Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

BACKGROUND: Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. METHODS: Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. RESULTS: Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. CONCLUSIONS: A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT04574362 Date registered: 2020-10-05.

Comparison of Low-Frequency or High-Frequency Electrical Acupoint Stimulation on Hypotension After Spinal Anesthesia in Parturients: A Prospective Randomized Controlled Clinical Trial.

Objective: To investigate whether transcutaneous electrical acupoint stimulation (TEAS) at PC6 could reduce hypotension after spinal anesthesia (SA) in parturients and to compare the effect of TEAS at different frequencies. Methods: From February 20, 2023, to August 29, 2023, 90 parturients scheduled for c-section under SA were randomly assigned to receive no treatment (Control), TEAS at high frequency (TEAS-HF), or TEAS at low frequency (TEAS-LF). Treatments started immediately after SA and lasted for 30 min. The primary endpoint was incidence of hypotension by 30 min after SA. Secondary endpoints included lowest systolic blood pressure (SBP) during 30 min after SA, dose of ephedrine, dose of atropine, Apgar score at 1 min, and adverse events, including nausea, vomiting, dizziness, dyspnea, and chest congestion. Results: In the TEAS-HF group, the incidence of hypotension by 30 min after SA was lower (13.3%) than in the Control (53.3%, p = 0.001; OR 1.9, 95% confidence interval [CI]: 1.2-2.8) and TEAS-LF group (40.0%, p = 0.02, OR 1.4, 95% CI: 1.0-2.0). The lowest SBP during 30 min after SA was higher in the TEAS-HF group (100.0 ± 9.4 mm Hg) than in the Control group (91.5 ± 16.5 mm Hg) and TEAS-LF group (93.9 ± 16.6 mm Hg). Patients who received TEAS showed a lower score of nausea and vomiting (both p = 0.02). Patients in the group TEAS-HF showed a lower incidence of dizziness, dyspnea, and of chest congestion than those in the other two groups. There was no difference with respect to atropine consumption and neonatal Apgar score. Conclusions: TEAS-HF at PC6 reduced hypotension after SA in parturients, while TEAS-LF did not. Trial registration: ClinicalTrials.gov (NCT05724095).

Clinical Characteristics and Induced Pluripotent Stem Cells (iPSCs) Disease Model of Fabry Disease Caused by a Novel GLA Mutation.

BACKGROUND: Fabry disease (FD) is a rare X-linked inherited disease caused by mutations in the GLA gene. We established a cohort of FD patients and performed whole-exome sequencing (WES) to identify some novel mutations. AIM: The aim of this study is to investigate the etiology of the novel mutation (c.72G > A, p.Trp24*）in the GLA gene in affected patients by using induced pluripotent stem cells (iPSCs) as a valuable tool. METHODS: We explored the clinical implications of this proband and examined the deleteriousness and conservation of the mutation site through bioinformatics analysis. Simultaneously, we collected the peripheral blood mononuclear cells (PBMCs) of the affected patient, then reprogrammed them into iPSCs and assessed their enzymatic activity to confirm the function of lysosomal enzyme α-galactosidase A (α-Gal A). RESULTS: Clinical examination of the patient demonstrated a classical FD, such as neuropathic pain, gastrointestinal disorders, deficiency of α-Gal A activity, and accumulation of Lyso-Gb-3. The novel mutation located on the N-terminal region, leading to a truncation of the protein and remaining only 24 amino acids. The α-Gal A activity of the patient-specific iPSC (iPS-FD) was significantly lower (60%) than that of normal iPSCs derived from healthy donors (iPS-B1). CONCLUSION: This work not only elucidated the etiology of novel mutations in affected patients but also highlighted the utility of iPSCs as a valuable tool for clarifying the molecular mechanisms and providing new insights into the therapy of FD.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

Transcutaneous electric acupoint stimulation reduced consumption of profopol in patients undergoing laparoscopic surgery: A randomized clinical trial.

