Intranasal immunization with a helper-dependent adenoviral vector expressing the codon-optimized fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in BALB/c mice

BACKGROUND: Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract. Currently, there is no clinically approved vaccine against RSV infection. Recent studies have shown that helper-dependent adenoviral (HDAd) vectors may represent effective and safe vaccine vectors. However, viral challenge has not been investigated following mucosal vaccination with HDAd vector vaccines. METHODS: To explore the role played by HDAd as an intranasally administered RSV vaccine vector, we constructed a HDAd vector encoding the codon optimized fusion glycoprotein (Fsyn) of RSV, designated HDAd-Fsyn, and delivered intranasally HDAd-Fsyn to mice. RESULTS: RSV-specific humoral and cellular immune responses were generated in BALB/c mice, and serum IgG with neutralizing activity was significantly elevated after a homologous boost with intranasal (i.n.) application of HDAd-Fsyn. Humoral immune responses could be measured even 14 weeks after a single immunization. Immunization with i.n. HDAd-Fsyn led to effective protection against RSV infection on challenge. CONCLUSION: The results indicate that HDAd-Fsyn can induce powerful systemic immunity against subsequent i.n. RSV challenge in a mouse model and is a promising candidate vaccine against RSV infection

Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas

Student Modeling and Analysis in Adaptive Instructional Systems

There is a growing interest in developing and implementing adaptive instructional systems to improve, automate, and personalize student education. A necessary part of any such adaptive instructional system is a student model used to predict or analyze learner behavior and inform adaptation. To help inform researchers in this area, this paper presents a state-of-the-art review of 11 years of research (2010-2021) in student modeling, focusing on learner characteristics, learning indicators, and foundational aspects of dissimilar models. We mainly emphasize increased prediction accuracy when using multidimensional learner data to create multimodal models in real-world adaptive instructional systems. In addition, we discuss challenges inherent in real-world multimodal modeling, such as uncontrolled data collection environments leading to noisy data and data sync issues. Finally, we reinforce our findings and conclusions through an industry case study of an adaptive instructional system. In our study, we verify that adding multiple data modalities increases our model prediction accuracy from 53.3% to 69%. At the same time, the challenges encountered with our real-world case study, including uncontrolled data collection environment with inevitably noisy data, calls for synchronization and noise control strategies for data quality and usability

Self-reported Rates of Abuse, Neglect, and Bullying Experienced by Transgender and Gender-Nonbinary Adolescents in China

open access articleImportance This is the first comprehensive national study reporting the rates of abuse, neglect, and bullying from family and classmates or teachers among Chinese transgender and gender-nonbinary adolescents and identifying risk factors associated with poor mental health in this population. Objective To assess the rates of abuse, neglect, and bullying and their association with poor mental health among Chinese transgender and gender nonbinary adolescents. Design, Setting, and Participants This national survey study used an online self-selecting survey conducted between January 1, 2017, and September 29, 2017, in China. Eligibility criteria included reporting being aged 12 to 18 years and being transgender or gender nonbinary. Data analysis was performed from March 25 to 28, 2019. Main Outcomes and Measures The main outcome was self-reported poor mental health, including depressive symptoms, anxiety symptoms, and suicidal ideation. Depressive symptoms were measured using the Center for Epidemiological Studies Depression 9-item scale. Anxiety symptoms were measured using the 7-item General Anxiety Disorder scale. Suicidal ideation was measured using standardized questions adapted from previous Chinese studies. Abuse, neglect, and bullying were measured using specifically designed questions. Results Of 564 responses collected, 385 respondents (mean [SD] age, 16.7 [1.2] years) met inclusion criteria, including 109 (28.3%) transgender adolescent boys, 167 (43.4%) transgender adolescent girls, and 109 (28.3%) gender-nonbinary adolescents. Among 319 respondents who reported that their parents were aware of their gender identity, 296 (92.8%) reported having experienced parental abuse or neglect. Among the full cohort, 295 respondents (76.6%) reported having experienced abuse or bullying owing to being transgender or gender nonbinary in school from classmates or teachers. There were 173 respondents (44.9%) with Center for Epidemiological Studies Depression 9-item scale scores indicating they were at risk of major depressive disorder, and 148 respondents (38.4%) had 7-item General Anxiety Disorder scale scores indicating they were at risk of an anxiety disorder. In univariate analysis, reporting experiences of bullying from a classmate or teacher was significantly associated with suicidal ideation (odds ratio, 1.68 [95% CI, 1.04-2.70]; P = .03), but the association was no longer statistically significant after controlling for level of educational attainment, aversion to assigned sex, and depressed mood at the onset of puberty (odds ratio, 1.63 [95% CI, 0.97-2.73]; P = .06). Conclusions and Relevance In this survey study, transgender and gender-nonbinary adolescents in China reported high rates of abuse, neglect, and bullying at home and in school and high rates of symptoms associated with poor mental health. This study highlights the importance of reducing home- and school-based abuse, neglect, and bullying of transgender and gender-nonbinary adolescents in China to improve mental health outcomes; however, broader change in the social environment may be required to address the prejudice and stigma aimed at gender minorities

A new metric for rotating charged Gauss-Bonnet black holes in AdS spaces

This paper presents a new metric for slowly rotating charged Gauss-Bonnet black holes in higher dimensional anti-de Sitter spaces. Taking the angular momentum parameter $a$ up to second order, the slowly rotating charged black hole solutions are obtained by working directly in the action.Comment: 11 pages and accepted by Chin. Phys.