Global, regional, and national time trends in incidence for migraine, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: The majority of epidemiological studies on migraine have been conducted in a specific country or region, and there is a lack of globally comparable data. We aim to report the latest information on global migraine incidence overview trends from 1990 to 2019. METHODS: In this study, the available data were obtained from the Global Burden of Disease 2019. We present temporal trends in migraine for the world and its 204 countries and territories over the past 30 years. Meanwhile, an age-period-cohort model be used to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. RESULTS: In 2019, the global incidence of migraine increased to 87.6 million (95% UI: 76.6, 98.7), with an increase of 40.1% compared to 1990. India, China, United States of America, and Indonesia had the highest number of incidences, accounting for 43.6% of incidences globally. Females experienced a higher incidence than males, the highest incidence rate was observed in the 10-14 age group. However, there was a gradual transition in the age distribution of incidence from teenagers to middle-aged populations. The net drift of incidence rate ranged from 3.45% (95% CI: 2.38, 4.54) in high-middle Socio-demographic Index (SDI) regions to -4.02% (95% CI: -4.79, -3.18) in low SDI regions, 9 of 204 countries showed increasing trends (net drifts and its 95% CI were > 0) in incidence rate. The age-period-cohort analysis results showed that the relative risk of incidence rate generally showed unfavorable trends over time and in successively birth cohorts among high-, high-middle-, and middle SDI regions, but low-middle- and low-SDI regions keep stable. CONCLUSIONS: Migraine is still an important contributor to the global burden of neurological disorders worldwide. Temporal trends in migraine incidence are not commensurate with socioeconomic development and vary widely across countries. Both sexes and all age groups should get healthcare to address the growing migraine population, especially adolescents and females.

[Effect and mechanism of Dahuang Zhechong Pills against testicular aging in rats by inhibiting necroptosis signaling pathway].

To explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a classical prescription, in improving testicular aging(TA) in vivo, the authors randomly divided 24 male rats into four groups: the normal, model, DHZCP and vitamin E(VE) groups. The TA rat model was established by continuous gavage of D-galactose(D-gal). During the experiment, the rats in the DHZCP and VE groups were given DHZCP suspension and VE suspension, respectively by gavage, while those in the normal and model groups were gavaged saline separately every day. After the co-administration of D-gal and various drugs for 60 days, all rats were sacrificed, and their blood and testis were collected. Further, various indexes related to TA and necroptosis of testicular cells in the model rats were examined and investigated, which included the aging phenotype, total testicular weight, testicular index, histopathological features of testis, number of spermatogenic cells, sex hormone level, expression characteristics of reactive oxygen species(ROS) in testis, expression levels and characteristics of cyclins in testis, and protein expression levels of the key molecules in receptor-interacting serine/threonine-protein kinase 1(RIPK1)/receptor-interacting serine/threonine-protein kinase 3(RIPK3)/mixed lineage kinase domain like pseudokinase(MLKL) signaling pathway in each group. The results showed that, for the TA model rats, both DHZCP and VE improved their aging phenotype, total testicular weight, testicular index, pathological features of testis, number of spermatogenic cells, serum testosterone and follicle stimulating hormone levels, expression characteristics of ROS and protein expression levels and characteristics of P21 and P53 in testis. In addition, DHZCP and VE improved the protein expression levels of the key molecules in RIPK1/RIPK3/MLKL signaling pathway in testis of the model rats. Specifically, DHZCP was better than VE in the improvement of RIPK3. In conclusion, in this study, the authors found that DHZCP, similar to VE, ameliorated D-gal-induced TA in model rats in vivo, and its mechanism was related to reducing necroptosis of testicular cells by inhibiting the activation of RIPK1/RIPK3/MLKL signaling pathway. This study provided preliminary pharmacological evidence for the development and application of classical prescriptions in the field of men's health.

SPOT-Fold: Fragment-Free Protein Structure Prediction Guided by Predicted Backbone Structure and Contact Map.

