Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

Global, regional, and national burden of blindness and vision loss attributable to high fasting plasma glucose from 1990 to 2019, and forecasts to 2030: A systematic analysis for the Global Burden of Disease Study 2019.

AIMS: To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade. MATERIALS AND METHODS: We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden. RESULTS: In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade. CONCLUSIONS: The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.

Spatiotemporal heterogeneity and long-term impact of meteorological, environmental, and socio-economic factors on scrub typhus in China from 2006 to 2018.

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.

Global burden of all cause-specific injuries among children and adolescents from 1990 to 2019: a prospective cohort study.

BACKGROUND: To assess the burden and change in incidence, death, and disability-adjusted life years (DALYs) for all-cause-specific injuries among children and adolescents in 204 countries and territories between 1990 and 2019. MATERIALS AND METHODS: Data were extracted from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019). Global, regional, and country-level age-standardized rate (per 100 000) of incidence (ASRI), mortality (ASRM), and DALYs (ASRD) with 95% uncertainty interval (95% UI) of injuries were estimated by age, sex, socio-demographic index (SDI), and all-cause-specific injuries from 1990 to 2019. RESULTS: Overall, the ASRI, ASRM, and ASRD of injury were 9006.18 (95% UI: 7459.74-10 918.04), 23.04 (20.00-26.50), and 2020.19 (1759.47-2318.64) among children and adolescents worldwide in 2019, respectively. All the above indicators showed a downward trend from 1990 to 2019. In level 2 cause of injury, both the global transport injury and unintentional injury declined during the study years, while self-harm and interpersonal violence-related injury showed an increasing trend. High SDI regions had higher ASRI of injuries, but low SDI regions had higher ASRM and ASRD of injuries globally in 2019. Males had a higher burden of injuries than those in females. The ASRI of injuries is higher in adolescents aged 15-19 years, whereas the mortality and DALYs rate are higher among children under 5 years old. Moreover, adolescents aged 15-19 years and individuals living in Central Asia, Middle East, and Africa had higher ASRI, ASRM, and ASRD of injuries owing to self-harm and interpersonal violence. Generally, falls and road traffic injuries are the leading cause of injury among the population aged 0-19 years worldwide, but self-harm, interpersonal violence, and conflict and terrorism are also leading types of injuries in some regions, particularly in Low-Income Countries and Middle-Income Countries. CONCLUSIONS: Injury remains a major global public health problem among children and adolescents, although its burden at the worldwide level showed a decreasing trend from 1990 to 2019. Of concern, the burden of injuries caused by transport injuries, and unintentional injuries has shown a downward trend in most countries, while the burden caused by self-harm and interpersonal violence has shown an upward trend in most countries. These findings suggest that more targeted and specific strategies to prevent the burden of injuries should be reoriented, and our study provides important findings for decision-makers and healthcare providers to reduce injury burden among children and adolescents.

Exploring the clinical outcomes and safety profile of inetetamab treatment in metastatic breast cancer patients: A multicenter assessment of a Chinese-origin recombinant Anti-HER2 monoclonal antibody.

BACKGROUND: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. METHODS: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334-3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133-3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370-0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). CONCLUSION: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.

Analysis of the changing trend of economic burden of patients with chronic diseases under the Integrated Medical and Health Service System.

BACKGROUND: Integrating medical resources is one of the explorations of medical mechanism reform to meet the needs of whole-cycle health management and is an important initiative in the current round of China's healthcare system reform. 2015 saw the construction of county medical communities to promote the balanced layout of medical resources, which opened a new exploration of the construction of an integrated healthcare service system in China. 2017 saw the promotion of the pilot construction of compact county medical communities in Zhejiang Province, China. OBJECTIVE: From the perspective of alleviating the financial burden on those in need of health services, the characteristics of chronic disease patients' access to health care and the composition and changing curve of the medical cost burden are analyzed to provide a basis for the construction path of an integrated health care service system. METHODS: A retrospective cohort study was conducted to select 5739 permanent residents who met the inclusion and exclusion criteria in Z town, H city, Zhejiang province. This population's health insurance utilization data from 2015 to 2018 were retrieved, and their average annual costs, cost composition, and health insurance payments were analyzed. RESULTS: The average annual growth rates of medical insurance and out-of-pocket costs before and after the implementation of the Medical Community were 12.85% and 9.72%, respectively. The increase narrowed significantly after the construction of the Medical Community, with the ringgit growth rate dropping to 2.73% in 2018. The top three medical expenses that accounted for the highest percentage were drug, consultation, and treatment fees. The frequency of visits to primary health care consulting hospitals has increased yearly. CONCLUSIONS: By implementing various measures to strengthen the grassroots level, patients' choice of primary care has increased year by year in the early stages of the construction of the Medical Community. From the perspective of cost control, strengthening the regulation of drugs and tests and restricting the use of high-value consumables can further reduce medical costs and ease their financial burden.

