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Mother-child autonomic nervous system interaction as an indication of parental stress: 24-hour cross recurrence plot analysis
Mothers and children interact through behaviors and mutual physiological signals. Recent research has suggested that physiological interactions are sensitive biomarkers for parenting challenges such as childcare stress. Most studies have focused on short-term, activity-based interactions. However, few studies have examined longer timescale data, such as interactions containing circadian rhythms, which are closely associated with stress. This study aimed to explore the link between childcare stress and mother-child autonomic nervous system activities in daily interactions using 24-hour at-home data. Cross-recurrence plots were used to quantify interactive patterns to reflect the rich nonlinear dynamics of autonomic nervous system signals and the complex interplay between mothers and children. The relationships between quantified low-dimensional cross-recurrence plot representations and parenting stress were evaluated through multiple regression analysis. The cross-recurrence plots effectively quantified complex, nonlinear, day-to-night interactions of mother-child autonomous nervous system activities and significantly predicted maternal parenting stress, offering novel insights into daily parental stress dynamics beyond recurrence plots that merely quantify the activities from individual systems.
Comparison of laparoscopic tubal-preserving surgical management versus methotrexate therapy for tubal pregnancy: A conventional and network meta-analysis
Background Tubal pregnancy is one of the common emergencies in obstetrics and gynecology. There are various treatment options for tubal pregnancy. However, there is no consensus on how patients should choose among the treatment options that preserve the fallopian tube. This study aims to investigate the difference in prognosis between different treatment options when the tube is preserved in patients with tubal pregnancy. Methods We conducted a search for studies on tubal pregnancy in the PubMed, EMBASE, Web of Science, and Cochrane Library databases. Ultimately, we obtained 8 studies that met the screening criteria. The Jadad scale and NOS were used to evaluate the quality of the studies, and the evidence quality was evaluated and graded according to GRADE guidelines. Stata 17.0 software was used for data analysis. Result A total of 8 studies involving 677 patients were included. Meta-analysis revealed a significant overall difference in the failure rate between methotrexate treatment and salpingostomy for tubal pregnancy(OR=1.582, 95%CI(1.062, 2.358), p = 0.024). Subgroup analysis demonstrated that a single dose of methotrexate was associated with a higher failure rate compared to salpingostomy(OR = 2.044,95%CI(1.20, 3.47), p = 0.008). In contrast, two or more doses of methotrexate did not show a significant difference in failure rate compared to salpingostomy(OR = 1.130, 95% CI(0.62, 2.07), p = 0.692). However, salpingostomy combined with methotrexate showed a lower failure rate compared to salpingostomy alone(OR = 0.11, 95% CI (0.03–0.48), p = 0.003). Network meta-analysis indicated that the salpingostomy combined with methotrexate had the lowest failure rate, while there was no significant difference in failure rates between salpingostomy and methotrexate alone. Conclusion For hemodynamically stable patients with a desire for future fertility, salpingostomy combined with methotrexate is an excellent option for treating tubal pregnancy. This approach has a lower failure rate compared to either methotrexate or salpingostomy alone and appears to have minimal impact on the patient’s quality of life.
Effects of survey administration mode on response profiles are predictable, and robust across countries: Evidence from 29 countries using machine-learning models
Survey data collection can be administered in different modes, including face-to-face interviews and self-completion modes such as paper-and-pencil or web-based surveys. Do data collected in these different modes reliably differ across countries? We address this question using responses from 145,361 respondents in 29 countries to 46 questions in Rounds 8–10 of the European Social Survey (ESS), a large-scale social research project that conducts cross-national surveys in Europe and whose data has been used in thousands of publications. The ESS is typically administered in face-to-face interviews, but due to the COVID-19 pandemic data from nine countries in the tenth round were collected using self-completion methods. In line with previous findings demonstrating differences between administration modes, we show that machine-learning models can predict how surveys were administered, suggesting that data collected in the different modes are not comparable. More critically, we show that even when these models are trained on data from a set of countries, they can predict how surveys were administered in a completely novel country, which indicates that responses in different administration modes reliably differ across countries. Finally, we investigate extreme response styles as one difference in the response profiles of the two different modes. In addition to addressing concerns of data comparability in the ESS, these findings reveal that administration modes of surveys lead to reliable cross-national differences in response profiles.
