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Emergence agitation is a common paediatric complication after inhalational anaesthesia. Intranasal dexmedetomidine can prevent emergence agitation effectively, but the optimal dose is uncertain.The aim of our study was to investigate the 95% effective dose (ED 95 ) of intranasal dexmedetomidine for the prevention of emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery.A prospective, randomised, placebo-controlled, double-blind, clinical trial.The study was conducted in Guangzhou Women and Children's Medical Center in China from August 2017 to December 2018.Three hundred and eighteen children scheduled for ambulatory surgery were enrolled into two age groups of less than 3 years and at least 3 years.The children in each age group were randomised into five equal subgroups to receive either intranasal dexmedetomidine 0.5, 1.0, 1.5 or 2.0 μg kg -1 (Groups D 0.5 , D 1.0 , D 1.5 and D 2.0 ), or intranasal isotonic saline (group C) after induction.The primary outcome was the ED 95 dose of intranasal dexmedetomidine for preventing emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery.The incidences of emergence agitation for Groups C, D 0.5 , D 1.0 , D 1.5 and D 2.0 were 63, 40, 23, 13 and 3% in children less than 3 years, and 43, 27, 17, 7 and 3% in children at least 3 years. The ED 95 of intranasal dexmedetomidine for preventing emergence agitation was 1.99 μg kg -1 [95% confidence interval (CI), 1.83 to 3.80 μg kg -1 ] in children less than 3 years, and 1.78 μg kg -1 (95% CI, 0.93 to 4.29 μg kg -1 ) in children at least 3 years. LMA removal time for groups D 1.5 and D 2.0 was 9.6 ± 2.2 and 9.7 ± 2.5 min, respectively, for children less than 3 years, and 9.4 ± 2.0 and 9.9 ± 2.7 min in children at least 3 years, respectively. Length of stay in the postanaesthesia care unit for Groups D 1.5 and D 2.0 was 34.3 ± 9.6 and 37.1 ± 11.2 min, respectively, in children less than 3 years, and 34.7 ± 10.2 and 37.3 ± 8.3 min in children at least 3 years, respectively. These times were longer in the D 1.5 and D 2.0 subgroups than in the control subgroup in the two age groups of less than 3 years and at least 3 years, respectively: 7.2 ± 1.9 min in children less than 3 years and 7.3 ± 2.5 min in children at least 3 years for LMA removal time, 22.2 ± 7.9 min in children less than 3 years and 22.0 ± 7.7 min in children at least 3 years for PACU stay time in control subgroup, respectively ( P 0.05).Intranasal dexmedetomidine prevented emergence agitation after paediatric surgery in a dose-dependent manner. The optimal dose of intranasal dexmedetomidine for preventing emergence agitation was higher in younger children.chictr.org.cn: ChiCTR-IOR-17012415.

Previous studies on resting-state electroencephalographic responses in patients with depressive disorders have identified electroencephalogram (EEG) parameters as potential biomarkers for the early detection and diagnosis of depressive disorders. However, these studies did not investigate the relationship between resting-state EEG microstates and the early detection of depressive symptoms in preclinical individuals. To explore the possible association between resting-state EEG microstate temporal dynamics and depressive symptoms among college students, EEG microstate analysis was performed on eyes-closed resting-state EEG data for approximately 5 min from 34 undergraduates with high intensity of depressive symptoms and 34 age- and sex-matched controls with low intensity of depressive symptoms. Five microstate classes (A-E) were identified to best explain the datasets of both groups. Compared to controls, the mean duration, occurrence, and coverage of microstate class B increased significantly, whereas the occurrence and coverage of microstate classes D and E decreased significantly in individuals with high intensity of depressive symptoms. Additionally, the presence of microstate class B was positively correlated with participants' Beck Depression Inventory-II (BDI-II) scores, and the presence of microstate classes D and E were negatively correlated with their BDI-II scores. Further, individuals with high intensity of depressive symptoms had higher transition probabilities of A→B, B→A, B→C, B→D, and C→B, with lower transition probabilities of A→D, A→E, D→A, D→E, E→A, E→C, and E→D than controls. These results highlight resting-state EEG microstate temporal dynamics as potential biomarkers for the early detection and timely treatment of depression in college students.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, safe, and efficacious treatment for major depressive disorder (MDD). However, the antidepressant efficacy of rTMS greatly varies across individual patients. Thus, markers that can be used to predict the outcome of rTMS treatment at the individual level must be identified. Thalamo-cortical connectivity was abnormal in patients with MDD, and was normalized after rTMS treatment. In the current study, we investigated whether the resting-state functional and structural thalamo-cortical connectivity could be utilized to predict the rTMS treatment efficacy by employing support vector machine regression analysis. Results showed that the Hamilton Depression Scale scores of patients with MDD decreased after rTMS treatment. The functional connectivity of mediodorsal nucleus with prefrontal cortex predicted the rTMS treatment improvement, whereas the functional connectivity of other thalamic nuclei with cerebral cortex did not predict the treatment efficacy. The brain areas that contributed the most to the prediction were dorsal lateral prefrontal cortex, ventral lateral, and orbital and medial prefrontal areas. The improvement in the outcome of rTMS treatment could also be predicted by the thalamo-prefrontal structural connectivity. No statistically significantly difference in thalamo-cortical connectivity was observed between early improvers and early non-improvers. These results suggested that the thalamo-prefrontal connectivity can predict the rTMS treatment improvement. This study highlighted the crucial role of the thalamo-prefrontal connectivity as a neuroimaging marker in the treatment of depression via rTMS.

Previous test-retest analysis of EEG mostly focused on eyes open and eyes closed resting-state. However, less attention was paid to the EEG during the subject-driven mental imaginary task state. In the current study, we compared the test-retest reproducibility of EEG spectrum in three mental imaginary task states (i.e. performed mental arithmetic, recalled the events of their day, and silently sang lyrics) and two resting states (i.e. eyes open and closed) during three EEG sessions. The resting state with eyes closed has the highest reproducibility, while the resting state with eyes opened has the lowest reproducibility for the spectral features of EEG signals at the sensor level. However, the reproducibility during eyes-open ranked higher among the five states at the source level. Moreover, the mental arithmetic state has the highest reproducibility among all the three task states. And its reproducibility in certain rhythms (theta, gamma, etc) was higher than the resting states. The reproducibility of the EEG spectrum was also investigated from the perspective of large-scale brain networks. The dorsal attention network showed the highest reproducibility in a wide frequency range of the alpha and beta rhythms. Our study suggests the importance of task selection based on the target brain region and the target frequency band. This may provide some suggestions for future researchers to choose appropriate experimental paradigms and provide a guideline on EEG study for the basic and clinical applications.

