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BACKGROUND: Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement. METHODS: We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was measured by Euclidean distance for enrollment sequence in year two, total enrollment over time, and total weeks to enroll a fixed number of subjects, against the actual year two enrollment data. We compare the performance of the proposed method with an existing Bayesian method. RESULTS: Weighted resampling using GRIPS data resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, especially when enrollment gaps were filled prior to the weighted resampling. These scenarios also produced more accurate predictions for total enrollment and number of weeks to enroll 50 participants. These same scenarios outperformed an existing Bayesian method for all 3 accuracy measures. In PACE data, using a reduced year 1 enrollment resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, with the weighted resampling scenarios better reflecting the seasonal variation seen in year (1) The reduced enrollment scenarios resulted in closer prediction for total enrollment over 6 and 12 months into year (2) These same scenarios also outperformed an existing Bayesian method for relevant accuracy measures. CONCLUSION: The results demonstrate the feasibility and flexibility for a resampling-based, non-parametric approach for prediction of clinical trial recruitment with limited early enrollment data. Application to a wider setting and long-term prediction accuracy require further investigation.
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Teorema de Bayes , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Idoso , Pacientes Internados/estatística & dados numéricos , Estatísticas não Paramétricas , FemininoRESUMO
BACKGROUND: In the early stages of diabetic kidney disease (DKD), the pathogenesis involves abnormal angiogenesis in the glomerulus. Hirudin, as a natural specific inhibitor of thrombin, has been shown in previous studies to inhibit the migration of various tumor endothelial cells and abnormal angiogenesis. However, its role in DKD remains unclear. METHODS: The effects of hirudin in DKD were studied using spontaneous type 2 diabetic db/db mice (which develop kidney damage at 8 weeks). Network pharmacology was utilized to identify relevant targets. An in vitro high glucose model was established using mouse glomerular endothelial cells (MGECs) to investigate the effects of hirudin on the migration and angiogenic capacity of MGECs. RESULTS: Hirudin can ameliorate kidney damage in db/db mice. Network pharmacology suggests its potential association with the VEGFA/VEGFR2 pathway. Western blot and immunohistochemistry demonstrated elevated protein expression levels of VEGFA, VEGFR2, AQP1, and CD31 in db/db mice, while hirudin treatment reduced their expression. In the MGECs high glucose model, hirudin may reverse the enhanced migration and angiogenic capacity of MGECs in a high glucose environment by altering the expression of VEGFA, VEGFR2, AQP1, and CD31. Moreover, the drug effect gradually increases with higher concentrations of hirudin. CONCLUSIONS: This study suggests that hirudin can improve early-stage diabetic kidney disease kidney damage by inhibiting the migration and angiogenesis of glomerular endothelial cells, thereby further expanding the application scope of hirudin. Additionally, the study found increased expression of AQP1 in DKD, providing a new perspective for further research on the potential pathogenesis of DKD.
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BACKGROUND: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non-cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV-associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV-associated cancers in our analysis of IR in East TX and the TX-Mexico Border compared to other TX regions. METHODS: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV-associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient-level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county-level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences. RESULTS: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time. CONCLUSION: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations.
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Área Carente de Assistência Médica , Infecções por Papillomavirus , Humanos , Texas/epidemiologia , Feminino , Incidência , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Masculino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Idoso , Sistema de Registros , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/virologiaRESUMO
Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.
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BACKGROUND: Kidney transplant recipients (KTRs) have elevated risks of cervical pre-cancers and cancers, and guidelines recommend more frequent cervical cancer screening exams. However, little is known about current trends in cervical cancer screening in this unique population. We described patterns in the uptake of cervical cancer screening exams among female KTRs and identified factors associated with screening utilization. METHODS: This retrospective cohort study included female KTRs between 20-65 years old, with Texas Medicare fee-for-service coverage, who received a transplant between January 1, 2001, and December 31, 2017. We determined the cumulative incidence of receiving cervical cancer screening post-transplant using ICD-9, ICD-10, and CPT codes and assessed factors associated with screening utilization, using the Fine and Gray model to account for competing events. Subdistribution hazards models were used to assess factors associated with screening uptake. RESULTS: Among 2,653 KTRs meeting the inclusion and exclusion criteria, the 1-, 2-, and 3-year cumulative incidences of initiating a cervical cancer screening exam post-transplant were 31.7% (95% confidence interval (CI), 30.0-33.6%), 48.0% (95% CI, 46.2-49.9%), and 58.5% (95% CI, 56.7-60.3%), respectively. KTRs who were 55-64 years old (vs. <45 years old) and those with a higher Charlson Comorbidity Score post-transplant were less likely to receive cervical cancer screening post-transplant. CONCLUSIONS: Cervical cancer screening uptake is low in the years immediately following a kidney transplant. IMPACT: Our findings highlight a need for interventions to improve cervical cancer screening utilization among KTRs.
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Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in SARS-CoV-2-infected mice. Using IL-33-/- mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology. These improved outcomes in IL-33-/- mice also correlated with a reduction in innate immune cell infiltrates, i.e., neutrophils, macrophages, natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq results revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation, and cytokine/chemokine signals. Overall, these findings demonstrate that the alarmin IL-33 plays a pathogenic role in SARS-CoV-2 infection and provides new insights that will inform the development of effective therapeutic strategies for COVID-19.
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Polyethylene glycols (PEGs) are used in industrial, medical, health care, and personal care applications. The cycling and disposal of synthetic polymers like PEGs pose significant environmental concerns. Detecting and monitoring PEGs in the real world calls for immediate attention. This study unveils the efficacy of time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a reliable approach for precise analysis and identification of reference PEGs and PEGs used in cosmetic products. By comparing SIMS spectra, we show remarkable sensitivity in pinpointing distinctive ion peaks inherent to various PEG compounds. Moreover, the employment of principal component analysis effectively discriminates compositions among different samples. Notably, the application of SIMS two-dimensional image analysis visually portrays the spatial distribution of various PEGs as reference materials. The same is observed in authentic cosmetic products. The application of ToF-SIMS underscores its potential in distinguishing PEGs within intricate environmental context. ToF-SIMS provides an effective solution to studying emerging environmental challenges, offering straightforward sample preparation and superior detection of synthetic organics in mass spectral analysis. These features show that SIMS can serve as a promising alternative for evaluation and assessment of PEGs in terms of the source, emission, and transport of anthropogenic organics.
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Cosméticos , Polietilenoglicóis , Espectrometria de Massa de Íon Secundário , Cosméticos/análise , Cosméticos/química , Espectrometria de Massa de Íon Secundário/métodos , Polietilenoglicóis/química , Polietilenoglicóis/análise , Análise de Componente PrincipalRESUMO
Streptococcus suis (S. suis) disease is a prevalent zoonotic infectious threat that elicits a systemic inflammatory response in both swine and humans, frequently culminating in high mortality rates. The excessive inflammation triggered by S. suis infection can precipitate tissue damage and sudden death; however, a comprehensive strategy to mitigate this inflammatory response remains elusive. Our study examines the role of NLRP6 in S. suis infection, with a particular focus on its involvement in pathogen regulation. A marked upregulation of NLRP6 was observed in peritoneal macrophages post-infection with S. suis SC19 strain, consequently activating the NLRP6 inflammasome. Furthermore, SC19 infection was found to augment the secretion of pro-inflammatory cytokines IL-1ß via NLRP6 activation, while NLRP6 deficiency mitigates the invasion and adhesion of SC19 to macrophages. In vivo models revealed that NLRP6 deletion enhanced survival rates of SC19-infected mice, alongside a reduction in tissue bacterial load and inflammatory cytokine levels. NLRP6-/- mice were shown to exhibit attenuated inflammatory responses in pulmonary, hepatic, and splenic tissues post-SC19 infection, as evidenced by lower inflammation scores. Flow cytometry analyses further substantiated that NLRP6 is involved in modulating macrophage and neutrophil recruitment during infection. Our findings suggest that NLRP6 negatively regulates host resistance against S. suis infection; its absence results in reduced mortality, bacterial colonization, and a milder inflammatory response. Elucidating the mechanism of NLRP6 in S. suis-induced inflammation provides novel insights and theoretical underpinnings for the prophylaxis and therapeutics of S. suis diseases.
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Camundongos Endogâmicos C57BL , Infecções Estreptocócicas , Streptococcus suis , Streptococcus suis/imunologia , Streptococcus suis/patogenicidade , Streptococcus suis/genética , Animais , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Camundongos , Camundongos Knockout , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/microbiologia , Inflamassomos/imunologia , Inflamassomos/genética , Citocinas/metabolismo , Citocinas/genética , Inflamação/imunologia , Feminino , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Receptores de Superfície CelularRESUMO
Salmonella enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in Salmonella serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the trxB gene (trxB::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of trxB gene in the pathogenicity of SG. Our results showed that trxB::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to H2O2 and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of trxB::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the trxB::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the trxB::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1ß, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the trxB-deficient strain was significantly attenuated, indicating that the trxB gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that trxB may become a potentially effective target for controlling and preventing SG infection in chickens.
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AIMS: Conduct a secondary analysis of the TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, diabetes Education) made simple trial (SIMPLE) to evaluate healthcare utilization and explore variables that may have influenced HbA1c. METHODS: Participants (N = 134 [67/group]) were low-income, uninsured Hispanics with or at risk for type 2 diabetes mellitus. We included in-person and telehealth clinician visits, other visits, missed visits, orders placed, and guideline-adherence (e.g., vaccinations, quarterly HbA1c for uncontrolled diabetes). Using multivariable models, we explored for associations between HbA1c changes and these measures. RESULTS: The control arm had higher missed visits rates (intervention: 45 %; control: 56 %; p = 0.007) and missed telehealth appointments (intervention: 10 %; control: 27.4 %; p = 0.04). The intervention group received more COVID vaccinations than the control (p = 0.005). Other health measures were non-significant between groups. Intervention individuals' HbA1c improved with more missed visits (-0.60 %; p < 0.01) and worsened with improved guideline-adherent HbA1c measurements (HbA1c: 1.2 %; p = 0.057). The control group had non-significant HbA1c associations. CONCLUSIONS: Findings suggest that the SIMPLE trial's improved HbA1c levels stemmed from a CHW-driven intervention and not additional healthcare contact. Exploratory outcomes resulted in seemingly counterintuitive HbA1c associations with missed visits and guideline-adherent measurements; these may suggest that an intervention that enhances communication provides support to reduce the amount of follow-up needed by participants without sacrificing clinical improvements.
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Agentes Comunitários de Saúde , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Educação de Pacientes como Assunto , Autogestão , Telemedicina , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/epidemiologia , Pessoa de Meia-Idade , Autogestão/educação , Autogestão/métodos , Telemedicina/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Hemoglobinas Glicadas/análise , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Idoso , Hispânico ou Latino/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
Streptococcus suis (S. suis) type 2 (SS2) is an important zoonotic pathogen causing severe neural infections in pigs and causes serious threat to public health. Inflammasome activation plays an important role in the host against microbial infection but the role of inflammasome activation in the blood-brain barrier (BBB) integrity during S. suis infection is rarely studied. This study investigated the mechanism by which S. suis-induced NLRP3 inflammasome activation led to BBB disruption. Our results showed that S. suis infection activated NLRP3 inflammasome in brain microvascular endothelial cells (BMECs) leading to the secretion of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and chemokines (CCL-2 and CXCL-2) as well as the cleavage of Gasdermin D (GSDMD) which were significantly attenuated by inflammasome inhibitor MCC950. Furthermore, S. suis infection significantly downregulated expression of tight junctions (TJs) proteins and trans-endothelial electrical resistance (TEER) while NLRP3 inhibition rescued S. suis-induced degradation of TJs proteins and significantly reduced the number of S. suis crossing BBB in transwell infection model. Moreover, recombinant IL-1ß exacerbated the reduction of TJs proteins in BMECs. In murine S. suis-infection model, MCC950 reduced the bacterial load and the excessive inflammatory response in mice brain. In addition, the integrity of the BBB was protected with increased TJ proteins expression and decreased pathological injury after the inhibition of NLRP3 inflammasome, indicating NLRP3 inflammasome plays a destructive role in meningitis induced by S. suis. Our study expands the understanding on the role of NLRP3 inflammasome in bacterial meningitis, which provide the valuable information for the development of anti-infective agents targeting NLRP3 to treat bacterial meningitis.
