Medical diagnostic accuracy measures: an innovative approach based on the area under predictive values curves.

Positive and negative estimates are commonly used by clinicians to evaluate the likelihood of a disease stage being present based on test results. The predicted values are dependent on the prevalence of the underlying illness. However, for certain diseases or clinical conditions, the prevalence is unknown or different from one region to another or from one population to another, leading to an erroneous diagnosis. This article introduces innovative post-test diagnostic precision measures for continuous tests or biomarkers based on the combined areas under the predictive value curves for all possible prevalence values. The proposed measures do not vary as a function of the prevalence of the disease. They can be used to compare different diagnostic tests and/or biomarkers' abilities for rule-in, rule-out, and overall accuracy based on the combined areas under the predictive value curves. The relationship of the proposed measures to other diagnostic accuracy measures is discussed. We illustrate the proposed measures numerically and use a real data example on breast cancer.

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.

Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.

Altered dynamic functional network connectivity in rheumatoid arthritis associated with peripheral inflammation and neuropsychiatric disorders.

OBJECTIVE: This study explored the dynamic functional connective (DFC) alterations in patients with rheumatoid arthritis (RA) and investigated the correlation between the neuropsychiatric symptoms, peripheral inflammation and DFC alterations. METHOD: Using resting-state functional MRI, we investigated the DFC based on spatial independent component analysis and sliding window method for 30 patients with RA and 30 healthy controls (HCs). The Spearman correlation was calculated between aberrant DFC alterations, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HAD), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Diagnostic efficacy of indicators was assessed using receiver operating characteristic analysis (ROC). RESULTS: Three dynamic functional states were identified. Compared with HC, patients with RA showed reduced FC variabilities between sensorimotor network (SMN) and insula, SMN and orbitofrontal cortex, which were the crucial regions of sensory processing network. The above FC variabilities were correlated with the MoCA, HAD, CRP and ESR in patients with RA. Additionally, the CRP and ESR were negatively correlated to MoCA and positively related to HAD in patients with RA. The ROC analysis results showed that MoCA, HAD and FC variabilities of the sensory processing network could distinguish patients with RA from HC and also identify patients with RA with high ESR. CONCLUSION: Our findings demonstrated that abnormal DFC patterns in sensory processing networks in patients with RA were closely associated with peripheral inflammation and neuropsychiatric symptoms. This indicates that the dynamic temporal characteristics of the brain functional network may be potential neuroimaging biomarkers for revealing the pathological mechanism of RA.

Performance of diagnostic tests based on continuous bivariate markers.

In medical diagnostic research, it is customary to collect multiple continuous biomarker measures to improve the accuracy of diagnostic tests. A prevalent practice is to combine the measurements of these biomarkers into one single composite score. However, incorporating those biomarker measurements into a single score depends on the combination of methods and may lose vital information needed to make an effective and accurate decision. Furthermore, a diagnostic cut-off is required for such a combined score, and it is difficult to interpret in actual clinical practice. The paper extends the classical biomarkers' accuracy and predictive values from univariate to bivariate markers. Also, we will develop a novel pseudo-measures system to maximize the vital information from multiple biomarkers. We specified these pseudo-and-or classifiers for the true positive rate, true negative rate, false-positive rate, and false-negative rate. We used them to redefine classical measures such as the Youden index, diagnostics odds ratio, likelihood ratios, and predictive values. We provide optimal cut-off point selection based on the modified Youden index with numerical illustrations and real data analysis for this paper's newly developed pseudo measures.

Functional dysconnectivity and microstructural impairment of the cortico-thalamo-cortical network in women with rheumatoid arthritis: A multimodal MRI study.

Background: Cognitive deficits are common in rheumatoid arthritis (RA) patients, but the mechanisms remain unclear. We investigated the effective connectivity and structural alterations of the core brain regions in RA patients with cognitive impairment. Methods: Twenty-four female patients with RA and twenty-four healthy controls were enrolled. We analyzed abnormal brain activity patterns using functional MRI during the Iowa gambling task (IGT) and core regions effective connectivity using dynamic causal model (DCM). Structural alterations of white matter volume (WMV) and gray matter volume (GMV) were detected using voxel-based morphometry (VBM). Results: RA patients showed altered activation patterns of the cortico-thalamo-cortical network, increased coupling strength from the left ventromedial prefrontal gyrus to the anterior cingulate cortex (ACC), the ACC to the right thalamus, and decreased connectivity from the thalamus to left hippocampus. VBM structural analysis showed increased GMV in the bilateral orbital frontal gyrus, bilateral hippocampus and right putamen, and reduced GMV and WMV in the bilateral thalamus in RA patients. Right thalamic GMV and WMV were positively correlated with the right thalamus-to-hippocampus connective strength. Additionally, the bold signal, GMV and WMV of the right thalamus were positively correlated with cognitive performance (IGT score) in RA patients. Conclusion: Results suggest a structural and functional deficiency in the cortico-thalamo-cortical network, which is characterized by increased ACC-to-thalamus strength and reduced thalamus-to-hippocampus coupling in RA patients. The cognitive dysfunction may be the result of compensatory measures against imbalanced cortico-thalamic-cortical coupling.

