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INTRODUCTION: Mitral regurgitation (MR) is the most common valvular heart disorder, with a morbidity rate of 2.5%. While echocardiography is commonly used in assessing MR, it has many limitations, especially for large-scale MR screening. Cardiac auscultation with electronic stethoscope and artificial intelligence (AI) can be a fast and economical modality for assessing MR severity. Our objectives are (1) to establish a deep neural network (DNN)-based cardiac auscultation method for assessing the severity of MR; and (2) to quantitatively measure the performance of the developed AI-based MR assessment method by virtual clinical trial. METHODS AND ANALYSIS: In a cross-sectional design, phonocardiogram will be recorded at the mitral valve auscultation area of outpatients. The enrolled patients will be checked by echocardiography to confirm the diagnosis of MR or no MR. Echocardiographic parameters will be used as gold standard to assess the severity of MR, classified into four levels: none, mild, moderate and severe. The study consists of two stages. First, an MR-related cardiac sound database will be created on which a DNN-based MR severity classifier will be trained. The automatic MR severity classifier will be integrated with the Smartho-D2 electronic stethoscope. Second, the performance of the developed smart device will be assessed in an independent clinical validation data set. Sensitivity, specificity, precision, accuracy and F1 score of the developed smart MR assessment device will be evaluated. Agreement on the performance of the smart device between cardiologist users and patient users will be inspected. The interpretability of the developed model will also be studied with statistical comparisons of occlusion map-guided variables among the four severity groups. ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Ethics Committee of Huzhou Central Hospital, China (registration number: 202302009-01). Informed consent is required from all participants. Dissemination will be through conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300069496.
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Insuficiência da Valva Mitral , Humanos , Inteligência Artificial , Auscultação , China , Estudos Transversais , Insuficiência da Valva Mitral/diagnóstico por imagemRESUMO
Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos , PulmãoRESUMO
A new coordination polymer (CP) based on Co(II), namely, {[Co3(L)2(4,4'-bipy)(DMA)2]·H2O}n (1) has been synthesized after reacting Co(NO3)2·6H2O with H3L ligand in the existence of N-donor ligand 4,4'-bipyridine (4,4'-bipy), via utilizing a flexible tricarboxylic acid ligand 5-((formic acid-3-sulfur)methyl)isophthalic acid (H3L) with -S-CH2- joint. Additionally, the excellent blue fluorescence properties of CP 1 were confirmed through fluorescence spectroscopy compared to the original ligand. Using natural polysaccharide hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, HA/CMCS hydrogel was prepared by chemical synthesis method. Taking vitamin B2 as the drug model, we designed and synthesized gels loaded with vitamin B2 metal framework and evaluated their efficacy in the treatment of recurrent oral ulcer.
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AIMS AND OBJECTIVES: To investigate whether chronic diseases are associated with higher COVID-19 vaccine hesitancy and explore factors that influence COVID-19 vaccine hesitancy in patients with chronic diseases. BACKGROUND: Vaccine hesitancy has been acknowledged as one of the greatest hazards to public health. However, little information is available about COVID-19 vaccine hesitancy among patients with chronic diseases who may be more susceptible to COVID-19 infection, severe disease or death. METHODS: From 6 to 9 August 2021, we performed an internet-based cross-sectional survey with 22,954 participants (14.78% participants with chronic diseases). Propensity score matching with 1:1 nearest neighbourhood was used to reduce confounding factors between patients with chronic diseases and the general population. Using a multivariable logistic regression model, the factors impacting COVID-19 vaccine hesitancy were identified among patients with chronic diseases. RESULTS: Both before and after propensity score matching, patients with chronic diseases had higher COVID-19 vaccine hesitancy than the general population. In addition, self-reported poor health, multiple chronic diseases, lower sociodemographic backgrounds and lower trust in nurses and doctors were associated with COVID-19 vaccine hesitancy among patients with chronic diseases. CONCLUSIONS: Patients with chronic diseases were more hesitant about the COVID-19 vaccine. Nurses should focus on patients with chronic diseases with poor health conditions, low socioeconomic backgrounds and low trust in the healthcare system. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses are recommended to not only pay more attention to the health status and sociodemographic characteristics of patients with chronic diseases but also build trust between nurses and patients by improving service levels and professional capabilities in clinical practice. PATIENT OR PUBLIC CONTRIBUTION: Patients or the public were not involved in setting the research question, the outcome measures, or the design or implementation of the study. However, all participants were invited to complete the digital informed consent and questionnaires.