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Barreira Hematoencefálica , Células Endoteliais , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Infecções Estreptocócicas , Streptococcus suis , Animais , Barreira Hematoencefálica/microbiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/imunologia , Camundongos , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Células Endoteliais/microbiologia , Citocinas/metabolismo , Citocinas/genética , Camundongos Endogâmicos C57BL , Encéfalo/microbiologia , Encéfalo/imunologia , FemininoRESUMO
Salmonella enterica serovar Gallinarum (S. gallinarum) is an important host-specific pathogen that causes fowl typhoid, a severe systemic, septicemic, and fatal infection, in chickens. S. gallinarum causes high morbidity and mortality in chickens and poses a significant burden and economic losses to the poultry industry in many developing countries. However, the virulence factors and mechanisms of S. gallinarum-induced systemic infection in chickens remain poorly understood. In this study, we constructed a Salmonella pathogenicity island-14 (SPI-14) mutant strain (mSPI-14) of S. gallinarum and evaluated the pathogenicity of mSPI-14 in the chicken systemic infection model. The mSPI-14 exhibited the same level of bacterial growth and morphological characteristics but significantly reduced resistance to bile acids compared with the wild-type (WT) strain in vitro. The virulence of mSPI-14 was significantly attenuated in the chicken oral infection model in vivo. Chickens infected with WT showed typical clinical symptoms of fowl typhoid, with all birds succumbing to the infection within 6 to 9 days post-inoculation, and substantial increases in bacterial counts and significant pathological changes in the liver and spleen were observed. In contrast, all mSPI-14-infected chickens survived, the bacterial counts in the organs were significantly lower, and no significant pathological changes were observed in the liver and spleen. The expression of interleukin (IL)-1ß, IL-12, CXCLi1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the liver of mSPI-14-infected chickens were significantly lower than those in the WT-infected chickens. These results indicate that SPI-14 is a crucial virulence factor in systemic infection of chickens, and avirulent mSPI-14 could be used to develop a new attenuated live vaccine to prevent S. gallinarum infection in chickens.
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BACKGROUND: Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In this study, physiological, biochemical and morphological changes in Bougainvillea glabra leaves, leaf buds and bracts during seven developmental periods were systematically investigated. Moreover, transcriptomic data of B. glabra bracts were obtained using PacBio and Illumina sequencing technologies, and key genes regulating their development were screened. RESULTS: Scanning electron microscopy revealed that the bracts develop via a process involving regression of hairs and a color change from green to white. Transcriptome sequencing revealed 79,130,973 bp of transcript sequences and 45,788 transcripts. Differential gene expression analysis revealed 50 expression patterns across seven developmental periods, with significant variability in transcription factors such as BgAP1, BgFULL, BgCMB1, BgSPL16, BgSPL8, BgDEFA, BgEIL1, and BgBH305. KEGG and GO analyses of growth and development showed the involvement of chlorophyll metabolism and hormone-related metabolic pathways. The chlorophyll metabolism genes included BgPORA, BgSGR, BgPPH, BgPAO and BgRCCR. The growth hormone and abscisic acid signaling pathways involved 44 and 23 homologous genes, and coexpression network analyses revealed that the screened genes BgAPRR5 and BgEXLA1 are involved in the regulation of bract development. CONCLUSIONS: These findings improve the understanding of the molecular mechanism of plant bract development and provide important guidance for the molecular regulation and genetic improvement of the growth and development of ornamental plants, mainly ornamental bracts.
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Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Nyctaginaceae , Nyctaginaceae/genética , Nyctaginaceae/metabolismo , Transcriptoma , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Flores/genética , Flores/crescimento & desenvolvimentoRESUMO
Tungsten (W) and W alloys are considered as primary candidates for plasma-facing components (PFCs) that must perform in severe environments in terms of temperature, neutron fluxes, plasma effects, and irradiation bombardment. These materials are notoriously difficult to produce using additive manufacturing (AM) methods due to issues inherent to these techniques. The progress on applying AM techniques to W-based PFC applications is reviewed and the technical issues in selected manufacturing methods are discussed in this review. Specifically, we focus on the recent development and applications of laser powder bed fusion (LPBF), electron beam melting (EBM), and direct energy deposition (DED) in W materials due to their abilities to preserve the properties of W as potential PFCs. Additionally, the existing literature on irradiation effects on W and W alloys is surveyed, with possible solutions to those issues therein addressed. Finally, the gaps in possible future research on additively manufactured W are identified and outlined.
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Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.
