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Resistance to dual antiplatelet therapy (DAPT), including aspirin and clopidogrel, in patients who have undergone percutaneous coronary intervention (PCI) leads to the inability to prevent thrombotic complications. The present study aimed to evaluate early resistance to aspirin and clopidogrel in patients following PCI using the VerifyNow test and associated factors. A total of 50 patients diagnosed with acute coronary syndromes (ACS) who underwent emergency PCI and received DAPT were recruited in the present study. The detection of resistance to aspirin and clopidogrel was performed using the VerifyNow system. Resistance to aspirin was determined with VerifyNow Aspirin >550 aspirin reaction units (ARU). Resistance to clopidogrel was determined with VerifyNow P2Y12 >208 P2Y12 reaction units (PRU). The resistance rate to aspirin was 14%, while the resistance rate to clopidogrel was higher, at 34%. There were 2 patients with resistance to aspirin and clopidogrel (4%). Univariable logistic regression analysis revealed that diabetes, the use of ß-blockers, and low levels of hemoglobin and hematocrit were associated with resistance to clopidogrel. Following multivariable logistic regression analysis, only the use of ß-blockers was truly associated with resistance to clopidogrel. On the whole, the results of the present study may also prove to be helpful in the selection of therapeutic drugs for patients undergoing PCI and who are diagnosed with ACS.
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The primrose-willow (Ludwigia L.), a well-defined genus of the Onagraceae family, comprises 87 species widely distributed worldwide. In this study, we sequenced and characterized the complete chloroplast (cp) genomes of three species in the genus, including Ludwigia adscendens, Ludwigia hyssopifolia, and Ludwigia prostrata. Three Ludwigia cp genomes ranged from 158,354 to 159,592 bp in size, and each contained 113 genes, including 79 unique protein-coding genes (PCGs), four rRNA genes, and 30 tRNA genes. A comparison of the Ludwigia cp genomes revealed that they were highly conserved in gene composition, gene orientation, and GC content. Moreover, we compared the structure of cp genomes and reconstructed phylogenetic relationships with related species in the Onagraceae family. Regarding contraction/expansion of inverted repeat (IR) region, two kinds of expansion IR region structures were found in Oenothera, Chamaenerion, and Epilobium genera, with primitive IR structures in Ludwigia and Circeae genera. The regions clpP, ycf2, and ycf1 genes possessed highly divergent nucleotides among all available cp genomes of the Onagraceae family. The phylogenetic reconstruction using 79 PCGs from 39 Onagraceae cp genomes inferred that Ludwigia (including L. adscendens, L. hyssopifolia, L. prostrata, and Ludwigia octovalvis) clade was monophyletic and well-supported by the bootstrap and posterior probability values. This study provides the reference cp genomes of three Ludwigia species, which can be used for species identification and phylogenetic reconstruction of Ludwigia and Onagraceae taxa.
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Evolução Molecular , Genoma de Cloroplastos , Genômica , Filogenia , Genoma de Cloroplastos/genética , Onagraceae/genética , Onagraceae/classificação , Composição de BasesRESUMO
Callose, a ß-1,3-glucan plant cell wall polymer, regulates symplasmic channel size at plasmodesmata (PD) and plays a crucial role in a variety of plant processes. However, elucidating the molecular mechanism of PD callose homeostasis is limited. We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene was α1-COP, a member of the coat protein I (COPI) coatomer complex. We report that loss of function of α1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme PdBG2. This process is linked to the functions of ERH1, an inositol phosphoryl ceramide synthase, and glucosylceramide synthase through physical interactions with the α1-COP protein. Additionally, the loss of function of α1-COP alters the subcellular localization of ERH1 and GCS proteins, resulting in a reduction of GlcCers and GlcHCers molecules, which are key sphingolipid (SL) species for lipid raft formation. Our findings suggest that α1-COP protein, together with SL modifiers controlling lipid raft compositions, regulates the subcellular localization of GPI-anchored PDBG2 proteins, and hence the callose turnover at PD and symplasmic movement of biomolecules. Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.
