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Asian Pacific Journal of Cancer... Jun 2024Breast cancer represents one of the leading causes of death worldwide. Apart from genetic factors, the sex hormone estrogen plays a pivotal role in breast cancer...
BACKGROUND
Breast cancer represents one of the leading causes of death worldwide. Apart from genetic factors, the sex hormone estrogen plays a pivotal role in breast cancer development. We are exposed to a plethora of estrogen mimics on a daily basis via various routes. Nevertheless, how xenoestrogens, the exogenous estrogen mimics, modulate cancer-associated signaling pathways and interact with specific genes is still underexplored. Hence, this study aims to explore the direct or indirect binding partners of xenoestrogens and their expression upon exposure to these estrogenic compounds.
METHODS
The collection of genes linked to the xenoestrogens Octylphenol, Nonylphenol, Bisphenol-A, and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane were gathered from the Comparative Toxicogenomics Database. Venny 2.1 was utilized to pinpoint the genes shared by these xenoestrogens. Subsequently, the shared genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resource. A xenoestrogen-protein interaction network was constructed using Search Tool for Interactions of Chemicals. The expressions of common genes were studied with the microarray dataset GSE5200 from the Gene Expression Omnibus database. Also, the expression of a common gene set within different breast cancer subtypes was identified using the University of California, Santa Cruz Xena.
RESULTS
The genes linked to xenoestrogens were identified, and 13 genes were found to interact with all four xenoestrogens. Through DAVID analysis, the genes chosen are found to be enriched for various functions and pathways, including pathways in cancer, chemical carcinogenesis-receptor activation, and estrogen signaling pathways. The results of the Comparative Toxicogenomics Database and the chemical-protein interaction network derived from STITCH were similar. Microarray data analysis showed significantly high expression of all 13 genes in another study, with Bisphenol-A and Nonylphenol treated MCF-7 cells, most of the genes are expressed in luminal A or basal breast cancer subtype.
CONCLUSION
In summary, the genes associated with the four xenoestrogens were mostly linked to pathways related to tumorigenesis, and the expression of these genes was found to be higher in breast cancer.
Topics: Humans; Breast Neoplasms; Estrogens; Female; Computational Biology; Computer Simulation; Protein Interaction Maps; Signal Transduction; Gene Expression Regulation, Neoplastic; Benzhydryl Compounds
PubMed: 38918670
DOI: 10.31557/APJCP.2024.25.6.2077 -
Asian Pacific Journal of Cancer... Jun 2024The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors.
METHODS
We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial.
CONCLUSION
2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.
Topics: Humans; Metformin; Curcumin; Head and Neck Neoplasms; Double-Blind Method; Neoplasms, Second Primary; Male; Female; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Adult; Follow-Up Studies; Prognosis; Research Design; Aged; Randomized Controlled Trials as Topic
PubMed: 38918654
DOI: 10.31557/APJCP.2024.25.6.1935 -
EBioMedicine Jun 2024Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support...
BACKGROUND
Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.
METHODS
Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses.
FINDINGS
For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses.
INTERPRETATION
An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses.
FUNDING
This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.
PubMed: 38917512
DOI: 10.1016/j.ebiom.2024.105221 -
JMIR Formative Research Jun 2024Meaning in life is positively associated with health, well-being, and longevity, which may be partially explained by engagement in healthier behaviors, including...
BACKGROUND
Meaning in life is positively associated with health, well-being, and longevity, which may be partially explained by engagement in healthier behaviors, including physical activity (PA). However, promoting awareness of meaning is a behavior change strategy that has not been tested in previous PA interventions.
OBJECTIVE
This study aims to develop, refine, and pilot-test the Meaningful Activity Program (MAP; MAP to Health), a web-based mobile health PA intervention, theoretically grounded in meaning and self-determination theory, for insufficiently active middle-aged adults.
METHODS
Following an iterative user-testing and refinement phase, we used a single-arm double baseline proof-of-concept pilot trial design. Participants included 35 insufficiently active adults in midlife (aged 40-64 years) interested in increasing their PA. After a 4-week baseline period, participants engaged in MAP to Health for 8 weeks. MAP to Health used a web-based assessment and just-in-time SMS text messaging to individualize the intervention; promote meaning salience; support the basic psychological needs of autonomy, competence, and relatedness; and increase PA. Participants completed measures of the hypothesized mechanisms of behavior change, including meaning salience, needs satisfaction, and autonomous motivation at pretest (-4 weeks), baseline (0 weeks), midpoint (4 weeks), and posttest (8 weeks) time points, and wore accelerometers for the study duration. At the end of the intervention, participants completed a qualitative interview. Mixed models compared changes in behavioral mechanisms during the intervention to changes before the intervention. Framework matrix analyses were used to analyze qualitative data.
