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To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level.
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Background: Few studies have focused on the region-specific relationship between cardiovascular disease (CVD) and low temperature worldwide. Objective: We aimed to provide an overview of trends in mortality and disability-adjusted life years (DALYs) for CVD and its subtypes attributable to low temperature over the past 30 years in 204 countries and regions, along with the associations of these trends with age, period, and birth cohorts. Methods: Data on the estimated burden of CVDs (including ischemic heart disease, hypertensive heart disease, and stroke) attributable to low temperature were obtained from the Global Burden of Disease Study 2019. We utilized an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 15 ~ 19 to 81 ~ 85 years (local drifts), and period and cohort relative risk (period/cohort effects) between 1990 and 2019. Results: Among noncommunicable diseases, CVDs had the highest mortality rate and DALY loss attributable to low temperature worldwide and has increased from 65.7 to 67.3%, which is mainly attributed to the increase in East Asia and Pacific region. In terms of the level of economic and social development, an inverted U-shape was found in the age-standardized mortality rates (ASMR) due to low-temperature across different sociodemographic indices (SDI) regions. Both high CVD mortality (19.45, 95% CI [14.54, 24.17%]) and a decreasing mortality rate related to low temperature (from 1990 to 2019, net drift, -3.25% [-3.76, 2.73%] per year) was found in high SDI countries or territories, with opposite outcome found in low SDIs regions. The older adults (70+) and men share the highest rate of CVD ASMR and DALY attributed to low temperature across all regions, especially in North America and Europe and Central Asia. Conclusion: Mortality and DALY loss from CVD attributable to low temperature showed an overall decreasing trend globally except for East Asia and Pacific region. SDI, sex, age and geographic location contributed to the diversity of the CVD disease burden associated with low temperature worldwide. More attention should be given to the older adults, men, and low SDI regions.
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Doenças Cardiovasculares , Temperatura Baixa , Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Saúde Global , Humanos , Doenças Cardiovasculares/mortalidade , Carga Global da Doença/tendências , Idoso , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , Temperatura Baixa/efeitos adversos , Saúde Global/estatística & dados numéricos , Adolescente , Adulto Jovem , Mortalidade/tendênciasRESUMO
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with circulatory and/or pulmonary failure; however, the rate of complications remains high. ECMO induces systemic inflammation, which may activate and damage the endothelium, thereby causing edema and organ dysfunction. Advancing our understanding in this area is crucial for improving patient outcomes during ECMO. The goal of this review is to summarize the current evidence of the effects of ECMO on endothelial activation and damage in both animals and patients. PubMed and Embase databases were systematically searched for both clinical and animal studies including ECMO support. The outcome parameters were markers of endothelial activation and damage or (in)direct measurements of endothelial permeability, fluid leakage and edema. In total, 26 studies (patient n = 16, animal n = 10) fulfilled all eligibility criteria, and used VA-ECMO (n = 13) or VV-ECMO (n = 6), or remained undefined (n = 7). The most frequently studied endothelial activation markers were adhesion molecules (ICAM-1) and selectins (E- and P-selectin). The levels of endothelial activation markers were comparable to or higher than in healthy controls. Compared to pre-ECMO or non-ECMO, the majority of studies showed stable or decreased levels. Angiopoietin-2, von Willebrand Factor and extracellular vesicles were the most widely studied circulating markers of endothelial damage. More than half of the included studies showed increased levels when compared to normal ranges, and pre-ECMO or non-ECMO values. In healthy animals, ECMO itself leads to vascular leakage and edema. The effect of ECMO support in critically ill animals showed contradicting results. ECMO support (further) induces endothelial damage, but endothelial activation does not, in the critically ill. Further research is necessary to conclude on the effect of the underlying comorbidity and type of ECMO support applied on endothelial dysfunction.
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Endotélio Vascular , Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Animais , Endotélio Vascular/metabolismo , Biomarcadores , Endotélio/metabolismoRESUMO
OBJECTIVES: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a defect in the production, secretion or action of gonadotropin-releasing hormone. The absence of puberty and varying degrees of gonadotropic deficiency are common symptoms of this disorder. Heterogeneity exists in the clinical presentation of the different clinical subtypes and multiple genes have been implicated in CHH. A number of genetic defects have been identified as causes normosmic CHH, including mutations of GnRHR, GNRH1, KISS1R, KISS1, TACR3 and TAC3. Loss-of-function mutations in KISS1R gene are a rare cause of normosmic CHH. CASE PRESENTATION: We described an 11.5 years old Chinese patient who presented at birth with micropenis, microorchidia and bilateral cryptorchidism. Whole-exome sequencing was also performed and identified a homozygous mutation of KISS1R gene, c.1010_1028del (p.V337Afs*82). The variant was predicted as "deleterious" and classified as "likely pathogenic". This variant has never been reported in patients with CHH. Furthermore, we summarized the clinical presentations and analyzed the phenotype-genotype correlation between CHH and KISS1R mutations in previous reports. CONCLUSIONS: This study details the clinical phenotypes and hormone levels of the patient and expands the spectrum of mutations in the KISS1R gene associated with CHH.