BACKGROUND: Propofol is a common regimen for general anesthesia maintenance. But propofol can dose-dependently generate cardiopulmonary depression. Thus, any strategy to reduce propofol dosage during laparoscopic surgery may have underlying beneficial effect for patient prognosis. Previous studies indicated both analgesic and sedative effect of acupoint stimulation. However, its main sedative effect on patients under general anesthesia remains unclear. OBJECTIVE: The aim of this study was to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) on patients scheduled for laparoscopic surgery under general anesthesia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized clinical trial, patients scheduled for laparoscopic surgery under general anesthesia in Xijing hospital were randomly assigned to 3 groups, receiving electrical stimulation at the Shenmen (HT7)/Ximen (PC4) (TEAS group), stimulation at the shoulder (non-acupoint group) or no stimulation (control group), respectively. MAIN OUTCOME MEASURES: One hundred sixty-two patients completed the study. The primary outcome was the consumption of propofol, and secondary outcomes included features of recovery after surgery, major complications after surgery and by 1 year after surgery. RESULTS: In patients undergoing laparoscopic surgery, the doses of propofol decreased significantly in the TEAS group compared (0.10 ±â€…0.02 mg·kg-1·min-1) with the other 2 groups (both 0.12 ±â€…0.02 mg·kg-1·min-1, P < .001). The mean differences (95% confidence interval) for non-acupoint versus TEAS and control versus TEAS were 0.021 (0.012, 0.030) and 0.024 (0.013, 0.034), respectively. Time to awake and to extubation were not significantly different among the groups. The incidences of major complications after surgery and by 1 year after surgery were not significantly different among the groups. CONCLUSION: TEAS could induce additional sedative effect in patients during laparoscopic surgery and reduce propofol consumption.

Effect of remimazolam vs propofol on emergence from general anesthesia in patients undergoing cerebral endovascular procedures: A randomized controlled, non-inferiority trial.

STUDY OBJECTIVE: This study aimed to compare the time to emergence from general anesthesia with remimazolam versus propofol in patients undergoing cerebral endovascular procedures. DESIGN: A prospective, double-blind, randomized controlled, non-inferiority trial. SETTING: An academic hospital. PATIENTS: Adult patients scheduled for cerebral endovascular procedures. INTERVENTIONS: Patients were randomized at a 1:1 ratio to undergo surgery under general anesthesia with remimazolam (0.1 mg kg-1 for induction and 0.3-0.7 mg kg-1 h-1 for maintenance) or propofol (1-1.5 mg kg-1 for induction and 4-10 mg kg-1 h-1 for maintenance). MEASUREMENTS: The primary outcome was the time to emergence from anesthesia. The non-inferiority margin was -2.55 min in group difference. Major secondary outcomes included hypotension during induction, incidence of postoperative delirium and Modified Rankin Scale (mRs) at 30 days and 90 days after surgery. MAIN RESULTS: Of the 142 randomized patients, 129 completed the trial. In the modified intention-to-treat analysis, the mean time to emergence from anesthesia was 16.1 [10.4] min in the remimazolam group vs. 19.0 [11.2] min in the propofol group. The group difference was -2.9 min [95% CI -6.5, 0.7] (P = 0.003 for non-inferiority). The remimazolam group had lower rate of hypotension during induction (11.3% vs 25.4%, P = 0.03) and use of vasopressors during surgery (29.6% vs 62.0%, P < 0.001). The two groups did not differ in postoperative delirium and mRs at 30 and 90 days after surgery. CONCLUSIONS: In patients undergoing cerebral endovascular procedures, remimazolam did not increase the time from anesthesia vs propofol.

The effect of four-phonon interaction on phonon thermal conductivity of hexagonal VTe2 and puckered pentagonal VTe2.

The traditional view is that complex structures have lower lattice thermal conductivity. However, it is observed that complex structures have higher lattice thermal conductivity than simple atomic structures in VTe2 systems after considering the four-phonon scattering effect. In this work, we calculate the lattice thermal conductivity of an H-VTe2 monolayer with a simple atomic structure and that of a PP-VTe2 monolayer with a complex atomic arrangement using first-principles calculations combined with the Boltzmann transport theory under the conditions of with and without the four-phonon scattering process. Our findings reveal that the lattice thermal conductivity of the PP-VTe2 monolayer along the x or y direction is 3-4 times lower than that of the H-VTe2 monolayer when only considering the three-phonon scattering process. After taking into account the four-phonon scattering process, the lattice thermal conductivity of both monolayers decreases. For the H-VTe2 monolayer, the lattice thermal conductivity decreases by 88.7% (from 1.33 to 0.15 W m-1 K-1) compared to only considering the three-phonon scattering process, mainly due to strong four-phonon scattering. In addition, the PP-VTe2 monolayer experiences a lower decrease in lattice thermal conductivity, with reductions of 12.5% (from 0.4 to 0.35 W m-1 K-1) and 11.7% (from 0.34 to 0.3 W m-1 K-1) in the x and y directions, respectively, because of the weak four-phonon scattering. Notably, the lattice thermal conductivity with the four-phonon scattering process of the H-VTe2 monolayer is twice as low as that of the PP-VTe2 monolayer. Hence, our findings suggest that even simple atomic structures can exhibit lower lattice thermal conductivity than complex structures when considering four-phonon interaction.

