The inverse probability of treatment weighted (IPTW) estimator can be used to make causal inferences under two assumptions: (1) no unobserved confounders (ignorability) and (2) positive probability of treatment and of control at every level of the confounders (positivity), but is vulnerable to bias if by chance, the proportion of the sample assigned to treatment, or proportion of control, is zero at certain levels of the confounders. We propose to deal with this sampling zero problem, also known as practical violation of the positivity assumption, in a setting where the observed confounder is cluster identity, i.e., treatment assignment is ignorable within clusters. Specifically, based on a random coefficient model assumed for the potential outcome, we augment the IPTW estimating function with the estimated potential outcomes of treatment (or of control) for clusters that have no observation of treatment (or control). If the cluster-specific potential outcomes are estimated correctly, the augmented estimating function can be shown to converge in expectation to zero and therefore yield consistent causal estimates. The proposed method can be implemented in the existing software, and it performs well in simulated data as well as with real-world data from a teacher preparation evaluation study.

Accurate assessment of a student’s ability is the key task of a test. Assessments based on final responses are the standard. As the infrastructure advances, substantially more information is observed. One of such instances is the process data that is collected by computer-based interactive items and contain a student’s detailed interactive processes. In this paper, we show both theoretically and with simulated and empirical data that appropriately including such information in the assessment will substantially improve relevant assessment precision.

Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.

With the advantages of short duration and extreme brightness, laser proton accelerators (LPAs) show great potential in many fields for industrial, medical, and research applications. However, the quality of current laser-driven proton beams, such as the broad energy spread and large divergence angle, is still a challenge. We use numerical simulations to study the propagation of such proton bunches in the plasma. Results show the bunch will excite the wakefield and modulate itself. Although a small number of particles at the head of the bunch cannot be manipulated by the wakefield, the total energy spread is reduced. Moreover, while reducing the longitudinal energy spread, the wakefield will also pinch the beam in the transverse direction. The space charge effect of the bunch is completely offset by the wakefield, and the transverse momentum of the bunch decreases as the bunch transports in the plasma. For laser-driven ion beams, our study provides a novel idea about the optimization of these beams.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.

The contemporary expansion of English is becoming remarkably rapid and exceptionally global (Ostler, 2011). In present-day China, English has gained unprecedented popularity, fueled by the nation's current political and social development (Bolton & Graddol, 2012). There is a notable trend of bilingual education using English as a medium of instruction in Chinese schools (Wei, 2013). Therefore, an increasing number of Chinese are enthusiastic about learning and using English in communication. With the active participation of youths, ‘Internet English’ has been used widely in social networking spaces. The practice of ‘English mixing’ in various Chinese homegrown social networking sites has become the most remarkable intranational use of English in today's mainland China (Zhang, 2012). Interestingly, youngsters1 often create novel meanings when using languages on the Internet as ‘teenagers are well-known for introducing innovations into language, and indeed are generally regarded as prime agents of language change’ (Palacios Martínez, 2018: 363). Many linguistic studies have dealt with the mechanisms of the evolution of word meanings in past decades (Kachru, 1983; Qin & Guo, 2020; Tan, 2009; Yang, 2005). Much evidence indicates that meanings and usages of words are variable and composite, and may turn out differently depending on how words are used in contexts.

Carbon nanotube foams (CNFs) have been successfully used as near-critical-density targets in the laser-driven acceleration of high-energy ions and electrons. Here we report the recent advances in the fabrication technique of such targets. With the further developed floating catalyst chemical vapor deposition (FCCVD) method, large-area ($>25\kern0.5em {\mathrm{cm}}^2$) and highly uniform CNFs are successfully deposited on nanometer-thin metal or plastic foils as double-layer targets. The density and thickness of the CNF can be controlled in the range of $1{-}13\kern0.5em \mathrm{mg}/{\mathrm{cm}}^3$ and $10{-}200\kern0.5em \mu \mathrm{m}$, respectively, by varying the synthesis parameters. The dependence of the target properties on the synthesis parameters and the details of the target characterization methods are presented for the first time.

In late December 2019, patients of atypical pneumonia due to an unidentified microbial agent were reported in Wuhan, Hubei Province, China. Subsequently, a novel coronavirus was identified as the causative pathogen which was named SARS-CoV-2. As of 12 February 2020, more than 44 000 cases of SARS-CoV-2 infection have been confirmed in China and continue to expand. Provinces, municipalities and autonomous regions of China have launched first-level response to major public health emergencies one after another from 23 January 2020, which means restricting movement of people among provinces, municipalities and autonomous regions. The aim of this study was to explore the correlation between the migration scale index and the number of confirmed coronavirus disease 2019 (COVID-19) cases and to depict the effect of restricting population movement. In this study, Excel 2010 was used to demonstrate the temporal distribution at the day level and SPSS 23.0 was used to analyse the correlation between the migration scale index and the number of confirmed COVID-19 cases. We found that since 23 January 2020, Wuhan migration scale index has dropped significantly and since 26 January 2020, Hubei province migration scale index has dropped significantly. New confirmed COVID-19 cases per day in China except for Wuhan gradually increased since 24 January 2020, and showed a downward trend from 6 February 2020. New confirmed COVID-19 cases per day in China except for Hubei province gradually increased since 24 January 2020, and maintained at a high level from 24 January 2020 to 4 February 2020, then showed a downward trend. Wuhan migration scale index from 9 January to 22 January, 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Wuhan from 22 January to 4 February. Hubei province migration scale index from 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Hubei province from 22 January to 4 February. Our findings suggested that people who left Wuhan from 9 January to 22 January, and those who left Hubei province from 10 January to 24 January, led to the outbreak in the rest of China. The ‘Wuhan lockdown’ and the launching of the first-level response to this major public health emergency may have had a good effect on controlling the COVID-19 epidemic. Although new COVID-19 cases continued to be confirmed in China outside Wuhan and Hubei provinces, in our opinion, these are second-generation cases.

For the guarantee of the long-distance transport of the bunches of China Initiative Accelerator Driven System (CIADS), a new scheme is proposed that extra magnetic field is used in the accelerator-target coupling section before the windowless target to minimize the self-modulation (SM) mechanism. Particle-in-cell simulations are carried out to study the influence of the solenoidal magnetic field on the self-modulation mechanism when long proton bunches move in the background plasmas. The long proton bunches used in the simulations are similar to these in the linear accelerator of CIADS. It is found that the presence of the solenoidal magnetic field will significantly inhibit the self-modulation process. For the strong magnetic field, the longitudinal separation and transverse focusing of the long bunches disappear. We attribute these phenomena to the reason that the strong solenoidal magnetic field restricts the transverse movement of plasma electrons. Thus, there are not enough electrons around the bunch to compensate the space charge effect. Moreover, without transverse current, the longitudinal pinched effect disappears, and the long bunch can not be separated into small pulses anymore.

The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.

The COVID-19 outbreak is ongoing in China. Here, Boltzmann function-based analyses reveal the potential total numbers of COVID-19 deaths: 3,260 (95% confidence interval [CI], 3187–3394) in China; 110 (95% CI, 109–112) in Hubei Province; 3,174 (95% CI, 3095–3270) outside Hubei; 2,550 (95% CI, 2494–2621) in Wuhan City; and 617 (95% CI, 607–632) outside Wuhan.