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Disulfidptosis, a new form of cell death, may be induced by disulfide stress associated with cystine disulfide buildup, which can promote cell toxicity, leading to cell death. Nevertheless, the role of direct prognosis and the mechanism underlying the regulation of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) are still unknown. This study aimed to investigate the role of DRGs in LUAD prognosis and diagnosis through multiomics analysis. First, copy number variations (CNVs) and mutations in the 10 genes were assessed. Considering that five differentially expressed genes (DEGs) were associated with disulfidptosis, a novel DRG score that can be utilized to anticipate LUAD prognosis was developed. Next, the generated receiver operating characteristic (ROC) and survival curves demonstrated that the model had an excellent predictive quality in LUAD in both the training and validation cohorts. Meanwhile, substantial functional disparities between the high DRG group and the low DRG group were observed, and the second gap mitosis (G2M) checkpoint, E2 promoter-binding factor (E2F) targets, and myelocytomatosis (MYC) target activities were consistently higher in the high DRG group than in the low DRG group. Additionally, the T-cell dysfunction score and tumor inflammation signature (Merck18) were negatively correlated with DRGs, whereas myeloid-derived suppressor cells (MDSCs) were positively correlated with DRGs. Moreover, DRGs were negatively linked to most of the immunological checkpoints. Meanwhile, samples of low DRGs benefited more from immune checkpoint blockade (ICB). The correlation analysis between DRGs and clinical characteristics revealed increasing malignancy with increasing DRG scores. Drug sensitization experiment results indicated that sensitivity to cisplatin, vincristine, docetaxel, and gemcitabine was higher in the high DRG group than in the low DRG group. The function of model genes in LUAD was also verified using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, 5-ethynyl-2'-deoxyuridine (EDU), and clonogenic formation.
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Objective: Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the effectiveness of rTMS on executive function in VCI. Methods: The databases selected for this study included Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biology Medicine Disc (CBM). The screening times were conducted from the time of library construction until August 23, 2023. The inclusion criteria for this meta-analysis were randomized controlled trials (RCTs) on rTMS for VCI, which include executive function scores. The primary metrics were executive subscale scores of the Cognitive Comprehensive Scale and total scores of the Executive Specificity Scale. The secondary metrics were subscale scores of the Executive Specificity Scale. The quality of each eligible study was assessed using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: A total of 20 high-quality clinical RCTs with 1,049 samples were included in this paper. The findings from the primary outcomes revealed that within the rTMS group, there were significantly higher scores observed for the executive sub-item on the cognitive composite scale (SMD = 0.93, 95% CI = 0.77-1.08, p < 0.00001, I 2 = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, p < 0.00001, I 2 = 0%) compared to the control group. As for the secondary outcome measures, as shown by the Trail Making Test-A (time) (MD = -35.75, 95% CI = -68.37 to -3.12, p = 0.03, I 2 = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, p = 0.02, I 2 = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, p = 0.03, I 2 = 0%), the experimental group shorts time and enhances accuracy of executive task in comparison to the control group. Subgroup analysis of the main outcome demonstrated that intermittent theta burst stimulation (iTBS), higher frequency, lower intensity, longer duration, and combined comprehensive therapy exhibited superior efficacy. Conclusion: rTMS is effective in the treatment of the executive function of VCI. The present study has some limitations, so multi-center, large-sample, objective indicators and parameters are needed to further explore in the future.Systematic review registration:https://www.crd.york.ac.uk/prospero/, CRD42023459669.
