When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted. In this study, we investigated the impact of the COVID-19 ...outbreak on stroke care across China.
Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy. We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes. The survey was distributed to the leaders of stroke centers in these 280 hospitals.
From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% (
<0.0001) and 25.3% (
<0.0001), respectively, in February 2020 as compared with February 2019. We retrieved 227 valid complete datasets from the 280 stroke centers. Nearly 50% of these hospitals were designated hospitals for COVID-19. The capacity for stroke care was reduced in the majority of the hospitals. Most of the stroke centers stopped or reduced their efforts in stroke education for the public. Hospital admissions related to stroke dropped ≈40%; thrombolysis and thrombectomy cases dropped ≈25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019. Many factors contributed to the reduced admissions and prehospital delays; lack of stroke knowledge and proper transportation were significant limiting factors. Patients not coming to the hospital for fear of virus infection was also a likely key factor.
The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy. Although many factors contributed, patients not coming to the hospital was probably the major limiting factor. Recommendations based on the data are provided.
Guiding an aircraft to 4D waypoints at a certain heading is a multi-dimensional goal aircraft guidance problem. d=ZuIn order to improve the performance and solve this problem, this paper proposes a ...multi-layer RL approach.To enhance the performance, in the present study, a multi-layer RL approach to solve the multi-dimensional goal aircraft guidance problem is proposed. The approach d=Zuenablesassists the autopilot in an ATC simulator to guide an aircraft to 4D waypoints at certain latitude, longitude, altitude, heading, and arrival time, respectively. To be specific, a multi-layer RL d=Zuapproach is proposedmethod to simplify the neural network structure and reduce the state dimensions. A shaped reward function that involves the potential function and Dubins path method is applied. d=ZuExperimental and simulation results show that the proposed approachExperiments are conducted and the simulation results reveal that the proposed method can significantly improve the convergence efficiency and trajectory performance. d=ZuFurthermoreFurther, the results indicate possible application prospects in team aircraft guidance tasks, since the aircraft can directly approach a goal without waiting in a specific pattern, thereby overcoming the problem of current ATC simulators.
IntroductionStroke is the leading cause of death and disability in China. The median time of stroke pre-hospital delay is more than 15 hours, mainly due to the lack of awareness on stroke symptoms ...and calling emergency services. We developed Stroke 1-2-0 recognition tool in China, by adapting Face, Arm, Speech and Time. Our preliminary findings suggested that Stroke 1-2-0 can improve public’s knowledge of the stroke symptoms, but its impact on the prehospital delay is still unclear. Furthermore, these findings were mainly obtained from Shanghai, one of the largest metropolises in China. However, more than half of population in China lives in the rural area. Given the striking disparities in socioeconomic status and quality of stroke care across the nation, a multicentre trial is warranted.Methods and analysisStroke 1-2-0 education programme will adopt a multicentre, cluster-randomised controlled design. We aimed to recruit 32 communities from 16 counties across China. Each county includes two communities having more than 100 000 residents. The two communities sampled in the same county will be randomly assigned to receive either Stroke 1-2-0 education programme or usual care. The primary objective of this study is to evaluate the impact of Stroke 1-2-0 public education programme in reducing stroke prehospital delay among adults residing in the community, compared with the usual care. The intervention will be implemented for 1 year. The primary outcomes are the symptom onset to hospital arrival time (‘onset-to-door time’, ODT) and 3-hour hospital arriving rate. We will use an intention-to-treat approach. A linear mixed model will be used to control for potential cluster effects.Ethics and disseminationThis study is approved by the Shanghai Minhang District Central Hospital Institutional Review Board (Shanghai, China). The findings will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberChiCTR2000040782.
