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Somatic mosaicism is defined as the occurrence and accumulation of somatic mutations in humans, and mosaic chromosomal alterations (mCA) are recognized as one of the aging phenotypes due to their impact on genome integrity. With the coming acceleration of global population aging, understanding the prevalence and influencing factors of mCA will help to explore the "genomic instability" of human aging and its biological mechanisms and provide the scientific basis for the primary prevention of age-related diseases. This review aims to summarize the epidemiological distribution and influencing factors of autosomal mCA in peripheral blood based on previous large-scale population-based studies.人类体细胞突变的发生和积累，又称体细胞嵌合现象。其中，嵌合染色体变异（mCA）对基因组完整性的影响最为显著，被视为人类衰老的表型之一。随着全球人口老龄化进程的加速，了解mCA的人群流行病学分布及其影响因素，有助于探索人体衰老进程中“基因组失稳”及其相关生物学机制，为人类年龄相关疾病的一级预防提供科学依据。本文旨在汇总既往大规模人群研究结果，对外周血常染色体mCA的人群流行病学分布及其影响因素进行综述。.

The intensively intermittent use of antibiotics promotes the rapid evolution of tolerance, which may lead to resistance acquisition in the following evolutionary trajectory. In addition to directly exporting antibiotics as an instant resistance strategy, efflux pumps are overexpressed in tolerant strains.

Curcumin has been testified to repress the development of multiple tumor cells. Nevertheless, the function of curcumin in colorectal cancer (CRC) is not completely clarified. This research was to explore the influence of curcumin on the development of CRC cells and its mechanism. An examination of circular RNA (circ) HN1, microRNA (miR)-302a-3p and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) levels in clinical tissues was performed. Assessments of cell development including proliferation, apoptosis, migration, invasion, as well as epithelial-mesenchymal transition were conducted. The effects of curcumin and circHN1 were verified by in vivo tumor implantation experiments. The interaction of miR-302a-3p with circHN1 or PIK3R3 was analyzed. Curcumin repressed CRC cell development in a concentration-dependent manner. CircHN1 expression was augmented in CRC. Augmentation of circHN1 was able to turn around the repressive effects of curcumin on CRC cells. In vivo experiments indicated that low expression of circHN1 further promoted curcumin-mediated inhibition of CRC tumor growth. MiR-302a-3p was a target of circHN1, and suppression of miR-302a-3p was able to turn around the treatment effect of curcumin on CRC cells. Additionally, PIK3R3 was targeted by miR-302a-3p, and curcumin modulated the malignancy of CRC cells through the circHN1/miR-302a-3p/PIK3R3 pathway.

Background and objectives: Primary percutaneous coronary intervention (PCI)-related outcomes in acute myocardial infarction (AMI) have improved over time, but there are limited data on the length of stay (LOS) in relation to in-hospital mortality. Materials and Methods: A retrospective cohort of adult AMI admissions was identified from the National Inpatient Sample (2000–2017) and stratified into short (≤3 days) and long (>3 days) LOS. Outcomes of interest included temporal trends in LOS and associated in-hospital mortality, further sub-stratified based on demographics and comorbidities. Results: A total 11,622,528 admissions with AMI were identified, with a median LOS of 3 (interquartile range [IQR] 2–6) days with 49.9% short and 47.3% long LOS, respectively. In 2017, compared to 2000, temporal trends in LOS declined in all AMI, with marginal increases in LOS >3 days and decreases for ≤3 days (median 2 [IQR 1–3]) vs. long LOS (median 6 [IQR 5–9]). Patients with long LOS had lower rates of coronary angiography and PCI, but higher rates of non-cardiac organ support (respiratory and renal) and use of coronary artery bypass grafting. Unadjusted in-hospital mortality declined over time. Short LOS had comparable mortality to long LOS (51.3% vs. 48.6%) (p = 0.13); however, adjusted in-hospital mortality was higher in LOS >3 days when compared to LOS ≤ 3 days (adjusted OR 3.00, 95% CI 2.98–3.02, p < 0.001), with higher hospitalization (p < 0.001) when compared to long LOS. Conclusions: Median LOS in AMI, particularly in STEMI, has declined over the last two decades with a consistent trend in subgroup analysis. Longer LOS is associated with higher in-hospital mortality, higher hospitalization costs, and less frequent discharges to home compared to those with shorter LOS.