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Background and objectives: Comprehensive data analyses in heart failure research can provide academics with information and help policymakers formulate relevant policies. We collected data from reports published between 1945 and 2021 to identify research topics, trends, and cross-domains in the heart failure disease literature. Methods: Text fragments were extracted and clustered from the titles and abstracts in 270617 publications using artificial intelligence techniques. Two algorithms were used to corroborate the results and ensure that they were reliable. Experts named themes and document clusters based on the results of these semiautomated methods. Using consistent methods, we identified and flagged 107 heart failure topics and 16 large document clusters (divided into two groups by time). The annual vocabularies of research hotspots were calculated to draw attention to niche research fields. Results: Clinical research is an expanding field, followed by basic research and population research. The most frequently raised issues were intensive care treatment for heart failure, applications of artificial intelligence technologies, cardiac assist devices, stem cells, genetics, and regional distribution and use of heart failure-related health care. Risk scoring and classification, care for patients, readmission, health economics of treatment and care, and cell regeneration and signaling pathways were among the fastest-growing themes. Drugs, signaling pathways, and biomarkers were all crucial issues for clinical and basic research in the entire population. Studies on intelligent medicine and telemedicine, interventional therapy for valvular disease, and novel coronavirus have emerged recently. Conclusion: Clinical and population research is increasingly focusing on the customization of intelligent treatments, improving the quality of patients' life, and developing novel treatments. Basic research is increasingly focusing on regenerative medicine, translational medicine, and signaling pathways. Additionally, each research field exhibits mutual fusion characteristics. Medical demands, new technologies, and social support are all potential drivers for these changes.
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Insertion sequences (ISs) exist widely in bacterial genomes, but their roles in the evolution of bacterial antiphage defense remain to be clarified. Here, we report that, under the pressure of phage infection, the IS1096 transposition of Mycobacterium smegmatis into the lsr2 gene can occur at high frequencies, which endows the mutant mycobacterium with a broad-spectrum antiphage ability. Lsr2 functions as a negative regulator and directly silences expression of a gene island composed of 11 lipid metabolism-related genes. The complete or partial loss of the gene island leads to a significant decrease of bacteriophage adsorption to the mycobacterium, thus defending against phage infection. Strikingly, a phage that has evolved mutations in two tail-filament genes can re-escape from the lsr2 inactivation-triggered host defense. This study uncovered a new signaling pathway for activating antimycobacteriophage immunity by IS transposition and provided insight into the natural evolution of bacterial antiphage defense.
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Objective: To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion. Methods: This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed. Results: The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05). Conclusion: The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes.
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AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.
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Carga Global da Doença , Saúde Global , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/epidemiologia , Feminino , Masculino , Carga Global da Doença/tendências , Prevalência , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , Seguimentos , Estudos Retrospectivos , Distribuição por IdadeRESUMO
BACKGROUND: While most complications of cervical surgery are reversible, some, such as symptomatic postoperative spinal epidural hematoma (SEH), which generally occurs within 24 h, are associated with increased morbidity and mortality. Delayed neurological dysfunction is diagnosed in cases when symptoms present > 3 d postoperatively. Owing to its rarity, the risk factors for delayed neurological dysfunction are unclear. Consequently, this condition can result in irreversible neurological deficits and serious consequences. In this paper, we present a case of postoperative SEH that developed three days after hematoma evacuation. CASE SUMMARY: A 68-year-old man with an American Spinal Injury Association (ASIA) grade C injury was admitted to our hospital with neck pain and tetraplegia following a fall. The C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth day. Postoperatively, the patient showed no changes in muscle strength or ASIA grade. The patient experienced neck pain and subcutaneous swelling on the third day postoperatively, his muscle strength decreased, and his ASIA score was grade A. Magnetic resonance imaging showed hypointense signals on T1 weighted image (T1WI) and T2WI located behind the epidural space, with spinal cord compression. Emergency surgical intervention for the hematoma was performed 12 h after onset. Although hypoproteinemia and pleural effusion did not improve in the perioperative period, the patient recovered to ASIA grade C on day 30 after surgery, and was transferred to a functional rehabilitation exercise unit. CONCLUSION: This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical surgery. Surgery to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.