Association of intraoperative cerebral and somatic tissue oxygen saturation with postoperative acute kidney injury in adult patients undergoing multiple valve surgery.

BACKGROUND: The association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied. METHODS: In this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association. RESULTS: AKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238-17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025-7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively). CONCLUSION: The SrrO2 desaturation, defined as < baseline - 2.5 SD or < baseline - 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.

Low skeletal muscle mass as an early sign in children with fabry disease.

BACKGROUND & AIMS: Fabry disease (FD) is a rare X-linked metabolic storage disorder due to the deficiency of lysosomal α-galactosidase A which causes the accumulation of glycosphingolipids throughout the body. Underweight and low BMI have been occasionally reported in FD patients previously. Whether underweight is common in the early stage of FD and body composition analysis to determine the cause have not been reported. METHODS: Children who were diagnosed with FD in the Children's Hospital of Zhejiang University School of Medicine from July 2014 to December 2022 were enrolled. Clinical data were obtained from medical records. Whole body dual energy X-ray absorptiometry scans (DXA) were used to assess body composition (fat mass, FM; fat free mass, FFM and bone mass) according to the International Society of Clinical Densitometry's standard operating method. Whole body muscle mass was calculated as fat-free mass minus bone mass. Appendicular skeletal muscle mass (ASM) was calculated as the sum of the arm and the leg muscle mass. The FM, FFM, ULSM and LLSM indices were calculated by dividing the total FM, FFM, and upper and lower limb skeletal muscle mass (ULSM and LLSM) by the height squared. RESULTS: A total of eighteen children (14 boys and 4 girls) were enrolled. Thirteen boys had the classical phenotype, and five children (1 boy with the N215S mutation and 4 girls) had the late-onset phenotype. Seven children with the classical phenotype (53.8%) and two of the five children (40%) with the late-onset phenotype had abnormal BMIs. Sixteen of the eighteen children (88.9%) had a height in the normal range, suggesting that low BMI was mainly due to underweight. By DXA body composition analysis, the FMI was abnormal in 3 children (2 boys and 1 girl), and the FFMI was abnormal in 12 children (9 boys and 3 girls). For the classical phenotype, 2 of the 13 children (15.4%) had abnormal FMI values, while 10 (76.9%) had abnormal FFMI values. Eight patients (61.5%) with the classical phenotype had a significant reduction in muscle mass index, ASM index and LLSM index values compared with age- and sex- matched Chinese controls. Late-onset patients also had mild low skeletal muscle mass compared to controls. The results suggested that low skeletal muscle mass is common in early FD. CONCLUSIONS: This is the first study to examine body composition and muscle mass in early Fabry disease patients. Low skeletal muscle mass is a common early symptom in children with Fabry disease, suggesting that skeletal muscle is significantly affected in the early stages of FD.

Acupuncture-related techniques for postoperative cognitive complications: a systemic review and meta-analysis.