Protein structure determination has long been one of the most challenging problems in molecular biology for the past 60 years. Here we present an ab initio protein tertiary-structure prediction method assisted by predicted contact maps from SPOT-Contact and predicted dihedral angles from SPIDER 3. These predicted properties were then fed to the crystallography and NMR system (CNS) for restrained structure modeling. The resulted structures are first evaluated by the potential energy calculated by CNS, followed by dDFIRE energy function for model selections. The method called SPOT-Fold has been tested on 241 CASP targets between 67 and 670 amino acid residues, 60 randomly selected globular proteins under 100 amino acids. The method has a comparable accuracy to other contact-map-based modeling techniques. © 2019 Wiley Periodicals, Inc.

miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1.

AIM OF THE STUDY: To investigate the role of microRNA-221 (miR-221) in the airway epithelial cell injury in asthma and delineate the underlying mechanism that may involve with SIRT1. MATERIALS AND METHOD: Bronchial epithelial cells from asthma patients and healthy controls were obtained by bronchoscopic brushing. The miR-221 and SIRT1 mRNA level in collected cells were detected by qRT-CPR. BEAS2B cell lines were cultured in vitro. In order to up-regulate miR-221 and SIRT1, miR-221 mimic and pcDNA3.1-SIRT1 vector was transfected into BEAS2B cells, respectively. The expression changes of miR-221 and SIRT1 after transfection was observed by qRT-PCR and Western blot. The target relationship between miR-221 and SIRT1 was confirmed using dual-luciferase reporter assay.The cell viability changes after transfection was measured using cellTiter-blue reagent. The apoptosis rate was detected by flow cytometry. RESULT: Compared with healthy controls, miR-221 expression significantly increased in bronchial epithelial cells from patients subjects. In contrast, the level of SIRT1 mRNA reduced in the bronchial epithelial cell from asthma patients. In vitro, up-regulation of miR-221 could inhibit the expression of SIRT1 both at mRNA and protein level in BEAS2B cells. A negative correlation between miR-221 and SIRT1 mRNA in samples from patients was confirmed and dual-luciferase reporter assay showed that miR-221 directly binds to the 3'UTR of SIRT1 mRNA. Overexpression of miR-221 or SIRT1 knockdown could inhibit proliferation but induce apoptosis in BEAS2B cells. Moreover, up-regulation of SIRT1 could antagonize miR-221's inhibitory effect. CONCLUSION: miR-221 may participate in the airway epithelial cells injury in asthma via targeting SIRT1.

Modulation of HIV protease flexibility by the T80N mutation.

The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle X-ray scattering (WAXS) data was measured for a series of HIVp variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared with the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIVp and is critical to catalytic function.

Desulfurization of immobilized sulfur-oxidizing bacteria, Thialkalivibrio versutus, by magnetic nanaoparticles under haloalkaliphilic conditions.

OBJECTIVES: As a haloalkaliphilic, sulfur-oxidizing bacteria, Thialkalivibrio versutus D301 can remove sulfide, thiosulfate and polysulfide in wastewater, we investigated how it might be reused when mixed with high concentrations of elemental sulfur. RESULTS: A process is described to immobilize T. versutus cells by using superparamagnetic Fe3O4 nanoparticles (NPs) under haloalkaliphilic conditions (i.e. pH 9.5, 0.5 M Na(+)). The saturation magnetization value (δs) of immobilized cells was 55.1 emu/g. The Fe3O4 NPs-coated cells had the similar sulfur oxidization activity to that of free cells, and they could be reused six batch cycles. Analysis of hydraulic diameters showed that bacterial cells were immobilized by Fe3O4 NPs due to the nano-size effects. CONCLUSIONS: Magnetic immobilization is a convenient technique for cell immobilization under haloalkaliphilic conditions and is a promising technology for large scale application.

Drug resistance conferred by mutations outside the active site through alterations in the dynamic and structural ensemble of HIV-1 protease.

HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRV-protease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure and dynamic ensemble of HIV-1 protease active site. These alterations correlate with the observed inhibitor binding affinities for the mutants, and suggest a network hypothesis on how the effect of distal mutations are propagated to pivotal residues at the active site and may contribute to conferring drug resistance.

Prediction of mortality events of patients with acute heart failure in intensive care unit based on deep neural network.