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BACKGROUND: The status of the hypothalamic-pituitary-gonadal (HPG) axis is important for assessing the onset of physiological or pathological puberty. The reference standard gonadotropin-releasing hormone (GnRH) stimulation test requires hospital admission and repeated blood samples. A simple noninvasive method would be beneficial. OBJECTIVES: To explore a noninvasive method for evaluating HPG axis activation in children using an MRI radiomics model. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty-nine children (83 male; 3.6-14.6 years) with hypophysial MRI and GnRH stimulation tests, randomly divided a training set (168 children) and a test set (71 children). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D isotropic fast spin echo (CUBE) T1-weighted imaging (T1WI) sequences. ASSESSMENT: Radiomics features were extracted from sagittal 3D CUBE T1WI, and imaging signatures were generated using the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation. Diagnostic performance for differential diagnosis of HPG status was compared between a radiomics model and MRI features (adenohypophyseal height [aPH] and volume [aPV]). STATISTICAL TESTS: Receiver operating characteristic (ROC) and decision curve analysis (DCA). A P value <0.05 was considered statistically significant. RESULTS: Eight hundred fifty-one radiomics features were extracted and reduced to 10 by the LASSO method in the training cohort. The radiomics model based on CUBE T1WI showed good performance in assessment of HPG axis activation with an area under the ROC curve (AUC) of 0.81 (95% CI: 0.71, 0.91) in the test set. The AUC of the radiomics model was significantly higher than that of aPH (0.81 vs. 0.65) but there was no significant difference compared to aPV (0.81 vs. 0.78, P = 0.58). In DCA analysis, the radiomics signature showed higher net benefit over the aPV and aPH models. DATA CONCLUSIONS: The MRI radiomics model has potential to assess HPG axis activation status noninvasively, potentially providing valuable information in the diagnosis of patients with pathological puberty onset. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Eixo Hipotalâmico-Hipofisário-Gonadal , Adeno-Hipófise , Criança , Humanos , Masculino , Estudos Retrospectivos , Radiômica , Imageamento por Ressonância Magnética/métodos , Adeno-Hipófise/diagnóstico por imagem , Hormônio Liberador de GonadotropinaRESUMO
Objective: Echocardiography (ECG) is the most common method used to diagnose heart failure (HF). However, its accuracy relies on the experience of the operator. Additionally, the video format of the data makes it challenging for patients to bring them to referrals and reexaminations. Therefore, this study used a deep learning approach to assist physicians in assessing cardiac function to promote the standardization of echocardiographic findings and compatibility of dynamic and static ultrasound data. Methods: A deep spatio-temporal convolutional model r2plus1d-Pan (trained on dynamic data and applied to static data) was improved and trained using the idea of "regression training combined with classification application," which can be generalized to dynamic ECG and static cardiac ultrasound views to identify HF with a reduced ejection fraction (EF < 40%). Additionally, three independent datasets containing 8976 cardiac ultrasound views and 10085 cardiac ultrasound videos were established. Subsequently, a multinational, multi-center dataset of EF was labeled. Furthermore, model training and independent validation were performed. Finally, 15 registered ultrasonographers and cardiologists with different working years in three regional hospitals specialized in cardiovascular disease were recruited to compare the results. Results: The proposed deep spatio-temporal convolutional model achieved an area under the receiveroperating characteristic curve (AUC) value of 0.95 (95% confidence interval [CI]: 0.947 to 0.953) on the training set of dynamic ultrasound data and an AUC of 1 (95% CI, 1 to 1) on the independent validation set. Subsequently, the model was applied to the static cardiac ultrasound view (validation set) with simultaneous input of 1, 2, 4, and 8 images of the same heart, with classification accuracies of 85%, 81%, 93%, and 92%, respectively. On the static data, the classification accuracy of the artificial intelligence (AI) model was comparable with the best performance of ultrasonographers and cardiologists with more than 3 working years (P = 0.344), but significantly better than the median level (P = 0.0000008). Conclusion: A new deep spatio-temporal convolution model was constructed to identify patients with HF with reduced EF accurately (< 40%) using dynamic and static cardiac ultrasound images. The model outperformed the diagnostic performance of most senior specialists. This may be the first HF-related AI diagnostic model compatible with multi-dimensional cardiac ultrasound data, and may thereby contribute to the improvement of HF diagnosis. Additionally, the model enables patients to carry "on-the-go" static ultrasound reports for referral and reexamination, thus saving healthcare resources.
