to 51.2%. The percentage of stage IV increased from 58.6% in 1988 to 70.8% in 2010, without further increase. The most common sites of metastasis at diagnosis were mediastinal lymph nodes (75.3%) liver (31.6%), bone (23.7%), and brain (16.4%). The 1-year and 5-year overall survival rate increased from 23% and 3.6%, respectively, in 1975-1979 to 30.8% and 6.8%, respectively, in 2010-2019.

CONCLUSIONS: The incidence of SCLC peaked in 1988 followed by a gradual decline. Other notable changes include increased median age at diagnosis, the percentage of women, and the percentage of stage IV at diagnosis. The improvement in 5-year overall survival has been statistically significant but clinically modest.

PMID:38470453 | DOI:10.1002/cncr.35281

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The role of epigenetic mechanisms in the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring in laboratory rats and mice

Dev Psychobiol. 2024 Apr;66(3):e22479. doi: 10.1002/dev.22479.

ABSTRACT

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of this review is dedicated to pharmacological interventions and epigenetic editing as tools for studying the causal role of epigenetic mechanisms in the development of physiological and behavioral profiles. A special section of the manuscript will discuss the translational potential of the discussed research.

PMID:38470450 | DOI:10.1002/dev.22479

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Effects of Coriander on the Repair Process of Experimentally-induced Periodontitis in Rats

J Vet Dent. 2024 Mar 12:8987564241232862. doi: 10.1177/08987564241232862. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the effects of Coriandrum sativum L. (CSL) seed extract on gingival levels of antioxidant enzymes, pro-inflammatory cytokines and on alveolar bone and attachment levels after experimental periodontitis induction in rats and compare it with low-dose doxycycline (LDD). Forty adult male Wistar Albino rats were divided randomly into 5 groups as follows: 1 = periodontally healthy (control); 2 = periodontitis; 3 = periodontitis + CSL (32 mg/kg); 4 = periodontitis + CSL (200 mg/kg); and 5 = periodontitis + LDD (6 mg/kg). Gingival superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) levels were evaluated by enzyme-linked immunosorbent assay. The presence of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1βeta (IL-1β) immunoreactivity was detected immunohistochemically. Alveolar bone area in the furcation space (ABA), alveolar bone loss (ABL), and attachment loss (AL) were evaluated histomorphometrically. The SOD level was lower in group 5 than in groups 2, 3, and 4. The IL-1β level was highest in group 4. The TNF-α level was statistically higher in groups 2 and 4 than in groups 1, 3, and 5. The IL-6 level was highest in group 4. Its level was higher in groups 2 and 3 than in group 5. ABA was less in groups 2, 3, and 4 compared to groups 1 and 5. ABL was less in group 5 than in groups 2, 3, and 4. AL was greater in group 4 than in group 5. The use of 200 mg/kg CSL showed a pro-inflammatory effect and IL-1β and TNF-α levels decreased after 32 mg/kg CSL application in the treatment of periodontitis.

PMID:38470443 | DOI:10.1177/08987564241232862

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Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US

JAMA Netw Open. 2024 Mar 4;7(3):e240555. doi: 10.1001/jamanetworkopen.2024.0555.

ABSTRACT

IMPORTANCE: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives.

OBJECTIVE: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children’s hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded.

EXPOSURE: Any opioid exposure and methadone treatment.

MAIN OUTCOMES AND MEASURES: Regional and institutional variations in opioid exposure.

RESULTS: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

PMID:38470421 | DOI:10.1001/jamanetworkopen.2024.0555

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Health Professional vs Layperson Values and Preferences on Scarce Resource Allocation

JAMA Netw Open. 2024 Mar 4;7(3):e241958. doi: 10.1001/jamanetworkopen.2024.1958.

ABSTRACT

IMPORTANCE: COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems’ ability to provide critical care. While SRA policies follow general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical.

OBJECTIVE: To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC).

DESIGN, SETTING, AND PARTICIPANTS: This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants’ values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024.

MAIN OUTCOMES AND MEASURES: Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis.

RESULTS: A total of 1545 participants aged older than 18 years (mean [SD] age 49 [16] years; 1149 female participants [74%], 478 health care practitioners [30%]) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items.

CONCLUSIONS AND RELEVANCE: This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.

PMID:38470416 | DOI:10.1001/jamanetworkopen.2024.1958