RESULTS
Participants were aged 50.8 (SD 8.2) years on average; predominantly female (27/35, 77%); and 20% (7/35) Asian, 9% (3/35) Black or African American, 66% (23/35) White, and 6% (2/35) other race. Most (32/35, 91%) used MAP to Health for ≥5 of 8 weeks. Participants rated the intervention as easy to use (mean 4.3, SD 0.8 [out of 5.0]) and useful (mean 4.3, SD 0.6). None of the hypothesized mechanisms changed significantly during the preintervention phase (Cohen d values <0.15). However, autonomy (P<.001; Cohen d=0.76), competence (P<.001; Cohen d=0.65), relatedness (P=.004; Cohen d=0.46), autonomous motivation (P<.001; Cohen d=0.37), and meaning salience (P<.001; Cohen d=0.40) increased significantly during the intervention. Comparison of slopes before the intervention versus during the intervention revealed that increases during the intervention were significantly greater for autonomy (P=.002), competence (P<.001), and meaning salience (P=.001); however, slopes were not significantly different for relatedness (P=.10) and autonomous motivation (P=.17). Qualitative themes offered suggestions for improvement.
CONCLUSIONS
MAP to Health was acceptable to participants, feasible to deliver, and associated with increases in the target mechanisms of behavior change. This is the first intervention to use meaning as a behavior change strategy in a PA intervention. Future research will test the efficacy of the intervention in increasing PA compared to a control condition.
PubMed: 38917457
DOI: 10.2196/55722 -
PloS One 2024The aim of this research was to evaluate the incidence of congenital syphilis and the ratio between congenital syphilis and syphilis in pregnant women in Brazil...
The aim of this research was to evaluate the incidence of congenital syphilis and the ratio between congenital syphilis and syphilis in pregnant women in Brazil according to socioeconomic indicators (inadequate water supply and sanitation; illiteracy at 15 years of age or older; household income per capita; proportion of poor people; Gini index; human development index; and average health expenditure per inhabitant by the health system) and prenatal quality-of-care indicators. We conducted an ecological study using a sample composed of 257 municipalities, each with ≥ 100,000 inhabitants. Data was collected from four public databases: the Brazilian Institute of Geography and Statistics, comprising socioeconomical data from the 2010 census; and the data of 2019 available in the databases of the Department of Informatics of the Brazilian Health System, Information and Management of Primary Care, and the Electronic Citizen Information System. Descriptive analysis of dependent and independent variables and bivariate analysis by Negative Binomial regression were carried out. The mean incidence of congenital syphilis was 38% higher in municipalities with a Human Development Index up to 0.785 (ratio of means [RM] = 1.38; p = 0.049) and 57% higher among populations where less than 50% of primary healthcare services provided a rapid test for syphilis (RM = 1.57; p < 0.001). The ratio between congenital syphilis and syphilis in pregnant women was 29% higher in municipalities with a low household income per capita (RM = 1.29; p < 0.001) and 28% higher in locations where less than 50% of the primary healthcare services provided a rapid test for syphilis (RM = 1.28; p < 0.001). There was no statistical significance of the quality of prenatal care compared to the outcomes. This result underscores the challenges in detecting syphilis infections among pregnant women during prenatal care, consequently increasing the risk of vertical transmission of the disease to the fetus. Traits of inequality in the occurrence of congenital syphilis also draw attention to strategies to reduce health inequities and improve prenatal care.
Topics: Humans; Pregnancy; Female; Brazil; Syphilis, Congenital; Prenatal Care; Pregnancy Complications, Infectious; Incidence; Adult; Socioeconomic Factors; Syphilis; Adolescent; Young Adult
PubMed: 38917233
DOI: 10.1371/journal.pone.0306120 -
PloS One 2024This study aims to enhance the post-training evaluation of the annual performance agreement (APA) training organized by the Bangladesh Public Administration Training...