There has been conflicting reports on the effect of new trainees on clinical outcomes at teaching hospitals in the first training month (July in the United States of America). We sought to assess this "July effect" in a contemporary acute myocardial infarction (AMI) population.Adult (18 years) AMI hospitalizations in May and July in urban teaching and urban nonteaching hospitals in the United States were identified from the HCUP-NIS database (2000-2017). In-hospital mortality was compared between May and July admissions. A difference-in-difference analysis comparing a change in outcome from May to July in teaching hospitals to a change in outcome from May to July in nonteaching hospitals was also performed.A total of 1,312,006 AMI hospitalizations from urban teaching (n = 710,593; 54.2%) or nonteaching (n = 601,413; 45.8%) hospitals in the months of May and July were evaluated. May admissions in teaching hospitals, had greater comorbidity, higher rates of acute multiorgan failure (10.6% vs. 10.2%, p 0.001) and lower rates of cardiac arrest when compared to July admissions. July AMI admissions had lower in-hospital mortality compared to May (5.6% vs. 5.8%; adjusted odds ratio 0.94 [95% confidence interval 0.92-0.97]; p 0.001) in teaching hospitals. Using the difference-in-difference model, there was no evidence of a July effect for in-hospital mortality (p = 0.19).There was no July effect for in-hospital mortality in this contemporary AMI population.

Whether extensive intraoperative peritoneal lavage (EIPL) after gastrectomy is beneficial to patients with locally advanced gastric cancer (AGC) is not clear. This phase 3, multicenter, parallel-group, prospective randomized study (NCT02745509) recruits patients between April 2016 and November 2017. Eligible patients who had been histologically proven AGC with T3/4NxM0 stage are randomly assigned (1:1) to either surgery alone or surgery plus EIPL. The results of the two groups are analyzed in the intent-to-treat population. A total of 662 patients with AGC (329 patients in the surgery alone group, and 333 in the surgery plus EIPL group) are included in the study. The primary endpoint is 3-year overall survival (OS). The secondary endpoints include 3-year disease free survival (DFS), 3-year peritoneal recurrence-free survival (reported in this manuscript) and 30-day postoperative complication and mortality (previously reported). The trial meets pre-specified endpoints. Estimated 3-year OS rates are 68.5% in the surgery alone group and 70.6% in the surgery plus EIPL group (log-rank p = 0.77). 3-year DFS rates are 61.2% in the surgery alone group and 66.0% in the surgery plus EIPL group (log-rank p = 0.24). The pattern of disease recurrence is similar in the two groups. In conclusion, EIPL does not improve the 3-year survival rate in AGC patients., Extensive intraoperative peritoneal lavage (EIPL) has been proposed as an approach to reduce peritoneal metastasis in patients with locally advanced gastric cancer undergoing gastrectomy. Here the authors report the results of the multicentric phase III SEIPLUS trial, showing that EIPL does not improve 3-year survival rate in patients with advanced gastric cancer.