Meaning in life, positive cognition, and learning motivation: A mediational analysis among Chinese college students
Background While a sense of meaning in life is known to boost students' learning motivation, the psychological process explaining how this happens is not well understood. This study investigated whether positive thinking (positive cognition) acts as the crucial bridge connecting these two. Methods We conducted a survey with 345 university students in Chongqing, China. They completed questionnaires measuring their sense of meaning in life (both the search for meaning and the feeling of having it), their tendency for positive thinking, and their motivation for learning (both for internal satisfaction and external rewards). Results We found a clear link: students with a stronger sense of life meaning also reported higher levels of positive thinking and greater learning motivation. More importantly, positive thinking was a key pathway. A students' sense of life meaning appeared to first nurture a more positive mindset, and this positive mindset, in turn, was what fueled their motivation to learn. This effect was particularly strong for intrinsic motivation (learning for the love of it). For extrinsic motivation (learning for rewards), positive thinking was also a vital link, sometimes serving as the primary channel through which life meaning influenced motivation. Conclusion Positive thinking is a key ingredient that transforms a sense of life meaning into tangible motivation for learning. Our findings suggest that universities could better support students by not only helping them explore life's meaning but also by actively fostering positive cognitive skills. Such programs could improve students' academic engagement and overall well-being.
Mechanisms that link circadian preference to problematic smartphone and social media use in young adults
Evening-types are at higher risk of problematic smartphone use and addiction to social media, but little is known about the possible mediating factors. Given the rising prevalence and broad negative impacts of smartphone and social media addiction, these factors require identification. Young adults (N = 407) aged 18–25, with an average age of 19.8 years, completed a battery of validated measures online. We tested mental health (anxiety and depression symptoms), loneliness, and poorer sleep quality as potential mediators in the relationships between eveningness and problematic smartphone use and social media addiction. As expected, evening types had higher prevalence of problematic smartphone use and social media addiction. Eveningness was also associated with higher anxiety and depression symptoms, loneliness, and poorer sleep quality. Two separate parallel mediation analyses were then conducted, with these three factors entered simultaneously as mediators. For problematic smartphone use, a partial mediation occurred, with loneliness as the significant mediating variable. For social media addiction, both loneliness and anxiety were significant mediators, and a full mediation was found. These important findings point to loneliness and anxiety as crucial explanatory variables for problematic technology use in young adults, suggesting that young adult evening types resort to smartphone/social media use as a dysfunctional coping strategy for loneliness and anxiety. Given the prevalence of problematic smartphone use and social media addiction amongst young people worldwide, and their wide-ranging negative impacts, this has important implications for prevention and intervention strategies to enhance young adults’ mental health, functioning, and well-being.
Evaluation of the Xpert MTB/XDR test for detection of isoniazid, fluoroquinolones, and second-line injectable drugs resistance to Mycobacterium tuberculosis—Anhui Province, China
Introduction The emergence of drug-resistant tuberculosis (DR-TB) has posed significant challenges to TB control. This study assessed the diagnostic performance of the Xpert MTB/XDR test for detecting drug resistance in TB patients. Methods This study analyzed 276 samples collected from clinically suspected MDR-TB patients in Auhui Chest Hospital from 01/03/2022–01/03/2023. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLIDs) compared with phenotypic drug susceptibility testing (pDST). Specimens were investigated by Sanger sequencing, where the MTB/XDR test and pDST results were inconsistent. Afterward, the clinical performance of the Xpert MTB/XDR test was also evaluated with the composite reference test (pDST + sequencing). Results The sensitivity of the Xpert MTB/XDR test against pDST in detecting resistance to INH and FLQ using 276 samples was 95.77% (95% CI: 91.83–98.16) and 93.83% (95% CI: 86.18–97.97), respectively. In contrast, a lower sensitivity of the MTB XDR test in predicting SLIDs and ETH resistance (sensitivity < 75%) compared with pDST was demonstrated in this study. The specificity for detecting all drugs was greater than 90%. Thirty-three samples were retested by sequencing, which identified mutations predicting INH and FLQ resistance, determining whether resistant or not by combining pDST and sequencing results. When considering pDST + sequencing, the sensitivity and specificity of the MTB/XDR assay for INH and FLQ drug targets increased, especially the detection specificity of FLQ has reached 100% (95% CI: 97.95–100). Conclusion The Xpert MTB/XDR has high sensitivity and specificity in drug-resistant tuberculosis patients, making it better suited to meet the needs of rapid, sensitive, and accurate detection for drug-resistant tuberculosis in resource-limited settings, and serving as a critical tool for achieving personalized treatment and TB control.
