Relationship between occupational stress and job burnout among rural-to-urban migrant workers in Dongguan, China: a cross-sectional study

Objectives: In China, there have been an increasing number of migrant workers from rural to urban areas, and migrant workers have the highest incidence of occupational diseases. However, few studies have examined the impact of occupational stress on job burnout in these migrant workers. This study aimed to investigate the relationship between occupational stress and job burnout among migrant workers. Design: This study used a cross-sectional survey. Setting: This investigation was conducted in Dongguan city, Guangdong Province, China. Participants: 3806 migrant workers, aged 18–60 years, were randomly selected using multistage sampling procedures. Primary and secondary outcome measures: Multistage sampling procedures were used to examine demographic characteristics, behaviour customs and jobrelated data. Hierarchical linear regression and logistic regression models were constructed to explore the relationship between occupational stress and burnout. Results: Demographics, behaviour customs and jobrelated characteristics significantly affected on burnout. After adjusting for the control variable, a high level of emotional exhaustion was associated with high role overload, high role insufficiency, high role boundary, high physical environment, high psychological strain, high physical strain, low role ambiguity, low responsibility and low vocational strain. A high level of depersonalisation was associated with high role overload, high role ambiguity, high role boundary, high interpersonal strain, high recreation, low physical environment and low social support. A low level of personal accomplishment was associated with high role boundary, high role insufficiency, low responsibility, low social support, low physical environment, low self-care and low interpersonal strain. Compared to the personal resources, the job strain and personal strain were more likely to explain the burnout of rural-to-urban migrant workers in our study. Conclusions: The migrant workers have increased job burnouts in relation to occupational stress. Relieving occupational stress and maintaining an appropriate quantity and quality of work could be important measures for preventing job burnout among these workers

Endocrine treatment mechanisms in triple-positive breast cancer: from targeted therapies to advances in precision medicine

Triple-positive breast cancer (TPBC), defined by the co-expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), poses unique therapeutic challenges due to complex signaling interactions and resulting treatment resistance. This review summarizes key findings on the molecular mechanisms and cross-talk among ER, PR, and HER2 pathways, which drive tumor proliferation and resistance to conventional therapies. Current strategies in TPBC treatment, including endocrine and HER2-targeted therapies, are explored alongside emerging approaches such as immunotherapy and CRISPR/Cas9 gene editing. Additionally, we discuss the tumor microenvironment (TME) and its role in treatment resistance, highlighting promising avenues for intervention through combination therapies and predictive biomarkers. By addressing these interdependent pathways and optimizing therapeutic strategies, precision medicine holds significant potential for improving TPBC patient outcomes and advancing individualized cancer care

Microwave-assisted aqueous two-phase extraction of alkaloids from Radix Sophorae Tonkinensis with ethanol/Na2HPO4 system: process optimization, composition identification and quantification analysis

A rapid method for simultaneous extraction and separation of multiple alkaloids from Radix Sophorae Tonkinensis (RST) was developed by microwave-assisted aqueous two-phase extraction (MAATPE) using the aqueous two-phase extraction system (ATPS) of ethanol/Na2HPO4 as the extraction solvent. The effects of key factors on extraction yield were investigated by utilizing single-factor experiment coupled to response surface methodology (RSM). The regression model by RSM was significant (p < 0.0001) and adequate for prediction of process efficacy, the optimized conditions were successfully validated by the parallel experiments with the yield very close to the predicted value. The optimum conditions were summarized as follows: the phase ratio of 2.60 for the ATPS, the particle size of 100 mesh, the liquid-to-material ratio of 75:1, the extraction temperature of 90 °C and the extraction time of 5 min, respectively. In MAATPE process, alkaloids were extracted preferentially from RST in the top phase with a higher yield and shorter extraction time than those of heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE). Nine alkaloids extracted were identified and quantified by high-resolution ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap/MS) and HPLC with UV detection. The contents of matrine, sophocarpine, oxymatrin, sophoranol, oxysophocarpine, 5α-hydroxysophocarpine, sophoridine, cytisine and N-methylcytisine in RST were quantified in range of 0.493–10.284 mg/g with recoveries of 90.26–106.3% and RSD’s of 0.8–2.1%, respectively. Moreover, the MAATPE mechanism was explored using the different extraction systems in combination of scanning electron microscopy (SEM) morphological studies. Significant differences in extraction yield and cell rupture exhibited that the addition of the salt in the ethanol-water mixture not only improved the thermal and demixing effects, but also accelerated the mass transfer and biphasic extraction processes. MAATPE integrated the advantages of microwave-assisted extraction (MAE) and aqueous two-phase extraction (ATPE) was proved as a green, efficient and promising alternative to extraction of alkaloids from RST

deepDriver: Predicting Cancer Driver Genes Based on Somatic Mutations Using Deep Convolutional Neural Networks