Evaluating joint confidence region of hypervolume under ROC manifold and generalized Youden index.

In biomarker evaluation/diagnostic studies, the hypervolume under the receiver operating characteristic manifold ( HUM K $$ {\mathrm{HUM}}_K $$ ) and the generalized Youden index ( J K $$ {J}_K $$ ) are the most popular measures for assessing classification accuracy under multiple classes. While HUM K $$ {\mathrm{HUM}}_K $$ is frequently used to evaluate the overall accuracy, J K $$ {J}_K $$ provides direct measure of accuracy at the optimal cut-points. Simultaneous evaluation of HUM K $$ {\mathrm{HUM}}_K $$ and J K $$ {J}_K $$ provides a comprehensive picture about the classification accuracy of the biomarker/diagnostic test under consideration. This article studies both parametric and non-parametric approaches for estimating the confidence region of HUM K $$ {\mathrm{HUM}}_K $$ and J K $$ {J}_K $$ for a single biomarker. The performances of the proposed methods are investigated by an extensive simulation study and are applied to a real data set from the Alzheimer's Disease Neuroimaging Initiative.

Validation and modification of simplified Geriatric Assessment and Elderly Prognostic Index: Effective tools for older patients with diffuse large B-cell lymphoma.

Geriatric assessment can aid in optimizing treatment strategies and supportive interventions for older patients with diffuse large B-cell lymphoma (DLBCL). Fondazione Italiana Linformi has recently introduced novel geriatric assessment tools, simplified Geriatric Assessment (sGA) and Elderly Prognostic Index (EPI), aimed at tailoring the treatment and predicting the outcomes for older patients with DLBCL. The objectives of this study are the validation and possible modification of the sGA and EPI in China. In the study, both sGA and EPI demonstrated the predictive capabilities for overall survival (OS) and early mortality (both p < 0.05) in older individuals with DLBCL. Albumin, serving as an independent predictive biomarker for OS (p = 0.006), was utilized to adjust the measurements, resulting in the establishment of sGA-A and EPI-A. The sGA-A effectively addressed the shortcomings of the sGA and EPI in predicting PFS and surpassed them in predicting OS and early mortality. Nevertheless, there is insufficient evidence to support the use of sGA and EPI as treatment guidance tools. In conclusion, the modified sGA-A model proved to be a successful instrument for geriatric assessment of older patients with DLBCL.

Inhibition of SF3B1 improves the immune microenvironment through pyroptosis and synergizes with αPDL1 in ovarian cancer.

Ovarian cancer is resistant to immune checkpoint blockade (ICB) treatment. Combination of targeted therapy and immunotherapy is a promising strategy for ovarian cancer treatment benefit from an improved immune microenvironment. In this study, Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) cohorts were used to screen prognosis and cytotoxic lymphocyte infiltration-associated genes in upregulated genes of ovarian cancer, tissue microarrays were built for further verification. In vitro experiments and mouse (C57/BL6) ovarian tumor (ID8) models were built to evaluate the synergistic effect of the combination of SF3B1 inhibitor and PD-L1 antibody in the treatment of ovarian cancer. The results show that SF3B1 is shown to be overexpressed and related to low cytotoxic immune cell infiltration in ovarian cancer. Inhibition of SF3B1 induces pyroptosis in ovarian cancer cells and releases mitochondrial DNA (mtDNA), which is englobed by macrophages and subsequently activates them (polarization to M1). Moreover, pladienolide B increases cytotoxic immune cell infiltration in the ID8 mouse model as a SF3B1 inhibitor and increases the expression of PD-L1 which can enhance the antitumor effect of αPDL1 in ovarian cancer. The data suggests that inhibition of SF3B1 improves the immune microenvironment of ovarian cancer and synergizes ICB immunotherapy, which provides preclinical evidence for the combination of SF3B1 inhibitor and ICB to ovarian cancer treatment.