The Coronavirus disease of 2019 (COVID-19) and measures to curb it created population-level changes in male-dominant impulsive and risky behaviors such as violent crimes and gambling. One possible explanation for this is that the pandemic has been stressful, and males, more so than females, tend to respond to stress by altering their focus on immediate versus delayed rewards, as reflected in their delay discounting rates. Delay discounting rates from healthy undergraduate students were collected twice during the pandemic. Discounting rates of males (n=190) but not of females (n=493) increased during the pandemic. Using machine learning, we show that prepandemic functional connectome predict increased discounting rates in males (n=88). Moreover, considering that delay discounting is associated with multiple psychiatric disorders, we found the same neural pattern that predicted increased discounting rates in this study, in secondary datasets of patients with major depression and schizophrenia. The findings point to sex-based differences in maladaptive delay discounting under real-world stress events, and to connectome-based neuromarkers of such effects. They can explain why there was a population-level increase in several impulsive and risky behaviors during the pandemic and point to intriguing questions about the shared underlying mechanisms of stress responses, psychiatric disorders and delay discounting.

Background The spread of spinal anesthesia was influenced by many factors, and the effect of body height on spinal anesthesia is still arguable. This study aimed to explore the impact of height on the spread of spinal anesthesia and the stress response in parturients. Methods A total of ninety-seven parturients were allocated into two groups according to their height: the shorter group (body height was shorter than 158 cm) and taller group (body height was taller than 165 cm). Spinal anesthesia was performed with the same amount of 12 mg plain ropivacaine in mothers of different heights. The primary outcome of the study was the success or failure of the spinal anesthesia. The secondary outcomes of the study were stress response, time to T6 sensory level, the incidence of hypotension, the satisfaction of abdominal muscle relaxation and patient VAS scores. Results The rate of successful spinal anesthesia in the shorter group was significantly higher than that in the taller group (p = 0.02). The increase of maternal cortisol level in the shorter group was lower than that in the taller group at skin closure (p = 0.001). The incidence of hypotension (p = 0.013), time to T6 sensory block (p = 0.005), the quality of abdominal muscle relaxation (p p p p = 0.022), amniotic fluid index (p = 0.022) were significantly associated with successful spinal anesthesia. Conclusions It’s difficult to use a single factor to predict the spread of spinal anesthesia. Patient’s vertebral column length, amniotic fluid index and abdominal girth were the high determinant factors for predicting the spread of spinal anesthesia. Trials registration ChiCTR-ROC-17012030 (Chictr.org.cn), registered on 18/07/2017.

Here we present a test-retest dataset of electroencephalogram (EEG) acquired at two resting (eyes open and eyes closed) and three subject-driven cognitive states (memory, music, subtraction) with both short-term (within 90 mins) and long-term (one-month apart) designs. 60 participants were recorded during three EEG sessions. Each session includes EEG and behavioral data along with rich samples of behavioral assessments testing demographic, sleep, emotion, mental health and the content of self-generated thoughts (mind wandering). This data enables the investigation of both intra- and inter-session variability not only limited to electrophysiological changes, but also including alterations in resting and cognitive states, at high temporal resolution. Also, this dataset is expected to add contributions to the reliability and validity of EEG measurements with open resource.

This study examined the relationship between older adults’ subjective versus objective sleep and subjective cognitive decline (SCD), and explored the role of depression on this association. One hundred and four community-dwelling older adults underwent a week of actigraphic sleep monitoring, and completed a series of neuropsychological screeners. Older adults’SCD score was positively correlated with subjective insomnia, but not with objective sleep parameters. Further mediation modeling revealed that older adults’depression mediated the association between subjective insomnia and SCD. Subjective sleep, rather than objective sleep, may be a more sensitive indicator for older adults’ SCD, with depression symptoms appearing to account for most of the variance. These findings extend our perspective on the relationship between sleep disruption and cognitive decline, and highlight the necessity of early targeted interventions on sleep to reduce the risk of cognitive impairment in the elderly with SCD.

Stressful life events are significant risk factors for depression, and increases in depressive symptoms have been observed during the COVID-19 pandemic. The aim of this study is to explore the neural makers for individuals' depression during COVID-19, using connectome-based predictive modeling (CPM). Then we tested whether these neural markers could be used to identify groups at high/low risk for depression with a longitudinal dataset. The results suggested that the high-risk group demonstrated a higher level and increment of depression during the pandemic, as compared to the low-risk group. Furthermore, a support vector machine (SVM) algorithm was used to discriminate major depression disorder patients and healthy controls, using neural features defined by CPM. The results confirmed the CPM's ability for capturing the depression-related patterns with individuals' resting-state functional connectivity signature. The exploration for the anatomy of these functional connectivity features emphasized the role of an emotion-regulation circuit and an interoception circuit in the neuropathology of depression. In summary, the present study augments current understanding of potential pathological mechanisms underlying depression during an acute and unpredictable life-threatening event and suggests that resting-state functional connectivity may provide potential effective neural markers for identifying susceptible populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.

Previous studies identified the effects of daytime activity, sleep quality and ambient light exposure on individual well-being. These factors have been greatly changed as people are required to stay home during the COVID-19 pandemic; thus, it is necessary to verify whether these factors effect well-being during the pandemic. We recruited 70 adults (females: 46; age range: 31-60) during a high incidence of COVID-19 in China (17-27 February 2020). Both subjective measurements based on self-report scales and objective measurements collected using wrist actigraphy were employed to investigate the effects of night-time sleep and daytime activity on subjective well-being. The actigraphy data show that participants' total sleep time (>8 hr) is sufficient. Self-reported sleep quality was significantly worse than pre-pandemic, and self-reported daytime activity levels significantly decreased during the pandemic. Physical activity was positively related to well-being, both for self-reported daytime activity (r = .346, p = .003) and for objective measurements (r = .234, p = .051). Our study found that sleep and daytime activity levels were negatively affected by the pandemic. However, increased daytime physical activity could potentially reduce these negative effects.