Background Although immunotherapy shows tremendous potential in the treatment of bladder cancer (BLCA), the overall prognosis and response rates to immunotherapy in BLCA remain suboptimal. Methods We ...performed an extensive evaluation of glycosyltransferase expression patterns in BLCA patients by analyzing 210 glycosyltransferase-related genes. Subsequently, we established correlations between these glycosyltransferase patterns, prognosis, and tumor microenvironment (TME) phenotypes. To offer personalized patient assessments, we developed a glycosyltransferase risk score that accurately predicts prognosis, TME phenotypes, and molecular subtypes. Importantly, we developed a RNA-seq cohort, named Xiangya cohort, to validate our results. Results Two distinct patterns of glycosyltransferase expression were identified, corresponding to inflamed and noninflamed TME phenotypes, and demonstrated the potential to predict prognosis. We developed and validated a comprehensive risk score that accurately predicted individual patient prognosis in the TCGA-BLCA cohort. Additionally, we constructed a nomogram that integrated the risk score with several key clinical factors. Importantly, this risk score was successfully validated in external cohorts, including the Xiangya cohort and GSE48075. Furthermore, we discovered a positive correlation between this risk score and tumor-infiltrating lymphocytes in both the TCGA-BLCA and Xiangya cohorts, suggesting that patients with a higher risk score exhibited an inflamed TME phenotype and were more responsive to immunotherapy. Finally, we observed that the high and low risk score groups were consistent with the luminal and basal subtypes of BLCA, respectively, providing further validation of the risk score's role in the TME in terms of molecular subtypes. Conclusions Glycosyltransferase patterns exhibit distinct TME phenotypes in BLCA. Our comprehensive risk score provides a promising approach for prognostic prediction and assessment of immunotherapy efficacy, offering valuable guidance for precision medicine. Keywords: Glycosyltransferase, Bladder cancer, Prognosis, Tumor microenvironment, Immunotherapy
Although dezocine is a partial μ-opioid receptor agonist, it is not a controlled substance. Thus, the characterization of the molecular targets of dezocine is critical for scientific and clinical ...implications. The goal of this study is to characterize molecular targets for dezocine and determine their implications.
A binding screen for dezocine was performed on 44 available receptors and transporter proteins. Functional assays for the novel targets were performed along with computation calculations to locate the binding site. A G protein activation study was performed for the human κ opioid receptor to determine whether dezocine is a κ-antagonist. Data are presented as mean ± standard error.
The affinities for dezocine were 3.7 ± 0.7 nM for the μ receptor, 527 ± 70 nM for the δ-receptor, and 31.9 ± 1.9 nM for the κ-receptor. Dezocine failed to induce G protein activation with κ-opioid receptor and concentration dependently inhibited κ-agonist (salvinorin A and nalbuphine)-induced receptor activation, indicating that dezocine is a κ-antagonist. Two novel molecular targets (norepinephrine transporter and serotonin transporter) were identified. Dezocine concentration-dependently inhibited norepinephrine and serotonin reuptake in vitro. The half maximal inhibitory concentrations (expressed as pIC50) were 5.68 ± 0.11 for norepinephrine transporter and 5.86 ± 0.17 for serotonin transporter. Dezocine occupied the binding site for known norepinephrine transporter and serotonin transporter inhibitors.
The unique molecular pharmacological profile of dezocine as a partial μ-receptor agonist, a κ-receptor antagonist, and a norepinephrine and serotonin reuptake inhibitor (via norepinephrine transporter and serotonin transporter) was revealed. These discoveries reveal potentially important novel clinical implications and drug interactions of dezocine.
Background
In this brief report, we investigated the impact of COVID‐19 on outpatient stroke clinics and inpatient services and their recovery process.
Methods
We sent a survey to physicians ...worldwide through the network of the World Stroke Organization to investigate the impact of COVID‐19 on stroke clinics. To farther along in recovering from the outbreak, we reviewed stroke and other neurology outpatient clinic visits (approximately 50% were stroke related) and the number of inpatient services from December 2019 to July 2020 in a large neurology department in Shanghai, China, where there was no official city lockdown.
Results
We received 112 valid survey responses from 46 countries, representing all continents except for Antarctica. Only seven of the survey responders (7/112, 6.3%) reported that they have kept their outpatient clinics open as usual, but they did exercise increased precautions for COVID‐19 by following recent guidelines regarding use of personal protective equipment and isolation techniques. The remainder of the respondents have either reduced outpatient clinic services or suspended outpatient clinics completely. Telephone consultation or telemedicine with video capability was used for new patients or follow‐ups, with limited in‐person evaluations when necessary. Outpatient clinic visits and inpatient services from a large tertiary hospital in China decreased dramatically during the peak period of the outbreak, but then rebounded back quickly following the partial or full recovery from the outbreak. Compared with the recovery process of inpatient services, outpatient clinic visits decreased faster and recovered much slower. This is consistent with our global survey data which indicates that some outpatient clinics have rescheduled their outpatient visits for 3 to 6 months.