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Vacinas contra COVID-19 , COVID-19 , Pontuação de Propensão , Hesitação Vacinal , Humanos , Estudos Transversais , Masculino , Feminino , Vacinas contra COVID-19/administração & dosagem , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/psicologia , Doença Crônica/psicologia , Adulto , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , Idoso , Internet , Inquéritos e Questionários , SARS-CoV-2RESUMO
Objective: As the frontoparietal network underlies recovery from coma, a limited frontoparietal montage was used, and the prognostic values of EEG features for comatose patients were assessed. Methods: Collected with a limited frontoparietal EEG montage, continuous EEG recordings of 81 comatose patients in ICU were used retrospectively. By the 60-day Glasgow outcome scale (GOS), the patients were dichotomized into favorable and unfavorable outcome groups. Temporal-, frequency-, and spatial-domain features were automatically extracted for comparison. Partial correlation analysis was applied to eliminate redundant factors, and multiple correspondence analysis was used to explore discrimination between groups. Prognostic characteristics were calculated to assess the performance of EEG feature-based predictors established by logistic regression. Analyses were performed on all-patients group, strokes subgroup, and traumatic brain injury (TBI) subgroup. Results: By analysis of all patients, raised burst suppression ratio (BSR), suppressed root mean square (RMS), raised power ratio of ß to α rhythm (ß/α), and suppressed phase-lag index between F3 and P4 (PLI [F3, P4]) were associated with unfavorable outcome, and yielded AUC of 0.790, 0.811, 0.722, and 0.844, respectively. For the strokes subgroup, the significant variables were BSR, RMS, θ/total, θ/δ, and PLI (F3, P4), while for the TBI subgroup, only PLI (F3, P4) was significant. BSR combined with PLI (F3, P4) gave the best predictor by cross-validation analysis in the all-patients group (AUC = 0.889, 95% CI: 0.819-0.960). Conclusion: Features extracted from limited frontoparietal montage EEG served as valuable coma prognostic tools, where PLI (F3, P4) was always significant. Combining PLI (F3, P4) with features in other domains may achieve better performance. Significance: A limited-montage EEG coupled with an automated algorithm is valuable for coma prognosis.
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BACKGROUND: Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches. RESULTS: In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs. CONCLUSIONS: Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions.
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DNA , Genômica , Humanos , RNA Mensageiro/metabolismo , Éxons , Genômica/métodos , Mutagênese Insercional , Processamento AlternativoRESUMO
Several interventional therapies are in development to treat functional tricuspid regurgitation. Most have failed to achieve adequate efficacy, as animal models of this lesion are lacking. We developed a new image-guided technique in swine, by tethering the tricuspid valve chordae using echo-guided chordal encircling snares. Five swine underwent baseline echocardiographic assessment of tricuspid valve function, followed by echo-guided placement of snares that encircle the chordae inserting into the anterior and posterior tricuspid valve leaflets. Tethering these snares and stabilizing them on the right ventricle caused the regurgitant fraction to increase from 8.48±5.38% to 48.76±12.5%, and the valve tenting area to increase from 60.26±52.19 to 160.9±86.92 mm2. Image-guided chordal encircling snares could reproducibly induce clinically significant levels of functional tricuspid regurgitation and create a valve geometry like that seen in patients, providing a new animal model for use to study novel interventional devices.
