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Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells 1 – 5 , are formed by back-splicing of precursor mRNAs in the nucleus 6 – 10 . circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export. Circular RNAs are exported from the nucleus by Ran-GTP, exportin-2 and IGF2BP1 in a mechanism analogous to protein export rather than mRNA export.

Robust data on trends in stroke hospitalisation rate and outcomes are needed to improve stroke care, yet are sparse and show conflicting results. We investigated the trends in hospitalisation rate, survival, and risk of stroke recurrence following an acute stroke using population-wide data from Australia and New Zealand over a 10-year period. We included adults aged ≥ 18 years hospitalised with an acute stroke from 2008 to 17. Age- and sex-standardized trends of stroke hospitalisation were calculated. Flexible parametric survival models were used to estimate and assess trends in survival and cumulative incidence of stroke recurrence at 30 days, 1 year and 5 years. 331,016 patients were included (mean age 73.2 ± 14.5 years, 48.0% female), with ischaemic stroke (185,800, 56.1%) being the most common type, followed by haemorrhagic stroke (81,877, 24.7%) and unspecified stroke (63,339, 19.1%). The overall age- and sex-standardised stroke hospitalisation rate decreased by 13.5% (179.3/100,000 person-years in 2008 to 155.1/100,000 person-years in 2017, P for trend < 0.01). However, the decline was limited to those ≥ 65 years, with the hospitalisation rate rising in those aged 55–64 years and stagnant in those aged 18–54 years. The adjusted survival probability at 30-day (83.4% in 2008/2009 to 85.9% in 2016/2017), 1-year (70.5% to 74.3%), and 5-year (51.4% to 53.0%) following a stroke has improved over time ( P for trend < 0.01). The adjusted risk of stroke recurrence at 30 days and 5 years was unchanged over time, whereas the 1-year risk increased from 9.8% in 2008–2009 to 10.8% in 2016 ( P for trend < 0.01). In patients hospitalised for acute stroke in Australia and New Zealand, the overall stroke hospitalisation rate and mortality declined over 10 years. However, this was accompanied by a static or rising stroke hospitalisation rate in younger patients and a concerning lack of improvement in the risk of stroke recurrence.

Zinc oxide/reduced graphene oxide nanocomposites (ZnO/rGO) are synthesized via a simple one-pot solvothermal technique. The nanoparticle–nanorod turnability was achieved with the increase in GO additive, which was necessary to control the defect formation. The optimal defect in ZnO/rGO not only increased ZnO/rGO surface and carrier concentration, but also provided the alternative carrier pathway assisted with rGO sheet for electron–hole separation and prolonging carrier recombination. These properties are ideal for photodetection and photocatalytic applications. For photosensing properties, ZnO/rGO shows the improvement of photosensitivity compared with pristine ZnO from 1.51 (ZnO) to 3.94 (ZnO/rGO (20%)). Additionally, applying bending strain on ZnO/rGO enhances its photosensitivity even further, as high as 124% at r = 12.5 mm, due to improved surface area and induced negative piezoelectric charge from piezoelectric effect. Moreover, the photocatalytic activity with methylene blue (MB) was studied. It was observed that the rate of MB degradation was higher in presence of ZnO/rGO than pristine ZnO. Therefore, ZnO/rGO became a promising materials for different applications.

In 2019 the Canadian Space Agency initiated development of a dedicated wildfire monitoring satellite (WildFireSat) mission. The intent of this mission is to support operational wildfire management, smoke and air quality forecasting, and wildfire carbon emissions reporting. In order to deliver the mission objectives, it was necessary to identify the technical and operational challenges which have prevented broad exploitation of Earth Observation (EO) in Canadian wildfire management and to address these challenges in the mission design. In this study we emphasize the first objective by documenting the results of wildfire management end-user engagement activities which were used to identify the key Fire Management Functionalities (FMFs) required for an Earth Observation wildfire monitoring system. These FMFs are then used to define the User Requirements for the Canadian Wildland Fire Monitoring System (CWFMS) which are refined here for the WildFireSat mission. The User Requirements are divided into Observational, Measurement, and Precision requirements and form the foundation for the design of the WildFireSat mission (currently in Phase-A, summer 2020).