With the advances in high-throughput technologies, millions of somatic mutations have been reported in the past decade. Identifying driver genes with oncogenic mutations from these data is a critical and challenging problem. Many computational methods have been proposed to predict driver genes. Among them, machine learning-based methods usually train a classifier with representations that concatenate various types of features extracted from different kinds of data. Although successful, simply concatenating different types of features may not be the best way to fuse these data. We notice that a few types of data characterize the similarities of genes, to better integrate them with other data and improve the accuracy of driver gene prediction, in this study, a deep learning-based method (deepDriver) is proposed by performing convolution on mutation-based features of genes and their neighbors in the similarity networks. The method allows the convolutional neural network to learn information within mutation data and similarity networks simultaneously, which enhances the prediction of driver genes. deepDriver achieves AUC scores of 0.984 and 0.976 on breast cancer and colorectal cancer, which are superior to the competing algorithms. Further evaluations of the top 10 predictions also demonstrate that deepDriver is valuable for predicting new driver genes

Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system

AimThe aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database.MethodsAll data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI &gt;1, based on at least 3 reports.ResultsTotal of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (&gt;65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)].ConclusionThis study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks

Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a group of clinically and genetically heterogeneous neurodevelopmental disorders. Recent tremendous advances in the whole exome sequencing (WES) enable rapid identification of variants associated with ASD including single nucleotide variations (SNVs) and indels. To further explore genetic etiology of ASD in Chinese children with negative findings of copy number variants (CNVs), we applied WES in 80 simplex families with a single affected offspring with ASD or suspected ASD, and validated variations predicted to be damaging by Sanger sequencing. The results showed that an overall diagnostic yield of 8.8% (9.2% in the group of ASD and 6.7% in the group of suspected ASD) was observed in our cohort. Among patients with diagnosed ASD, developmental delay or intellectual disability (DD/ID) was the most common comorbidity with a diagnostic yield of 13.3%, followed by seizures (50.0%) and craniofacial anomalies (40.0%). All of identified de novo SNVs and indels among patients with ASD were loss of function (LOF) variations and were slightly more frequent among female (male vs. female: 7.3% vs. 8.5%). A total of seven presumed causative genes (CHD8, AFF2, ADNP, POGZ, SHANK3, IL1RAPL1, and PTEN) were identified in this study. In conclusion, WES is an efficient diagnostic tool for diagnosed ASD especially those with negative findings of CNVs and other neurological disorders in clinical practice, enabling early identification of disease related genes and contributing to precision and personalized medicine

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted ‘blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Shenkang Hospital Development Center Shanghai Municipal Education Commission National Natural Science Foundation of China Shanghai Committee of Science and Technology Xinhua Hospital of Shanghai Jiao Tong University School of Medicine Guangdong Key Project in "Development of new tools for diagnosis and treatment of Autism "Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Municipal Education Commission National Natural Science Foundation of China the National Key Research and Development Program of China ZJ LabFunder: National Human Genetic Resources Sharing Service Platform 111 Project ZJ LabFunder: National Natural Science Foundation of China ZJ LabAbstract: Bumetanide has been reported to alter synaptic excitation–inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

The GTPase Activating Rap/RanGAP Domain-Like 1 Gene Is Associated with Chicken Reproductive Traits

BACKGROUND: Abundant evidence indicates that chicken reproduction is strictly regulated by the hypothalamic-pituitary-gonad (HPG) axis, and the genes included in the HPG axis have been studied extensively. However, the question remains as to whether any other genes outside of the HPG system are involved in regulating chicken reproduction. The present study was aimed to identify, on a genome-wide level, novel genes associated with chicken reproductive traits. METHODOLOGY/PRINCIPAL FINDING: Suppressive subtractive hybridization (SSH), genome-wide association study (GWAS), and gene-centric GWAS were used to identify novel genes underlying chicken reproduction. Single marker-trait association analysis with a large population and allelic frequency spectrum analysis were used to confirm the effects of candidate genes. Using two full-sib Ningdu Sanhuang (NDH) chickens, GARNL1 was identified as a candidate gene involved in chicken broodiness by SSH analysis. Its expression levels in the hypothalamus and pituitary were significantly higher in brooding chickens than in non-brooding chickens. GWAS analysis with a NDH two tail sample showed that 2802 SNPs were significantly associated with egg number at 300 d of age (EN300). Among the 2802 SNPs, 2 SNPs composed a block overlapping the GARNL1 gene. The gene-centric GWAS analysis with another two tail sample of NDH showed that GARNL1 was strongly associated with EN300 and age at first egg (AFE). Single marker-trait association analysis in 1301 female NDH chickens confirmed that variation in this gene was related to EN300 and AFE. The allelic frequency spectrum of the SNP rs15700989 among 5 different populations supported the above associations. Western blotting, RT-PCR, and qPCR were used to analyze alternative splicing of the GARNL1 gene. RT-PCR detected 5 transcripts and revealed that the transcript, which has a 141 bp insertion, was expressed in a tissue-specific manner. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the GARNL1 gene contributes to chicken reproductive traits