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Endogenous single-stranded DNA (essDNA) can form in a mammalian genome as the result of a variety of molecular processes and can both play important roles inside the cell as well as have detrimental consequences to genome integrity, much of which remains to be fully understood. Here, we established the SSiNGLe-P1 approach based on limited digestion by P1 endonuclease for high-throughput genome-wide identification of essDNA regions. We applied this method to profile essDNA in both human mitochondrial and nuclear genomes. In the mitochondrial genome, the profiles of essDNA provide new evidence to support the strand-displacement model of mitochondrial DNA replication. In the nuclear genome, essDNA regions were found to be enriched in certain types of functional genomic elements, particularly, the origins of DNA replication, R-loops, and to a lesser degree, in promoters. Furthermore, interestingly, many of the essDNA regions identified by SSiNGLe-P1 have not been annotated and thus could represent yet unknown functional elements.
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DNA Mitocondrial , DNA de Cadeia Simples , Animais , Humanos , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Replicação do DNA/genética , Núcleo Celular/metabolismo , Mamíferos/genéticaRESUMO
BACKGROUND: Conversion or editing of adenosine (A) into inosine (I) catalyzed by specialized cellular enzymes represents one of the most common post-transcriptional RNA modifications with emerging connection to disease. A-to-I conversions can happen at specific sites and lead to increase in proteome diversity and changes in RNA stability, splicing, and regulation. Such sites can be detected as adenine-to-guanine sequence changes by next-generation RNA sequencing which resulted in millions reported sites from multiple genome-wide surveys. Nonetheless, the lack of extensive independent validation in such endeavors, which is critical considering the relatively high error rate of next-generation sequencing, leads to lingering questions about the validity of the current compendiums of the editing sites and conclusions based on them. RESULTS: Strikingly, we found that the current analytical methods suffer from very high false positive rates and that a significant fraction of sites in the public databases cannot be validated. In this work, we present potential solutions to these problems and provide a comprehensive and extensively validated list of A-to-I editing sites in a human cancer cell line. Our findings demonstrate that most of true A-to-I editing sites in a human cancer cell line are located in the non-coding transcripts, the so-called RNA 'dark matter'. On the other hand, many ADAR editing events occurring in exons of human protein-coding mRNAs, including those that can recode the transcriptome, represent false positives and need to be interpreted with caution. Nonetheless, yet undiscovered authentic ADAR sites that increase the diversity of human proteome exist and warrant further identification. CONCLUSIONS: Accurate identification of human ADAR sites remains a challenging problem, particularly for the sites in exons of protein-coding mRNAs. As a result, genome-wide surveys of ADAR editome must still be accompanied by extensive Sanger validation efforts. However, given the vast number of unknown human ADAR sites, there is a need for further developments of the analytical techniques, potentially those that are based on deep learning solutions, in order to provide a quick and reliable identification of the editome in any sample.
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Proteoma , Edição de RNA , Humanos , Proteoma/genética , RNA/metabolismo , RNA Mensageiro/metabolismo , Linhagem Celular , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismoRESUMO
The proper replication of mitochondrial DNA is key to the maintenance of this crucial organelle. Multiple studies aimed at understanding the mechanisms of replication of the mitochondrial genome have been conducted in the past several decades; however, while highly informative, they were conducted using relatively low-sensitivity techniques. Here, we established a high-throughput approach based on next-generation sequencing to identify replication start sites with nucleotide-level resolution and applied it to the genome of mitochondria from different human and mouse cell types. We found complex and highly reproducible patterns of mitochondrial initiation sites, both previously annotated and newly discovered in this work, that showed differences among different cell types and species. These results suggest that the patterns of the replication initiation sites are dynamic and might reflect, in some yet unknown ways, the complexities of mitochondrial and cellular physiology. Overall, this work suggests that much remains unknown about the details of mitochondrial DNA replication in different biological states, and the method established here opens up a new avenue in the study of the replication of mitochondrial and potentially other genomes.