General and special education teachers’ readiness for artificial intelligence in classrooms: A structural equation modeling study of knowledge, attitudes, and practices in select UAE public and private schools
As artificial intelligence (AI) reshapes global education systems, understanding educators’ readiness to integrate AI into classroom practices is essential. This study examines the knowledge, attitudes, and practices (KAP) of general and special education teachers in the United Arab Emirates (UAE) regarding AI in education. Drawing on the Concerns-Based Adoption Model (CBAM) and Universal Design for Learning (UDL), we used structural equation modeling (SEM) to assess the relationships among KAP domains, including the moderating effects of demographic factors such as teaching experience, academic role, and prior exposure to AI tools. Data were collected from 161 educators in selected public and private schools across four UAE emirates, with the majority representing private and urban school settings. The findings revealed that teachers’ attitudes significantly predicted AI-related classroom practices, whereas knowledge had a weaker, but positive association. Mediation analysis further showed that knowledge had a significant indirect effect on practice through attitudes, confirming the hypothesized KAP pathway. Moderation analyses highlighted the variability in AI engagement based on gender and academic position, suggesting differentiated readiness across the subgroups. This study contributes to global conversations on teacher preparedness by offering a model for assessing institutional and pedagogical readiness for AI integration in urban school contexts. Implications for professional development, inclusive curriculum design, and educational technology policy are discussed, with relevance to digitally transforming educational systems in comparable settings.
Correction: Identification of the AKCDPK gene family and AkCDPK15 functional analysis under drought and salt stress
Virulence gene profile and antimicrobial resistance patterns of Aeromonas hydrophila in farmed catfishes (Heteropneustes fossilis and Pangasianodon hypophthalmus) for the first time in Bangladesh
Among several Aeromonas spp., causing diseases in fishes, Aeromonas hydrophila is the most predominant and pathogenic one. This study represents the first molecular detection, virulence profiling, and antibiogram analysis of Aeromonas hydrophila isolated from stinging catfishes (shing; Heteropneustes fossilis) and shark catfishes (pangasius; Pangasianodon hypophthalmus) in Bangladesh. Whole fish samples (n = 140) were collected from fish farming areas of Trishal upazila (stinging catfish 50; shark catfish 20) and Muktagachha upazila (stinging catfish 50; shark catfish 20), under Mymensingh district. Isolation and identification were accomplished through cultural, morphological, biochemical and finally, polymerase chain reaction (PCR) using genus- and species-specific primers, targeting 16S rDNA gene. Out of 140 samples, 38 (27.14%) isolates were found positive for A. hydrophila via conventional and PCR. The PCR-based virulence profiling showed that aerA (44.73%), hlyA (39.74%), asa1 (39.47%), ahyB (60.52%), act (21.5%), ast (28.94), alt (47.36%), ser (44.73%), lip (50%), gcat (23.68%), and ascV (21.05%) genes were detected, however, no aexT was detected. Antibiotic susceptibility test (using disc diffusion method) revealed that highest resistance (other than Penicillin Group) against Aztreonam and Cefuroxime (73.68%), and lowest against Gentamicin and Azithromycin (5.26%). MDR was detected in 71.05% isolates, and 92.11% isolates had MAR index ≥ 0.2. Statistically significant associations were observed between phenotypic resistance and specific virulence genes p ≤ 0.05. It could be concluded that MDR and virulent potential A. hydrophila are prevalent in stinging and shark catfishes of Mymensingh region, which might be a serious threat to sustainable aquaculture, food safety and public health.
