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Abstract Background Patients with moderate‐to‐severe atopic dermatitis (AD) refractory to topical therapy might require treatment with systemic therapies, including biologics. Objectives To assess the efficacy and safety of abrocitinib monotherapy in patients who previously received systemic therapies. Methods This post hoc analysis included patients receiving abrocitinib (200 mg/100 mg) or placebo in the phase 2b and phase 3 JADE MONO‐1 and MONO‐2, REGIMEN (abrocitinib 200 mg; open‐label period) and EXTEND (patients enrolled from MONO‐1 and MONO‐2) trials. Patients who were systemic therapy‐naive or had received prior oral systemic or biologic therapies were assessed for Investigator's Global Assessment (IGA) response of 0 (clear) or 1 (almost clear) and ≥2‐point improvement from baseline, ≥75% or ≥90% improvement in Eczema Area and Severity Index (EASI‐75 or EASI‐90), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), PP‐NRS score of 0 or 1 and change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) and Patient‐Oriented Eczema Measure (POEM) scores. Safety was assessed. Results This analysis included 1579 patients (systemic therapy‐naive, n = 997; prior exposure to oral systemic, n = 429; biologic therapies, n = 153). At Week 12, IGA 0/1 response rates (95% confidence intervals) among patients who were systemic therapy‐naive, had received prior oral systemic therapy or had received biologic therapy were 44.4% (37.5–51.4), 34.5% (22.3–46.7) and 43.5% (23.2–63.7) with abrocitinib 200 mg, 30.9% (24.2–37.5), 16.4% (7.1–25.7) and 24.1% (8.6–39.7) with abrocitinib 100 mg and 9.6% (4.2–14.9), 5.9% (0.0–13.8) and 0.0% (0.0–23.2) with placebo in the pooled monotherapy trials; and 67.0% (62.8–71.2), 62.2% (56.4–68.0) and 53.5% (42.9–64.0) in REGIMEN. Across subgroups, abrocitinib showed greater improvement in EASI‐75, PP‐NRS4, EASI‐90, PP‐NRS 0/1, PSAAD and POEM scores versus placebo. Similar results were seen at Week 48. No new safety signals were observed. Conclusions Prior use of oral systemic or biologic therapies did not seem to impact the efficacy and safety of abrocitinib in patients with moderate‐to‐severe AD.

Abstract Background It is unclear whether regional anesthesia with infraclavicular nerve block or general anesthesia provides better postoperative analgesia after distal radial fracture fixation, especially when combined with regular postoperative analgesic medications. The aim of this study was to compare the postoperative analgesic effects of regional versus general anesthesia. Methods In this prospective, observer blinded, randomized controlled trial, 52 patients undergoing distal radial fracture fixation received either general anesthesia (n = 26) or regional anesthesia (infraclavicular nerve block, n = 26). Numerical rating scale pain scores, analgesic consumption, patient satisfaction, adverse effects, upper limb functional scores (Patient-Rated Wrist Evaluation, QuickDASH), health related quality of life (SF12v2), and psychological status were evaluated after surgery. Result Regional anesthesia was associated with significantly lower pain scores both at rest and with movement on arrival to the post-anesthetic care unit; and at 1, 2, 24 and 48 h after surgery (p ≤ 0.001 at rest and with movement). Morphine consumption in the post-anesthetic care unit was significantly lower in the regional anesthesia group (p

A new instrument for high-resolution optical logging has been built and tested in Antarctica. Its purpose is to obtain records of volcanic products and other scattering features, such as bubbles and impurities, preserved in polar ice sheets, and it achieves this by using long wavelength near-infrared light that is absorbed by the ice before many scattering events occur. Longer wavelengths ensure that the return signal is composed primarily of a single or few backscattering event(s) that limit its spatial spread. The compact optical logger features no components on its body that draw power, which minimizes its size and weight. A prototype of the logger was built and tested at Siple Dome A borehole, and the results were correlated with prior optical logging profiles and records of volcanic products from collected ice core samples.

Recently published international guidelines recommend the clinical use of noninvasive prenatal test (NIPT) for aneuploidy screening only among pregnant women whose fetuses are deemed at high risk. The applicability of NIPT to aneuploidy screening among average risk pregnancies requires additional supportive evidence. A key determinant of the reliability of aneuploidy NIPT is the fetal DNA fraction in maternal plasma. In this report, we investigated if differences in fetal DNA fractions existed between different pregnancy risk groups. One hundred and ninety-five singleton pregnancies with male fetuses divided into 3 groups according to first trimester screening parameters were examined for fetal DNA percentage by counting Y chromosome DNA sequences using massively parallel sequencing. Fetal DNA fractions were compared between risk groups and assessed for correlations with first trimester screening parameters. There was no statistically significant difference in fetal DNA fractions across the high, intermediate and low risk groups. Fetal DNA fraction showed a strong negative correlation with maternal weight. Fetal DNA fraction also showed weak but significant correlations with gestational age, crown-rump length, multiple of medians of free β-subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Similar fetal DNA fractions in maternal plasma between high, intermediate and low risk pregnant women is a precondition for uniform performance of the aneuploidy NIPTs for the general population. This study thus shows that the aneuploidy screening by NIPT is likely to offer similar analytical reliability without respect to the a priori fetal aneuploidy risk.