Chronotype is an appropriate variable to investigate sleep homeostatic and circadian rhythm. Based on functional MRI, the resting-state functional connectivity (rsFC) of insula-angular decrease with the increase in homeostatic sleep pressure (HSP). However, the distinct neural response of different chronotype remained to be clarified. Therefore, we investigated how HSP influenced insular-angular neural interaction of different chronotype.64 morningness-chronotype (MCPs) and 128 eveningness-chronotype participants (ECPs) received resting-state functional MRI (rsfMRI) scan. HSP was divided into three levels (Low, Medium, and High) based on the elapsed time awake. Insular-angular rsFC was calculated for MCPs and ECPs on each HSP.As the levels of HSP increased, the negative rsFC between right insular and bilateral angular increased in MCPs while decreased in ECPs. Specifically, ECPs compared with MCPs showed lower rsFC at medium levels of HSP, but higher rsFC at high levels of HSP. In addition, ECPs compared with MCPs exhibited lower rsFC between right insular and right angular at low levels of HSP.The distinct modes of rsFC was found in different chronotype in response to HSP. The results provided the foundation and evidence for investigating the processes of circadian rhythm and sleep homeostatic.

Human life is deeply influenced by infectious diseases. A vaccine, when available, is one of the most effective ways of controlling the spread of an epidemic. However, vaccine shortage and uncertain vaccine effectiveness in the early stage of vaccine production make vaccine allocation a critical issue. To tackle this issue, we propose a multi-objective framework to optimize the vaccine allocation strategy among different age groups during an epidemic under vaccine shortage in this study. Minimizing total disease onsets and total severe cases are the two objectives of this vaccine allocation optimization problem, and the multistage feature of vaccine allocation are considered in the framework. An improved Strength Pareto Evolutionary Algorithm (SPEA2) is used to solve the optimization problem. To evaluate the two objectives under different strategies, a deterministic age-stratified extended SEIR model is developed. In the proposed framework, different combinations of vaccine effectiveness and vaccine production capacity are investigated, and it is identified that for COVID-19 the optimal strategy is highly related to vaccine-related parameters. When the vaccine effectiveness is low, allocating most of vaccines to 0–19 age group or 65+ age group is a better choice under a low production capacity, while allocating most of vaccines to 20–49 age group or 50–64 age group is a better choice under a relatively high production capacity. When the vaccine effectiveness is high, a better strategy is to allocate vaccines to 65+ age group under a low production capacity, while to allocate vaccines to 20–49 age group under a relatively high production capacity.

ObjectiveTo evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) and culture in pathogen detection among intensive care unit (ICU) and non-ICU patients with suspected pulmonary infection.MethodsIn this prospective study, sputum samples were collected from patients with suspected pulmonary infection for 2 consecutive days and then subjected to DNA or RNA sequencing by mNGS or culture; 62 ICU patients and 60 non-ICU patients were admitted. In the end, comparisons were made on the pathogen species identified by mNGS and culture, the overall performance of these two methods in pathogen detection, and the most common pathogens detected by mNGS between the ICU and non-ICU groups.ResultsIn DNA and RNA sequencing, the positive rate of pathogen detection reached 96.69% (117/121) and 96.43% (108/112), respectively. In culture tests, the positive rate of the pathogen was 39.34% (48/122), much lower than that of DNA and RNA sequencing. In general, the positive rate of pathogen detection by sputum mNGS was significantly higher than that of sputum culture in the total and non-ICU groups (p < 0.001) but did not show a significant difference when compared to the result of sputum culture in the ICU group (p = 0.08). Haemophilus spp., Candida albicans, Enterococcus spp., and viruses from the mNGS results were excluded before comparing the overall performance of these two methods in pathogen detection. Specifically, among the 10 most common bacteria implied from the mNGS results, significant differences were observed in the number of cases of Haemophilus parainfluenzae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Enterococcus faecalis between the ICU and non-ICU groups (p < 0.05).ConclusionsThis study demonstrated the superiority of mNGS over culture in detecting all kinds of pathogen species in sputum samples. These results indicate that mNGS may serve as a valuable tool to identify pathogens, especially for ICU patients who are more susceptible to mixed infections.

Background Previous neuroimaging studies revealed abnormal resting-state functional connectivity between distributed brain areas in patients with major depressive disorder. Those abnormalities were normalized after treatment. Moreover, the functional connectivity could predict clinical response to those treatments. However, there has currently been no meta-analysis to verify these findings. Methods The current study aimed to investigate how the resting-state connectivity patterns predict antidepressant response to various treatments across depressive studies by using coordinate-based meta-analysis named activation likelihood estimation. The relevant articles were obtained by searching on PubMed and Web of Science. Results Following exclusion criteria of inappropriate studies, seventeen papers with 392 individual depressive patients were included. Those articles contained repetitive transcranial magnetic stimulation (rTMS) treatment, pharmacotherapy, cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT) and transcutaneous vagus nerve stimulation in patients with depression. Meta-analysis revealed that clinical response to all treatments could be predicted by baseline default mode network connectivity in patients with depression. The rTMS treatment had larger effect size compared to other treatment strategies. Furthermore, subgroup meta-analysis showed that the baseline connectivity of perigenual anterior cingulate cortex (pgACC) and ventral medial prefrontal cortex could predict symptoms improvement of rTMS treatment. Limitations More resting-state connectivity studies of CBT and ECT treatment are needed. Conclusions This study highlighted crucial role of DMN, especially the pgACC, in understanding the underlying treatment mechanism of depression.