Prognostic follow-up of high-grade squamous intraepithelial lesions of the cervix near the conization margin: A retrospective cohort study
Objective This study explored the prognosis of high-grade squamous intraepithelial lesion (HSIL) patients with negative margins, investigating the impact of different distances between lesions and incisal margins in conization specimens. Methods This retrospective cohort study included 240 HSIL patients. Patients with negative incisal margins were divided into 3 groups according to the distance between the lesion and the incisal margin in the conization tissue. Group 1 consisted of a distance of <1 mm (n = 23), Group 2 of 1–3 mm (n = 15), and Group 3 of >3 mm (n = 202). For patients with lesions close to the incisal margin (≤3 cm), the decision between total hysterectomy and clinical observation was made based on patient preference following detailed counseling of disease characteristics and prognosis. Thinprep cytologic test (TCT) and HPV testing were performed during follow-up at 6 and 12 months after the operation. Results No significant difference in HPV and TCT positive rate was observed among the three groups at 6 months and 12 months after the operation (P = 0.561, 0.561 and P = 0.324, 0.268). In the group with a distance shorter than 3 mm, no difference in HPV positive rate was found between the total hysterectomy and observation groups (P = 0.480, 0.737). Additionally, no difference in HPV positive rate was observed between patients who underwent total hysterectomy compared to clinical observation in groups 1 and 2 (P = 0.565, 0.692; P = 0.758, 0.593). Stratified analysis revealed that HPV positive rates at 6 months and 12 months had no statistical significance with any factor. Conclusion Different distances between conization tissue lesions and incisal edges have no direct impact on the prognosis of HSIL patients with negative conization biopsy tissues; excessive hysterectomy is not recommended in patients (≤3 mm) close to incisal edges.
Association between hair cortisol levels and keratoconus: A prospective study
Introduction Keratoconus is a progressive corneal disorder characterized by corneal thinning often leading to significant visual impairment. Recent research suggests a potential role of cortisol in the development and progression of keratoconus. However, the relationship between cortisol levels and keratoconus severity remains poorly understood. Purpose To investigate the association between hair cortisol levels and keratoconus severity in a Jordanian population, exploring whether cortisol could serve as a potential biomarker for disease progression or stability. Methods We conducted a prospective, observational study at King Abdullah University Hospital in Jordan. Sixty participants aged 18–30 years were categorized into three groups: Healthy (n = 20), Progressive Keratoconus (n = 20), and Stable Keratoconus (n = 20). Demographic, clinical, and ocular data were collected, including age, gender, hair cortisol levels, and corneal topography indices (Kmax, Kmean, and thinnest corneal location). Results The median cortisol level was significantly higher in the Progressive Keratoconus group (987 pg/mL) compared to the Stable group (300 pg/mL, p-value <0.001). Regression analysis revealed a significant negative association between cortisol levels and stable keratoconus (β = −1.31, p < 0.001). No significant association was observed for progressive keratoconus after adjustment for age and gender. Correlation analysis showed no significant associations between cortisol levels and BMI, Kmax, or Kmean. Cortisol levels also did not vary significantly across keratoconus severity categories in either eye. Conclusion Elevated cortisol levels may be associated with keratoconus progression, while lower levels appear linked to disease stability. Cortisol could serve as a potential biomarker for disease monitoring; however, further multicenter studies are needed to validate these findings and clarify cortisol’s role in keratoconus pathogenesis.