Global, Regional, and National Burdens of Blindness and Vision Loss in Children and Adolescents from 1990 to 2019: A Trend Analysis.

PURPOSE: To provide estimates for regional and national burdens of blindness and vision loss among children and adolescents between 1990 and 2019 by disease, age, and sociodemographic index (SDI). DESIGN: This was a retrospective demographic analysis based on aggregated data. METHODS: This was a population-based study using 1990-2019 data on the burden of vision loss and blindness from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of vision loss and blindness was evaluated in terms of case numbers, rates per 100 000 population, and average annual percentage changes (AAPCs) in prevalence rates and years lived with disability (YLDs). RESULTS: Globally, the rates of blindness and vision loss per 100 000 population decreased in all age groups between 1990 and 2019, with prevalence rates decreasing from 1091.4 (95% uncertainty interval [UI], 895.2-1326.1) to 1036.9 (95% UI, 847.8-1265.9, AAPC, -0.2) and YLDs decreasing from 44.5 (95% UI, 28.1-66.5) to 40.2 (95% UI, 25.1-60.7, AAPC, -0.4). Most of these reductions in prevalence rates (AAPC, -0.2, 95% confidence interval [CI], -0.2 to -0.1) and YLDs (AAPC, -0.2, 95% CI, -0.3 to -0.2) were due to decreases in refractive disorder. Notably, near-vision loss prevalence (AAPC, 0.3, 95% CI, 0.2-0.4) and YLDs (AAPC, 0.3, 95% CI, 0.2-0.4) substantially increased in all age groups. Children and adolescents in low- and low-middle SDI countries exhibited substantial decreases in the prevalence rates and YLDs of blindness and vision loss, but their counterparts in high- and middle-high SDI countries experienced a substantial increase in prevalence. CONCLUSIONS: Globally, efforts in the past 3 decades have substantially decreased the burdens of blindness and vision loss among children and adolescents. However, there is extensive variation according to the kind of impairment, age group, and country SDI. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Can the organization of health resource integration be analyzed in terms of the current state of unmet demand for health services? take the health needs of the elderly in a place in zhejiang province, china, as an example.

BACKGROUND: The aging of the population has made the health problems of the elderly increasingly prominent, and their health needs are increasing. Existing studies on health resource integration approaches are mostly incomplete in assessing the health service capacity from the perspective of the health service provider. OBJECTIVE: The unmet health needs of the elderly were sampled and analyzed from the perspective of health service demanders. To explore how to build an integrated medical organization structure to better meet the health needs of the elderly. METHODS: A whole-group sampling method was used to conduct a questionnaire survey of 1527 older adults in N district of H city, Zhejiang province, China, to cross-sectionally analyze their current status of unmet health needs. RESULTS: The survey and analysis found that the needs of the elderly in this community to obtain disease-related knowledge, rational exercise, a healthy diet, and access to health information were not met. There were more patients with chronic diseases, and the top three chronic disease prevalence rates were hypertension (40.2%), dyslipidemia (8.4), and diabetes (7%). Chronic disease co-morbidities accounted for 13.3%. CONCLUSION: The relatively independently set up health service system at the present stage in China can no longer fully meet the health needs of the elderly, and the health service providers should provide integrated and continuous health services to meet the needs of whole-cycle health management. Therefore, we believe that effectively integrating various health service providers in the region and building an integrated health service organization with general practitioners as the core may be a solution to the current situation of unmet health needs of the elderly.

HITAC-seq enables high-throughput cost-effective sequencing of plasmids and DNA fragments with identity.