Sleep inertia refers to a distinct physiological state of waking up from sleep accompanied by performance impairments and sleepiness. The neural substrates of sleep inertia are unknown, but growing evidence suggests that this inertia state maintains certain sleep features. To investigate the neurophysiological mechanisms of sleep inertia, a comparison of pre‐sleep and post‐sleep wakefulness with eyes‐open resting‐state was performed using simultaneous EEG‐fMRI, which has the potential to reveal the dynamic details of neuroelectric and hemodynamic responses with high temporal resolution. Our data suggested sleep‐like features of slow EEG power and decreased BOLD activity were persistent during sleep inertia. In the pre‐sleep phase, participants with stronger EEG vigilance showed stronger activity in the fronto‐parietal network (FPN), but this phenomenon disappeared during sleep inertia. A time course analysis confirmed a decreased correlation between EEG vigilance and the FPN activity during sleep inertia. This simultaneous EEG‐fMRI study advanced our understanding of sleep inertia and revealed the importance of the FPN in maintaining awareness. This is the first study to reveal the dynamic brain network changes from multi‐modalities perspective during sleep inertia., This study used simultaneous EEG‐fMRI to compare pre‐sleep and post‐sleep wakefulness with eyes‐open resting‐state to investigate the neurophysiological mechanisms of sleep inertia. We report that low EEG power was increased, and BOLD activity and functional connectivity were decreased during sleep inertia. The correlation of EEG vigilance and FPN activity disappeared during sleep inertia. Further, simultaneous EEG‐fMRI revealed that the disappearance of this correlation persisted in a volume‐by‐volume based analysis with high temporal resolution. We believe that our study makes a significant contribution to the literature because we highlight the neural substrates underscoring dynamic brain network changes of EEG vigilance during sleep inertia.

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.

Causes of mortality in EC patients are not confined to cancer-specific mortality but include various protein expressions of SOX2 and mTOR in Esophageal Cancer patients and their correlation with the clinical stage. Data about the risk factors and involvement of cancer-specific protein are still lacking. This study aimed to define the risk factors and association of SOX2 and mTOR expression in mortality in patients with EC. We conducted a retrospective cohort study to assess the risk factors for cancer-specific mortality and cardiovascular mortality in patients with esophageal cancer (EC). The expression rates of SOX2, as well as MTO, were checked in patients. The multivariate analysis revealed a high-risk EC mortality with age ≥ 65 years, black race, grade, stage, and sequence of treatment; radiation after surgery; radiation before and after surgery; Surgery both before and after radiation. While the cardiovascular mortality increased with age ≥ 65 years, adenocarcinoma type, grade, stage, and sequence of treatment. The expression rates of SOX2, as well as mTOR, were 75.5 percent and 86.8 percent in Esophageal Cancer, while were 10.7 percent and 7.5 percent in osteochondroma, respectively, which was statistically significant (P

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

BackgroundSeveral studies have evaluated the relationship between tumor mutational burden (TMB) and outcomes of immune checkpoint inhibitors. In the phase II KEYNOTE-158 study of pembrolizumab monotherapy for previously treated recurrent or metastatic cancer, high TMB as assessed by the FoundationOne CDx was associated with an improved objective response rate (ORR).MethodsWe retrospectively assessed the relationship between TMB and efficacy in participants with previously treated advanced solid tumors enrolled in 12 trials that evaluated pembrolizumab monotherapy, including 3 randomized trials that compared pembrolizumab with chemotherapy. TMB was assessed in formalin-fixed, paraffin-embedded pretreatment tumor samples by whole-exome sequencing. High TMB was defined as ≥175 mutations/exome. Microsatellite instability (MSI) phenotype was based on whole-exome sequencing results. Programmed death ligand 1 (PD-L1) expression was assessed by immunohistochemistry. The primary end point was ORR assessed per RECIST V.1.1 by independent central review. Other end points included progression-free survival (PFS) assessed per RECIST V.1.1 by independent central review and overall survival (OS).ResultsOf the 2234 participants in the analysis, 1772 received pembrolizumab monotherapy and 462 received chemotherapy. Among the pembrolizumab-treated participants, ORR was 31.4% (95% CI 27.1 to 36.0) in the 433 participants with TMB ≥175 mutations/exome and 9.5% (95% CI 8.0 to 11.2) in the 1339 participants with TMB ConclusionsTMB ≥175 mutations/exome is associated with clinically meaningful improvement in the efficacy of pembrolizumab monotherapy and improved outcomes for pembrolizumab versus chemotherapy across a wide range of previously treated advanced solid tumor types. These data suggest TMB has broad clinical utility irrespective of tumor type, PD-L1 expression, or MSI status and support its use as a predictive biomarker for pembrolizumab monotherapy in participants with previously treated advanced solid tumors.

Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs. A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients). 21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P

Multiple neuroimaging studies have examined the neural underpinnings of body image disturbances in patients with eating disorders. However, key brain regions related to body image, such as body-esteem (BE), among healthy individuals are understudied. Given the extremely crucial role of BE in eating behaviors and physical and mental health, the current study conducted data-driven analysis and characterized the neurobiological correlates of BE with the network properties of the resting brain using the voxel-wise degree centrality (DC) measures of resting-state functional magnetic resonance imaging (rs-fMRI) data and seed-based resting-state functional connectivity (RSFC). A total of 694 healthy young adults (females = 474, mean age = 18.38 years, range = 17-22) underwent rs-fMRI, and completed the Body-Esteem Scale for Adolescents and Adults, the Eating Disorder Diagnosis Scale, and the Restraint Scale. After correcting for differences in age, gender, body mass index, and head motion, whole-brain correlation analyses revealed that a high level of BE was associated with increased DC within the right midcingulate cortex (MCC) and subsequent high levels of MCC-based RSFC strengths. Furthermore, MCC connectivity patterns related to BE were inversely associated with disordered eating behaviors. These findings suggest that adaptive cognitive and emotional regulation (i.e., self-evaluation and emotion based on body image) may explain the potential relationship between MCC connectivity patterns and BE to a certain extent. As such, future studies should investigate these interesting possibilities.

Background To investigate the role of transmuscular quadratus lumborum block (TMQLB) for postoperative pain control, patient satisfaction and recovery in laparoscopic adrenalectomy. Methods Seventy-two patients aged between 18 and 70 years with an ASA I-II and scheduled for laparoscopic adrenalectomy were randomized to receive a single-shot TMQLB with 0.4 ml/kg 0.5 % ropivacaine or 0.4 ml/kg 0.9 % saline as placebo. The primary endpoint was pain on movement at 12 h after surgery evaluated by the numeric rating scale (NRS, 0–10). P-values Results NRS on movement at 12 h after surgery was lower in the TMQLB group compared with the control (median 2 vs. 3, p = 0.024). Intraoperative fentanyl consumption was lower in the TMQLB group (247.08 ± 63.54 vs. 285.44 ± 74.70, p = 0.022). The rate of using postoperative rescue tramadol was also lower in the TMQLB group (5.6 vs. 27.8 %, p = 0.027). Similar incidences of nausea and vomiting were observed (11.1 vs. 25 %, p = 0.220). Patient satisfaction of pain service was better in the TMQLB group (83.3 vs. 25 %, p p = 0.004) and flatus (18.5 vs. 23.5 h, p = 0.006). Conclusions TMQLB showed better control of postoperative pain on movement for laparoscopic adrenalectomy with improved patients’ satisfaction of anesthesia, shorter time to ambulation and flatus. Trial registration This study was registered at Clinicaltrials.gov (NCT03942237; registration date: 08/05/2019; enrollment date: 10/05/2019).