When treated with retinoic acid (RA), a human embryonal carcinoma (EC) cell line, NTera2 cl.D/1 (NT2), differentiates into several morphologically distinct cell types, which include terminally differentiated postmitotic central nervous system (CNS) neurons. Accumulating evidence has demonstrated the significant potential of NT2 cells in studies related to cancer therapy and neurodegenerative diseases. However, preparation of enriched NT2 neurons often requires a lengthy period (ca. five weeks) and depends largely on tedious techniques similar to those used for primary neuronal cultures. Here, we report a rapid protocol for the preparation of these human CNS neurons. Using the method of cell aggregation, enriched NT2 neurons can be obtained in approximately two weeks. We also demonstrated that cell aggregation reduced the time normally required for the induction of neuronal differentiation, as revealed by the early expression of neuronal markers. The period of RA treatment could also be reduced if NT2 cells were maintained as aggregates for a sufficient period of time. Taken together, our findings demonstrated that cell aggregation promoted RA-induced neuronal differentiation of NT2 cells and provided a rapid protocol for the efficient production of NT2 neurons. The ability to produce large quantities of human CNS neurons should facilitate future use of these neurons for basic research and applications in cell therapy.

LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.

BACKGROUND: Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. PRINCIPAL FINDINGS: Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056). CONCLUSION: We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.

BACKGROUND: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21. Here we apply this epigenetic-genetic (EGG) chromosome dosage approach to detect Edwards syndrome (trisomy 18) in the fetus noninvasively. PRINCIPAL FINDINGS: We have systematically identified methylated fetal epigenetic markers on chromosome 18 by methylated DNA immunoprecipitation (MeDIP) and tiling array analysis with confirmation using quantitative DNA methylation assays. Methylated DNA sequences from an intergenic region between the VAPA and APCDD1 genes (the VAPA-APCDD1 DNA) were detected in pre-delivery, but not post-delivery, maternal plasma samples. The concentrations correlated positively with those of an established fetal genetic marker, ZFY, in pre-delivery maternal plasma. The ratios of methylated VAPA-APCDD1(chr18) to ZFY(chrY) were higher in maternal plasma samples of 9 male trisomy 18 fetuses than those of 27 male euploid fetuses (Mann-Whitney test, P=0.029). We defined the cutoff value for detecting trisomy 18 fetuses as mean+1.96 SD of the EGG ratios of the euploid cases. Eight of 9 trisomy 18 and 1 of 27 euploid cases showed EGG ratios higher than the cutoff value, giving a sensitivity of 88.9% and a specificity of 96.3%. CONCLUSIONS: Our data have shown that the methylated VAPA-APCDD1 DNA in maternal plasma is predominantly derived from the fetus. We have demonstrated that this novel fetal epigenetic marker in maternal plasma is useful for the noninvasive detection of fetal trisomy 18.

According to the census data published by the government in 2016, 92% of the Hong Kong Special Administrative Region population is ethnic Chinese, while the number of ethnic minorities increased significantly by around 70% over the past decade. Enhancing the youth's intercultural sensitivity is becoming critical. Although many of the schools start to provide intercultural sensitivity training as extra-curriculum activities, students often find them unattractive while teachers question their effectiveness. In this paper, we present a virtual reality enabled approach for enhancing the youth's intercultural sensitivity. The objective is to design and develop an approach that can benefit from using virtual reality to deliver the instructional materials, making the learning more effective. A total number of three different virtual reality learning scenarios have been created, covering topics such as views of marriage and family, religious beliefs, and language barrier. The empirical study found significantly increase of intercultural sensitivity among the 67 qualified participants after joining the session. The calculated linear regression model also suggested that the participants' perceived motivation from the virtual reality learning content positively contributed to the intercultural sensitivity increase, while interestingly the perceived enjoyment during the virtual reality exposure may negatively affected the learning outcomes.