DNA sequencing is vital for many aspects of biological research and diagnostics. Despite the development of second and third generation sequencing technologies, Sanger sequencing has long been the only choice when required to precisely track each sequenced plasmids or DNA fragments. Here, we report a complete set of novel barcoding and assembling system, Highly-parallel Indexed Tagmentation-reads Assembled Consensus sequencing (HITAC-seq), that could massively sequence and track the identities of each individual sequencing sample. With the cost of much less than that of single read of Sanger sequencing, HITAC-seq can generate high-quality contiguous sequences of up to 10 kilobases or longer. The capability of HITAC-seq was confirmed through large-scale sequencing of thousands of plasmid clones and hundreds of amplicon fragments using approximately 100 pg of input DNAs. Due to its long synthetic length, HITAC-seq was effective in detecting relatively large structural variations, as demonstrated by the identification of a ∼1.3 kb Copia retrotransposon insertion in the upstream of a likely maize domestication gene. Besides being a practical alternative to traditional Sanger sequencing, HITAC-seq is suitable for many high-throughput sequencing and genotyping applications.

Assessment of Binocular Imbalance with an Augmented Virtual Reality Platform in a Normal Population.

We examined and analyzed binocular imbalance in a group of randomly selected normal subjects with corrected visual acuity of 0.8 or more in both eyes without ocular diseases, by using augmented virtual reality system. This study will quantify the correlation between binocular imbalance in these normal subjects and various spatial frequencies and temporal frequencies in the integrated binocular stimulation mode. A retrospective study was carried out and data from 97 patients (51 males and 46 females) who were diagnosed with no eye diseases, and with corrected binocular visual acuity of 0.8 or more, were collected. Their binocular visual function, Hirschberg test refraction status, and binocular imbalance were assessed using the quantified visual perception stimulation mode in an augmented virtual reality platform. When normal subjects (with corrected binocular vision of 0.8 or more without ocular diseases) were assessed using the integrated binocular stimulation mode with different temporal and spatial frequencies, a gradual reduction of binocular imbalance could be observed when spatial frequencies were increased. When contrast balance was adjusted, binocular imbalance was more prevalent in the horizontal state compared with the vertical state. This was seen when patients were stimulated by different temporal frequencies in the virtual reality testing mode. 17.53% and 29.90% of participants reached complete binocular fusion under low temporal frequency stimulation and high temporal frequency stimulation, respectively, while binocular imbalance was found in 65.9% and 62.89% of participants who were stimulated, respectively, by low temporal frequency and high temporal frequency. In addition, 16.5% and 7.21% experienced severe binocular imbalance under low temporal and high temporal frequency stimulation, respectively. The integrated binocular stimulation mode under low temporal frequency was more sensitive in detecting binocular imbalance. The status of binocular balance in normal subjects was not the same when stimulated by the augmented virtual reality platform, as many showed varying degrees of binocular imbalance. The results from our clinical study demonstrate that integrated binocular stimulation with different spatial and temporal frequencies enables a more sensitive detection of binocular imbalance, making it a powerful new tool for the diagnosis and analysis of clinical binocular abnormalities. In addition, since more than half of the normal subjects (without eye diseases who has corrected vision of 0.8 or more) exhibited binocular imbalance in our study, we believe that this brief binocular imbalance is likely a transient physiological phenomenon, which is not pathological to visual acuity and function, and should only be seen as pathological when binocular imbalance is prolonged, causing functional deficits such as reading impairment.

Risk assessment model for invasive breast cancer in Hong Kong women.

No risk assessment tool is available for identifying high risk population of breast cancer (BCa) in Hong Kong. A case-control study including 918 BCa cases and 923 controls was used to develop the risk assessment model among Hong Kong Chinese women.Each participant received an in-depth interview to obtain their lifestyle and environmental risk factors. Least absolute shrinkage and selection operator (LASSO) selection model was used to select the optimal risk factors (LASSO-model). A risk score system was constructed to evaluate the cumulative effects of selected factors. Bootstrap simulation was used to test the internal validation of the model. Model performance was evaluated by receiver-operator characteristic curves and the area under the curve (AUC).Age, number of parity, number of BCa cases in 1st-degree relatives, exposure to light at night, and sleep quality were the common risk factors for all women. Alcohol drinking was included for premenopausal women; body mass index, age at menarche, age at 1st give birth, breast feeding, using of oral contraceptive, hormone replacement treatment, and history of benign breast diseases were included for postmenopausal women. The AUCs were 0.640 (95% CI, 0.598-0.681) and 0.655 (95% CI, 0.621-0.653) for pre- and postmenopausal women, respectively. Further subgroup evaluation revealed that the model performance was better for women aged 50 to 70 years or ER-positive.This BCa risk assessment tool in Hong Kong Chinese women based on LASSO selection is promising, which shows a slightly higher discriminative accuracy than those developed in other populations.