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Replicação do DNA , Genoma Mitocondrial , Animais , Humanos , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mamíferos/metabolismoRESUMO
A unified strategy for accessing the core structure of cyathane diterpenoids has been developed, enabling the formal synthesis of (-)-erinacine B. The key feature includes an organocatalyzed asymmetric intramolecular vinylogous aldol reaction for convergently building up the 5-6-6 tricyclic ring system. This strategy also highlights a hydroxyl-directed cyclopropanation/ring opening sequence to stereoselectively set up 1,4-anti and -cis angular-methyl quaternary carbon centers.
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RATIONALE: Although urban-rural residency has been shown to influence individual COVID-19 vaccine hesitancy, the differences between urban and rural China have yet to be uncovered. OBJECTIVE: This study aims to assess the current prevalence and factors associated with COVID-19 vaccine hesitancy in urban and rural areas and explore whether the rural versus urban residency is associated with COVID-19 vaccine hesitancy. METHODS: A national, cross-sectional, online survey among Chinese urban and rural adults (≥18 years old) was conducted from 6th to August 9, 2021. A questionnaire was used to collect data on sociodemographic factors, perceptions of the COVID-19 pandemic and vaccination status. A multivariable logistic regression model was used to identify the factors that influence COVID-19 vaccine hesitancy. Propensity score matching (PSM) analysis was performed to explore the association between urban versus rural residency and COVID-19 vaccine hesitancy. RESULTS: In total, 29,925 participants (80.56% urban participants) were recruited. Urban participants had a higher COVID-19 vaccine hesitancy than their rural counterparts (9.39% vs. 4.26%). After adjusting for potential confounders, we found that COVID-19 vaccine hesitancy among females was lower than that in males in both urban (aOR = 0.78, 95% CI [0.69-0.88]) and rural areas (aOR = 0.54, 95% CI [0.39-0.75]). The lack of trust towards vaccine producers was found to be associated with vaccine hesitancy among the urban participants (aOR = 2.76, 95% CI [2.22-3.43]). The rural floating population had a lower COVID-19 vaccine hesitancy than the rural permanent residents (aOR = 0.58, 95% CI [0.42-0.80]). PSM analysis revealed a 2.38% difference in COVID-19 vaccine hesitancy between urban and rural participants. CONCLUSIONS: Urban participants were more hesitant to receive the COVID-19 vaccine than rural participants. Priority should be placed on boosting confidence in the healthcare system to reduce COVID-19 vaccine hesitancy among urban residents. Furthermore, we advocate for extra incentives and vaccination education for rural permanent residents.
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COVID-19 , Internato e Residência , Adulto , Feminino , Masculino , Humanos , Adolescente , Vacinas contra COVID-19 , Estudos Transversais , Pandemias , VacinaçãoRESUMO
Objective.Cardiopulmonary auscultation is promising to get smart due to the emerging of electronic stethoscopes. Cardiac and lung sounds often appear mixed at both time and frequency domain, hence deteriorating the auscultation quality and the further diagnosis performance. The conventional cardiopulmonary sound separation methods may be challenged by the diversity in cardiac/lung sounds. In this study, the data-driven feature learning advantage of deep autoencoder and the common quasi-cyclostationarity characteristic are exploited for monaural separation.Approach.Different from most of the existing separation methods that only handle the amplitude of short-time Fourier transform (STFT) spectrum, a complex-valued U-net (CUnet) with deep autoencoder structure, is built to fully exploit both the amplitude and phase information. As a common characteristic of cardiopulmonary sounds, quasi-cyclostationarity of cardiac sound is involved in the loss function for training.Main results. In experiments to separate cardiac/lung sounds for heart valve disorder auscultation, the averaged achieved signal distortion ratio (SDR), signal interference ratio (SIR), and signal artifact ratio (SAR) in cardiac sounds are 7.84 dB, 21.72 dB, and 8.06 dB, respectively. The detection accuracy of aortic stenosis can be raised from 92.21% to 97.90%.Significance. The proposed method can promote the cardiopulmonary sound separation performance, and may improve the detection accuracy for cardiopulmonary diseases.