BACKGROUND: Postoperative cognitive complications are major challenges for postoperative recovery. Acupuncture-related techniques have been used for treating neurocognitive dysfunctions. However, whether they help to prevent postoperative cognitive complicationss remains unclear. We intend to evaluate the effect of acupuncture-related techniques on the incidence of postoperative cognitive complications (PCC) in patients undergoing surgery under general anesthesia. METHODS: Based on PRISMA guidelines, a search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov was performed to identify eligible trials published from inception to June 6, 2021. The search was performed in June 2021. The inclusion criteria were prospective, randomized, controlled clinical trials that compared acupuncture-related techniques with other techniques or non-acupuncture treatment in patients undergoing surgery under general anesthesia. Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using fixed and random effects statistical models. RESULTS: The analysis included 12 studies with 1058 patients. Compared with patients not receiving acupuncture, patients treated with acupuncture-related techniques had a lower incidence of PCCs (OR, 0.44; 95% CI, 0.33 to 0.59; P < 0.001; n = 968) and lower levels of biomarkers, including IL-6, TNF-α, and S100ß. Acupuncture with needles and without needles showed similar effects on the prevention of PCCs. The effects of acupuncture-related techniques on PCCs were observed in both English and non-English articles. Subgroup analyses showed that both agitation and/or delirium (OR, 0.51; 95% CI, 0.34 to 0.76; P < 0.001; n = 490) and delayed cognitive recovery (OR, 0.33; 95% CI, 0.21 to 0.51; P < 0.001; n = 478) were reduced after treatment with acupuncture-related techniques. In adult studies evaluating MMSE scores, the scores were not different between groups (SMD, - 0.71; 95% CI, - 1.72 to 0.3; P = 0.17; n = 441). CONCLUSIONS: Acupuncture-related techniques, including needle techniques and electrical techniques, are associated with fewer postoperative cognitive complications, suggesting that acupuncture could be considered a potential option in the perioperative setting. Additional research is needed to develop higher-quality evidence and optimal regimens. TRIAL REGISTRATION: PROSPERO (CRD42021258378).

Early onset of nephrogenic diabetes insipidus due to fabry disease in a child with GLA N215S mutation: Case report and literature review.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder. Renal involvement in FD is characterized by proteinuria and progressive renal decline. Reports on FD with nephrogenic diabetes insipidus as the initial manifestation are rare. In this paper, we report a pediatric case with an N215S variant. Results: A boy with an onset of polydipsia and polyuria at approximately 4 years of age was diagnosed with nephrogenic diabetes insipidus. Whole-exome sequencing showed a GLA N215S variation with no secondary cause of diabetes insipidus. No family history of polydipsia or polyuria was reported; however, the patient's maternal grandmother and her two younger brothers had hypertrophic cardiomyopathy. Both brothers required surgery due to severe cardiac involvement, and the youngest brother died of heart disease at the age of 50 years. The patient's polydipsia and polyuria worsened over the next 7 years. Serum sodium was normal, but the patient required high-dose potassium chloride to maintain normal serum potassium levels. His physical and intellectual development was normal, with no common complications of nephrogenic diabetes insipidus, such as anemia, malnutrition, vomiting, high fever, or convulsions. Dried blood spot testing showed α-galactosidase A (α-gal A) activity of 0.6 µmol/L/h and a Lyso-GL-3 level of 7.01 ng/ml. The patient developed mild proteinuria and mild myocardial hypertrophy. Renal biopsy showed myeloid bodies and zebra bodies. After more than 1 year of ERT, his urine specific gravity increased to 1.005-1.008, which was a new sign reflecting the efficacy of ERT, although urine output was maintained at 3-5 ml/kg/hour. We will continue to monitor the patient's renal tubular function and urine output. Conclusions: Nephrogenic diabetes insipidus may be the initial manifestation in children with FD and/or N215S variation. In FD, the same mutation in a family may present a completely different phenotype.

Tuning the lattice thermal conductivity of Sb2Te3 by Cr doping: a deep potential molecular dynamics study.

Element doping is a prominent method for reducing the lattice thermal conductivity and optimizing the thermoelectric performance of materials in the thermoelectric field. However, determination of the thermal conductivity of element-doped systems is a challenging task, especially when the elements are randomly doped. In this work, a first-principles based deep neural network potential (NNP) is developed to investigate the lattice thermal transport properties of Cr-doped Sb2Te3 using molecular dynamics simulations. Compared with pure Sb2Te3, the thermal conductivity of orderly Cr-doped Sb2Te3 with Cr atoms locating at specific atomic layer positions decreases slightly in the in-plane direction, but sharply in the out-of-plane direction. The decrease of the low frequency phonon density of states and the enhancement of phonon scattering near 2.5 THz are the primary reasons for the decrease in the thermal conductivity of Cr-doped Sb2Te3, while the decrease of phonon velocity due to band flattening is the reason for the sharp decrease of thermal conductivity in the out-of-plane direction. Moreover, the thermal conductivities of randomly Cr-doped Sb2Te3 with different Cr concentrations are also investigated using the NNP. It is found that the thermal conductivities in both the in-plane and out-of-plane directions are reduced by 76% and 80%, respectively, for Sb36Cr36Te108. Furthermore, the influence of different Cr dopant arrays on the thermal conductivity of Sb2Te3 is also predicted using the NNP. Our work provides a good example for predicting the thermal conductivity of element-doped systems using the NNP combined with molecular dynamics simulations.

Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Integration of ATAC-Seq and RNA-Seq identifies key genes and pathways involved in the neuroprotection of S-adenosylmethionine against perioperative neurocognitive disorder.

The gene-regulatory landscape is highly dynamic in healthy and diseased brains. DNA methylation is a well-known epigenetic modification that regulates gene expression, and our previous study demonstrated that S-adenosylmethionine (SAM), a methylome modulator, was a neuroprotectant against perioperative neurocognitive disorder (PND). However, the underlying mechanism remains to be elucidated. Here, we integrated an assay for transposase-accessible chromatin by sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to identify the key genes and pathways involved in the neuroprotection of SAM against PND. Our RNA-seq data demonstrated that genes involved in biological processes such as Wnt signaling, inflammatory response, transcription and long-term potentiation likely mediate the neuroprotection of SAM. Our ATAC-seq data provided comprehensive maps of chromatin accessibility changes induced by laparotomy and laparotomy + SAM treatment, and functional annotation of the regions with high variations in chromatin accessibility highlighted the role of the Wnt signaling pathway in PND pathogenesis and SAM treatment. Further motif analysis identified key transcription factors (e.g., CTCF, TFDP1, TCFL5, KLF15, ZBTB14, TFAP2E) that may participate in the neuroprotection of SAM. In conclusion, the current study provides an epigenomic perspective to understand the pathogenesis of PND and its treatment by SAM.

Control and regulation of skyrmionic topological charge in a novel synthetic antiferromagnetic nanostructure.

Skyrmionium is a combination of a skyrmion with a topological charge (Q is +1 or -1), resulting in a magnetic configuration with a total topological charge of Q = 0. Skyrmionium has distinctive characteristics, including a slightly higher velocity, motion restricted to the middle of the track without the skyrmion Hall effect (SkHE), and absence of an acceleration phase. However, there is little stray field due to the zero net magnetization, the topological charge Q is zero due to the magnetic configuration, and detecting skyrmionium is still challenging. In the present work, we propose a novel nanostructure composed of triple nanowires with a narrow channel. It was found that the skyrmionium is converted into a DW pair or skyrmion by the concave channel. It was also found that the topological charge Q can be regulated by Ruderman-Kittel-Kasuya-Yosida (RKKY) antiferromagnetic (AFM) exchange coupling. Moreover, we analyzed the mechanism of the function based on the Landau-Lifshitz-Gilbert (LLG) equation and energy variation and constructed a deep spiking neural network (DSNN) with a recognition accuracy of 98.6% with supervised learning via the spike timing dependent plasticity rule (STDP) by considering the nanostructure as an artificial synapse device corresponding to the electrical properties of the nanostructure. These results provide the means for skyrmion-skyrmionium hybrid application and neuromorphic computing applications.

Pharmacokinetics and Safety of Single and Multiple Daily Dosing of 75-mg Rimegepant Orally Disintegrating Tablets in Healthy Chinese Adults: A Randomized Placebo-Controlled Trial.