Knockout of OsWRKY71 impairs Bph15-mediated resistance against brown planthopper in rice.

The Bph15 gene, known for its ability to confer resistance to the brown planthopper (BPH; Nilaparvata lugens Stål), has been extensively employed in rice breeding. However, the molecular mechanism by which Bph15 provides resistance against BPH in rice remains poorly understood. In this study, we reported that the transcription factor OsWRKY71 was highly responsive to BPH infestation and exhibited early-induced expression in Bph15-NIL (near-isogenic line) plants, and OsWRKY71 was localized in the nucleus of rice protoplasts. The knockout of OsWRKY71 in the Bph15-NIL background by CRISPR-Cas9 technology resulted in an impaired Bph15-mediated resistance against BPH. Transcriptome analysis revealed that the transcript profiles responsive to BPH differed between the wrky71 mutant and Bph15-NIL, and the knockout of OsWRKY71 altered the expression of defense genes. Subsequent quantitative RT-PCR analysis identified three genes, namely sesquiterpene synthase OsSTPS2, EXO70 family gene OsEXO70J1, and disease resistance gene RGA2, which might participate in BPH resistance conferred by OsWRKY71 in Bph15-NIL plants. Our investigation demonstrated the pivotal involvement of OsWRKY71 in Bph15-mediated resistance and provided new insights into the rice defense mechanisms against BPH.

MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.

BACKGROUND: Although the clinical application of PARP inhibitors has brought hope to ovarian cancer, the problem of its resistance has become increasingly prominent. Therefore, clinical experts have been focused on finding specific indicators and therapeutic targets that can be used for resistance monitoring of PARP inhibitors. RESULTS: By cfDNA detecting during Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer, we found the presence of MRE11:p.K464R mutation was strongly associated with acquired Olaparib resistance. Structural analysis revealed that the MRE11:p.K464R mutation is situated at a critical site where the MRE11 protein interacts with other biomolecules, leading to potential structural and functional abnormalities of MRE11 protein. Functionally, MRE11:p.K464R mutation enhanced the tolerance of Olaparib by reducing the DNA damage. Mechanistically, MRE11:p.K464R mutation improved the efficiency of DNA damage repair and induce Olaparib resistance by enhancing its binding activity with the interacting proteins (including RAD50 and RPS3). Among them, the enhanced binding of MRE11:p.K464R mutation to RAD50/RPS3 facilitated non-homologous end joining (NHEJ) repair in tumor cells, thereby expanding the scope of research into acquired resistance to PARP inhibitors. CONCLUSIONS: Our findings provide a theoretical basis for MRE11:p.K464R mutation as a specific indicator of resistance monitoring in Olaparib treatment, and the exploration of its resistance mechanism provides a novel insights for the formulation of combination ther therapies after Olaparib resistance.

Effects of Educational Interventions in Facilitating Mammography Screening Among Asian American Women: A Meta-Analysis.

PROBLEM IDENTIFICATION: This meta-analysis evaluated the effects of various types of educational interventions on increasing breast cancer screening uptake among Asian American women. LITERATURE SEARCH: Web of Science, MEDLINE®, PubMed®, and Cochrane Library were searched for randomized controlled trials published from 2010 to 2020 of interventions developed to promote mammography uptake among Asian American women. DATA EVALUATION: A random-effects model was used to estimate pooled effect sizes using relative risk measures. A funnel plot was used to assess publication bias. SYNTHESIS: Seven studies were included in this review. Educational interventions identified were primarily culturally sensitive approaches combined with access-enhancing, individually tailored, or group-based approaches. The interventions were effective at increasing the receipt of mammography. IMPLICATIONS FOR NURSING: This review provides insight into the importance of combining other approaches with educational interventions to increase their effectiveness for Asian American women. Future interventions can incorporate various approaches to enhance the ability of Asian American women to overcome barriers to breast cancer screening.

Enhanced activity of the left precuneus as a predictor of visuospatial dysfunction correlates with disease activity in rheumatoid arthritis.

