Submission of Evidence on Online Violence Against Women to the UN Special Rapporteur on Violence Against Women, its Causes and Consequences, Dr Dubravka Šimonović

Figure S1. B3GALNT2 levels determined by W.B. and ROC curve. a–c Relative mRNA expression of B3GALNT2 in HCC tumor tissues and normal liver tissues obtained from GSE76427, GSE36376, and TCGA-LIHC datasets. d Western blot analysis of B3GALNT2 levels in 24 pairs of HCC tissues. T HCC tumor tissue, N adjacent non-tumor tissue. e ROC curve analysis of the sensitivity and specificity for the predictive value of TNM model, B3GALNT2 expression, and the combination model. (TIFF 546 kb

Clinical characteristics and related influencing factors of common rheumatic diseases concomitant with tuberculosis

ObjectiveTo explore the clinical characteristics and risk factors of common systemic rheumatism concomitant with tuberculosis (TB).MethodsA total of 3,906 patients of RA, SLE, and SS diagnosed in the People's Hospital of Sichuan Province from January 2007 to January 2017 were collected. One hundred and five patients with TB were included as TB group, including 42 RA, 41 SLE, and 22 SS patients. In the non-TB group, 84 RA, 82 SLE, and 44 SS patients were randomly selected during the same period.ResultsFever was the most common symptom among RA, SLE, and SS patients with TB, accounting for 83.3%, 92.7%, and 68.2%, respectively. Cough, weight loss or fatigue were the next common. RA patients with TB were mostly pulmonary TB (PTB), accounting for 64.3%. The proportion of PTB for SLE and SS were 46.3%, 59.01%, respectively. In TB group, 59% RA, 57% SLE, and 62% SS with PTB had two or more chest CT findings. There were 48 TB cases received both Interferon Gamma Release Assay (IGRA) and Tuberculin skin test (TST) with positive rates of 91.8%, 45.8%, respectively. The daily average dose of glucocorticoids within 1 year in TB group was higher than that in non-TB group of SLE patients, lower counts of CD4+ T cell count were found in TB group (P < 0.05), while no such differences were found in RA and SS patients.ConclusionRA patients with TB are mainly pulmonary TB. For SLE and SS patients, the chance of PTB and extrapulmonary tuberculosis is similar. Daily average dose of glucocorticoids within 1 year may be a common risk factor for RA, SLE and SS patients developing TB. Decreased CD4+ T cell count may also be a risk factor for SLE patients with TB. Symptoms of RA, SLE, SS with TB, are similar with the primary disease or other infection. It is recommended to conduct both TST and IGRA to help diagnose TB

Prevalence and related factors of epilepsy in children and adolescents with cerebral palsy: a systematic review and meta-analysis

Objective: To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups. Method: We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger’s test were used to investigate potential publication bias. Results: Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%–41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%–51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%–34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP. Conclusion: Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population

Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water

Chronic arsenic exposures via the consumption of contaminated drinking water are clearly associated with many deleterious health outcomes, including anemia. Following exposure, trivalent inorganic arsenic (AsIII) is methylated through a series of arsenic (+III oxidation state) methyltransferase (As3MT)-dependent reactions, resulting in the production of several intermediates with greater toxicity than the parent inorganic arsenicals. The extent to which inorganic vs. methylated arsenicals contribute to AsIII-induced hematotoxicity remains unknown. In this study, the contribution of As3MT-dependent biotransformation to the development of anemia was evaluated in male As3mt-knockout (KO) and wild-type, C57BL/6J, mice following 60-day drinking water exposures to 1 mg/L (ppm) AsIII. The evaluation of hematological indicators of anemia revealed significant reductions in red blood cell counts, hemoglobin levels, and hematocrit in AsIII-exposed wild-type mice as compared to unexposed controls. No such changes in the blood of As3mt-KO mice were detected. Compared with unexposed controls, the percentages of mature RBCs in the bone marrow and spleen (measured by flow cytometry) were significantly reduced in the bone marrow of AsIII-exposed wild-type, but not As3mt-KO mice. This was accompanied by increased levels of mature RBCS in the spleen and elevated levels of circulating erythropoietin in the serum of AsIII-exposed wild-type, but not As3mt-KO mice. Taken together, the findings from the present study suggest that As3MT-dependent biotransformation has an essential role in mediating the hematotoxicity of AsIII following drinking water exposures

ESNOQ, Proteomic Quantification of Endogenous S-Nitrosation

S-nitrosation is a post-translational protein modification and is one of the most important mechanisms of NO signaling. Endogenous S-nitrosothiol (SNO) quantification is a challenge for detailed functional studies. Here we developed an ESNOQ (Endogenous SNO Quantification) method which combines the stable isotope labeling by amino acids in cell culture (SILAC) technique with the detergent-free biotin-switch assay and LC-MS/MS. After confirming the accuracy of quantification in this method, we obtained an endogenous S-nitrosation proteome for LPS/IFN-γ induced RAW264.7 cells. 27 S-nitrosated protein targets were confirmed and using our method we were able to obtain quantitative information on the level of S-nitrosation on each modified Cys. With this quantitative information, over 15 more S-nitrosated targets were identified than in previous studies. Based on the quantification results, we found that the S-nitrosation levels of different cysteines varied within one protein, providing direct evidence for differences in the sensitivity of cysteine residues to reactive nitrosative stress and that S-nitrosation is a site-specific modification. Gene ontology clustering shows that S-nitrosation targets in the LPS/IFN-γ induced RAW264.7 cell model were functionally enriched in protein translation and glycolysis, suggesting that S-nitrosation may function by regulating multiple pathways. The ESNOQ method described here thus provides a solution for quantification of multiple endogenous S-nitrosation events, and makes it possible to elucidate the network of relationships between endogenous S-nitrosation targets involved in different cellular processes

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs