Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa).Methods/designNighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles.DiscussionTranscutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness.Clinical Trial RegistrationChinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Base

Corrigendum: Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale-Revised as an Example.

[This corrects the article DOI: 10.3389/fnint.2021.685627.]

Response of Land Surface Temperature to Heatwave-Induced Bio-Geophysical Changes in Tropical Forests on Hainan Island from 2010 to 2022

Land surface temperature plays an important role in the water cycle and surface energy balance. Using data collected by a vorticity covariance tower from 2010 to 2022, the relative threshold method and TRM method were employed to study the land–atmosphere exchange of water and the heat flux of rubber forest ecosystems under heatwave and non-heatwave conditions. The results show that the latent heat flux, sensible heat flux, and incoming and outgoing radiation increase from non-heatwave to heatwave conditions. In addition, the multi-year average LST was 6.7 °C higher under HW conditions than under non-HW conditions at the 99% confidence level. Further attribution analysis demonstrates that heatwave-induced land surface temperature change is mainly governed by atmospheric factors rather than by land surface factors. Specifically, radiative forcing shows the largest positive contribution, which is partly offset by the negative contributions of air temperature and relative humidity. In particular, the contributions of radiative forcing, air temperature, relative humidity, and atmospheric pressure to LST were 14.70 K, −4.76 K, −5.86 K, and −0.04 K, respectively. Moreover, surface resistance contributed to LST by 2.42 K, aerodynamic resistance by −0.23 K, and soil heat flux by −0.91 K

Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale-Revised as an Example.

Objective: The aim of this study was to develop a general method to estimate the minimal number of repeated examinations needed to detect patients with random responsiveness, given a limited rate of missed diagnosis. Methods: Basic statistical theory was applied to develop the method. As an application, 100 patients with disorders of consciousness (DOC) were assessed with the Coma Recovery Scale-Revised (CRS-R). DOC patients were supposed to be examined for 13 times over 20 days, while anyone who was diagnosed as a minimally conscious state (MCS) in a round would no longer be examined in the subsequent rounds. To test the validation of this method, a series of the stochastic simulation was completed by computer software under all the conditions of possible combinations of three kinds of distributions for p, five values of p, and four sizes of the sample and repeated for 100 times. Results: A series of formula was developed to estimate the probability of a positive response to a single examination given by a patient and the minimal number of successive examinations needed based on the numbers of patients detected in the first i (i =1, 2,.) rounds of repeated examinations. As applied to the DOC patients assessed with the CRS-R, with a rate of missed diagnosis < 0.0001, the estimate of the minimal number of examinations was six in traumatic brain injury patients and five in non-traumatic brain injury patients. The outcome of the simulation showed that this method performed well under various conditions possibly occurring in practice. Interpretation: The method developed in this paper holds in theory and works well in application and stochastic simulation. It could be applied to any other kind of examinations for random responsiveness, not limited to CRS-R for detecting MCS; this should be validated in further research

Data_Sheet_1_Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol.doc

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa).Methods/designNighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles.DiscussionTranscutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness.Clinical Trial RegistrationChinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021.</p

Mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia

The mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML, are unclear. In order to explore the prognostic significance of the mutational spectrum in IR-AML, 106 IR-AML patients were collected from The Cancer Genome Atlas database. Sixty-two patients underwent chemotherapy-only, forty-four proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fifty-five patients had more than five recurrent genetic mutations. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, RUNX1, IDH2, IDH1, and TET2. In all patients, allo-HSCT was an independent favorable factor for EFS and OS (P = 0.036, P = 0.001, respectively); age >= 60 years, FLT3-ITD and mutations in DNMT3A and RUNX1 were independent risk factors for survival (all P <0.05). In the chemotherapy-only group, multivariate analysis showed that age 60 years was an independent risk factor for EFS and OS (P = 0.008, P = 0.017, respectively). In the allo-HSCT group, multivariate analysis indicated that MLL-PTD was an independent risk fact for EFS (P = 0.037), FLT3-ITD and RUNX1 mutations independently contributed to poor OS (P = 0.035, P = 0.014, respectively). In conclusion, older age was an important risk factor for IR-AML patients undergoing chemotherapy-only; FLT3-ITD, MLL-PTD and RUNX1 mutations were significant risk factors for IR-AML patients who received allo-HSCT