OBJECTIVE: To identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI). METHODS: A total of 27 RA patients (11 in remission, 16 in active) and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT. Brain activity data were collected using blood oxygen level dependent fMRI technique under MRT. Disease activity score 28 (DAS28) was used to evaluate the disease severity of RA patients. An analysis of the correlations between abnormal visuospatial-related brain regions, MRT performance, and DAS28 was conducted. RESULTS: RA patients performed worse on MRT than controls. Compared to the control group, RA patients showed enhanced activation in the left precuneus, left superior frontal gyrus and right cingulate gyrus during the rotation task, with left hemisphere dominance. RA patients in active showed enhanced activation in the left precuneus, left middle frontal gyrus and right cingulate gyrus compared to the patients in remission. The left precuneus activation was negatively correlated with MRT accuracy (r = -0.621, p = 0.01) and positively correlated with DAS28 (r = 0.710, p = 0.002), and MRT accuracy was negatively correlated with DAS28 in RA patients (r = -0.702, p = 0.002). CONCLUSION: Enhanced activation of the left precuneus in RA patients affects visuospatial function and is closely related to disease activity. These changes may provide a valuable diagnostic neuroimaging biomarker of RA.

How does the pattern of root metabolites regulating beneficial microorganisms change with different grazing pressures?

Grazing disturbance can change the structure of plant rhizosphere microbial communities and thereby alter the feedback to promote plant growth or induce plant defenses. However, little is known about how such changes occur and vary under different grazing pressures or the roles of root metabolites in altering the composition of rhizosphere microbial communities. In this study, the effects of different grazing pressures on the composition of microbial communities were investigated, and the mechanisms by which different grazing pressures changed rhizosphere microbiomes were explored with metabolomics. Grazing changed composition, functions, and co-expression networks of microbial communities. Under light grazing (LG), some saprophytic fungi, such as Lentinus sp., Ramichloridium sp., Ascobolus sp. and Hyphoderma sp., were significantly enriched, whereas under heavy grazing (HG), potentially beneficial rhizobacteria, such as Stenotrophomonas sp., Microbacterium sp., and Lysobacter sp., were significantly enriched. The beneficial mycorrhizal fungus Schizothecium sp. was significantly enriched in both LG and HG. Moreover, all enriched beneficial microorganisms were positively correlated with root metabolites, including amino acids (AAs), short-chain organic acids (SCOAs), and alkaloids. This suggests that these significantly enriched rhizosphere microbial changes may be caused by these differential root metabolites. Under LG, it is inferred that root metabolites, especially AAs such as L-Histidine, may regulate specific saprophytic fungi to participate in material transformations and the energy cycle and promote plant growth. Furthermore, to help alleviate the stress of HG and improve plant defenses, it is inferred that the root system actively regulates the synthesis of these root metabolites such as AAs, SCOAs, and alkaloids under grazing interference, and then secretes them to promote the growth of some specific plant growth-promoting rhizobacteria and fungi. To summarize, grasses can regulate beneficial microorganisms by changing root metabolites composition, and the response strategies vary under different grazing pressure in typical grassland ecosystems.

DNA methylation mediates overgrazing-induced clonal transgenerational plasticity.

Overgrazing generally induces dwarfism in grassland plants, and these phenotypic traits could be transmitted to clonal offspring even when overgrazing is excluded. However, the dwarfism-transmitted mechanism remains largely unknown, despite generally thought to be enabled by epigenetic modification. To clarify the potential role of DNA methylation on clonal transgenerational effects, we conducted a greenhouse experiment with Leymus chinensis clonal offspring from different cattle/sheep overgrazing histories via the demethylating agent 5-azacytidine. The results showed that clonal offspring from overgrazed (by cattle or sheep) parents were dwarfed and the auxin content of leaves significantly decreased compared to offspring from no-grazed parents'. The 5-azaC application generally increased the auxin content and promoted the growth of overgrazed offspring while inhibited no-grazed offspring growth. Meanwhile, there were similar trends in the expression level of genes related to auxin-responsive target genes (ARF7, ARF19), and signal transduction gene (AZF2). These results suggest that DNA methylation leads to overgrazing-induced plant transgenerational dwarfism via inhibiting auxin signal pathway.

Healthy Eating for All? The Challenge of Adhering to Dietary Guidelines for Low-Income Groups in China.

The Chinese Dietary Guidelines propose a balanced diet for healthy living, but the affordability of this diet needs to be considered, especially for low-income households. To investigate the affordability of a healthy diet, this study analyzes the daily retail prices of 46 food items in 36 Chinese cities from 2016 to 2021. This study compares expenditure, diet composition, and nutritional status in two scenarios aligned with the guidelines. The results show that the mean minimum cost of a balanced diet exceeds the current per capita food expenditure for at least 182.85 million urban households. This suggests that low-income people would need to increase their expenditure by at least 20-121% to achieve the recommended diets. This study also identifies affordable and nutrient-dense foods such as standard flour, eggs, black beans, and cabbage, which policymakers should focus on when monitoring food prices. The findings recommend a combination of social and food system policies to reduce prices and make healthy diets accessible. This study identifies the gaps in the Chinese Dietary Guidelines for ensuring accessibility for vulnerable groups and provides a template for policymakers and researchers to track diet affordability using available food price data in China, contributing to China's 2030 Health Plan and the UN's Sustainable Development Goals.

