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Forecasting wind structure of tropical cyclone (TC) is vital in assessment of impact due to high winds using Numerical Weather Prediction (NWP) model. The usual verification technique on TC wind structure forecasts are based on grid-to-grid comparisons between forecast field and the actual field. However, precision of traditional verification measures is easily affected by small scale errors and thus cannot well discriminate the accuracy or effectiveness of NWP model forecast. In this study, the Method for Object-Based Diagnostic Evaluation (MODE), which has been widely adopted in verifying precipitation fields, is utilized in TC's wind field verification for the first time. The TC wind field forecast of deterministic NWP model and Ensemble Prediction System (EPS) of the European Centre for Medium-Range Weather Forecasts (ECMWF) over the western North Pacific and the South China Sea in 2020 were evaluated. A MODE score of 0.5 is used as a threshold value to represent a skillful (or good) forecast. It is found that the R34 (radius of 34 knots) wind field structure forecasts within 72 h are good regardless of DET or EPS. The performance of R50 and R64 is slightly worse but the R50 forecasts within 48 h remain good, with MODE exceeded 0.5. The R64 forecast within 48 h are worth for reference as well with MODE of around 0.5. This study states that the TC wind field structure forecast by ECMWF is skillful for TCs over the western North Pacific and the South China Sea.

The phylum of Apicomplexa groups intracellular parasites that employ substrate-dependent gliding motility to invade host cells, egress from the infected cells, and cross biological barriers. The glideosome-associated connector (GAC) is a conserved protein essential to this process. GAC facilitates the association of actin filaments with surface transmembrane adhesins and the efficient transmission of the force generated by myosin translocation of actin to the cell surface substrate. Here, we present the crystal structure of Toxoplasma gondii GAC and reveal a unique, supercoiled armadillo repeat region that adopts a closed ring conformation. Characterisation of the solution properties together with membrane and F-actin binding interfaces suggests that GAC adopts several conformations from closed to open and extended. A multi-conformational model for assembly and regulation of GAC within the glideosome is proposed.

Abstract Background COVID-19, caused by the SARS-CoV-2 virus, is a severe inflammatory condition. Patients with pre-existing conditions including diabetes, hypertension, and cardiovascular disease are at particularly high risk of complications. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and debilitating genetic disorder that is characterized by a pro-inflammatory state, which leads to progressive heterotopic ossification and complications after trauma, including intramuscular vaccinations. To better understand the impact of COVID-19 on patients with FOP, we first examined the social impact of the pandemic using data from the FOP Registry managed by the International FOP Association. We also identified patients with FOP who were exposed to or contracted the SARS-CoV-2 virus, or who received a COVID-19 vaccine, to investigate if patients with FOP were at increased risks of complications from SARS-CoV2 exposure or vaccination. Results Data from 326 individuals in 69 countries in the International FOP Association FOP Connection Registry were examined using patient-reported outcomes measurement information system (PROMIS) global health scale scores. Twenty-six (28.9%) participants aged ≥ 15 years old rated their satisfaction with their social activities and relationships as poor in 2020, which was an increase from 18 (18.9%) in 2019, prior to the SARS-CoV-2 outbreak. Similar trends were noted for physical and mental health in the pediatric population. Frequency of physician visits was not changed, but a larger portion of patients reported missing dental visits in 2020 compared with 2019 (31.5% vs. 41.7%). A second cohort with 32 subjects was tracked after SARS-CoV-2 exposure or vaccination. Ten subjects were positively diagnosed with COVID-19, 15 received a COVID-19 vaccine, and seven had high-risk SARS-CoV-2 exposure but either did not have a confirmed clinical diagnosis or tested negative. Subjects who tested positive for the virus showed no major complications or increased FOP disease activity, though our sample size is very limited. Among the 15 subjects who received a COVID-19 vaccine, using the International Clinical Council on FOP guidelines for prophylaxis with ibuprofen or acetaminophen, only one person experienced flare-like activity at the injection site. Conclusions Patients with FOP showed a significant decrease in social activities that was reflective of the isolation and mobility changes in this debilitated population. In our limited cohort, the majority of the patients with FOP who tested positive for COVID-19 showed no major complications. Also, although limited in sample size, the majority of patients who received a COVID-19 vaccination and followed guidelines from the FOP International Clinical Council tolerated vaccination well. Only one person experiencing flare activity following their injection. Thus, the risks and benefits of COVID-19 vaccination needs to be discussed carefully so as to support informed decisions.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta (Aβ) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aβ for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1β), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1β in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

Highlights In the current preliminary study, serum proteins associated with pain severity were identified in JIA patients. Pain-associated proteins had functional roles predominantly in immune or inflammatory processes. Correlations of pain-associated proteins with ESR and altered CNS morphology were also observed with ESR and altered CNS morphology were also observed. Larger-scale as well as longitudinal studies are needed to determine if evaluation of the proteome may provide a platform for identifying novel analgesic targets in JIA.