This research delves into the crucial role of groundwater in underpinning ecosystems and human resilience amidst drastic and unpredictable climate change, particularly as water resources face increasing sustainability concerns due to population surges and climate change. Utilizing a combined approach of SWAT-MODFLOW models, we estimate the streamflow discharge and groundwater recharge in the Choushui River Alluvial Fan, Taiwan. These models allow evaluation of the distribution and proportion of recharge areas as well as the accuracy and the potential influence of future climate change scenarios on groundwater recharge. The findings show a strong correlation between the simulation and actual observations, evidenced by the Nash–Sutcliffe model efficiency coefficients (NSE) of 0.920 and 0.846 for calibration and validation in the Choushui River, and 0.549 and 0.548 for the Pei-Kang River, respectively. The model demonstrates a reliable representation of the watershed response, supported by robust statistical performance. The analysis reveals the variable impacts of climate change on groundwater recharge, dependent on the chosen scenario and period. Some scenarios indicate that the maximum observed increase in groundwater recharge is 66.36% under the RCP2.6 scenario in the long-term period (2061–2080), while the minimum observed increase is 29.67% under the RCP4.5 scenario in the initial time frame; however, all demonstrate a decrease ranging from 23.05% to 41.92% across different RCPs in the impact of climate change over time, suggesting a potential long-term decrease in the impact of climate change on groundwater recharge. This study provides indispensable insights into the spatial hotspots in the top fan and the potential range of impact rates of climate change on groundwater recharge, underscoring the importance of continuous research and the thorough evaluation of multiple scenarios. Moreover, we establish a primary framework for using a top-ranked MIROC5 projection of general circulation models (GCMs) to delineate an essential premise that facilitates the advanced exploration of alternative scenario augmentations, bolstering the comprehensive investigation of climate change impacts on groundwater recharge. It is proposed that these findings serve as a guidepost for sustainable water resource management and policy-making in the face of climate change and escalating water demand.

Objectives. We investigated the relationships among early childhood caries (ECC), mouth pain, and nutritional status in children aged 1 to 6 years in Southern and Central Vietnam. Methods. A total of 593 parent–child pairs were recruited from 5 kindergartens or preschools in Ho-Chi Minh City and Da Nang. Parents completed surveys about dietary habits, oral health practices, and children’s mouth pain experience; children received anthropometric assessment and dental examinations. Results. There was a high prevalence of dental caries (74.4%), mostly untreated, and mouth pain (47.1%). Moderate correlations were found between parents’ and children’s consumption of soda (ρ = 0.361; P < .001) and salty snacks (ρ = 0.292; P < .001). Severity of ECC was associated with decreased weight- and body mass index-for-age z-scores. Presence of pulp-involved caries was associated with strikingly lower height-for-age (mean difference = 0.66; P = .001), weight-for-age (mean difference = 1.17; P < .001), and body mass index-for-age (mean difference = 1.18; P < .001) z-scores. Mouth pain was associated with lower body mass index-for-age z-scores (mean difference = 0.29; P = .013). Conclusions. ECC might negatively affect children’s nutritional status, which might be mediated by the depth of decay, chronic inflammation, and mouth pain. Family-based and prevention-oriented nutrition and oral health programs are needed and should start during pregnancy and infancy.