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Proteínas de Arabidopsis , Arabidopsis , Glucanos , Plasmodesmos , Esfingolipídeos , Plasmodesmos/metabolismo , Glucanos/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Esfingolipídeos/metabolismo , Glucosiltransferases/metabolismo , Glucosiltransferases/genéticaRESUMO
Severe tricuspid regurgitation remains largely undertreated given limited treatment options. Transcatheter tricuspid valve interventions have emerged as a promising therapy for these patients, and the TRISCEND II pivotal trial is the first randomized controlled trial to evaluate transcatheter tricuspid valve replacement (TTVR). The TRISCEND II pivotal trial studies the transcatheter EVOQUE (Edwards Lifesciences, Irvine, California) tricuspid valve replacement system using a United States Food and Drug Administration Breakthrough Device Designation-a program intended to provide timely access to medical devices by speeding up development, assessment, and review. The TRISCEND II trial is a prospective, multicenter trial that randomizes patients with symptomatic severe tricuspid regurgitation to treatment with either TTVR in conjunction with optimal medical therapy or optimal medical therapy alone. The trial's novel 2-phase design evaluates 30-day safety and 6-month effectiveness end points for the first 150 patients in the initial phase and a 1-year safety and effectiveness end point for the full cohort of 400 patients in the second phase. The TRISCEND II trial's 2-phase trial design provided an opportunity for early review and led to the first commercial approval of a TTVR system. In conclusion, the design of the TRISCEND II trial will likely inform future transcatheter tricuspid device trials.
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Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Valva Tricúspide , Humanos , Insuficiência da Valva Tricúspide/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Cateterismo Cardíaco/métodos , Valva Tricúspide/cirurgia , Estudos Prospectivos , Próteses Valvulares Cardíacas , Resultado do TratamentoRESUMO
Solid-state polymer electrolytes can enable the safe operation of high energy density lithium metal batteries; unfortunately, they have low ionic conductivity and poor redox stability at electrode interfaces. Fluorinated ether polymer electrolytes are a promising approach because the ether units can solvate and conduct ions, while the fluorinated moieties can increase oxidative stability. However, current perfluoropolyether (PFPE) electrolytes exhibit deficient lithium-ion coordination and ion transport. Here, we incorporate cross-linked poly(ethylene glycol) (PEG) units within the PFPE matrix and increase the polymer blend electrolyte conductivity by 6 orders of magnitude as compared to pure PFPE at 60 °C from 1.55 × 10-11 to 2.26 × 10-5 S/cm. Blending varying ratios of PEG and PFPE induces microscale phase separation, and we show the impact of morphology on ion solvation and dynamics in the electrolyte. Spectroscopy and simulations show weak ion-PFPE interactions, which promote salt phase segregation into-and ion transport within-the PEG domain. These polymer electrolytes show promise for use in high-voltage lithium metal batteries with improved Li|Li cycling due to enhanced mechanical properties and high-voltage stability beyond 6 V versus Li/Li+. Our work provides insights into transport and stability in fluorinated polymer electrolytes for next-generation batteries.
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Dicliptera tinctoria is a member of Acanthaceae, which has a wide distribution and contains potentially medicinal species, and exhibited pharmaceutical potentials. This study sequenced and characterized the complete chloroplast genome of Dicliptera tinctoria. The newly sequenced cpDNA of D. tinctoria was 150,733 bp in length and had a typical quadripartite structure consisting of a large single copy (LSC, 82,895 bp), a small single copy (SSC, 17,249 bp), and two inverted repeat (IRs, 25,295 bp each) regions. This genome also contained 80 protein-coding genes, 30 transfer RNAs, and four ribosomal RNAs, which is identical to other chloroplast genomes in Acanthaceae family. Nucleotides diversity analysis among chloroplast genomes of Acanthaceae species revealed eight hypervariable regions, including trnK_UUU-matK, trnC_GCA-petN, accD, rps12-clpP, rps3-rps19, ycf1-ndhF, ccsA-ndhD, and ycf1. Phylogenetic analysis revealed the paraphyly of Dicliptera species and monophyly in four Acanthaceae subfamilies. These results provide an overview of genomic variations in Acanthaceae chloroplast genome, which is helpful for further genomic studies.
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In this paper, we propose a Transformer-based encoder architecture integrated with an unsupervised denoising method to learn meaningful and sparse representations of vibration signals without the need for data transformation or pre-trained data. Existing Transformer models often require transformed data or extensive computational resources, limiting their practical adoption. We propose a simple yet competitive modification of the Transformer model, integrating a trainable noise reduction method specifically tailored for failure mode classification using vibration data directly in the time domain without converting them into other domains or images. Furthermore, we present the key architectural components and algorithms underlying our model, emphasizing interpretability and trustworthiness. Our model is trained and validated using two benchmark datasets: the IMS dataset (four failure modes) and the CWRU dataset (four and ten failure modes). Notably, our model performs competitively, especially when using an unbalanced test set and a lightweight architecture.