To explore the relationship between PD-L1 expression and gene mutations and survival. PD L1, ALK and MET protein expression were detected by immunohistochemistry, and EGFR gene mutation by RT-PCR in 209 cases of NSCLC. The correlations between PD-L1 expression and gene mutations, clinicopathological features and survival was analyzed. PD-L1 was expressed in 99/209 cases (47.4%) of NSCLC, including score 1 (≥ 1% to < 5%) 23 cases (11%), score 2 (≥ 5% to 50%) 40 cases (19.1%). There were 89 cases (42.6%) of EGFR mutation, 12 (5.7%) of ALK and 90 (43.1%) of MET protein positive. PD-L1 positive expression occurred more frequently in men and non-adenocarcinoma, and was negatively correlated with EGFR mutation and histological differentiation of NSCLC. PD-L1 expression was concordant in primary and metastatic cancers. There was no any effect of PD-L1 expression on overall survival of patients with NSCLC. These results suggested that PD-L1 expression is not an independent risk factor for survival of patients with NSCLC. Because of mutual complementarities of PD-L1 expression and EGFR mutation in NSCLC, both should be simultaneously detected for the patients to achieve eligible treatments.

Background: In the last two decades, electrical stimulation (ES) has been tested in patients with various eye diseases and shows great treatment potential in retinitis pigmentosa and optic neuropathy. However, the clinical application of ES in ophthalmology is currently limited. On the one hand, optimization and standardization of ES protocols is still an unmet need. On the other hand, poor understanding of the underlying mechanisms has hindered clinical exploitation. Main Text: Numerous experimental studies have been conducted to identify the treatment potential of ES in eye diseases and to explore the related cellular and molecular mechanisms. In this review, we summarized the in vitro and in vivo evidence related to cellular and tissue response to ES in eye diseases. We highlighted several pathways that may be utilized by ES to impose its effects on the diseased retina. Conclusions: Therapeutic effect of ES in retinal degenerative diseases might through preventing neuronal apoptosis, promoting neuronal regeneration, increasing neurotrophic factors production in Müller cells, inhibiting microglial activation, enhancing retinal blood flow, and modulating brain plasticity. Future studies are suggested to analyse changes in specific retinal cells for optimizing the treatment parameters and choosing the best fit ES delivery method in target diseases.

Abstract Background Sensitive, rapid, and accessible diagnostics continue to be critical to track the COVID-19 pandemic caused by the SARS-CoV-2 virus. RT-qPCR is the gold standard test, and comparison of methodologies and reagents, utilizing patient samples, is important to establish reliable diagnostic pipelines. Methods Here, we assessed indirect methods that require RNA extraction with direct RT-qPCR on patient samples. Four different RNA extraction kits (Qiagen, Invitrogen, BGI and Norgen Biotek) were compared. For detection, we assessed two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). We also tested and optimized direct, extraction-free detection using these RT-qPCR systems and performed a cost analysis of the different methods evaluated here. Results Most RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system provided overall superior performance (lower detection limit, lower Ct values and higher sensitivity), generating comparable results to original clinical diagnostic data, and identifying samples ranging from 65 copies to 2.1 × 105 copies of viral genome/μl. However, the BGI detection system is more expensive than other options tested here. With direct RT-qPCR, simply adding an RNase inhibitor greatly improved detection, without the need for any other treatments (e.g. lysis buffers or boiling). The best direct methods detected ~ 10 fold less virus than indirect methods, but this simplified approach reduced sample handling, as well as assay time and cost. Conclusions With extracted RNA, the BGI RT-qPCR detection system exhibited superior performance over the Norgen system, matching initial clinical diagnosis with the Seegene Allplex assay. The BGI system was also suitable for direct, extraction-free analysis, providing 78.4% sensitivity. The Norgen system, however, still accurately detected samples with a clinical Ct

Wide-spread outbreaks of pathogens require high intensity testing to manage. Here, the authors present C19-SPAR-Seq, a scalable and automated platform to analyse tens of thousands of SARS-CoV-2 patient samples in a single run.

Prime editing guide RNA design is more complex than for standard CRISPR-based nucleases or base editors. Here the authors present PrimeDesign and PrimeVar for the rapid and simplified design of pegRNA and ngRNA combinations.

