• Byskov Gordon opublikował 1 rok, 3 miesiące temu

    Background The Single Simple Question (SSQ) is a simple and validated question asking what percentage of normal a patient feels with respect to their myasthenia gravis (MG), with 100% being normal. Patient Acceptable Symptom States (PASS), are based on a dichotomous 'Yes’ or 'No’ response, asking whether a patient is satisfied overall with their current status and thus, measures holistic satisfaction with their MG state. Both are patient-reported self assessments but assess different dimensions of MG. Objective To determine thresholds for the SSQ when patients with MG achieve an acceptable PASS status. Methods We performed a retrospective chart review of consecutive MG patients attending a neuromuscular clinic and extracted SSQ and PASS responses, demographic, clinical and serological characteristics and disease severity by the myasthenia gravis impairment index (MGII). Results 157 consecutive patients were identified 43 (27.4%) patients responded 'No’ to the PASS question. Between the PASS 'Yes’/ 'No’ groups, only SSQ (87.5 ±13.4 vs 52.3 ±23.3; p less then 0.001) and MGII scores (9.2±10.3 vs 29.6 ±16; p less then 0.001) were significantly different. The ROC curve for PASS and SSQ had an area under the curve of 0.92±0.024 (CI 0.872-0.965, p less then 0.001). An SSQ score ≥ 72.5% had 84.2% sensitivity and 86% specificity to classify patients as PASS positive. Conclusion The PASS and SSQ patient reported outcomes are closely associated and a SSQ threshold ≥ 72.5% predicts an acceptable MG state. Other demographic and disease-related factors did not influence the PASS response in this study.Current understanding of human brain development is rudimentary due to suboptimal in vitro and animal models. In particular, how initial cell positions impact subsequent human cortical development is unclear because experimental spatial control of cortical cell arrangement is technically challenging. 3D cell printing provides a rapid customized approach for patterning. However, it has relied on materials that do not represent the extracellular matrix (ECM) of brain tissue. Therefore, in the present work, a lipid-bilayer-supported printing technique is developed to 3D print human cortical cells in the soft, biocompatible ECM, Matrigel. Printed human neural stem cells (hNSCs) show high viability, neural differentiation, and the formation of functional, stimulus-responsive neural networks. By using prepatterned arrangements of neurons and astrocytes, it is found that hNSC process outgrowth and migration into cell-free matrix and into astrocyte-containing matrix are similar in extent. However, astrocytes enhance the later developmental event of axon bundling. Both young and mature neurons migrate into compartments containing astrocytes; in contrast, astrocytes do not migrate into neuronal domains signifying nonreciprocal chemorepulsion. Therefore, precise prepatterning by 3D printing allows the construction of natural and unnatural patterns that yield important insights into human cerebral cortex development.When a recurrent event process is ended by death, this may imply dependent censoring if the two processes are associated. Such dependent censoring would have to be modeled to obtain a valid inference. Moreover, the dependence between the recurrence process and the terminal event may be the primary topic of interest. Joint frailty models for recurrent events and death, which include a separate dependence parameter, have been proposed for exactly observed recurrence times. However, in many situations, only the number of events experienced during consecutive time intervals are available. We propose a method for estimating a joint frailty model based on such interval counts and observed or independently censored terminal events. The baseline rates of the two processes are modeled by piecewise constant functions, and Gaussian quadrature is used to approximate the marginal likelihood. Covariates can be included in a proportional rates setting. The observation intervals for the recurrent event counts can differ between individuals. Furthermore, we adapt a score test for the association between recurrent events and death to the setting in which only individual interval counts are observed. We study the performance of both approaches via simulation studies, and exemplify the methodology in a biodemographic study of the dependence between budding rates and mortality in the species Eleutheria dichotoma.Head and neck squamous cell carcinoma (HNSCC) is the one of the most frequently found cancers in the world. The aim of the study was to find the genes responsible and enriched pathways associated with HNSCC using bioinformatics and survival analysis methods. A total of 646 patients with HNSCC based on clinical information were considered for the study. HNSCC samples were grouped according to the parameters (RFS, DFS, PFS, or OS). The probe ID of these 11 genes was retrieved by Affymetrix using the NetAffx Query algorithm. The protein-protein interaction (PPI) network and Kaplan-Meier curve were used to find associations among the genes’ expression data. We found that among these 11 genes, nine genes, CCNA1, MMP3, FLRT3, GJB6, ZFR2, PITX2, SYCP2, MEI1, and UGT8 were significant (p less then .05). A survival plot was drawn between the p value and gene expression. This study helped us find the nine significant genes which play vital roles in HNSCC along with their key pathways and their interaction with other genes in the PPI network. Finally, we found the biomarker index for relapse time and risk factors for HNSCC in cancer patients.We report the unique self-assembling features of N -annulated perylene bisimides (PBIs) 1 and 2 . The stability of the aggregates of diester 1 , in which no H-bonding interactions are operative, corroborates the significance of long-range van-der-Waals and dipole-dipole electrostatic interactions in the construction of stable