This study aims to enhance the post-training evaluation of the annual performance agreement (APA) training organized by the Bangladesh Public Administration Training Centre (BPATC), the apex training institute for civil servants. Utilizing fuzzy-set qualitative comparative analysis (fsQCA) and artificial neural network (ANN) techniques within Kirkpatrick's four-stage model framework, data were collected from a self-administered questionnaire survey of 71 in-service civil servants who participated in the APA training program. This study employs an asymmetric, non-linear model analyzed through a configurational approach and ANN to explore interrelationships among the four Kirkpatrick levels namely, reaction, learning, behavior, and results. Findings indicate that trainees were satisfied across all levels, identifying a non-linear relationship among these levels in post-training evaluation process. The research highlights that "learning skills" are most significant in the APA post-training evaluation, followed by behavior, results, and reaction. Theoretically, this research advances Kirkpatrick's model and adds to the literature on public service post-training evaluation. Practically, it recommends prioritizing strategies that address cognitive barriers to enhance training effectiveness. This study's innovative approach lies in its concurrent use of fsQCA and ANN methods to analyze the success or failure of APA-related trainees, offering alternative pathways to desired outcomes and contrasting traditional quantitative methods that provide a single solution. The findings have practical implications for public service training institutions and bureaucratic policymakers involved in capacity development, guiding the creation of more effective in-service training courses for public officials. The methodology and analysis can be applied in other contexts, allowing bureaucratic policymakers to replicate these findings in their learning institutes to identify unique configurations that lead to successful or unsuccessful training outcomes, adopt effective strategies, and avoid detrimental ones.
Topics: Humans; Neural Networks, Computer; Bangladesh; Surveys and Questionnaires; Male; Female; Adult; Learning
PubMed: 38917194
DOI: 10.1371/journal.pone.0305916 -
PloS One 2024Young calves are more susceptible to cold than older animals due to their limited ability to regulate body temperature and lack of fat reserves and may have difficulty...
Young calves are more susceptible to cold than older animals due to their limited ability to regulate body temperature and lack of fat reserves and may have difficulty consuming the energy needed to cope with the cold by maintaining body temperature and meeting their metabolic needs, especially when fed constant levels of waste milk (WM) with less solids, which can be detrimental to health and future performance. An alternative to overcome this problem is increasing the milk's solids content to the existing volume by using different sources [milk replacer powder (MR) or transition milk (TM)]. Thus, we aimed to evaluate the effects of increasing the total solids of WM via MR (WM+MR) or TM (WM+TM) on the performance, feeding behavior, and health-related variables of cold-stressed dairy calves during pre- and post-weaning. We hypothesized that feeding WM supplemented with MR or TM as potential liquid feed enhancers would improve milk dry matter and energy intake of the calves with a positive impact on body development and have no negative impact on feeding behavior and health. Additionally, we hypothesized that MR would not differ from TM. As a sample size calculation at 80% power using power analysis (PROC POWER) in SAS 9.4, a total of 51 Holstein-Friesian vigorous male calves [vigor score 21-27; 17 per treatment; 4-d old; body weight (BW) = 40.0 ± 0.63 kg (mean ± SD)] were selected, assigned randomly to treatments, and housed in individual pens in an outdoor barn. Irrespective of the type of treatment, all calves were fed 6 kg/d liquid feed from d 1 to d 53 of the experiment. In a step-down weaning program, calves received 0.5 kg liquid feed from d 54 to d 60. All calves were weaned on d 61 and remained in the study until d 101 as post-weaning evaluation. The calves had ad libitum access to starter feed and fresh drinking water across the experiment. Intake, growth, and behavior data were analyzed using a general linear mixed model and health data were analyzed using mixed logistic regression, mixed linear regression, and survival analysis models in SAS. We found that supplementation was responsible for a greater dry matter intake (DMI; P = 0.004), superior average BW (P = 0.037), and increased crude protein (CP; P = 0.001) and crude fat (CF; P = 0.001) intakes, with the most favorable outcomes observed for the WM+TM group when compared with WM+MR. Animals fed WM (control group; CON) showed a smaller average daily gain during the first 40-d of life (P = 0.026), showing slight changes during the whole period of evaluation when compared with the supplemented groups (SUP; WM+MR and WM+TM). No difference between MR- and TM-SUP groups, probability of having abnormal appearance (P = 0.032) and pneumonia occurrence (P = 0.022) was reduced in the SUP than in CON animals, with no effect on diarrhea among treatment groups (P = 0.461). Using milk supplements added to WM is an alternative to improve the intake, performance, and health of young calves under cold stress. Our findings showed that SUP animals outperformed the CON group in terms of DMI, average BW, and intake of CP and CF, with the TM-SUP group displaying the most favorable outcomes. Moreover, the SUP groups demonstrated reduced odds of experiencing abnormal appearance and pneumonia, highlighting the positive impact of supplementation on calf health.
Topics: Animals; Cattle; Milk; Animal Feed; Feeding Behavior; Dietary Supplements; Animals, Newborn; Cold Temperature; Weaning; Female; Male; Milk Substitutes; Powders
PubMed: 38917166
DOI: 10.1371/journal.pone.0305227 -
PloS One 2024Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have...