Background Numerous studies have shown that older adults have positive emotional bias. However, how sleep characteristics such as sleep continuity moderate this emotional bias in older adults is less understood. Objectives The present study aimed to determine whether positive emotional memory bias is associated with sleep continuity in older adults. Methods We recruited 92 community-dwelling older adults for a cross-sectional study. Participants underwent 1 week of objective actigraphic sleep monitoring and completed a visuospatial associative memory task at baseline and 1 week later. Results Older adults exhibited better memory performance for positive pictures than for neutral and negative pictures at baseline, and this positive emotional bias was maintained for at least 1 week. Crucially, this effect was moderated by sleep continuity: Older adults with shorter wake after sleep onset times (WASO) exhibited this positive bias, whereas those with longer WASO did not. Discussion The present results are the first to demonstrate that positive emotional bias is moderated by sleep continuity in older adults. These findings have implications for emotion regulation in older adults and highlight the need for targeted interventions to increase their sleep continuity, which may help to improve emotional processing in this population.

Insomnia disorder (ID) has become the second-most common mental disorder. Despite burgeoning evidence for increased high-frequency electroencephalography (EEG) activity and cortical hyperarousal in ID, the detailed spectral features of this disorder during wakefulness and different sleep stages remain unclear. Therefore, we adopted a meta-analytic approach to systematically assess existing evidence on EEG spectral features in ID. Hedges's g was calculated by 148 effect sizes from 24 studies involving 977 participants. Our results demonstrate that, throughout wakefulness and sleep, patients with ID exhibited increased beta band power, although such increases sometimes extended into neighboring frequency bands. Patients with ID also exhibited increased theta and gamma power during wakefulness, as well as increased alpha and sigma power during rapid eye movement (REM) sleep. In addition, ID was associated with decreased delta power and increased theta, alpha, and sigma power during NREM sleep. The EEG measures of absolute and relative power have similar sensitivity in detecting spectral features of ID during wakefulness and REM sleep; however, relative power appeared to be a more sensitive biomarker during NREM sleep. Our study is the first statistics-based review to quantify EEG power spectra across stages of sleep and wakefulness in patients with ID.

China was a major hotspot during the beginning of the COVID‐19 pandemic. Several studies have reported changes in residents' eating behaviors and appetite during city wide lockdowns and home confinements. However, few have investigated how neuroticism interacts with the impact of COVID‐19 to influence eating behaviors during city lockdowns. Thus, the current study aims to establish a pathway model to understand social media exposure, negative affect, neuroticism, and their interaction with eating behaviors during the COVID‐19 lockdowns. We present data from 1,128 participants (Mage = 24.34 ± 10.48 years) who completed an online survey between February 17 and 27, 2020. The extent of respondents' social media exposure, negative affect, eating behaviors, and desire for high‐calorie food during city lockdowns, as well as the personality trait of neuroticism, were measured. Results show that city lockdowns and home confinements had a negative impact on residents' eating behaviors and appetite. Forty‐eight percent of respondents showed moderate to constant emotional overeating, and respondents' desire for high‐calorie food significantly increased. Correlation analysis showed that emotional overeating is positively associated with social media exposure, neuroticism, and anxiety. Then, a moderated mediation model was established, showing that heavy social media exposure could lead to emotional overeating through anxiety, and the association between social media exposure and anxiety varies depending on the extent of neuroticism. The current study provides novel insight into how the interaction of a personality trait and the stressful situation of COVID‐19 influence people's negative emotions and eating behaviors.

Background Displaced aggression is a specific form of attack prompted by rumination on anger experiences and revenge thought which might lead to expression of anger on innocent people. There is sufficient evidence demonstrating the potential role of agreeableness in reducing displaced aggression in theory. However, little is known about the neural basis of displaced aggression and how agreeableness and the underlying neural mechanisms link to displaced aggression. Methods In this investigation, we examined these issues on 123 college students by assessing resting-state brain activity (i.e. amplitude of low-frequency fluctuation, ALFF) and connectivity (i.e. resting-state functional connectivity, RSFC). Results Whole-brain correlation analysis revealed that a higher level of displaced aggression was linked with decreased ALFF in the left dorsomedial prefrontal cortex (dmPFC) and decreased RSFC between the left dmPFC and left ventromedial prefrontal cortex (vmPFC). Mediation analysis further revealed that left dmPFC activity and the left dmPFC–vmPFC connectivity mediated the relationship between agreeableness and displaced aggression, as well as agreeableness mediated the relation between left dmPFC activity and the left dmPFC–vmPFC connectivity and displaced aggression. Limitations Only ALFF and RSFC were used as indicators of brain function in this study. The two mediation models need to be further tested by longitudinal design or experimental methods in further studies. Conclusions This study suggested that dmPFC and vmPFC might be the functional neural markers of displaced aggression and provided two possible mediation models regarding the relationship among the resting-state brain activity and connectivity, agreeableness and displaced aggression.