Rimegepant is an oral small-molecule calcitonin gene-related peptide antagonist for acute migraine treatment with or without aura and prevention of episodic migraine in adults. This was a rimegepant single- and multiple-dose phase 1, randomized, placebo-controlled, double-blind study to evaluate the pharmacokinetics and confirm safety in healthy Chinese participants. Participants received a 75-mg rimegepant orally disintegrating tablet (ODT) (N = 12) or matching placebo (N = 4) ODT on days 1 and 3-7 after fasting for pharmacokinetic assessments. Safety assessments included 12-lead electrocardiograms, vital signs, clinical laboratory data, and adverse events (AEs). After a single dose (9 females, 7 males) median time to maximum plasma concentration was 1.5 hours; mean values were 937 ng/mL (maximum concentration), 4582 h*ng/mL (area under the concentration-time curve, 0 to infinity), 7.7 hours (terminal elimination half-life), and 19.9 L/h (apparent clearance). Similar results were seen after 5 daily doses, with minimal accumulation. Six (37.5%) participants experienced ≥1 treatment-emergent AE: 4 (33.3%) had received rimegepant and 2 (50.0%) had received placebo. All AEs were grade 1 and resolved by the end of the study with no deaths, serious/significant AEs, or AEs leading to discontinuation. Overall, single- and multiple-dose rimegepant ODT 75 mg was safe and well-tolerated in healthy Chinese adults with similar pharmacokinetics to non-Asian healthy participants. Trial registration: This trial is registered with the China Center for Drug Evaluation (CDE): CTR20210569.

A severe complication of J-tip guide wire during catheterization: A case report and discussion.

J-tip guide wire entrapment within the heart is a serious and dangerous complication that is rarely mentioned. We present a case in which the J-tip guide wire was entrapped in the right atrium during tunneled cuffed venous catheterization. We were unable to remove the guide wire using previously reported methods and concluded with surgery. Owing to the special structure of the guide wire itself, a safe removal process needs to be discussed. Patient consent for publication was obtained prior to the submission of the manuscript.

Accessing the thermal conductivities of Sb2Te3 and Bi2Te3/Sb2Te3 superlattices by molecular dynamics simulations with a deep neural network potential.

Phonon thermal transport is a key feature for the operation of thermoelectric materials, but it is challenging to accurately calculate the thermal conductivity of materials with strong anharmonicity or large cells. In this work, a deep neural network potential (NNP) is developed using a dataset based on density functional theory (DFT) and applied to describe the lattice dynamics of Sb2Te3 and Bi2Te3/Sb2Te3 superlattices. The lattice thermal conductivities of Sb2Te3 are first predicted using equilibrium molecular dynamics (EMD) simulations combined with an NNP and the results match well with experimental values. Then, through further exploration of weighted phase spaces and the Grüneisen parameter, we find that there is a stronger anharmonicity in the out-of-plane direction in Sb2Te3, which is the reason why the thermal conductivities are overestimated more in the out-of-plane direction than in the in-plane direction by solving the phonon Boltzmann transport equation (BTE) with only three-phonon scattering processes being considered. More importantly, the lattice thermal conductivities of Bi2Te3/Sb2Te3 superlattices with different periods are accurately predicted using non-equilibrium molecular dynamics (NEMD) simulations together with an NNP, which serves as a good example to explore the thermal transport physics of superlattices using a deep neural network potential.

The high magnetoresistance performance of epitaxial half-metallic CrO2-based magnetic junctions.

Half-metallic chromium dioxide (CrO2) is an ideal spintronic material due to its near-full spin polarization and ultralow Gilbert damping at room temperature. Based on theoretical calculations, we found that the tunneling magnetoresistance (TMR) ratios of the CrO2/XO2/CrO2 (X= Ti and Sn) magnetic tunnel junctions (MTJs) can reach up to the order of magnitude of 105%, and the magnetoresistance (MR) ratio of CrO2/RuO2/CrO2 magnetic junctions (MJs) can reach the order of magnitude of 104%. In addition, we succeeded in fabricating epitaxial CrO2-based MTJs (CrO2/TiO2/CrO2 and CrO2/TiO2/Co2FeAl) with TiO2 tunnel barriers of varying thickness. Evident TMR effects were observed for all CrO2-based MTJs with the highest MR ratio of 8.55% for the CrO2/TiO2/Co2FeAl MTJ at 10 K. The MR ratios of CrO2-based MTJs in our studies were lower than theoretical expectations, which could be due to the possible mixture of interface atoms and Cr magnetization reversal. Moreover, the existence of oxygen vacancies in the TiO2 tunnel barrier also weakened the TMR effect significantly due to increased spin scattering, and the annealing treatment in an oxygen atmosphere led to an increase in the MR ratio of the CrO2/TiO2/Co2FeAl MTJ by about 33% in comparison with the unannealed MTJ, which is consistent with theoretical calculations.