supramolecular assemblies. The incorporation of amide functional groups to the N -annulated PBI in 2 results in a stimulating pathway differentiation to achieve up to three J-type aggregates and a fourth H-type aggregate depending on the experimental conditions. The results presented demonstrate unprecedented levels of control over synthetic supramolecular self-assembly and the rich differentiation that N -annulated PBIs exhibit, opening the door to new, complex, functional supramolecular materials.Purpose To determine the relationship between the anxiety states and knowledge levels of female midwifery students about COVID-19 during the outbreak. Design and methods This cross-sectional study carried out with online participation of 972 female midwifery students. Findings The anxiety levels of the female midwifery students were high among those visiting the hospital during the pandemic and having parents or relatives who had chronic diseases. Female midwifery students had a high level of knowledge regarding COVID-19. Practice implications Female midwives of the future will take part in primary health care services in the protection and promotion of health as an important occupational group in the public health system. To determine mental health and psychological needs of them during the outbreak will greatly contribute to the pandemic management process.Background The prevalence of vitamin D deficiency and insufficiency is extremely high in pregnant women worldwide. However, the association between single nucleotide polymorphisms (SNPs) in vitamin D metabolic pathway genes and 25-hydroxyvitamin D (25(OH)D) concentration among Chinese pregnant women is seldom reported. The risk of adverse neonatal outcomes due to maternal vitamin D deficiency has not been well investigated. Methods A total of 815 pregnant women and 407 infants were enrolled in this study. Serum 25(OH)D concentration was detected. DNA was extracted from the maternal blood for genotyping genetic SNPs in vitamin D pathway. An XGBoost model was established based on SNPs combined with external variables. Results Mean serum 25(OH)D level was 15.67 ± 7.98 ng/mL among the pregnant women. Seventy-five percent of pregnant women had 25(OH)D deficiency in China. SNPs of GC (rs17467825, rs4588, rs2282679, rs2298850, and rs1155563) were significantly associated with maternal 25(OH)D concentration. The influence of variants of rs17467825, rs4588, rs2282679, and rs2298850 on maternal 25(OH)D might be modified by vitamin D supplementation and sunshine exposure. An XGBoost model was established for monitoring 25(OH)D status in pregnant women and provided clinical advice to reduce the risk of 25(OH)D deficiency. Mothers with 25(OH)D deficiency hinted a risk for macrosomia. Conclusion A high prevalence of vitamin D deficiency in China has been confirmed. A clinical model was established to guide pregnant women to supplement vitamin D according to genotype. Furthermore, we suggest the effect of maternal vitamin D status on the risk of macrosomia.Triple-negative breast cancer (TNBC) is a very aggressive subtype with high recurrence rate and no molecular targets for therapies. This subtype is characterized by high expression/secretion of the proinvasive/metastatic interleukin-6 (IL-6) cytokine. In the present study, we have shown that tocilizumab inhibits the IL-6/STAT3 signaling and suppresses the cancer/inflammatory epigenetic IL-6/STAT3/NF-κB positive feedback loop. Furthermore, tocilizumab inhibited the proliferative and the migratory/invasiveness capacities as well as the epithelial-to-mesenchymal transition (EMT) process in TNBC cells. Importantly, tocilizumab suppressed the stemness-related characteristics of TNBC cells, through the inhibition of the Wnt/β-catenin breast cancer stem cell-related pathway. Additionally, we have shown that tocilizumab suppresses the paracrine activation of normal breast stromal fibroblasts to myofibroblats. Moreover, tocilizumab sensitized TNBC cells to the cytotoxic effect of cisplatin in vitro. Furthermore, pharmacological inhibition of IL-6 by tocilizumab had great inhibitory effect on tumor growth and the EMT process in humanized orthotopic breast tumors in mice. In addition, tocilizumab potentiated the proapoptotic effect of cisplatin in humanized breast tumors. Together, these findings indicate that tocilizumab can suppress the prometastatic capacity of TNBC cells and enhances the cytotoxic effect of cisplatin against these cells. Therefore, tocilizumab could be of great therapeutic value for these hard-to-treat TNBC patients.Herein, the recent advances in realizing highly efficient cellulose-based solar evaporators for alleviating the global water crisis are summarized. Fresh water scarcity is one of the most threatening issues for sustainable development. Solar steam generation, which harnesses the abundant sunlight, has been recognized as a sustainable approach to harvest fresh water. In contrast to synthetic polymeric materials that can pose serious negative environmental impacts, cellulose-based materials, owing to their biocompatibility, renewability, and sustainability, are highly attractive for realizing solar steam generators. The molecular and macromolecular features of cellulose and the physicochemical properties of extracted cellulose nanoparticles (cellulose nanocrystals and cellulose nanofibrils (CNF)) and natural cellulose materials (wood and bacterial nanocellulose (BNC)) that make them attractive as supporting substrate materials in solar steam generators are briefly discussed. Recent progress in designing highly efficient cellulose-based solar evaporators, including utilizing extracted cellulose nanoparticles via bottom-up assembly CNF, natural cellulose materials with intrinsic hierarchical structure (wood and BNC), and commercial planar cellulose substrates (air-laid paper, cellulose paper, and cotton fabric) is reviewed.

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