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Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.
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Ecossistema , Água Doce , Atividades Humanas , Estresse FisiológicoRESUMO
AIM: Care for people with spina bifida can be improved. This may be done by evaluating mortality rates and causes of death. METHODS: Between 1973 and 2021, 1735 people with spina bifida appeared in registers of the Swedish population. Survival rates and causes of death were calculated according to age and decade. RESULTS: Over almost 50 years, the prevalence of spina bifida decreased from 5.2 to 1.2 per 10 000 births. Mortality fell sharply during the first year of life, with survival rising from 75% to 94%. For children aged 2-18 years and adults, mortality rates were low and differences between decades were minimal. Causes of childhood deaths were congenital abnormalities, hydrocephalus and infections, the latter two also in adults. Adult causes also included self-inflicted injuries and substance abuse, with suicidal or unclear intent, both more common than in the general population. Bladder malignancies were also more frequent, although after reconstructive bladder surgery, mortality rates were similar. CONCLUSION: Survival in the first year of life increased in children with spina bifida, whereas there was no difference in survival rates between adults born between 1973 and 1999. For adults, proactive prevention methods regarding self-inflicted injury, substance abuse and bladder cancer are warranted.
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Causas de Morte , Sistema de Registros , Disrafismo Espinal , Humanos , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/mortalidade , Adolescente , Criança , Pré-Escolar , Suécia/epidemiologia , Adulto , Lactente , Fatores de Risco , Feminino , Masculino , Adulto Jovem , Recém-Nascido , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.
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Spina bifida includes a spectrum of different neural tube defects. Myelomeningocele is the most serious type and is associated with a risk of paralysis and sensory dysfunction below the affected level, bladder/bowel dysfunction, brain dysmorphology, and impaired health-related quality of life (HRQoL). The aim of this study was to describe the establishment of linguistic, content and face validity of the Swedish version of a Quality-of-Life Assessment for children (QUALAS-C, n = 10 items), teenagers (QUALAS-T, n = 10 items) and adults with spina bifida (QUALAS-A, n = 15 items) based on the original US English versions. The process included close collaboration with the original instrument developer and complied with international standards on patient-reported outcome measurements. The procedure includes forward translation, expert and patient/parent review and reconciliation, back translation, back translation review and cognitive debriefing interviews with 16 people with spina bifida aged 8 to 33, providing them with the possibility of evaluating the clarity, adequacy, and comprehensiveness of QUALAS-C, QUALAS-T and QUALAS-A, respectively. The interviews lasted a median of 15 min (range 8-16) for QUALAS-C, 10 min (range 9-15) for QUALAS-T and 24 min (range 9-38) for QUALAS-A. Four main issues/topics needed attention and discussion after both the forward and back translation. Following the back translation review, all issues were resolved. The patient feedback revealed recognition of the HRQoL issues included in QUALAS, and also difficulties in understanding some questions. After the patients' evaluation, four items were reworded for clarity. No study participant reported a wish to add to or remove questions from QUALAS. Hence, the Swedish versions of QUALAS became conceptually equivalent to the original US English versions and achieved linguistic, content and face validity. While empowering the voices of people with spina bifida, these results also enable their HRQoL to be properly assessed in research and clinical care in Sweden and in international studies.
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Qualidade de Vida , Disrafismo Espinal , Humanos , Disrafismo Espinal/psicologia , Adolescente , Suécia , Adulto , Criança , Feminino , Masculino , Adulto Jovem , Inquéritos e Questionários , Reprodutibilidade dos Testes , LinguísticaRESUMO
Helicteres hirsuta Lour. 1790 is a precious medicinal plant species, especially for treating chronic liver diseases. Genomic data on H. hirsuta are limited. Therefore, this current study aimed to characterize the chloroplast genome of H. hirsuta and reconstruct the phylogenetic relationship among Helicteroideae taxa. Consequently, the complete chloroplast genome of H. hirsuta was 163,404 bp in length and contained 113 unique genes (79 protein-coding genes, 30 tRNA genes, and four rRNA genes). Notably, two introns of clpP gene of H. hirsuta were lost in comparison to that of other Helicteroideae species. The phylogenetic tree based on chloroplast genomes of eleven Helicteroideae species revealed that H. hirsuta was closely related to Reevesia species. In conclusion, our study described the first complete chloroplast genome of H. hirsuta, which is essential for tracing evolutionary history in the Helicteroideae subfamily.