BACKGROUND: Acute heart failure (AHF) in the intensive care unit (ICU) is characterized by its criticality, rapid progression, complex and changeable condition, and its pathophysiological process involves the interaction of multiple organs and systems. This makes it difficult to predict in-hospital mortality events comprehensively and accurately. Traditional analysis methods based on statistics and machine learning suffer from insufficient model performance, poor accuracy caused by prior dependence, and difficulty in adequately considering the complex relationships between multiple risk factors. Therefore, the application of deep neural network (DNN) techniques to the specific scenario, predicting mortality events of patients with AHF under intensive care, has become a research frontier. METHODS: This research utilized the MIMIC-IV critical care database as the primary data source and employed the synthetic minority over-sampling technique (SMOTE) to balance the dataset. Deep neural network models-backpropagation neural network (BPNN) and recurrent neural network (RNN), which are based on electronic medical record data mining, were employed to investigate the in-hospital death event judgment task of patients with AHF under intensive care. Additionally, multiple single machine learning models and ensemble learning models were constructed for comparative experiments. Moreover, we achieved various optimal performance combinations by modifying the classification threshold of deep neural network models to address the diverse real-world requirements in the ICU. Finally, we conducted an interpretable deep model using SHapley Additive exPlanations (SHAP) to uncover the most influential medical record features for each patient from the aspects of global and local interpretation. RESULTS: In terms of model performance in this scenario, deep neural network models outperform both single machine learning models and ensemble learning models, achieving the highest Accuracy, Precision, Recall, F1 value, and Area under the ROC curve, which can reach 0.949, 0.925, 0.983, 0.953, and 0.987 respectively. SHAP value analysis revealed that the ICU scores (APSIII, OASIS, SOFA) are significantly correlated with the occurrence of in-hospital fatal events. CONCLUSIONS: Our study underscores that DNN-based mortality event classifier offers a novel intelligent approach for forecasting and assessing the prognosis of AHF patients in the ICU. Additionally, the ICU scores stand out as the most predictive features, which implies that in the decision-making process of the models, ICU scores can provide the most crucial information, making the greatest positive or negative contribution to influence the incidence of in-hospital mortality among patients with acute heart failure.

Factors influencing user's health information discernment abilities in online health communities: based on SEM and fsQCA.

Introduction: Online health communities have become the main source for people to obtain health information. However, the existence of poor-quality health information, misinformation, and rumors in online health communities increases the challenges in governing information quality. It not only affects users' health decisions but also undermines social stability. It is of great significance to explore the factors that affect users' ability to discern information in online health communities. Methods: This study integrated the Stimulus-Organism-Response Theory, Information Ecology Theory and the Mindsponge Theory to constructed a model of factors influencing users' health information discernment abilities in online health communities. A questionnaire was designed based on the variables in the model, and data was collected. Utilizing Structural Equation Modeling (SEM) in conjunction with fuzzy-set Qualitative Comparative Analysis (fsQCA), the study analyzed the complex causal relationships among stimulus factors, user perception, and the health information discernment abilities. Results: The results revealed that the dimensions of information, information environment, information technology, and information people all positively influenced health information discernment abilities. Four distinct configurations were identified as triggers for users' health information discernment abilities. The core conditions included information source, informational support, technological security, technological facilitation, and perceived risk. It was also observed that information quality and emotional support can act as substitutes for one another, as can informational support and emotional support. Discussion: This study provides a new perspective to study the influencing factors of health information discernment abilities of online health community users. It can provide experiences and references for online health community information services, information resource construction and the development of users' health information discernment abilities.

Identification of a CircRNA-miRNA-mRNA Network and Integrated Analysis of Immune Infiltration in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly invasive type of head and neck cancer. Circular RNA (circRNA) acts as a competing endogenous RNA (ceRNA) and involves in pathogenesis of many diseases. However, the circRNA-miRNA-mRNA network and relationship between ceRNA and immune infiltration in OSCC remain unknown. In this study, we established a ceRNA network, including 89 circRNAs, 43 miRNAs and 223 mRNAs, and found that 233 genes are mainly related to malignant signalling pathways (including "Integrin family cell surface interactions" and "Epithelial-to-mesenchymal transition" pathways) and five potential biomarkers (SLC20A1, PITX2, hsa-mir-135b, hsa-mir-377 and hsa-let-7c). Meanwhile, we established a prognostic model based on clinical risk, and revealed the relationship between immune infiltrating cells and biomarkers in OSCC. Taken together, our study is helpful to reveal the pathogenesis of oral squamous cell carcinoma.