Aromatic amines in nature are typically installed with Glu or Gln as the nitrogen donor. Here we report a pathway that features glycyl-tRNA instead. During the biosynthesis of pyrroloiminoquinone-type natural products such as ammosamides, peptide-aminoacyl tRNA ligases append amino acids to the C-terminus of a ribosomally synthesized peptide. First, $${\mathrm{Amm}}{{{\mathrm{B}}}}_{{{\mathrm{C}}}}^{{{{\mathrm{Trp}}}}}$$ adds Trp in a Trp-tRNA-dependent reaction and the flavoprotein AmmC1 then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, $${\mathrm{Amm}}{{{\mathrm{B}}}}_{{{\mathrm{D}}}}^{{{{\mathrm{Gly}}}}}$$ attaches Gly to the indole ring in a Gly-tRNA dependent fashion. Subsequent decarboxylation and hydrolysis results in an amino-substituted indole. Similar transformations are catalysed by orthologous enzymes from Bacillus halodurans. This pathway features three previously unknown biochemical processes using a ribosomally synthesized peptide as scaffold for non-ribosomal peptide extension and chemical modification to generate an amino acid-derived natural product. Biosynthesis of aromatic amines typically uses glutamic acid or glutamine as the nitrogen donor. Now, a biosynthetic pathway to aromatic amines has been reported that uses glycyl-tRNA as the nitrogen donor. The myosin-targeting ammosamide is made via a pathway that involves the post-translational modification of a tryptophan, which is added to the end of a peptide in a tryptophanyl-tRNA-dependent step.

By analyzing 4.48 × 108 ψ(3686) events collected with the BESIII detector, we observe the decays χ cJ → nK S 0 Λ ¯ $$ {nK}_S^0\overline{\Lambda} $$ + c.c. (J = 0, 1, 2) for the first time, via the radiative transition ψ(3686) → γχ cJ . The branching fractions are determined to be (6.65 ± 0.26stat ± 0.41syst) × 10 −4, (1.66 ± 0.12stat ± 0.12syst) × 10 −4, and (3.58 ± 0.16stat ± 0.23syst) × 10 −4 for J = 0, 1, and 2, respectively.

For structural bending crashworthiness, previous studies mostly focused on thin-walled tubes with multi-cell cross-sections, while the double-tube configuration was seldom studied. In this paper, the bending crashworthiness of thin-walled tubes with multi-cell and double-tube configurations was compared based on three-point bending tests conducted using the ABAQUS/Explicit code. The numerical results reveal that the reinforcements significantly improve the bending crashworthiness beyond the conventional empty tube according to the two indicators: specific energy absorption (SEA) and crash load efficiency (CLE). For the ratio of cross-sectional width to wall thickness b/t = 100, the double-tube configuration has a similar bending crashworthiness performance to the multi-cell configuration. The asymmetric multi-cell configurations are found to demonstrate more excellent SEA performance than their symmetric counterparts in most cases. For the case b/t = 50, the double-tube configuration significantly prevails over the multi-cell configuration.

A general sliding block model for calculating permanent displacement of slope is presented. Ground shaking can be applied to base or block in a direction horizontal or parallel to the inclined plane, with or without a simultaneous vertical component of ground motion, and the azimuth of the examined slope can be considered in the model. The effects of the application of excitation, the vertical component of ground motions, and the slope azimuth on earthquake-induced permanent displacements of near-fault seismic slopes are investigated using the model. The results indicate that: (1) The application of excitation has significant influence on the permanent displacements. (2) The influence of the vertical component of ground motion on the permanent displacement depends more on the phase synchronization of the horizontal and vertical components than on the amplitude. (3) The computed displacements are found to be very sensitive to the azimuth of the slope.

We present the $NuSTAR$ extragalactic survey of the $James$ $Webb$ $Space$ $Telescope$ ($JWST$) North Ecliptic Pole (NEP) Time-Domain Field. The survey covers a $\sim$0.16 deg$^2$ area with a total exposure of 681 ks acquired in a total of nine observations from three epochs. The survey sensitivities at 20% of the area are 2.39, 1.14, 2.76, 1.52, and 5.20 $\times$ 10$^{-14}$ erg cm$^{-2}$ s$^{-1}$ in the 3-24, 3-8, 8-24, 8-16, and 16-24 keV bands, respectively. The NEP survey is one of the most sensitive extragalactic surveys with $NuSTAR$ so far. A total of 33 sources were detected above 95% reliability in at least one of the five bands. We present the number counts, log$N$-log$S$, measured in the hard X-ray 8-24 and 8-16 keV bands, uniquely accessible by $NuSTAR$ down to such faint fluxes. We performed source detection on the XMM-$Newton$ and $Chandra$ observations of the same field to search for soft X-ray counterparts of each $NuSTAR$ detection. The soft band positions were used to identify optical and infrared associations. We present the X-ray properties (hardness ratio and luminosity) and optical-to-X-ray properties of the detected sources. The measured fraction of candidate Compton-thick (N$\rm _H\ge10^{24} cm^{-2}$) active galactic nuclei, derived from the hardness ratio, is between 3% to 27%. As this survey was designed to have variability as its primary focus, we present preliminary results on multi-epoch flux variability in the 3-24 keV band., Comment: 22 pages, 17 figures