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Background: Atrial fibrillation/flutter (AF/AFL) significantly impacts countries with varying income levels. We aimed to present worldwide estimates of its burden from 1990 to 2019 using data from the Global Burden of Disease (GBD) study. Methods: We derived cause-specific AF/AFL mortality and disability-adjusted life-year (DALY) estimates from the GBD 2019 study data. We used an age-period-cohort (APC) model to predict annual changes in mortality (net drifts), annual percentage changes from 50-55 to 90-95 years (local drifts), and period and cohort relative risks (period and cohort effects) between 1990 and 2019 by sex and sociodemographic index (SDI) quintiles. This allowed us to determine the impacts of age, period, and cohort on mortality and DALY trends and the inequities and treatment gaps in AF/AFL management. Results: Based on GBD data, our estimates showed that 59.7 million cases of AF/AFL occurred worldwide in 2019, while the number of AF/AFL deaths rose from 117 000 to 315 000 (61.5% women). All-age mortality and DALYs increased considerably from 1990 to 2019, and there was an increase in age risk and a shift in death and DALYs toward the older (>80) population. Although the global net drift mortality of AF/AFL decreased overall (-0.16%; 95% confidence interval (CI) = -0.20, 0.12 per year), we observed an opposite trend in the low-middle SDI (0.53%; 95% CI = 0.44, 0.63) and low SDI regions (0.32%; 95% CI = 0.18, 0.45). Compared with net drift among men (-0.08%; 95% CI = -0.14, -0.02), women had a greater downward trend or smaller upward trend of AF/AFL (-0.21%; 95% CI = -0.26, -0.16) in mortality in middle- and low-middle-SDI countries (P < 0.001). Uzbekistan had the largest net drift of mortality (4.21%; 95% CI = 3.51, 4.9) and DALYs (2.16%; 95% CI = 2.05, 2.27) among all countries. High body mass index, high blood pressure, smoking, and alcohol consumption were more prevalent in developed countries; nevertheless, lead exposure was more prominent in developing countries and regions. Conclusions: The burden of AF/AFL in 2019 and its temporal evolution from 1990 to 2019 differed significantly across SDI quintiles, sexes, geographic locations, and countries, necessitating the prioritisation of health policies based on risk-differentiated, cost-effective AF/AFL management.
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Fibrilação Atrial , Carga Global da Doença , Masculino , Humanos , Feminino , Anos de Vida Ajustados por Qualidade de Vida , Fibrilação Atrial/epidemiologia , Fatores Socioeconômicos , Estudos de Coortes , Saúde GlobalRESUMO
BACKGROUND: We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine. CASE PRESENTATION: A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month. CONCLUSION: This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.
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Doenças da Coroide , Microftalmia , Masculino , Humanos , Adulto , Microftalmia/induzido quimicamente , Microftalmia/complicações , Microftalmia/diagnóstico , Tartarato de Brimonidina/efeitos adversos , Corioide , Doenças da Coroide/diagnóstico , Procedimentos Cirúrgicos OftalmológicosRESUMO
Plant height is an important agronomic trait that is closely associated with crop yield and quality. Gibberellins (GAs), a class of highly efficient plant growth regulators, play key roles in regulating plant height. Increasing reports indicate that transcriptional regulation is a major point of regulation of the GA pathways. Although substantial knowledge has been gained regarding GA biosynthetic and signaling pathways, important factors contributing to the regulatory mechanisms homeostatically controlling GA levels remain to be elucidated. Here, we provide an overview of current knowledge regarding the regulatory network involving transcription factors, noncoding RNAs, and histone modifications involved in GA pathways. We also discuss the mechanisms of interaction between GAs and other hormones in plant height development. Finally, future directions for applying knowledge of the GA hormone in crop breeding are described.
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Giberelinas , Melhoramento Vegetal , Giberelinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Plantas/metabolismo , Homeostase , Regulação da Expressão Gênica de PlantasRESUMO
AIM: To increase the comprehensive understanding of trends in the burden of cardiovascular disease (CVD) attributable to low physical activity in the Western Pacific Region. METHODS: Based on data from the Global Burden of Disease (GBD) study for the years 1990-2019, an age-period-cohort (APC) analysis was conducted to investigate trends in CVD-related mortality attributable to low physical activity in the Western Pacific Region and associations with age, period, and birth cohort. We also used joinpoint regression analysis to identify the periods with the most substantial changes. RESULTS: The Western Pacific Region witnessed a substantial increase in CVD deaths attributable to low physical activity, accompanied by a rise in all-age CVD-related mortality. However, the age-standardized death rate was lower in the region than the global level, highlighting the importance of considering the age composition of CVD burden in the region. Countries with higher SDI levels exhibited lower mortality than those with lower SDI levels. The longitudinal analysis using the APC model indicated an overall improvement in CVD-related mortality attributable to low physical activity in the region, but with differences between sexes and CVD subtypes. Specific period in which CVD-related mortality decreased significantly were 2011-2016, for the average annual percentage change for the period was -0.69%. CONCLUSION: The study highlights the significance of addressing low physical activity as a modifiable risk factor for CVD burden in the Western Pacific Region. Further research is essential to understand the factors contributing to inter-country variations, sex disparities, and CVD subtypes distinctions.