Various countries have alternative pathway policies for 2-year community college graduates to articulate to 2-year university study, forming a “2+2” pathway. However, few studies have explored university staff members’ perceptions of this “2+2” transfer pathway and their understanding of transfer students’ (TSs) transition experiences. This descriptive qualitative study addressed this research gap. Forty-two academic and supporting staff participated in the focus group interviews. Specifically, the study explored the assets and challenges of the “2+2” pathway from the university staff perspective in Hong Kong. The articulation pathway and TSs are highly recognized for their prior learning, academic performances, and the value of the second chance. However, while the university staff were sympathetic to the challenges filling these transfer pathways, their offering of help was limited by government funding and policies restrictions. It is recommended that policies should be established at government and university levels to recognize and tackle TSs’ unique needs to alleviate their heavy workloads through better articulation between community college and university studies. Improving articulation will allow TSs time for social involvement in university life and thus enhance their mental well-being.

Abstract Background Firefighters’ health is often affected by a high prevalence of obesity and cardiovascular diseases, which are common risk factors for sudden cardiac death. The aim of this study is to investigate the feasibility of enhancing healthy eating habits in firefighters through an education programme. Methods This will be a cluster randomized control trial study. The participants will be assigned randomly into either control (health promotion pamphlet) or intervention (health promotion pamphlet and education materials through WhatsApp) groups. Changes in healthy eating habits will be assessed by a self-administered questionnaire and anthropometric measurements at three different time points. Discussion More education is required in order to improve firefighters’ eating habits. Trial registration ISRCTN registry identifier: Registered on 8 April 2019 ISRCTN95472464 .

In Alzheimer's disease (AD), amyloid β deposition-induced hippocampal synaptic dysfunction generally begins prior to neuronal degeneration and memory impairment. Lycium barbarum extracts (LBE) have been demonstrated to be neuroprotective in various animal models of neurodegeneration. In this study, we aimed to investigate the effects of LBE on the synapse loss in AD through the avenue of the retina in a triple transgenic mouse model of AD (3xTg-AD). We fed 3xTg-AD mice with low (200 mg/kg) or high (2 g/kg) dose hydrophilic LBE daily for 2 months from the starting age of 4- or 6-month-old. For those started at 6 month age, at 1 month (though not 2 months) after starting treatment, mice given high dose LBE showed a significant increase of a wave and b wave in scotopic ERG. After 2 months of treatment with high dose LBE, calpain-2, calpain-5, and the oxidative RNA marker 8-OHG were downregulated, and presynaptic densities in the inner plexiform layer but not the outer plexiform layer of the retina were significantly increased, suggesting the presynaptic structure of retina was preserved. Our results indicate that LBE feeding may preserve synapse stability in the retina of 3xTg-AD mice, probably by decreasing both oxidative stress and intracellular calcium influx. Thus, LBE might have potential as a neuroprotectant for AD through synapse preservation.

In Hong Kong, transfer students encounter different challenges unfolding in their transition from community college to university study. However, limited research has been conducted to explore their discipline-specific challenges. To address this gap, in this study three engineering and science faculties were selected from which to collect data through 35 in-depth interviews with transfer students, followed by a thorough thematic analysis. With the concept of in-betweenness, three main themes were identified: (1) “shifted the focus of study” (three sub-themes: (i) academic excellence in community college; (ii) future career in the university; and (iii) university life); (2) “encountered challenges in the transition” (four sub-themes: (i) non-matching program articulation; (ii) heavy study workload and its associated consequences; and (iii) non-specific administration arrangement and support from university); and (3) “students’ voices to enhance learning experiences” (four sub-themes: (i) modify the study duration; (ii) improve program articulation; (iii) improve social adjustment; and (iv) overseas exchange). The results of this study indicate the challenges faced by transfer students in their transition from community college to university and have implications for universities to design and implement appropriate strategies to prepare for the future.

Abstract Intensity prediction of tropical cyclones (TC) has been one of the major challenges for the operational forecast and warning service, as well as consequential assessment of impacts including high winds, storm surge and heavy rainfall caused by TC. With the advances in global numerical weather prediction (NWP) modelling systems, TC track and intensity forecasts for medium range are available every 6 or 12 h, and ensemble prediction system (EPS) outputs provide various scenarios for producing probabilistic forecasts. The TC intensity forecast from the EPS of the European Centre for Medium‐Range Weather Forecasts (ECMWF) has shown systematic negative biases, although the performance is better than other global models in general. A machine learning model based on XGBoost, a decision‐tree‐based machine learning algorithm, is introduced in this paper to post‐process ECMWF EPS outputs and generate an improved forecast of TC intensity. The predictors such as selected percentiles of ensemble members in maximum wind and minimum pressure of previous TC cases were applied in the XGBoost model to generate a calibrated forecast for the maximum wind of TCs. Verification of the XGBoost model was made using TCs over the western North Pacific during 2016–2019. It is found that the negative biases of the intensity forecast from ECMWF EPS and HRES can be reduced with improvement in the overall accuracy.