Video-based flipped class instruction can strengthen the learning motivation of students. The effectiveness of flipped class instruction on teaching effectiveness and subject satisfaction has been evaluated previously. The present study aims to examine the impact of two aspects of subject reading motivation. A total of 100 secondary school students were recruited from 4 classes of 25 students (ie, video-based flipped Mathematics class, traditional Mathematics class, video-based flipped Liberal Studies (LS) class and traditional LS class) in two local secondary schools. The same teachers taught both the traditional and video-based flipped classes in their subject. The students filled in questionnaires which measured: motivation for general reading; motivation for subject reading; academic subject satisfaction and perceived teaching effectiveness of the teachers. Analysis of covariance controlling for motivation for general reading revealed that students in the flipped classes reported significantly lower motivation for subject reading including reading curiosity, reading importance and reading compliance (t (1,98) = 10.52, p < 0.001; t (1,98) = 7.68, p < 0.001; t (1,98) = 20.39, p < 0.001, respectively). However, students in the flipped classes reported significantly higher satisfaction and teaching effectiveness than those in the traditional classes (t (1,98) = -15.61. p < 0.001; t (1,98) = -11.98, p <0.001, respectively). A partial correlation controlling for motivation for general reading indicated that motivation for subject reading was negatively associated with academic subject satisfaction and perceived teaching effectiveness of teachers (rs ranged from -0.51 to -0.62, p < 0.001). Video-based flipped class instruction was not only related to increased academic subject satisfaction and teaching effectiveness but also associated with lower motivation for subject reading. These findings suggest that video-based flipped class instruction had limited capability to strengthen the learning motivation of students.

In recent years, the sediment compartment has gained more attention when performing toxicity tests, with a growing emphasis on gaining more ecological relevance in testing. Though many standard guidelines recommend using artificially formulated sediment, most sediment studies are using natural sediment collected in the field. Although the use of natural field‐collected sediment contributes to more environmentally realistic exposure scenarios and higher well‐being for sediment‐dwelling organisms, it lowers comparability and reproducibility among studies as a result of, for example, differences in the base sediment depending on sampling site, background contamination, particle size distribution, or organic matter content. The aim of this methodology contribution is to present and discuss best practices related to collecting, handling, describing, and applying natural field‐collected sediment in ecotoxicological testing. We propose six recommendations: (1) natural sediment should be collected at a well‐studied site, historically and by laboratory analysis; (2) larger quantities of sediment should be collected and stored prior to initiation of an experiment to ensure a uniform sediment base; (3) any sediment used in ecotoxicological testing should be characterized, at the very least, for its water content, organic matter content, pH, and particle size distribution; (4) select spiking method, equilibration time, and experimental setup based on the properties of the contaminant and the research question; (5) include control‐, treated similarly to the spiked sediment, and solvent control sediment when appropriate; and (6) quantify experimental exposure concentrations in the overlying water, porewater (if applicable), and bulk sediment at least at the beginning and the end of each experiment. Environ Toxicol Chem 2024;43:1757–1766. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

The space weather effects at the Earth's magnetosphere are mostly driven by the solar wind that carries the interplanetary magnetic field (IMF). In this paper, we use 2 years of data in the solar wind from lunar orbiting ARTEMIS and MMS spacecraft upstream of the Earth's bow shock to study the structure of the IMF. We determine the lag times of IMF structures and their dependence on spacecraft positions by conducting an information theory analysis and comparing it with two traditional analysis methods: cross‐correlation (CC) analysis and minimum variance of magnetic field analysis (MVAB). For the events with long time intervals (i.e., >4 hr) and with small‐spatial separation between the MMS and ARTEMIS along the yGSM‐direction (i.e., <40Re, where Re is the Earth's radius), the lag times based on the CC and the mutual information (MI) analyses statistically agree with each other, with p‐values of 1.675 × 10−7 and 4.833 × 10−9, with the confidence of 95%. Both the results based on MI and CC have a large deviation from the results from MVAB. For some of the events, such a deviation could be improved by taking the fast mode speed into account; however, p‐tests showed that they were not statistically significant to the 95% confidence level. Plain Language Summary: Typically, single‐point measurements from the Earth‐Sun Lagrange Point‐1 are used to forecast space weather. However, it is important to understand that multi‐point measurements are required to further understand and predict geo‐effective solar wind structures. Three analysis methods using multi‐point measurements from the MMS and THEMIS missions of large solar wind structures as they move from regions around the Moon to regions around Earth's bow shock, are presented and compared in this paper. Information theory analysis (specifically Mutual Information) determines dependence between two variables by quantifying the entropy (uncertainty) in the two variables. Minimum variance analysis calculates the direction of least change in a magnetic field and assumes the solar wind is propagating in that direction. Lag time is calculated by taking the dot products of this direction with both the displacement vector between the two spacecraft, to get a distance, and the ion velocity (from ARTEMIS) to get a speed. The distance is divided by the speed to get a lag time. Cross‐Correlation analysis is a traditional method for measuring similarity between two variables. This paper shows that information theory analysis along with cross‐correlation analysis could be used successfully for space weather forecasting. Key Points: The solar wind data by MMS and THEMIS are analyzed by using information theory to understand the propagation of solar wind structuresMutual information, linear cross‐correlation, and minimum variance analyses sometimes give different lag‐timesInformation theory analysis along with the traditional method of cross‐correlation analysis could be used successfully for space weather forecasting [ABSTRACT FROM AUTHOR]