[Simultaneous determination of 43 antibacterials from nine categories in water using automatic sample loading-solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry].

Antibacterials represent a pharmaceutical class that is extensively used and consumed worldwide. The presence of a large number of antibacterial agents in water could result in antibiotic resistance. Thus, the development of a fast, accurate, and high-throughput method to analyze these emerging contaminants in water is necessary. Herein, a method was developed to achieve the simultaneous determination of 43 antibacterials from nine pharmaceutical categories (i.e., sulfonamides, quinolones, fluoroquinolones, tetracyclines, lincosamides, macrolides, nitroimidazoles, diterpenes, and dihydrofolate reductase inhibitors) in water using automatic sample loading-solid phase extraction (SPE)-ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Because the properties of these 43 antibacterials are quite different, the main objective of this work is to develop an extraction procedure that would enable the simultaneous analysis of a wide range of multiclass antibacterials. Given this context, the work presented in this paper optimized the SPE cartridge type, pH, and sample loading amount. Multiresidue extraction was performed as follows. The water samples were filtered through 0.45 µm filter membranes, added with Na2EDTA and NaH2PO4, and pH-adjusted to 2.34 using H3PO4. The solutions were then mixed with the internal standards. An automatic sample loading device fabricated by the authors was used for sample loading, and Oasis HLB cartridges were used for enrichment and purification. The optimized UPLC conditions were as follows: chromatographic column, Waters Acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm); mobile phases, methanol-acetonitrile (2∶8, v/v) solution containing 0.1% formic acid and 0.1% formic acid aqueous solution; flow rate, 0.3 mL/min; injection volume, 10 µL. The compounds were step scanned using an electrospray ionization source in the positive and multiple-reaction monitoring (MRM) modes, and analyzed by internal and external standard methods. The results showed that the 43 compounds achieved high linearity in their respective linear ranges, with correlation coefficients (r2) greater than 0.996. The limits of detection (LODs) of the 43 antibacterial agents ranged from 0.004 ng/L to 1.000 ng/L, and their limits of quantification (LOQs) ranged from 0.012 ng/L to 3.000 ng/L. The average recoveries ranged from 53.7% to 130.4%, and the relative standard deviations (RSDs) were between 0.9% and 13.2%. The method was successfully applied to the determination of six tap water samples from different districts and six water samples obtained from the Jiangyin section of the Yangtze River and Xicheng Canal. No antibacterial compound was detected in any of the tap water samples, but a total of 20 antibacterial compounds were detected in the river and canal water samples. Among these compounds, sulfamethoxazole showed the highest mass concentrations, ranging from 8.92 to 11.03 ng/L. The types and contents of antibacterials detected in the Xicheng Canal were greater than those found in the Yangtze River, and two kinds of diterpenes, namely tiamulin and valnemulin, were found easily and commonly in water sample. The findings indicate that antibacterial agents are widespread in environmental waters. The developed method is accurate, sensitive, rapid, and suitable for the detection of the 43 antibacterial compounds in water samples.

On diagnostic accuracy measure with cut-points criterion for ordinal disease classification based on concordance and discordance.

The accuracy of a diagnostic test has always been essential in detecting disease staging. Many diagnostic tests of accuracy measures are used in binary diagnosis tests. Some measures apply to multi-stage diagnosis. Yet, there are limitations to the implementation, and the performance highly depends on the distribution of diagnostic outcomes. Another essential aspect of medical diagnostic testing using biomarkers is to find an optimal cut-point that categorizes a patient as diseased or healthy. This aspect was extended to the diseases with more than two stages. We propose a diagnostic accuracy measure and optimal cut-points selection (CD), using concordance and discordance for k-stages diseases. The CD measure uses the classification agreement and disagreement between tests outcomes and diseases stages. Simulations for power studies suggest that CD can detect the differences between the null and alternative hypotheses that other methods cannot for some scenarios. Simulation results indicate that using CD measures to select optimal cut-points can provide relatively high correct classification rates than the existing measures and more balanced accurate classification rates than the generalized Youden Index (GYI). An illustration is provided using the ANDI data to choose biomarkers for diagnosing Alzheimer's Disease (AD) and select optimal cut-points for the chosen biomarkers.