Assessment of apparent diffusion coefficient of normal fetal brain development from gestational age week 24 up to term age: a preliminary study.

OBJECTIVES: This study was designed to investigate the feasibility of apparent diffusion coefficient (ADC) values in evaluating normal fetal brain development from gestational week 24 up to term age. METHODS: Diffusion-weighted imaging (DWI) was performed on 40 normal fetuses (with normal results on sonography and normal fetal MRI results), with two b-values of 0 and 600 s/mm² in the three (x, y, z) orthogonal axes. Ten regions of interest (ROIs) were manually placed symmetrically in the bilateral frontal white matter (FWM), occipital white matter (OWM), thalamus (THAL), basal ganglia (BG), and cerebellar hemispheres (CH). ADC values of the ten ROIs in all subjects were measured by two radiologists independently. One-way ANOVA was used to calculate the differences among the five regions in the fetal brain and linear regression analysis was used to evaluate the correlation between ADC values and gestational age (GA). p < 0.05 was considered significantly different. RESULTS: Mean GA was 31.3 ± 3.9 (range 24-41) weeks. The overall mean ADC values (× 10⁻6 mm²/s) of the fetuses were 1,800 ± 214 (FWM), 1,400 ± 100 (BG), 1,300 ± 126 (THAL), 1,700 ± 133 (OWM) and 1,400 ± 155 (CH), respectively. The ADC value of BG was not significantly different from those of THAL and CH, while the other four ROIs had significant differences with each other. The ADC values of BG, THAL, OWM and CH had strong negative correlations with increasing GA (R were -0.568, -0.716, -0.830 and -0.700, respectively, all p < 0.01), OWM declined fastest with GA, followed by CH and THAL, the slowest being BG. The ADC value of FWM had no significant change with GA (p = 0.366). CONCLUSIONS: The measurement of ADC values is feasible to evaluate fetal brain development with high reliability and reproducibility.

Strategies for the prevention of acute mountain sickness and treatment for large groups making a rapid ascent in China.

Approximately 26.8% of China's land area has an elevation of 3000 m above sea level or higher. Because of recent demands for economic development and new construction in highland areas, many people have relocated from the plains to high plateau regions and have to face the possibility of contracting acute mountain sickness. Therefore, prevention and treatment strategies are necessary to reduce the incidence of acute mountain sickness in people who rapidly ascend to plateau areas. This paper describes the Chinese experience when large numbers of people moved to the plateau and the steps that were taken to deal with this illness. These steps included implementing basic prevention measures, increasing medical awareness among populations ascending to high altitudes, and installing standardized medical management systems to prevent and treat acute mountain sickness before, during, and after ascent. The incidence of acute mountain sickness can be reduced by improving prevention and treatment and by implementing the recommendations described in this manuscript.

Adherence to treatment and influencing factors in a sample of Chinese epilepsy patients.

AIM: To assess adherence to antiepileptic drugs (AEDs) and factors associated with non-adherence in a sample of Chinese patients with epilepsy. METHODS: A cross-sectional descriptive study was carried out on patients who had no change in treatment regimen over the last six months. Data on adherence to medication and related factors for each patient were gathered using a questionnaire. RESULTS: Of a total of 368 patients studied, 48.1% of patients were non-adherent with regards to AEDs. There were no demographic differences (based on gender, age, seizure type, and rural or urban location) between adherent and non-adherent patients. Adherence was positively and significantly correlated with duration of illness (p=0.007). The primary reason for non-adherence was forgetfulness or not having medication on hand (69.6%), followed by a negative attitude (12.8%), a bad patient-prescriber relationship (9.5%), side effects (5.4%), inability to buy drugs (1.9%), and other reasons (0.8%). CONCLUSION: The non-adherence of epilepsy patients is common in China. Targeted management programs and communication strategies are necessary to improve adherence to AED treatments in patients with epilepsy and avoid the clinical consequences of poor adherence.

Risk assessment of groundwater contamination: a multilevel fuzzy comprehensive evaluation approach based on DRASTIC model.