Retinitis pigmentosa (RP) is a photoreceptor-degenerating disease with no effective treatment. Trans-corneal electrical stimulation has neuroprotective effects in degenerating retinas, but repeated applications cause corneal injury. To avoid the risk of corneal damage, here we tested whether repetitive trans-sclera electrical stimulation (TsES) protects degenerating retinas in rd10 mice, a model of RP. At postnatal day 20 (P20), the right eyes of rd10 mice were exposed to 30 min of TsES daily or every other day till P25, at the amplitude of 50 or 100 μA, with zero current as the sham. Immunostaining, multi-electrode-array (MEA) recording, and a black-and-white transition box were applied to examine the morphological and functional changes of the treated retina. Functionally, TsES modified the retinal light responses. It also reduced the high spontaneous firing of retinal ganglion cells. TsES at 100 μA but not 50 μA increased the light sensitivities of ganglion cells as well as their signal-to-noise ratios. TsES at 100 μA increased the survival of photoreceptors without improving the visual behavior of rd10 mice. Our data suggest that repetitive TsES improves the retinal function of rd10 mice at the early degenerating stage, therefore, it might be an effective long-term strategy to delay retinal degeneration in RP patients.

BackgroundControlling blood pressure (BP) is an international health concern, and high BP is a major contributor to cardiovascular disease mortality. Evidence has shown that educational interventions directed at patients potentially improve BP control and adherence to medications and lifestyle modifications. In addition, a text messaging intervention has a potential effect on BP control; however, the dosage of a text messaging intervention has not been determined in previous reviews, resulting in difficult application in practice. ObjectiveThis review aimed to identify the effectiveness of a text messaging intervention on hypertension management with a specific focus on the dosage of text messaging and the type of additional interventions with text messaging. MethodsA systematic review was conducted and reported on in accordance with PRISMA guideline. Participants were aged 18 years and older and diagnosed with primary hypertension. The included studies used text messaging as a component of the intervention. We searched for randomized controlled trials published until June 30, 2020, from the following health-related electronic databases: Embase, Medline, CINAHL Complete, PsycINFO, and Scopus. Data were extracted for qualitative synthesis and meta-analysis. The Physiotherapy Evidence Database Scale was used to assess the methodological quality of each study, and the quality of the included studies was assessed independently by two authors. ResultsTwelve studies met the inclusion criteria. The overall methodological quality was fair (mean score 5.75). The frequency of text message delivery varied from daily to biweekly. Health education was identified in 4 studies as an additional intervention with text messaging. The overall results showed that the text messaging intervention significantly reduced systolic BP (SBP) but not diastolic BP (DBP). There was no significant difference in BP reduction between studies that lasted 6 months or less and those that lasted more than 7 months. Seven studies that lasted 6 months or less involving 1428 patients with hypertension were pooled for further meta-analysis. Text messages delivered at a lower frequency (once per week or less) had a small effect on SBP reduction (effect size 0.35, P

One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

Nursing assistants (NAs) working in nursing homes (NHs) are at higher risk for work-related musculoskeletal symptoms (WRMSs) than their counterparts working in other health care settings. Worldwide, NAs have ranked shoulders in the top three body parts at risk of WRMSs. However, factors associated with their shoulder WRMSs are currently unknown. The aim of this study was to identify these associated risk factors among NAs working in NHs. 440 NAs from 47 nursing homes (with 60–90% response rate from each nursing home), recruited by convenience sampling, participated in this cross-sectional study in 2014–2015. A validated and reliable questionnaire was used for data collection. Information on demographic, job content questionnaire (JCQ), perceived physical exertion (PE), workstyle, ergonomic and manual handling knowledge and other work-related factors was collected using a self-administered questionnaire. 53% of the participants reported experiencing with WRMSs in their shoulders. Nine associated factors of shoulder WRMSs were identified using bivariate analysis. With the adjustment of age and gender using multivariable logistic regression, body mass index (OR = .931, 95% CI [.874–.991]), job title of health workers (OR = 2.72, 95% CI [1.18–6.25]) and workstyle-working through pain (OR = 1.06, 95% CI [1.01–1.11]) remained as predictors. Effort should be directed at integrating “workstyle intervention” into lifestyle physical activity training for NAs.