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Surveillance of the SARS-CoV-2 genome has become a crucial technique in the management of COVID-19, aiding the pandemic response and supporting effective public health interventions. Typically, whole-genomic sequencing is used along with PCR-based target enrichment techniques to identify SARS-CoV-2 variants, which is a complicated and time-consuming process that requires central laboratory facilities. Thus, there is an urgent need to develop rapid and cost-effective tools for precise on-site detection and identification of SARS-CoV-2 strains. In this study, we demonstrate the rapid diagnosis of COVID-19 and identification of SARS-CoV-2 variants by amplification and sequencing of the entire SARS-CoV-2 S gene using isothermal enzymatic recombinase amplification combined with the advanced Oxford nanopore sequencing technique. The entire procedure, from sampling to sequencing, takes less than 8 hours and can be performed with limited resources. The newly developed method has noteworthy implications for examining the transmission dynamics of the virus, detecting novel genetic variants, and assessing the effect of mutations on diagnostic approaches, antiviral treatments, and vaccines.
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COVID-19 , Sequenciamento por Nanoporos , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Teste para COVID-19RESUMO
OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.
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Trombose , Tromboembolia Venosa , Humanos , Neutrófilos , Tromboembolia Venosa/diagnóstico , Estudos Retrospectivos , Estudos Transversais , Linfócitos , Curva ROC , PrognósticoRESUMO
The COVID-19 pandemic greatly impacted the in vitro diagnostic market, leading to the development of new technologies such as point-of-care testing (POCT), multiplex testing, and digital health platforms. In this study, we present a self-contained microfluidic chip integrated with an internet-of-things (IoT)-based point-of-care (POC) device for rapid and sensitive diagnosis of respiratory viruses. Our platform enables sample-to-answer diagnostics within 70 min by automating RNA extraction, reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and fluorescence detection. The microfluidic chip is designed to store all the necessary reagents for the entire diagnostic assay, including a lysis buffer, a washing buffer, an elution buffer, and a lyophilized RT-LAMP cocktail. It can perform nucleic acid extraction, aliquoting, and gene amplification in multiple reaction chambers without cross-contamination. The IoT-based POC device consists of a Raspberry Pi 4 for device control and data processing, a CMOS sensor for measuring fluorescence signals, a resistive heater panel for temperature control, and solenoid valves for controlling the movement of on-chip reagent solutions. The proposed device is portable and features a touchscreen for user control and result display. We evaluated the performance of the platform using 11 clinical respiratory virus samples, including 5 SARS-CoV-2 samples, 2 influenza A samples, and 4 influenza B samples. All tested clinical samples were accurately identified with high specificity and fidelity, demonstrating the ability to simultaneously detect multiple respiratory viruses. The combination of the integrated microfluidic chip with the POC device offers a simple, cost-effective, and scalable solution for rapid molecular diagnosis of respiratory viruses in resource-limited settings.
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COVID-19 , Internet das Coisas , Dispositivos Lab-On-A-Chip , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Técnicas de Diagnóstico Molecular/instrumentação , Desenho de Equipamento , Testes Imediatos , RNA Viral/análise , RNA Viral/isolamento & purificação , RNA Viral/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologiaRESUMO
Controlling complex networks of nonlinear limit-cycle oscillators is an important problem pertinent to various applications in engineering and natural sciences. While in recent years the control of oscillator populations with comprehensive biophysical models or simplified models, e.g., phase models, has seen notable advances, learning appropriate controls directly from data without prior model assumptions or pre-existing data remains a challenging and less developed area of research. In this paper, we address this problem by leveraging the network's current dynamics to iteratively learn an appropriate control online without constructing a global model of the system. We illustrate through a range of numerical simulations that the proposed technique can effectively regulate synchrony in various oscillator networks after a small number of trials using only one input and one noisy population-level output measurement. We provide a theoretical analysis of our approach, illustrate its robustness to system variations, and compare its performance with existing model-based and data-driven approaches.