Study protocol for the development and validation of a questionnaire evaluating predisposition to immunosuppressant medication non-adherence of kidney pre-transplant patients. The KATITA project.
Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.
Topics: Humans; Kidney Transplantation; Immunosuppressive Agents; Surveys and Questionnaires; Medication Adherence; Prospective Studies; Reproducibility of Results; Graft Rejection; Pilot Projects; Female; Male
PubMed: 38917103
DOI: 10.1371/journal.pone.0305953 -
PloS One 2024Early life adversity (ELA) increases the likelihood of later-life neuropsychiatric disorders and cognitive dysfunction. Importantly, ELA, neuropsychiatric disorders, and...
Early life adversity (ELA) increases the likelihood of later-life neuropsychiatric disorders and cognitive dysfunction. Importantly, ELA, neuropsychiatric disorders, and cognitive deficits all involve aberrant immune signaling. Microglia are the primary neuroimmune cells and regulate brain development. Microglia are particularly sensitive to early life insults, which can program their responses to future challenges. ELA in the form of maternal separation (MS) in rats alters later-life microglial morphology and the inflammatory profile of the prefrontal cortex, a region important for cognition. However, the role of microglial responses during MS in the development of later cognition is not known. Therefore, here we aimed to determine whether the presence of microglia during MS mediates long-term impacts on adult working memory. Clodronate liposomes were used to transiently deplete microglia from the brain, while empty liposomes were used as a control. We hypothesized that if microglia mediate the long-term impacts of ELA on working memory in adulthood, then depleting microglia during MS would prevent these deficits. Importantly, microglial function shifts throughout the neonatal period, so an exploratory investigation assessed whether depletion during the early versus late neonatal period had different effects on adult working memory. Surprisingly, empty liposome treatment during the early, but not late, postnatal period induced microglial activity changes that compounded with MS to impair working memory in females. In contrast, microglial depletion later in infancy impaired later life working memory in females, suggesting that microglial function during late infancy plays an important role in the development of cognitive function. Together, these findings suggest that microglia shift their sensitivity to early life insults across development. Our findings also highlight the potential for MS to impact some developmental processes only when compounded with additional neuroimmune challenges in a sex-dependent manner.
Topics: Animals; Microglia; Female; Maternal Deprivation; Rats; Male; Cognition; Memory, Short-Term; Animals, Newborn; Prefrontal Cortex; Rats, Sprague-Dawley; Age Factors
PubMed: 38917075
DOI: 10.1371/journal.pone.0306022 -
PloS One 2024The propensity to accept vaccines and factors that affect vaccine acceptance and hesitancy will determine the overall success of the COVID-19 vaccination program....
The propensity to accept vaccines and factors that affect vaccine acceptance and hesitancy will determine the overall success of the COVID-19 vaccination program. Therefore, countries need to understand the factors that influence vaccine acceptance and hesitancy to prevent further future shocks, and it is necessary to have a thorough understanding of these factors. As a result, this study aims to review selected published works in the study's domain and conduct valuable analysis to determine the most influential factors in COVID-19 vaccine acceptance and hesitancy in Ghana. The review also explored the acceptance rate of COVID-19 vaccines in Ghana. We selected published works from 2021 to April 2023 and extracted, analyzed, and summarized the findings based on the key factors that influence COVID-19 vaccine acceptance and hesitancy in Ghana, the acceptance rate in Ghana, the demographic factors that are often examined, and the study approach used to examine these factors. The study found that positive vaccination perception, safety, belief in vaccine efficacy, knowledge of COVID-19, and a good vaccine attitude influence COVID-19 vaccine acceptance in Ghana. The negative side effects of the vaccines, mistrust in the vaccine, lack of confidence in the vaccine's safety, fear, and spiritual and religious beliefs all played significant roles in influencing COVID-19 vaccine hesitancy. For this study, the COVID-19 acceptance rates observed in the reviewed articles ranged from 17.5% to 82.6%. The demographic parameters frequently included in these studies that have a significant impact include educational attainment, gender, religious affiliation, age, and marital status. The positive perceptions of the COVID-19 vaccine and concerns about its negative effects influenced Ghanaians' acceptance and hesitancy.
Topics: Humans; Ghana; COVID-19 Vaccines; COVID-19; Vaccination Hesitancy; Patient Acceptance of Health Care; Vaccination; SARS-CoV-2; Health Knowledge, Attitudes, Practice
PubMed: 38917063
DOI: 10.1371/journal.pone.0305993