Childhood Asthma-Management Practices in Rural Nigeria: Exploring the Knowledge, Attitude, and Practice of Caregivers in Oyo State.

Background: Caregivers of asthmatic children have a poor knowledge of proper asthma-management practices in Nigeria. This study examined the knowledge, attitudes, and practice behaviors of caregivers in the management of asthma in children under 5 years of age in Oyo State, Nigeria. Methods: While a mixed method was used in the original research, this brief describes the quantitative method used in this study to evaluate caregivers' asthma-management practices. A 55-item questionnaire on childhood asthma knowledge, attitude, and practice was administered during child welfare-clinic visits to 118 caregivers. Data were analyzed using the IBM SPSS Version 25.0. Statistical significance was set at p < 0.05 and 95% CI. Result: More than 70% of caregivers knew that asthma is associated with airway inflammation and about 90% knew that flu infections triggered asthma attacks in their children. Caregivers with a higher income (OR = 3.0; 95% CI = 1.558-5.778; p = 0.001) were 3.0 times more likely to practice proper asthma-care behavior than those with a lesser income. Conclusions: Childhood asthma remains underdiagnosed and undertreated in Nigeria. An optimal public health approach is needed to identify and target underserved communities that suffer poorer asthma outcomes and to improve caregivers' knowledge and practices of asthma management.

STAT4, a potential predictor of prognosis, promotes CD8 T­cell infiltration in ovarian serous carcinoma by inducing CCL5 secretion.

Ovarian serous carcinoma (OC) is a common cause of mortality among gynecological malignancies. Although tumor­infiltrating CD8 T cells are associated with a favorable prognosis of OC, the underlying mechanisms are not clearly understood. The present study identified the key genes and potential molecular mechanisms associated with CD8 T­cell infiltration in OC. The score of CD8 T cells in The Cancer Genome Atlas dataset (376 samples from patients with OC) was estimated using the quanTIseq and MCP­counter algorithms. Thereafter, a protein­protein interaction network of differentially expressed genes was constructed and the hub genes were identified using cytoHubba in Cytoscape. The results revealed that signal transducer and activator of transcription 4 (STAT4) was strongly correlated with CD8 T­cell infiltration in OC. Furthermore, the prognostic value of STAT4 in OC was verified by Kaplan­Meier curve, and univariate and multivariate analyses. The biological functions of STAT4 were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, which revealed that STAT4 is closely related to cytokines in OC. Moreover, Spearman correlation analysis suggested that STAT4 was most positively correlated with CC chemokine ligand 5 (CCL5). CCL5 was revealed to be critical for orchestrating T­cell infiltration in tumors. Moreover, immunohistochemistry and reverse transcription­quantitative PCR showed that STAT4, CCL5 and CD8A (a marker for CD8 T cells) were closely related in OC. Moreover, in vitro analysis revealed that STAT4 knockdown led to a decrease in CCL5 expression and CD8 T­cell migration. Taken together, the present study suggested that STAT4 may regulate CD8 T­cell infiltration in OC tissues by inducing CCL5 secretion. Furthermore, STAT4 may be considered a promising prognostic biomarker for OC.

PIG-A gene mutation as a mutagenicity biomarker among coke oven workers.

PIG-A gene mutations can be detected in humans, and PIG-A assays can potentially predict the risk of exposure to carcinogens. However, extensive, population-based studies to validate this are lacking. We studied a cohort of occupational coke oven workers with chronic high exposure to carcinogenic polycyclic aromatic hydrocarbons, which are well-studied genotoxins classified by the IARC as carcinogenic to humans. Peripheral blood erythrocytes of workers were assessed for gene mutations using a PIG-A assay, and chromosome damage using the cytokinesis-block micronucleus test with lymphocytes. Two sample populations from a non-industrialized city and new employees in industrial plants were selected as controls. We observed a significantly elevated PIG-A mutation frequency (MF) and increased frequencies of micronuclei (MN) and nuclear buds (NBUDs) in coke oven workers, compared with levels in the control groups. We found that the coke oven workers with different lengths of service had a relatively high mutation frequency. Overall, the study findings showed that occupational exposure of coke oven workers increases the genetic damage and the PIG-A MF could be a potential biomarker for risk assessment of carcinogen exposure.