Gene expression alterations in testicular biopsies from males with spermatogenesis arrest identified by transcriptome analysis
Spermatogenesis is a complex biological process encompasses several stages of cellular divisions, ultimately resulting in producing mature spermatozoa capable of fertilization. Numerous factors involved in the precise regulation of the spermatogenesis, and any disruptions or alterations in these regulatory mechanisms can lead to spermatogenesis arrest, which may result in male infertility. Among these factors, genetic influences play essential role in regulating the process. This study aimed to identify genes that are differentially expressed in relation to spermatogenesis arrest. Testicular biopsy samples were collected from 22 non-obstructive azoospermic patients diagnosed with spermatogenesis arrest (cases) and nine obstructive azoospermic patients (controls). RNA sequencing (RNA-seq) was performed on five samples from the 22 non-obstructive azoospermic patients and compared to previously published transcriptomic data from obstructive azoospermic patients, which served as the control group. Differential expression analysis of the RNA-seq data identified 1,915 differentially expressed genes, comprising 337 upregulated and 1,578 downregulated genes. Among these, several key candidate genes were identified for further analysis, including the upregulation of FOS, FOSB, RGS1, and CXCL8, as well as the downregulation of TNP2, SPRR2C, LINC02314, and C16orf78. RT-qPCR validation confirmed the RNA-seq findings for these genes in the tested samples. Subsequently, RT-qPCR was performed on the remaining 17 non-obstructive (n = 17) and obstructive azoospermic samples (n = 9) collected in this study. The results from these additional samples were consistent with the RNA-seq data, further supporting the findings. Using gene ontology (GO) analysis and published literature, we linked these genes with spermatogenesis arrest, identifying promising targets that could serve as potential biomarkers for this condition in the future.
Impact of domestic and foreign investors on ESG disclosure quality in Chinese listed firms: Divergence or convergence?
Using the data of Chinese listed firms, this study constructs a two-layer complex network of Qualified Foreign Institutional Investors (QFII) and Domestic Institutional Investors (DII) to examine their influence on the quality of corporate ESG disclosures. By analyzing the credibility, consistency, and completeness of the network, it finds that improving a firm’s position within the QFII-DII complex network significantly enhances ESG disclosure quality. Key drivers include the knowledge transfer effect, information exchange effect, and market supervision effect. Additionally, executive green awareness and strong internal governance amplify the positive impact of network position on ESG quality. The study also reveals variations in the influence of QFII and DII over time and across industries, with similar overall effects. However, companies with higher centrality in the DII network layer are more likely to engage in ESG greenwashing behavior.
Pulsed electric field (PEF)–processed 6-shogaol-rich ginger extract protects β-Thalassemic red blood cells from iron-induced oxidative stress and hemolysis
β- thalassemia is the genetic blood disorder characterized by ineffective beta-globin chain synthesis. The increased iron absorption and frequently blood transfusion result in iron overload and the production of reactive oxygen species (ROS). ROS causes lipid peroxidation and membrane damage in red blood cells (RBCs), culminating in hemolysis and anemia. This study investigated the protective effects of ginger extract against iron induced oxidative damage in thalassemic RBCs. The pulsed electric field (PEF) technique with high-voltage electric pulses, was used for ginger extraction. The PEF significantly enhanced the yield of bioactive compounds, 6-shogaol and total phenolic content compared to conventional maceration technique. The 6-shogaol-rich ginger extract possessed a potent antioxidant activity by scavenging free radicals (ABTS•+ and DPPH•), and inhibiting of AAPH-induced RBC hemolysis in both healthy and β-thalassemic RBCs. Additionally, the extract exhibited iron-chelating properties by decreasing non-heme iron levels on the RBC membrane, thereby reducing lipid peroxidation reaction. These findings suggest that 6-shogaol-rich ginger extract processed with PEF could serve as a potential therapeutic agent, exhibiting powerful antioxidant and red blood cell membrane iron-chelating properties to protect against oxidative damage and hemolysis in iron-overloaded β-thalassemia patients.
Research on dual-waterway cooling system of high-power-density permanent magnet synchronous machine
The issue of temperature rise and heat dissipation becomes crucial to enhancing motor performance as permanent magnet synchronous motors (PMSMs) for electric vehicles (EVs) advance toward high power densities and heat load densities. A unique frame-rotor dual-waterway cooling system is developed to address the heat dissipation problem of high-power-density permanent magnet synchronous machines (HPDPMSMs). The frame contains the outside water circuit, whilst the rotor support cylinder is fitted with an inner water circuit. The dual water circuits constitute a cooling circulation system via a water-cooled bearing chamber and the spinning shaft. Through thermodynamic calculations of the waterway, the structural characteristics are ascertained, and a fluid-structure interaction temperature field simulation model is developed. The efficiency of the dual waterway cooling structure is validated by comparing its cooling impact to that of the single waterway structure. The analysis of temperature distribution in the motor with a dual-waterway cooling structure, under different coolants, extreme operational conditions, and variable water velocities, validates the efficacy of the developed frame-rotor dual-waterway cooling system.