Prognostic significance of serum microcystin in hepatocellular carcinoma has not been well investigated. The aim of the study was to reveal the relationship between serum microcystin-LR and prognosis in these patients. There were 650 early-stage hepatitis B-induced hepatocellular carcinoma patients, who were not affected by hepatitis C, cirrhosis, heavy drinking or excessive aflatoxin exposure. All of them underwent hepatectomy and were followed up for 5 years. Tumor relapse and overall death were recorded. Blood specimens were collected on admission and at the time of relapse. Serum levels of microcystin-LR and fluorescent oxidation products (FlOP_360, FlOP_320 and FlOP_400) were measured separately using enzyme-linked immunosorbent assay and fluorescence spectrometry. Multifactorial COX regression analysis suggested that serum microcystin-LR ≥ 0.97 ng/ml was associated with the increased risk of the tumor relapse (HR: 1.53, 95% CI: 1.35–1.77) and serum microcystin-LR ≥ 1.09 ng/ml was related to the higher risk of the overall death (HR: 1.58, 95% CI: 1.35–1.84) in the follow-up period. Furthermore, there was a linear relationship between serum level of microcystin-LR and serum levels of FlOP_360, FlOP_320 and FlOP_400 (P = 0.001, P = 0.023, P = 0.047). Serum levels of these fluorescent oxidation products were also higher in the patients with tumor relapse (P

In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel-a drug used for ovarian cancer treatment-via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients. 116 6 2210 2219

Listeria monocytogenes (LM) is a classical model intracellular pathogen and the leading cause of listeriosis, which has long been a global public health issue. The successful infection of LM is related to a series of virulence factors, such as the transpeptidase enzyme sortase A (SrtA) and listeriolysin O (LLO), which are crucial for bacterial internalization and escape from phagosomes respectively. It is speculated that targeting multiple virulence factors may be due to a synergistic effect on listeriosis therapy. In this study, an active flavonoids component of Scutellaria baicalensis Georgi, baicalein, was found to potently block both listerial SrtA catalyzed activity and LLO hemolytic activity within 16 μg/mL. After pretreatment with baicalein, 86.30 (±11.35) % of LM failed to associate with Caco‐2 cells compared to the LM without preincubation (regarded as 100% internalization). Furthermore, baicalein addition may aid in bacterial degradation and clearance in macrophagocytes. During a 5 h observation, LM in cells incubated with baicalein showed significantly decreased vacuole escapes and sluggish endocellular growth. In addition, baicalein directly prevented LM‐induced cells injury and mice fatality (survival rate from 10.00% to 54.55% in 4 days post‐intraperitoneal injection). Taken together, as an antagonist against SrtA and LLO, baicalein can be further developed into a biotherapeutic agent for listeriosis.

As the pace of life accelerates, poor sleep quality has become a common health problem. A wealth of sleep studies based on electroencephalogram (EEG) have found that poor sleep quality has decreased alpha rhythm during night-time sleep. However, whether the EEG rhythm during an afternoon nap has a similar impairment has seldom been investigated. By recruiting 35 subjects for a 90-min nap, we explored the relationship between sleep quality and the alpha rhythm, and the contribution of naps to subjective sleep experience. We found that the power of alpha rhythm in the occipital lobe negatively correlated with sleep quality. However, there was no correlation between the sleep quality at night and the sleep duration of the nap, nor the sleep quality and the proportion of each sleep period of a nap. Our present results indicated that the quality of night-time sleep did not affect the macrostructure of the nap. Interestingly, the negative correlation between the alpha rhythm of a nap and sleep quality at night continuously existed in Wake, N1 sleep, and N2 sleep, and had the most substantial value during N2 sleep of a nap. This implies that an impaired occipital lobe alpha rhythm is a robust biomarker for poor sleep. The research is of particular significance for developing electrical neural stimulation therapy to improve sleep quality, especially for the stimuli regions for selection and the time windows for implementation.

COVID-19 has become a long-term problem, and global pandemic conditions may persist for years. Researchers are providing mounting evidence of relationships between COVID-19 lockdowns and sleep problems. However, few studies have investigated the impact of home isolation on sleep time perception, especially in comparable social isolation situations with similar pressures. Subjective sleep time perception parameters were derived from sleep diaries. Objective parameters were derived from actigraphy. Subjective and objective data were obtained between February 17 and February 27, 2020 from 70 adult participants subject to COVID-19 related lockdown provisions in China. We divided participants into a home stayers (HS) group (subject to full stay-at home orders) and an area-restricted workers (ARW) group (permitted to work at their nearby workplaces). The HS group demonstrated significantly delayed actigraphy-defined sleep onset time compared to self-reported sleep onset time; this effect was absent in the ARW group. Between-group differences in actigraphy-defined sleep onset time and significant between-group differences for actigraphy-defined and self-reported wake-up time were observed. HS group participants also presented significantly delayed actigraphy-defined wake-up time compared with self-reported wake-up time. No significant effect was found on total sleep time perception. Moreover, sleep/wake time misperception were found to be associated with daylight exposure and physical activity levels respectively. To the extent they are generalizable, these results suggest that lockdown restrictions can affect sleep onset and wake-up time perception but not total sleep time perception. Public health policy should consider such effects in the present pandemic situation and in future emergent public health situations.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which is causing the coronavirus disease-2019 (COVID-19) pandemic, poses a global health threat. However, it is easy to confuse COVID-19 with seasonal influenza in preliminary clinical diagnosis. In this study, the differences between influenza and COVID-19 in epidemiological features, clinical manifestations, comorbidities and pathogen biology were comprehensively compared and analyzed. SARS-CoV-2 causes a higher proportion of pneumonia (90.67 vs. 17.07%) and acute respiratory distress syndrome (12.00 vs. 0%) than influenza A virus. The proportion of leukopenia for influenza patients was 31.71% compared with 12.00% for COVID-19 patients (P = 0.0096). The creatinine and creatine kinase were significantly elevated when there were COVID-19 patients. The basic reproductive number (R0) for SARS-CoV-2 is 2.38 compared with 1.28 for seasonal influenza A virus. The mutation rate of SARS-CoV-2 ranges from 1.12 × 10−3 to 6.25 × 10−3, while seasonal influenza virus has a lower evolutionary rate (0.60-2.00 × 10−6). Overall, this study compared the clinical features and outcomes of medically attended COVID-19 and influenza patients. In addition, the S477N and N439K mutations on spike may affect the affinity with receptor ACE2. This study will contribute to COVID-19 control and epidemic surveillance in the future.