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Ruídos Cardíacos , Estetoscópios , Humanos , Sons Respiratórios/diagnóstico , Processamento de Sinais Assistido por Computador , Auscultação/métodosRESUMO
Studies using highly sensitive targeted RNA enrichment methods have shown that a large portion of the human transcriptome remains to be discovered and that most of the genome is transcribed in a complex, interleaved fashion characterized by a complex web of transcripts emanating from protein coding and noncoding loci. These results resonate with those from single-cell transcriptome profiling endeavors that reveal the existence of multiple novel, cell type-specific transcripts and clearly demonstrate that our understanding of the complexities of the human transcriptome is far from being complete. Here, we review the current status of the targeted RNA enrichment techniques, their application to the discovery of novel cell type-specific transcripts, and their impact on our understanding of the human genome and transcriptome.
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RNA Longo não Codificante , Transcriptoma , Animais , Humanos , Transcriptoma/genética , RNA/genética , Análise de Sequência de RNA/métodos , Perfilação da Expressão Gênica/métodos , Genoma Humano , RNA Longo não Codificante/genética , Mamíferos/genéticaRESUMO
Herein, we describe a catalytic asymmetric intramolecular vinylogous aldol reaction by taking advantage of dual organocatalysts, which enables convergent synthesis of ortho-fused tricyclic diketones in excellent enantioselectivities and diastereoselectivities. Noteworthy is that the reaction stereoselectively forges three consecutive stereogenic carbon centers including a quaternary one. Density functional theory calculations reveal that the enantioselectivity was facilitated by a transannular hydrogen bonding between the protonated quinuclidine moiety of the chiral aminocatalyst and the diketone fragment of the substrate.
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Aldeídos , Cetonas , Estereoisomerismo , Aldeídos/química , Catálise , Cetonas/químicaRESUMO
Background: The optimal positions of different types of nebulizer for aerosol delivery remain unclear. Methods: Three ICU ventilators employing three types of nebulizer were separately connected to a simulated lung to simulate nebulization during invasive ventilation. Assist/control-pressure control (A/C-PC) mode was utilized, with inspiratory pressure (Pi) set to 12 cmH2O and positive end expiratory pressure (PEEP) set to 5 cmH2O, and with a target Vt of 500 ml. The bias flow of all the ventilators was set to 2 L/min. The three nebulizers were the continuous jet nebulizer (c-JN), the inspiratory synchronized jet nebulizer (i-JN), and the vibrating mesh nebulizer (VMN). The five nebulizer positions were as follows: at the Y-piece (position 1) and 15 cm from the Y-piece (position 2) between the endotracheal tube and the Y-piece, at the Y-piece (position 3) and 15 cm from the Y-piece (position 4) in the inspiratory limb; and at the humidifier inlet (position 5). Aerosols were collected with a disposable filter placed at the simulated lung outlet (n = 3) and were measured by UV spectrophotometry (276 nm). The measurements were compared under different experimental conditions. Results: The aerosol delivery of c-JN, i-JN, and VMN was 5.33 ± 0.49~11.12 ± 0.36%, 7.73 ± 0.76~13.75 ± 0.46% and 11.13 ± 56-30.2 ± 1.63%, respectively. The higher aerosol delivery: for c-JN~Positions 2 (10.95 ± 0.15%), fori-JN~Positions 1 or 2 (12.91 ± 0.88% or 13.45 ± 0.42%), for VMN~Positions 4(29.03 ± 1.08%); the lower aerosol delivery: for c-JN~Positions 1, 3 or 5, fori-JN~Positions 4 or 5, for VMN~Positions 5.The highest aerosol delivery:For c-JN at Position 2 (10.95 ± .15%), for i-JN at Position 1 or 2 (12.91 ± .88% or 13.45 ± .42%), for VMN at Positions 4 (29. 03 ± 1.08%); the lower aerosol delivery: for c-JN at Positions 1, 3 or 5, for i-JN at Positions 4 or 5, for VMN at Positions 5. The highest aerosol deliveryof c-JN was lower than that of i-JN while the VMN was the highest (all P < .05). However, no differences were observed between the highest aerosol delivery with c-JN and the lowest aerosol delivery with i-JN. Similar results were found between the lowest aerosol delivery with VMN and the highest aerosol delivery with c-JN /i-JN in the Avea ventilator. There were no differences in the highest aerosol delivery of each nebulizer among the different ventilators (all p > 0.05). Conclusion: During adult mechanical ventilation, the type and position of nebulizer influences aerosol delivery efficiency, with no differences between ventilators.