Genetic diversity and relationship of Bugesera and Rwamagana indigenous chicken populations with SASSO chickens using DArTseq SNPs
The genetic improvement of Rwandan indigenous chickens (IC) is becoming a priority and requires genetic characterization as the foundation for genetic improvement. The aim was to study the genetic diversity and relationship of IC from Bugesera and Rwamagana districts with SASSO chickens in Rwanda. Eighty-seven DNA samples were genotyped using Diversity Array Technology and generated 45,677 DArTseq SNPs. After the quality control, the genetic diversity and relationship were analyzed with dartR package, STRUCTURE and STRUCTURE Harvester. Only 8087 markers and 86 samples were remained for analysis. The high and low expected heterozygosity (He) were observed in Rwamagana (0.405) and SASSO (0.388) populations, respectively. The lowest difference was observed between SASSO and Rwamagana populations (0.018). The structure analysis separated IC (Cluster 1) from SASSO chickens (Cluster 2). Chickens from Rwamagana population were genetically related to SASSO indicating the uncontrolled crossbreeding. DArTseq SNPs were efficient and can be recommended for genomic studies in chickens.
Trend analysis and projection of the gastric cancer disease burden in Taiwan during 1990–2021: An analysis of the global burden of disease study 2021
Background Gastric cancer is a serious health threat to people in Taiwan. This study reports gastric cancer burden and trends in Taiwan, from 1990 to 2021, and projects the incidence and mortality trends through 2036. Methods Data on gastric cancer burden in Taiwan came from the 2021 GBD database. Trend changes were evaluated via joinpoint analysis, with the Age-Period-Cohort model estimating age, period, and cohort influences. Decomposition analysis measured contributions of population growth, aging, and epidemiological factors, and the BAPC model forecast future burden. Results Between 1990 and 2021, the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate (ASDR) of gastric cancer in Taiwan all showed a decreasing trend. In terms of absolute burden, the number of incident cases in 2021 was 4,839 (95% uncertainty interval [UI]: 4,272–5,352), representing a 41.20% increase, prevalent cases reached 9,835 (95% UI: 8,664–11,032), a 60.36% rise, deaths totaled 3,799 (95% UI: 3,345–4,220), up by 29.17%, and DALYs were 79,425 (95% UI: 71,168–87,813), with a 0.19% decrease. A significant gender disparity was observed, with males bearing a heavier burden. Projections indicate that incident cases and deaths will continue to rise through 2036. Conclusions Across the past 32 years, gastric cancer in Taiwan has exhibited a declining relative burden, yet the absolute burden has risen consistently and is forecast to keep increasing over the next 15 years. Precision risk control measures and context-specific public health policies are required to alleviate this burden.
Assessing the real-world safety of docetaxel for non-small cell lung cancer: Insights from a comprehensive analysis of FAERS data
Background Docetaxel is a key therapeutic agent in the treatment of non-small cell lung cancer (NSCLC), but comprehensive real-world data on its adverse effects remain scarce. This study aims to evaluate docetaxel-related adverse drug events by analyzing the Adverse Event Reporting System (FAERS) database of the U.S. Food and Drug Administration (FDA) from 2004 to 2024. Methods This study utilized descriptive analysis along with four heterogeneity analysis methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multivariate Gamma-Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN), to systematically analyze 1,535 adverse event reports. Results The results identified potential adverse reactions associated with docetaxel that were not included in the drug label, such as dehydration, leukopenia, acute kidney injury, and hemoptysis, in addition to well-established adverse effects. Subgroup analysis revealed that male patients were more likely to experience respiratory-related adverse events, while female patients had a higher incidence of endocrine, metabolic, and skin-related adverse events. Patients aged over 65 years exhibited an elevated risk of cardiovascular and respiratory complications. Conclusion These findings offer critical evidence for the individualized monitoring and risk management of docetaxel in clinical practice, providing healthcare professionals with the necessary information to optimize treatment regimens and ensure the safe use of docetaxel.