Analyzing texts from social media encounters many challenges due to their unique characteristics of shortness, massiveness, and dynamic. Short texts do not provide enough context information, causing the failure of the traditional statistical models. Furthermore, many applications often face with massive and dynamic short texts, causing various computational challenges to the current batch learning algorithms. This paper presents a novel framework, namely bag of biterms modeling (BBM), for modeling massive, dynamic, and short text collections. BBM comprises of two main ingredients: (1) the concept of bag of biterms (BoB) for representing documents, and (2) a simple way to help statistical models to include BoB. Our framework can be easily deployed for a large class of probabilistic models, and we demonstrate its usefulness with two well-known models: latent Dirichlet allocation (LDA) and hierarchical Dirichlet process (HDP). By exploiting both terms (words) and biterms (pairs of words), the major advantages of BBM are: (1) it enhances the length of the documents and makes the context more coherent by emphasizing the word connotation and co-occurrence via bag of biterms, and (2) it inherits inference and learning algorithms from the primitive to make it straightforward to design online and streaming algorithms for short texts. Extensive experiments suggest that BBM outperforms several state-of-the-art models. We also point out that the BoB representation performs better than the traditional representations (e.g., bag of words, tf-idf) even for normal texts.

Objective To compare the clinical characteristics, electrocardiographic characteristics, and outcomes of radiofrequency catheter ablation in patients with idiopathic right ventricular outflow tract ventricular arrhythmias originating near the Hisian bundle region versus other right ventricular outflow tract regions. Methods A single-center study analyzed 126 patients undergoing radiofrequency catheter ablation for right ventricular outflow tract ventricular arrhythmias from May 2020 to October 2022. Patients were classified into the near-Hisian group (n = 10) and the right ventricular outflow tract group (n = 116) based on the arrhythmia origin. Clinical, electrocardiographic, and procedural characteristics as well as ablation outcomes were compared. Results The near-Hisian group had narrower QRS duration (132.3 ± 24.1 vs. 146.1 ± 28.3 ms), 100% positive QRS in lead I, smaller R-wave ratio in leads III/II (0.65 ± 0.20 vs. 0.97 ± 0.31), smaller Q-wave ratio in leads aVL/aVR (0.31 ± 0.29 vs. 1.03 ± 0.37), and larger R/S ratio in lead V2 (18.8 ± 10.9 vs. 12.0 ± 6.7) (all p < 0.05). Procedural metrics, acute success (90%), and long-term success (80%) were comparable between the two groups, with no major complications reported. Conclusions Right ventricular outflow tract ventricular arrhythmias near the Hisian bundle region have distinct electrocardiographic features. Radiofrequency catheter ablation is safe and effective, emphasizing the need for precise electrocardiogram interpretation and meticulous procedural planning.

Background Novel immune checkpoint inhibitors have been often utilized for different types of malignancies as salvage therapy with varying success. One obstacle to immune checkpoint inhibitor use is the higher incidence of immune-mediated side effects that can prompt discontinuation of therapy. Remitting seronegative symmetrical synovitis with pitting edema has been described with immune checkpoint inhibitors only once previously. We report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema related to immune checkpoint inhibitor therapy and stress that these symptoms can be managed without cessation of immune checkpoint inhibitor therapy. Case presentation We present a 70-year-old white man who presented with 4 months of progressive inflammatory arthritis with pitting edema. He had been started on nivolumab therapy for his metastatic melanoma with excellent response prior to symptom onset. The symptoms started in his knees and subsequently involved both hands and feet. On evaluation, he was wheelchair bound and completely dependent for all activities of daily living. Evaluation revealed negative serological testing and plain film imaging. Ultrasound demonstrated diffuse flexor tenosynovitis and soft tissue swelling, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. He was treated with orally administered corticosteroids (0.5 mg/kg per day) which improved his symptoms significantly and allowed him to regain prior independent functioning. His corticosteroids were tapered (0.15 mg/kg per day) but not discontinued and his nivolumab treatment was not interrupted. In follow up he continued to have stable control of his melanoma as well as his remitting seronegative symmetrical synovitis with pitting edema. Conclusions In conclusion we present the first case of nivolumab-induced remitting seronegative symmetrical synovitis with pitting edema that is controlled by maintenance low-dose orally administered corticosteroids allowing for continuation of nivolumab therapy. Clinicians who encounter mild-to-moderate immune checkpoint inhibitor immune-mediated adverse effects can consider maintaining immune checkpoint inhibitor therapy with concomitant low-dose corticosteroids rather than abrupt cessation of the immune checkpoint inhibitor.