Conclusions
The COVID‐19 pandemic caused a significant drop of in‐person outpatient visits and inpatient services. Clinic visits recovered slower than inpatient services in stroke and other neurological diseases after the pandemic.
The changes in outpatient visits and inpatient services from the neurology department in a tertiary hospital in Shanghai, China, where there was no official city lockdown during the pandemic. A. It indicates the clinic visits from January 2019 to July 2020. Clinic visits dropped by 36.6% in February 2020 as compared to that in February in 2019, with a partial rebound as the effects of the pandemic waned; B. It indicates the inpatient services in stroke and all neurological diseases from January 2019 to July 2020. Inpatient services in stroke and all neurological diseases dropped by 27.4% and 23.8%, respectively, in February 2020 as compared to that in February in 2019 and then rose rapidly to a nearly normal status
This study tests the hypothesis that middle school and high school students can improve their stroke knowledge using Stroke 1-2-0, a stroke educational tool, and pass this knowledge on to their ...family members.
A total of 625 students and 198 parents/grandparents participated in learning about stroke using Stroke 1-2-0. After a group training session for the students by a neurologist at school, the students took educational material to home and educated their parents/grandparents. A questionnaire was given to students, parents/grandparents before, immediately after, and 1 year after the educational event.
All participants agreed that Stroke 1-2-0 was a much easier tool to remember than FAST. Almost all the students (96.4%) remembered the meaning of Stroke 1-2-0 as compared to 7.3% from the base line (p < 0.001). The rate of complete Stroke 1-2-0 mastery from 96.3% fell to 84.4% at 3 months and 63.8% at 1 year after training (p < 0.001). Following education from children, the proportion of parents/grandparents who mastered Stroke 1-2-0 was significantly higher than baseline (79.9 vs. 24.8%).
Middle school and high school students can effectively use Stroke 1-2-0 to improve their stroke knowledge and pass this knowledge to their family members. Sustained educational efforts and repeated educational events are needed though.
We demonstrate arrays of opioid biosensors based on chemical vapor deposition grown molybdenum disulfide (MoS2) field effect transistors (FETs) coupled to a computationally redesigned, water-soluble ...variant of the μ-opioid receptor (MOR). By transferring dense films of monolayer MoS2 crystals onto prefabricated electrode arrays, we obtain high-quality FETs with clean surfaces that allow for reproducible protein attachment. The fabrication yield of MoS2 FETs and biosensors exceeds 95%, with an average mobility of 2.0 cm(2) V(-1) s(-1) (36 cm(2) V(-1) s(-1)) at room temperature under ambient (in vacuo). An atomic length nickel-mediated linker chemistry enables target binding events that occur very close to the MoS2 surface to maximize sensitivity. The biosensor response calibration curve for a synthetic opioid peptide known to bind to the wild-type MOR indicates binding affinity that matches values determined using traditional techniques and a limit of detection ∼3 nM (1.5 ng/mL). The combination of scalable array fabrication and rapid, precise binding readout enabled by the MoS2 transistor offers the prospect of a solid-state drug testing platform for rapid readout of the interactions between novel drugs and their intended protein targets.
We have developed a novel, all-electronic biosensor for opioids that consists of an engineered μ-opioid receptor protein, with high binding affinity for opioids, chemically bonded to a graphene ...field-effect transistor to read out ligand binding. A variant of the receptor protein that provided chemical recognition was computationally redesigned to enhance its solubility and stability in an aqueous environment. A shadow mask process was developed to fabricate arrays of hundreds of graphene transistors with average mobility of ∼1500 cm2 V–1 s–1 and yield exceeding 98%. The biosensor exhibits high sensitivity and selectivity for the target naltrexone, an opioid receptor antagonist, with a detection limit of 10 pg/mL.
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