Analytical validation (accuracy, reproducibility, limit of detection) and gene expression analysis of FoundationOneRNA assay for fusion detection in 189 clinical tumor specimens
Targeted DNA-based comprehensive genomic profiling (CGP) to detect clinically significant alterations is increasingly becoming standard for patients with advanced or recurrent cancer. RNA-based sequencing, however, may improve performance of fusion detection. We developed a robust targeted RNA sequencing assay (FoundationOne®RNA) and evaluated its analytic performance. FoundationOne®RNA is a hybrid-capture based targeted RNA sequencing test designed to optimally detect fusions (318 genes) and measure gene expression (1521 genes). Analytical validation studies were performed in College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified lab to assess fusion call accuracy, assay reproducibility, limit of detection (LoD) and gene expression in 189 clinical solid tumor specimens. In the accuracy study, 160 out of 189 biopsy samples which were previously profiled using large-panel DNA- or RNA-based next-generation sequencing (NGS) passed quality control metrics and were studied using the FoundationOne®RNA assay. Analysis of all diagnostic fusions showed a positive percent agreement (PPA) of 98.28%, as well as a negative percent agreement (NPA) of 99.89% when compared to orthogonal assays. The FoundationOne®RNA assay was able to identify a low level BRAF fusion missed by orthogonal whole transcriptome RNA sequencing and was confirmed by fluorescence in situ hybridization (FISH). The range for the minimum RNA input and LoD was determined based on dilutions from 5 fusion-positive cell lines. It spans from 1.5ng (0.5% input) to 30ng (10% input) for RNA input and from 21 to 85 supporting reads for LoD. In the precision study, 10 out of 10 pre-defined target fusions had 100% reproducibility. In our gene expression analysis, multiple gene expression signatures were detected in fusion positive samples. FoundationOne®RNA assay successfully detected oncogenic fusions with high concordance to orthogonal NGS based tests, high reproducibility, and low limit of detection. This study demonstrated the robustness of FoundationOne®RNA and supports its use as a supplement to tissue DNA comprehensive genomic profiling (CGP) in routine clinical practice. Additional work is required to clarify optimal clinical scenarios for fusion detection and enable gene expression biomarkers for clinical use.
Application of machine learning algorithms to predict early childhood development in children aged 24–59 months across three East African countries
Background Early childhood development (ECD) plays a crucial role in shaping the future development of children and it influences their lifelong outcomes. The Early childhood development index 2030 (ECDI2030) serves as an effective tool for monitoring the overall development of children aged 24–59 months at the population level. This study employed machine learning algorithms to identify the predictors of ECD across three East African countries, using the ECDI2030. Methods Data were derived from the Demographic and Health Surveys of Kenya, Mozambique, and Tanzania. Seven supervised machine learning algorithms and an ensemble of the best performing models were utilized to predict ECD. The dataset was randomly divided into 80% training and 20% testing sets. The predictive ability of each machine learning model was evaluated using area under the curve (AUC) and the classification metrics. We used SHapley Additive exPlanations (SHAP) to explain the predictions by interpreting feature importance. Results About 57.4% (95% CI = 56.5, 58.3) children were developmentally on track in health, learning, and psychosocial well-being. The ensemble model of extreme gradient boosting and random forest was the best algorithm with accuracy of 66% and AUC of 71%. The top three most important predictors of ECD were child age, media exposure, and maternal education level with a mean absolute SHAP value of +0.17, + 0.12, and +0.1, respectively. The beeswarm plot of SHAP revealed that children aged 24–35 months, those whose mothers were not exposed to media, or those whose mothers had completed at least secondary education were more likely to be developmentally on track. Conclusion In East Africa, only the modest majority of children were developmentally on track. Policies should prioritize preprimary education, equitable access, and women’s education to empower mothers and improve parenting practices. Promoting appropriate media use while limiting maternal screen time can enhance children’s developmental outcomes in East Africa and other countries with similar socioeconomic contexts, including most sub-Saharan African countries.