The novel coronavirus (COVID-19) pandemic has led to a surge in mental distress and fear-related disorders, including posttraumatic stress disorder (PTSD). Fear-related disorders are characterized by dysregulations in fear and the associated neural pathways. In the present study, we examined whether individual variations in the fear neural connectome can predict fear-related symptoms during the COVID-19 pandemic. Using machine learning algorithms and back-propagation artificial neural network (BP-ANN) deep learning algorithms, we demonstrated that the intrinsic neural connectome before the COVID-19 pandemic could predict who would develop high fear-related symptoms at the peak of the COVID-19 pandemic in China (Accuracy rate = 75.00%, Sensitivity rate = 65.83%, Specificity rate = 84.17%). More importantly, prediction models could accurately predict the level of fear-related symptoms during the COVID-19 pandemic by using the prepandemic connectome state, in which the functional connectivity of lvmPFC (left ventromedial prefrontal cortex)—rdlPFC (right dorsolateral), rdACC (right dorsal anterior cingulate cortex)—left insula, lAMY (left amygdala)—lHip (left hippocampus) and lAMY—lsgACC (left subgenual cingulate cortex) was contributed to the robust prediction. The current study capitalized on prepandemic data of the neural connectome of fear to predict participants who would develop high fear-related symptoms in COVID-19 pandemic, suggesting that individual variations in the intrinsic organization of the fear circuits represent a neurofunctional marker that renders subjects vulnerable to experience high levels of fear during the COVID-19 pandemic.

With a greatly changed environment, sleep problem becomes a common phenomenon among college freshmen. However, this type of acute insomnia usually recovers after adapting to the circumstances, which can be defined as adaptive sleep problem (ASP). Few studies deal with this type of sleep problems. In this study, 991 first-year college freshmen were recruited on different days of the first semester to investigate their sleep status. We found that the sleep problem of college freshmen at the beginning of the semester was the most severe, compared with the other two-thirds of semester. Next, behavioral and resting-state functional magnetic imaging (rs-fMRI) data from 30 freshmen with ASP and 28 matched healthy controls (HC) were used to explore the neural basis of acute insomnia. Results showed that ASP group performed worse on many behavioral indices, such as fatigue, depression, and trait anxiety. Interestingly, students with ASP also showed significantly more negative functional connectivity between the anterior default mode network (aDMN) and the dorsal attentional network (DAN). Furthermore, a significant negative correlation was observed between Insomnia Severity Index (ISI) score and aDMN-DAN functional connectivity in the HC group, which was not observed in the case of ASP. In conclusion, the study explored the neural biomarker of adaptive sleep problem (ASP) in freshmen, and found its potentiating antagonism within the DMN-DAN. This enhanced anticorrelation may corroborate that students with ASP are in a hyperarousal state. Our current study may deepen our understanding of sleep disorders, and the enhanced anticorrelation may corroborate that ASP in due to a hyperarousal state.

Objectives Transmuscular quadratus lumborum block (TQLB) may provide postoperative analgesia in patients undergoing intraperitoneal surgeries. The purpose of this study was to examine the potential efficacy of TQLB among patients undergoing retroperitoneal procedures, such as the laparoscopic partial nephrectomy (LPN). Methods This prospective, randomized, controlled study was conducted from August 2017 to November 2018 at Peking Union Medical College Hospital (Beijing, China). Patients who were scheduled for a LPN, aged 18-70 years old with an ASA physical status score of I - II were randomly assigned to receive either TQLB with 0.6 ml/kg of 0.5% ropivacaine plus general anesthesia (TQLB group) or general anesthesia alone (control group). Patient-controlled intravenous analgesia with morphine was initiated immediately upon surgery completion. The primary outcome was the cumulative consumption of morphine within 8 h after surgery. The secondary outcome included postoperative consumptions of morphine at other time points, pain score at rest and during activity, postoperative nausea and vomitting (PONV), and recovery related parameters. Results Totally 30 patients per group were recruited in the study. The 8 h consumption of morphine was lower in the TQLB group than in the control group (median, 0.023 mg/kg vs. 0.068 mg/kg, U=207.5, P

Highlights • This study examined the resting-state functional network connectivity underlying eating disorder symptoms in a large sample of healthy young adults (n = 693). • Individuals with higher levels of eating disorder symptoms displayed weaker intra-network connectivity of the executive control network and basal ganglia network, as well as weaker inter-network connectivity in the three examined networks (i.e., the executive control network, basal ganglia network, and default mode network). • The findings suggest that these neural circuits may play a key role in symptoms of disordered eating in healthy adults. They further reveal that the less efficient information exchange within and between intrinsic networks associated with self-referential thinking, inhibitory control, and reward sensitivity are strongly related to eating disorder symptoms., Previous neuroimaging research of eating disorders such as anorexia nervosa and bulimia nervosa has mainly focused on clinical patients, indicating the crucial role of intrinsic connectivity networks involved in aberrant behavioral control (i.e., executive control network), reward reactivity (i.e., basal ganglia network), and excessive self-focused and body-focused ruminations (i.e., default mode network) in the onset and maintenance of eating disturbances. However, examinations of large-scale resting-state networks that support the role of cognitive control, reward sensitivity, and self-directed thinking in disordered eating have rarely involved non-clinical samples from the general population. This study, involving a total of 693 healthy young adults (68.69% females; mean age, 18.37 years), investigated these issues by using pre-defined functional regions of interest from the executive control network, basal ganglia network, default mode network, and a seed-based region of interest-to-region of interest approach. After statistically controlling for differences in age, sex, body mass index, and head motion, we observed significant associations of higher levels of eating disorder symptoms, especially bulimia-type eating (i.e., binge eating and a combination of binge eating and compensatory behaviors, such as purging via self-induced vomiting or laxative use, and compulsive exercise), with weaker intra-network and inter-network functional synchrony. These results remained significant after excluding underweight, overweight, and obese participants. These findings suggest that these neural circuits may play a key role in the symptoms of disordered eating in healthy adults. They further reveal that the less efficient information exchange within and between intrinsic networks associated with self-referential thinking, inhibitory control, and reward sensitivity are strongly related to eating disorder symptoms.