Background Falls and physical inactivity increase with age. However, physical activity, falls and their associations in older people born at different times are unclear. Methods Women born 1921–26 and 1946–51 who completed follow-up questionnaires in 1999 (n  = 8 403, mean (SD) age: 75 (1) years) and 2019 (n  = 7 555; 71 (1) years) in the Australian Longitudinal Study on Women's Health. Self-reported noninjurious and injurious falls in the previous 12 months and weekly amounts and types of physical activity (brisk walking, moderate- and vigorous-intensity) were compared between the cohorts using Chi-square tests. Associations between physical activity, and noninjurious and injurious falls were estimated using multinomial logistic regressions informed by a directed acyclic graph. Results A greater proportion of the later (1946–51) cohort (59%) reached 150–300 minutes of weekly physical activity, as recommended by the World Health Organization, compared to the earlier (1921–26) cohort (43%, p  < .001). A greater proportion of the later cohort reported noninjurious falls (14% vs 8%). Both cohorts reported similar proportions of injurious falls (1946–51:15%, 1921–26:14%). In both cohorts, participation in 150–300 minutes of physical activity was associated with lower odds of noninjurious falls (adjusted Odds Ratio, 95% CI: 1921–26: 0.66, 0.52–0.84; 1946–51: 0.78, 0.63–0.97) and injurious falls (1921–26: 0.72, 0.60–0.87; 1946–51: 0.78, 0.64–0.96). Conclusions Participation in recommended levels of physical activity was associated with reduced falls in both cohorts. However, generational differences were found with more falls and more physical activities in the women born later. Future studies could examine the reasons contributing to the generational differences. [ABSTRACT FROM AUTHOR]

Psychosis is a complex mental health condition that may involve experiences of hallucinations, delusional beliefs, high levels of emotional distress, and considerable disruption to daily life. Individuals with this condition experience greater levels of public stigmatisation and discrimination compared to other mental health difficulties. Particularly in collectivistic Asian cultures, those with psychosis often experience social exclusion and internalized shame. To explore the specificity of psychosis-related attitudes in Southeast Asia, this study investigated the perception of such conditions among young adults in Singapore. Qualitative methodology was employed and semi-structured interviews were conducted with study participants. Verbatim data were analysed using inductive thematic analysis embedded in a transparent reflexive approach. Five superordinate themes emerged, as follows: individual perceptions of people with psychosis, social attitudes and behavior towards people with psychosis, individual reactions towards psychosis, perceived causes of psychosis, and sources of knowledge about psychosis. Cultural implications are discussed and practical indications for counsellors are also considered. [ABSTRACT FROM AUTHOR]

Background There is strong evidence that exercise reduces falls in older people living in the community, but its effectiveness in residential aged care is less clear. This systematic review examines the effectiveness of exercise for falls prevention in residential aged care, meta-analysing outcomes measured immediately after exercise or after post-intervention follow-up. Methods Systematic review and meta-analysis, including randomised controlled trials from a Cochrane review and additional trials, published to December 2022. Trials of exercise as a single intervention compared to usual care, reporting data suitable for meta-analysis of rate or risk of falls, were included. Meta-analyses were conducted according to Cochrane Collaboration methods and quality of evidence rated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results 12 trials from the Cochrane review plus 7 new trials were included. At the end of the intervention period, exercise probably reduces the number of falls (13 trials, rate ratio [RaR] = 0.68, 95% confidence interval [CI] = 0.49–0.95), but after post-intervention follow-up exercise had little or no effect (8 trials, RaR = 1.01, 95% CI = 0.80–1.28). The effect on the risk of falling was similar (end of intervention risk ratio (RR) = 0.84, 95% CI = 0.72–0.98, 12 trials; post-intervention follow-up RR = 1.05, 95% CI = 0.92–1.20, 8 trials). There were no significant subgroup differences according to cognitive impairment. Conclusions Exercise is recommended as a fall prevention strategy for older people living in aged care who are willing and able to participate (moderate certainty evidence), but exercise has little or no lasting effect on falls after the end of a programme (high certainty evidence). [ABSTRACT FROM AUTHOR]