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Antibiotic-resistant bacteria are emerging all the time, but the continued emergence of novel resistance genes and genetic structures is even more alarming. Tigecycline is currently the important last barrier in the treatment of multidrug-resistant (MDR) infections. tet(X), a resistance gene to tigecycline, is the most prevalent and constantly emerging novel variants. In this research, we characterized two MDR Acinetobacter indicus strains to tigecycline that were identified and analyzed by antimicrobial susceptibility testing, conjugation transfer, whole genome sequencing (WGS) and bioinformatics analysis, and gene function analysis. The results showed that three tet(X) variants were carried in BDT201, including tet(X6) on the chromosome, tet(X3) on the plasmid pBDT201-2, and a novel tet(X5) variant adjacent to the ISAba1 elements on the plasmid pBDT201-3. The novel Tet(X5) variant showed 98.7% amino acid identity with Tet(X5) and was named Tet(X5.4). By expressing tet(X5.4) gene, the tigecycline minimum inhibitory concentration (MIC) values for Escherichia coli JM109 increased 32- fold (from 0.13 to 4 mg/L). BDT2076 contained tigecycline and carbapenems resistance genes, such as tet(X3), blaOXA-58, blaNDM-3, and blaCARB-2. The continuous emergence of MDR bacteria and resistance genes is a global environmental health issue that can not be ignored and therefore needs to pay more urgent attention to it.
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Acinetobacter , Antibacterianos , Animais , Suínos , Tigeciclina/farmacologia , Antibacterianos/farmacologia , Acinetobacter/genética , Escherichia coli/genética , Fazendas , Testes de Sensibilidade Microbiana/veterinária , Plasmídeos/genéticaRESUMO
Objective: This study aimed to elucidate the efficacy, safety, and long-term implications of vagus nerve stimulation (VNS) as a viable therapeutic option for patients with upper limb dysfunction following a stroke. Methods: Data from the following libraries were searched from inception to December 2022: PubMed, Wanfang, Scopus, China Science and Technology Journal Database, Embase, Web of Science, China Biology Medicine Disc, Cochrane Library, and China National Knowledge Infrastructure. Outcomes included indicators of upper limb motor function, indicators of prognosis, and indicators of safety (incidence of adverse events [AEs] and serious AEs [SAEs]). Two of the authors extracted the data independently. A third researcher arbitrated when disputes occurred. The quality of each eligible study was evaluated using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: Ten trials (VNS combined with rehabilitation group vs. no or sham VNS combined with rehabilitation group) with 335 patients were included in the meta-analysis. Regarding upper extremity motor function, based on Fugl-Meyer assessment scores, VNS combined with other treatment options had immediate (mean difference [MD] = 2.82, 95% confidence interval [CI] = 1.78-3.91, I2 = 62%, p < 0.00001) and long-term (day-30 MD = 4.20, 95% CI = 2.90-5.50, p < 0.00001; day-90 MD = 3.27, 95% CI = 1.67-4.87, p < 0.00001) beneficial effects compared with that of the control treatment. Subgroup analyses showed that transcutaneous VNS (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) may be superior to invasive VNS (MD = 3.56, 95% CI = 1.99-5.13, I2 = 77%, p < 0.0001) and that VNS combined with integrated treatment (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) is superior to VNS combined with upper extremity training alone (MD = 2.24, 95% CI = 0.55-3.93, I2 = 48%, p = 0.009). Moreover, lower frequency VNS (20 Hz) (MD = 3.39, 95% CI = 2.06-4.73, I2 = 65%, p < 0.00001) may be superior to higher frequency VNS (25 Hz or 30 Hz) (MD = 2.29, 95% CI = 0.27-4.32, I2 = 58%, p = 0,03). Regarding prognosis, the VNS group outperformed the control group in the activities of daily living (standardized MD = 1.50, 95% CI = 1.10-1.90, I2 = 0%, p < 0.00001) and depression reduction. In contrast, quality of life did not improve (p = 0.51). Safety was not significantly different between the experimental and control groups (AE p = 0.25; SAE p = 0.26). Conclusion: VNS is an effective and safe treatment for upper extremity motor dysfunction after a stroke. For the functional restoration of the upper extremities, noninvasive integrated therapy and lower-frequency VNS may be more effective. In the future, further high-quality studies with larger study populations, more comprehensive indicators, and thorough data are required to advance the clinical application of VNS. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023399820.
RESUMO
Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.