Groundwater contamination is a serious threat to water supply. Risk assessment of groundwater contamination is an effective way to protect the safety of groundwater resource. Groundwater is a complex and fuzzy system with many uncertainties, which is impacted by different geological and hydrological factors. In order to deal with the uncertainty in the risk assessment of groundwater contamination, we propose an approach with analysis hierarchy process and fuzzy comprehensive evaluation integrated together. Firstly, the risk factors of groundwater contamination are identified by the sources-pathway-receptor-consequence method, and a corresponding index system of risk assessment based on DRASTIC model is established. Due to the complexity in the process of transitions between the possible pollution risks and the uncertainties of factors, the method of analysis hierarchy process is applied to determine the weights of each factor, and the fuzzy sets theory is adopted to calculate the membership degrees of each factor. Finally, a case study is presented to illustrate and test this methodology. It is concluded that the proposed approach integrates the advantages of both analysis hierarchy process and fuzzy comprehensive evaluation, which provides a more flexible and reliable way to deal with the linguistic uncertainty and mechanism uncertainty in groundwater contamination without losing important information.

Comparison of SSRs and SNPs in assessment of genetic relatedness in maize.

Advances in high-throughput SNP genotyping and genome sequencing technologies have enabled genome-wide association mapping in dissecting the genetic basis of complex quantitative traits. In this study, 82 SSRs and 884 SNPs with minor allele frequencies (MAF) over 0.20 were used to compare their ability to assess population structure, principal component analysis (PCA) and relative kinship in a maize association panel consisting of 154 inbred lines. Compared to SNPs, SSRs provided more information on genetic diversity. The expected heterozygosity (He) of SSRs and SNPs averaged 0.65 and 0.44, and the polymorphic information content of these two markers was 0.61 and 0.34 in this panel, respectively. Additionally, SSRs performed better at clustering all lines into groups using STRUCTURE and PCA approaches, and estimating relative kinship. For both marker systems, the same clusters were observed based on PCA and the first two eigenvectors accounted for similar percentage of genetic variations in this panel. The correlation coefficients of each eigenvector from SSRs and SNPs decreased sharply when the eigenvector varied from 1 to 3, but kept around 0 when the eigenvector were over 3. The kinship estimates based on SSRs and SNPs were moderately correlated (r (2) = 0.69). All these results suggest that SSR markers with moderate density are more informative than SNPs for assessing genetic relatedness in maize association mapping panels.

Assessment of automated image analysis of breast cancer tissue microarrays for epidemiologic studies.

BACKGROUND: A major challenge in studies of etiologic heterogeneity in breast cancer has been the limited throughput, accuracy, and reproducibility of measuring tissue markers. Computerized image analysis systems may help address these concerns, but published reports of their use are limited. We assessed agreement between automated and pathologist scores of a diverse set of immunohistochemical assays done on breast cancer tissue microarrays (TMA). METHODS: TMAs of 440 breast cancers previously stained for estrogen receptor (ER)-alpha, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-beta, and aromatase were independently scored by two pathologists and three automated systems (TMALab II, TMAx, and Ariol). Agreement between automated and pathologist scores of negative/positive was measured using the area under the receiver operating characteristics curve (AUC) and weighted kappa statistics for categorical scores. We also investigated the correlation between immunohistochemical scores and mRNA expression levels. RESULTS: Agreement between pathologist and automated negative/positive and categorical scores was excellent for ER-alpha and PR (AUC range = 0.98-0.99; kappa range = 0.86-0.91). Lower levels of agreement were seen for ER-beta categorical scores (AUC = 0.99-1.0; kappa = 0.80-0.86) and both negative/positive and categorical scores for aromatase (AUC = 0.85-0.96; kappa = 0.41-0.67) and HER2 (AUC = 0.94-0.97; kappa = 0.53-0.72). For ER-alpha and PR, there was a strong correlation between mRNA levels and automated (rho = 0.67-0.74) and pathologist immunohistochemical scores (rho = 0.67-0.77). HER2 mRNA levels were more strongly correlated with pathologist (rho = 0.63) than automated immunohistochemical scores (rho = 0.41-0.49). CONCLUSIONS: Automated analysis of immunohistochemical markers is a promising approach for scoring large numbers of breast cancer tissues in epidemiologic investigations. This would facilitate studies of etiologic heterogeneity, which ultimately may allow improved risk prediction and better prevention approaches.