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COVID-19 , Modelos Animais de Doenças , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Animais , COVID-19/imunologia , SARS-CoV-2/imunologia , Camundongos , Humanos , Encéfalo/virologia , Encéfalo/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , FemininoRESUMO
Pyruvic acid (PA) is a ubiquitous 2-oxocarboxylic acid in the atmosphere. Its photochemical process at the air-liquid (a-l) interface has been suggested as an important source of aqueous secondary organic aerosols. We investigated the photochemical reaction pathways of PA at the a-l interface using synchrotron-based vacuum ultraviolet single-photon ionization mass spectrometry (VUV SPI-MS) coupled with the System for Analysis at the Liquid Vacuum Interface (SALVI) microreactor. Results from mass spectral analysis and the determination of appearance energies (AEs) indicate that photolysis of PA can generate radicals, then they recombine with carboxylic acids and simple molecular oligomers. Furthermore, the preliminary products could form larger oligomers via radical reaction or esterification in the presence of hydroxyl and carboxyl functional groups. Mass spectral comparison shows that most photochemical reactions would complete within 4 h. The expanded photochemistry-driven reaction flowchart of PA is proposed based on the newly discovered products. Our results reveal that the interfacial PA photochemical reactions have different mechanisms from the bulk liquid due to the interfacial properties, such as molecular density, composition, and ion concentration. Our findings show that in situ mass spectral analysis with bright photon ionization is useful to elucidate the contribution of a-l interfacial reactions leading to aqSOA formation.
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Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol-1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol-1/L. These results shed light on the plant's mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.
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The rise in universal population and accompanying demands have directed toward an exponential surge in the generation of polymeric waste. The estimate predicts that world-wide plastic production will rise to ≈590 million metric tons by 2050, whereas 5000 million more tires will be routinely abandoned by 2030. Handling this waste and its detrimental consequences on the Earth's ecosystem and human health presents a significant challenge. Converting the wastes into carbon-based functional materials viz. activated carbon, graphene, and nanotubes is considered the most scientific and adaptable method. Herein, this world provides an overview of the various sources of polymeric wastes, modes of build-up, impact on the environment, and management approaches. Update on advances and novel modifications made in methodologies for converting diverse types of polymeric wastes into carbon nanomaterials over the last 5 years are given. A remarkable focus is made to comprehend the applications of polymeric waste-derived carbon nanomaterials (PWDCNMs) in the CO2 capture, removal of heavy metal ions, supercapacitor-based energy storage and water splitting with an emphasis on the correlation between PWDCNMs' properties and their performances. This review offers insights into emerging developments in the upcycling of polymeric wastes and their applications in environment and energy.
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Metais Pesados , Nanoestruturas , Nanotubos , Humanos , Polímeros , EcossistemaRESUMO
Introduction: Similar proportions of women and men have entered medical school since 2003. However, career advancement and promotion for women continues to be fraught with disparities and inequalities. Building on current literature, this study explores the rates of change of female faculty in faculty ranks over the last 10 years to gain a more comprehensive view of the faculty trends of women in academic medicine. Methods: Using the Faculty Administrative Management Online User System database, counts by gender and faculty rank at each Association of American Medical Colleges (AAMC) academic medical school were obtained. Statistical analysis was done using generalized estimating equations modeling to assess rates of change for each gender from 2012 to 2021. Results: Higher proportions of female faculty are concentrated at the Instructor and Assistant Professor level and lower proportions at the Associate Professor and Professor rank compared to male faculty. Over the study period, female faculty showed increased rate change compared to male faculty of 1.007 (95% confidence interval [CI]: 1.002-1.012) for Associate Professor rank and 1.012 (95% CI: 1.007-1.016) for Professor rank. At the Instructor and Assistant Professor levels, female faculty decreased at a relative rate of 0.980 (95% CI: 0.969-0.990) and 0.995 (95% CI: 0.992-0.997) each year, respectively. Conclusion: Female faculty continue to be concentrated at the junior faculty rank. Rate changes at the senior faculty rank for female faculty have slightly improved over the last 10 years compared to male faculty. However, this improvement is minimal, and work is still needed to achieve true gender equity in academic medicine.
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Mobilidade Ocupacional , Docentes de Medicina , Médicas , Faculdades de Medicina , Humanos , Docentes de Medicina/estatística & dados numéricos , Feminino , Masculino , Médicas/tendências , Médicas/estatística & dados numéricos , Estados Unidos , Centros Médicos Acadêmicos , Sexismo/tendênciasRESUMO
Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.