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. Instituto de Patología Vegetal Fil: Kuhn, Jens H. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Integrated Research Facility at Fort Detrick; Estados Unidos Fil: Adkins, Scott. United States Department of Agriculture. Agricultural Research Service. US Horticultural Research Laboratory; Estados Unidos Fil: Agwanda, Bernard R. National Museums of Kenya. Zoology Department; Kenia Fil: Agwanda, Bernard R. Jomo Kenyatta University of Agriculture & Technology; Kenia Fil: Kubrusli, Rim Al. Humboldt-Universität zu Berlin. Faculty of Life Sciences. Division Phytomedicine; Alemania Fil: Alkhovsky, Sergey V. D.I. Ivanovsky Institute of Virology of N.F. Gamaleya National Center on Epidemiology and Microbiology of Ministry of Health of Russian Federation; Rusia Fil: Amarasinghe, Gaya K. Washington University School of Medicine. Department of Pathology and Immunology; Estados Unidos Fil: Avšič-Županc, Tatjana. University of Ljubljana. Faculty of Medicine; Eslovenia Fil: Ayllón, María A. Universidad Politécnica de Madrid—Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria. Campus de Montegancedo. Centro de Biotecnología y Genómica de Plantas; España Fil: Ayllón, María A. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas. Departamento de Biotecnología-Biología Vegetal; España Fil: Bahl, Justin. University of Georgia. Center for Ecology of Infectious Diseases, Department of Infectious Diseases, Department of Epidemiology and Biostatistics, Insitute of Bioinformatics; Estados Unidos Fil: Balkema-Buschmann, Anne. Institute of Novel and Emerging Infectious Diseases. Friedrich-Loeffler-Institut. Federal Research Institute for Animal Health; Alemania Fil: Bejerman, Nicolas Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina Fil: Bejerman, Nicolas Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina Fil: Debat, Humberto Julio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina Fil: Debat, Humberto Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina Fil: Zhou, Xueping. Chinese Academy of Agricultural Sciences. Institute of Plant Protection. State Key Laboratory for Biology of Plant Diseases and Insect Pests; China

BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies.OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants.METHODS: This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24.RESULTS: A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p CONCLUSION: Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment.REGISTRATION: ClinicalTrials.gov identifier NCT01721161.

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production., Platelets derive from megakaryocytes, which differentiate from hematopoietic stem/progenitor cells (HSPCs). Here, Qu et al show that platelet-derived microparticles carrying miR-1915-3p target HSPCs and promote megakaryopoiesis by suppressing RHOB expression levels.

BackgroundAlthough cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies.MethodsIn this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expressesE4ORF1stably by using a retroviral system.ResultsCoculture of CD34+hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38−, and CD34+CD38−CD90+HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+hCB cells amplified on HuAECs-E4orf1-GFP.ConclusionsCollectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.

The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Previous studies have shown that the vividness of autobiographical memory decreases over time, and older adults often retrieve fewer details than young adults. However, the age-by-temporal distance (i.e., recent versus remote events) effect on autobiographical memory and underlying neural mechanisms are less understood. We recruited 25 young adults and 27 older adults to perform an fMRI-adapted autobiographical memory task with different temporal distances. The results showed that older adults' vividness ratings were generally higher than that of young adults, but were less sensitive to temporal distances. For neural imaging, an age-by-temporal distance effect was found in the left precuneus, manifested as young adults had more activation for recent events than for remote events, whereas no temporal distance effect was found in older adults. Interestingly, for older adults, the temporal distance effect was reflected by functional connectivity within the default mode network (DMN), with a stronger anterior DMN-posterior DMN coupling for remote events than for recent events, whereas no temporal distance difference on functional connectivity was found in young adults. The results suggest that older adults exhibit age-related neural differences in both activation and functional connectivity during the processing of autobiographical memory with different temporal distances, shedding new light for the understanding of the relationship between the DMN, autobiographical memory, and aging.

Lying posture influences both neural activity and cognitive performance, and it is essential to sleep hygiene. Whereas, no neuroimaging research has investigated the effect of lying position on brain activity in waking and sleeping conditions. Therefore, we recruited 35 participants to perform a within-participant simultaneous EEG-fMRI recording with lying supine and lateral postures. Our results showed that sleep onset latency (SOL) was affected by both sleep position preference (SPP) and lying poses. SOL in supine was significantly shorter than that in lateral posture. The correlation analysis between SPP and sleep parameters indicated that individuals who prefer supine had less SOL and N2 sleep durations. However, we did not find this significant correlation in lateral-prefer individuals. Besides, different sleep positions mainly caused an alteration of the differences in brain activity patterns. In supine posture, the brain activities in the left precuneus, and anterior cingulate cortex were greater than those in lateral position. However, in the lateral posture, the status was just the opposite. Finally, we also found that the right putamen was sensitive to habitual sleep posture in the awake state. The participants who prefer to lie supine tend to have higher activity in the putamen. Our study may help with the understanding of the contribution of lying posture on brain activity and its relationship with posture preference in sleep.

Primary intracranial leiomyosarcomas (PILMSs) are extremely rare neoplasms, and their management remains unclear. The authors aimed to enunciate the radiological features and design a treatment protocol based on previously published cases combined with our series. Clinical data from all 12 cases of PILMS treated at their institute between 2008 and 2018 were reviewed. Meanwhile, they searched the Ovid MEDLINE, Embase, PubMed, Web of Science and Cochrane databases using the keywords "leiomyosarcoma" and "intracranial," "central nervous system," "cerebral," or "brain" Previously published data were processed and used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors' cohort included 4 males (33.3%) and 8 females (66.7%) ranging in age from 13 to 67 years with a mean of 44.1 ± 5.0 years. Gross total resection (GTR), subtotal resection, and partial resection were achieved in 8 (66.7%), 3 (25%), and 1 (8.3%) patient, respectively, and only four patients (33.3%) received adjuvant therapy after surgery. After a mean follow-up of 30.5 ± 7.6 months, 6 patients (50%) experienced recurrences, and all of them died at the final. Twenty-seven patients (15 were male and 12 were female), in the literature cases, were identified between January 1980 and November 2019, presenting with PILMS. GTR and non-GTR were achieved in 21 (77.8%) and 6 (22.2%) patients, respectively. Postoperative radiotherapy was administrated in 17 patients (63.0%), and postoperative chemotherapy was administrated in 9 patients (33.3%), After a mean follow-up of 22.2 ± 4.1 months, recurrence and death occurred in 8 (36.4%) and 4 (14.8%) cases, respectively. In the pooled cases, the univariate analysis model revealed that only GTR was a significantly favorable factor for increased progression-free survival (hazard ratio 0.270, 95% confidence interval = 0.093-0.787, p = 0.016) and overall survival (hazard ratio 0.255, 95% confidence interval = 0.073-0.890, p = 0.032). GTR was recommended as an optimal treatment; meanwhile, postoperative radiation was also a choice to help increase the survival of patients of PILMS.