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Objective: To assess lifestyles, COVID-19 vaccination coverage rates, and the relationships between lifestyles and COVID-19 vaccination among Chinese population. Methods: We collected data on sociodemographics, perception of the COVID-19 pandemic, lifestyles, and self-reported COVID-19 vaccination via an online survey in China. The chi-square goodness-of-fit test was used to monitor sample saturation throughout the formal online survey. The binary logistic regression analyses were conducted to examine the association between COVID-19 vaccination rate and lifestyle score. We assigned values to 12 lifestyles ranging from positive to negative, with positive lifestyles receiving a higher score and negative lifestyles receiving a lower score, ranging from 1 to 5. For each participant, the total lifestyle scored from 12 to 56. Restricted cubic spline (RCS) was used to visualize the trends and correlations between lifestyle score and COVID-19 vaccination coverage. Propensity score matching (PSM) was used to explore the association between specific lifestyles and COVID-19 vaccination. Results: A total of 29,925 participants (51.4% females) responded. The lifestyle score of the sample was 44.60 ± 6.13 (scoring range: 12-56). COVID-19 vaccination rate was found to be 89.4% (89.1-89.8%). Female participants reported a higher vaccination rate than male participants (91.5 vs. 87.1%). Compared to Q1, COVID-19 vaccination coverage rates increased with lifestyle total scores [OR Q2 = 1.901 (1.718-2.103), P < 0.001; OR Q3 = 2.373 (2.099-2.684), P < 0.001; and OR Q4 = 3.765 (3.209-4.417), P < 0.001]. After applying PSM, it was determined that all the 12 specific healthy lifestyles analyzed, including maintaining a healthy body weight, a healthy diet, regular physical exercises, adequate sleep, regular physical examination, and others, were found to be positive factors for COVID-19 vaccination. Conclusion: The majority of mainland Chinese lived a healthy lifestyle throughout the COVID-19 pandemic, and the rate of COVID-19 vaccination was high. Specific healthy lifestyles contributed to COVID-19 vaccination coverage rates significantly. According to the study's findings, global efforts to achieve herd immunity should be prioritized by continually promoting healthy lifestyles and improving public perception of COVID-19 vaccines.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Masculino , Feminino , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , Estilo de Vida , VacinaçãoRESUMO
Single-strand breaks (SSBs) represent one of the most common types of DNA damage, yet not much is known about the genome landscapes of this type of DNA lesions in mammalian cells. Here, we found that SSBs are more likely to occur in certain positions of the human genome-SSB hotspots-in different cells of the same cell type and in different cell types. We hypothesize that the hotspots are likely to represent biologically relevant breaks. Furthermore, we found that the hotspots had a prominent tendency to be enriched in the immediate vicinity of transcriptional start sites (TSSs). We show that these hotspots are not likely to represent technical artifacts or be caused by common mechanisms previously found to cause DNA cleavage at promoters, such as apoptotic DNA fragmentation or topoisomerase type II (TOP2) activity. Therefore, such TSS-associated hotspots could potentially be generated using a novel mechanism that could involve preferential cleavage at cytosines, and their existence is consistent with recent studies suggesting a complex relationship between DNA damage and regulation of gene expression.