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Nine pentacyclic triterpene derivatives including new 3-O-cis-p-coumaroyl trichadenic acid B (1) and two new ursane-type triterpene derivatives, 11α,12-[1-(methyl)-2-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (2) and 11α,12-[2-(methyl)-1-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (3) were isolated from the leaves of Camellia hakodae Ninh., along with six known compounds (4-9). This is the first report on pentacyclic triterpenoids from this species. New compounds 1-3 and compound 7 were tested for cytotoxic activity against four human cancer cell lines (KB; Hep-G2; Lu; MCF-7) using the MTT assay to show moderate activity.
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BACKGROUND: The COVID-19 pandemic has highlighted gaps in the current handling of medical resource demand surges and the need for prioritizing scarce medical resources to mitigate the risk of health care facilities becoming overwhelmed. OBJECTIVE: During a health care emergency, such as the COVID-19 pandemic, the public often uses social media to express negative sentiment (eg, urgency, fear, and frustration) as a real-time response to the evolving crisis. The sentiment expressed in COVID-19 posts may provide valuable real-time information about the relative severity of medical resource demand in different regions of a country. In this study, Twitter (subsequently rebranded as X) sentiment analysis was used to investigate whether an increase in negative sentiment COVID-19 tweets corresponded to a greater demand for hospital intensive care unit (ICU) beds in specific regions of the United States, Brazil, and India. METHODS: Tweets were collected from a publicly available data set containing COVID-19 tweets with sentiment labels and geolocation information posted between February 1, 2020, and March 31, 2021. Regional medical resource shortage data were gathered from publicly available data sets reporting a time series of ICU bed demand across each country. Negative sentiment tweets were analyzed using the Granger causality test and convergent cross-mapping (CCM) analysis to assess the utility of the time series of negative sentiment tweets in forecasting ICU bed shortages. RESULTS: For the United States (30,742,934 negative sentiment tweets), the results of the Granger causality test (for whether negative sentiment COVID-19 tweets forecast ICU bed shortage, assuming a stochastic system) were significant (P<.05) for 14 (28%) of the 50 states that passed the augmented Dickey-Fuller test at lag 2, and the results of the CCM analysis (for whether negative sentiment COVID-19 tweets forecast ICU bed shortage, assuming a dynamic system) were significant (P<.05) for 46 (92%) of the 50 states. For Brazil (3,004,039 negative sentiment tweets), the results of the Granger causality test were significant (P<.05) for 6 (22%) of the 27 federative units, and the results of the CCM analysis were significant (P<.05) for 26 (96%) of the 27 federative units. For India (4,199,151 negative sentiment tweets), the results of the Granger causality test were significant (P<.05) for 6 (23%) of the 26 included regions (25 states and the national capital region of Delhi), and the results of the CCM analysis were significant (P<.05) for 26 (100%) of the 26 included regions. CONCLUSIONS: This study provides a novel approach for identifying the regions of high hospital bed demand during a health care emergency scenario by analyzing Twitter sentiment data. Leveraging analyses that take advantage of natural language processing-driven tweet extraction systems has the potential to be an effective method for the early detection of medical resource demand surges.
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Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential.Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance.Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies.Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model.Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model.Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.
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Infecções por Helicobacter , Helicobacter pylori , Vacinas , Humanos , Masculino , Feminino , Camundongos , Animais , Infecções por Helicobacter/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Genótipo , Genômica , Sudeste Asiático/epidemiologiaRESUMO
Siganus virgatus Valenciennes 1835 is an essential species for examining reef ecosystems; however, its mitochondrial genome has not been studied. In this research, the mitogenome of S. virgatus was sequenced and characterized. The results revealed a circular genome of 16,505 bp that was composed of A (28.1%), C (31.3%), G (14%), and T nucleotides (26.6%). The genome contained 13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes. Most genes of the mitogenome were transcribed on the heavy strand (H-strand), whereas ND6 and eight tRNA genes (including tRNA-Ala, -Asn, -Cys, -Gln, -Glu, -Ser (1), -Pro, and -Tyr) were transcribed on the light strand (L-strand). Comparative analysis revealed a high degree of conservation of gene content and order among the Siganus mitogenomes. Phylogenetic analysis inferred from whole mitogenomes exhibited a close relationship between S. virgatus and S. guttatus. The newly completed mitogenome of S. virgatus provides essential genomic data for further studies on population genetics and the evolution of the Siganus genus and the Siganidae family.