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OBJECTIVE: To assess the association between lifestyle and COVID-19 vaccine hesitancy among Chinese adults and provide recommendations for increasing vaccination rates. METHODS: From August 6, 2021 to August 9, 2021, we recruited 29,925 participants from 31 Chinese provinces via an online questionnaire. We designed a question to assess COVID-19 vaccine hesitancy and used 16 items to assess lifestyle by calculating lifestyle scores. Odds ratios (OR) with 95 % confidence intervals (CI) were used to estimate the association by using binary logistic regression models. RESULTS: The overall prevalence of COVID-19 vaccine hesitancy was 8.40 % (95 % CI: 8.09-8.72), and the median lifestyle score was 65.00 (interquartile range: 59.00-71.00). After adjusting for potential confounders, the COVID-19 vaccine hesitancy rate decreased significantly with an increase in lifestyle score (P for Trend <0.001). Low COVID-19 vaccine hesitancy rate was associated with lifestyle factors including adequate sleep, never smoking, intermittent drinking, good relationships, working and studying, using hand sanitizer, wearing masks, less gathering activities, and keeping social distance (P < 0.05). CONCLUSION: Our findings indicate that high lifestyle score is associated with low vaccine hesitancy rate among Chinese. The government should view the smokers (or the drinkers) as the key to further boosting the vaccination rate. In addition, the publicity and education about wearing masks and keeping social distance should be prioritized.
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Vacinas contra COVID-19 , COVID-19 , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , China/epidemiologia , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estilo de Vida , Hesitação VacinalRESUMO
Objective: To investigate the feasibility of a hybrid material in which decellularized pericardial extracellular matrix is functionalized with polymeric nanofibers, for use as a cardiovascular tissue substitute. Background: A cardiovascular tissue substitute, which is gradually resorbed and is replaced by host's native tissue, has several advantages. Especially in children and young adults, a resorbable material can be useful in accommodating growth, but also enable rapid endothelialization that is necessary to avoid thrombotic complications. In this study, we report a hybrid material, wherein decellularized pericardial matrix is functionalized with a layer of polymeric nanofibers, to achieve the mechanical strength for implantation in the cardiovascular system, but also have enhanced cell honing capacity. Methods: Pericardial sacs were decellularized with sodium deoxycholate, and polycaprolactone-chitosan fibers were electrospun onto the matrix. Tissue-polymer interaction was evaluated using spectroscopic methods, and the mechanical properties of the individual components and the hybrid material were quantified. In-vitro blood flow loop studies were conducted to assess hemocompatibility and cell culture methods were used to assess biocompatibility. Results: Encapsulation of the decellularized matrix with 70 µm thick matrix of polycaprolactone-chitosan nanofibers, was feasible and reproducible. Spectroscopy of the cross-section depicted new amide bond formation and C-O-C stretch at the interface. An average peel strength of 56.13 ± 11.87 mN/mm2 was measured, that is sufficient to withstand a high shear of 15 dynes/cm2 without delamination. Mechanical strength and extensibility ratio of the decellularized matrix alone were 18,000 ± 4,200 KPa and 0.18 ± 0.03% whereas that of the hybrid was higher at 20,000 ± 6,600 KPa and 0.35 ± 0.20%. Anisotropy index and stiffness of the biohybrid were increased as well. Neither thrombus formation, nor platelet adhesion or hemolysis was measured in the in-vitro blood flow loop studies. Cellular adhesion and survival were adequate in the material. Conclusion: Encapsulating a decellularized matrix with a polymeric nanofiber coating, has favorable attributes for use as a cardiovascular tissue substitute.