The fungal family Serendipitaceae encompasses root-associated lineages with endophytic, ericoid, orchid, and ectomycorrhizal lifestyles. Switchgrass is an important bioenergy crop for cellulosic ethanol production owing to high biomass production on marginal soils otherwise unfit for food crop cultivation. The aim of this study was to investigate the host plant responses to Serendipita spp. colonization by characterizing the switchgrass root transcriptome during different stages of symbiosis in vitro. For this, we included a native switchgrass strain, Serendipita bescii, and a related strain, S. vermifera, isolated from Australian orchids. Serendipita colonization progresses from thin hyphae that grow between root cells to, finally, the production of large, bulbous hyphae that fill root cells during the later stages of colonization. We report that switchgrass seems to perceive both fungi prior to physical contact, leading to the activation of chemical and structural defense responses and putative host disease resistance genes. Subsequently, the host defense system appears to be quenched and carbohydrate metabolism adjusted, potentially to accommodate the fungal symbiont. In addition, prior to contact, switchgrass exhibited significant increases in root hair density and root surface area. Furthermore, genes involved in phytohormone metabolism such as gibberellin, jasmonic acid, and salicylic acid were activated during different stages of colonization. Both fungal strains induced plant gene expression in a similar manner, indicating a conserved plant response to members of this fungal order. Understanding plant responsiveness to Serendipita spp. will inform our efforts to integrate them into forages and row crops for optimal plant–microbe functioning, thus facilitating low-input, sustainable agricultural practices. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

This article presents a nonlinear site amplification model for ground-motion prediction equations (GMPEs), using site period as site-effect proxy based on the measured shear-wave velocity profiles of selected KiK-net and K-NET sites in Japan. This model was derived using 1D equivalent-linear site-response analysis for a total of 516 measured soil-site shear-wave velocity profiles subjected to a total of 912 components of rock-site records. The modulus reduction and damping curves for each soil layer were assigned based on the soil-type description for a particular layer. The site period and site impedance ratio affect both the linear and nonlinear parts of this study, and were used as the site parameters in the 1D amplification model. A large impedance ratio enhances the amplification ratios when the site responds elastically and enhances the nonlinear response when the site develops a significant nonlinear response. The effects of moment magnitude and source distance on the linear part of the 1D amplification model were also incorporated in the model. To implement the 1D amplification model into GMPEs, a model adjustment is required to match the GMPE amplification ratio at weak motion and to retain the nonlinear amplification ratio at the strong motion of the 1D model. The two-step adjustment method by Zhao, Hu, et al. (2015) was adopted in this study with significant modifications. It is not possible to obtain a credible second-step adjustment parameter using the GMPEs dataset only. We proposed three methods for calculating the scale factors. Method 1 is a constant angle in a 30°–60° range for all spectral periods; method 2 was based on the GMPE dataset and 1-D model parameters; and method 3 was based on the strong-motion records used for the 1D site modeling. A simple second-step adjustment factor leads to smoothing amplification ratios and soil-site spectrum.

Huntington disease (HD) is a single-gene autosomal dominant inherited neurodegenerative disease caused by a polyglutamine expansion of the protein huntingtin (HTT). Huntingtin-associated protein 1 (HAP1) is the first protein identified as an interacting partner of huntingtin, which is directly associated with HD. HAP1 is mainly expressed in the nervous system and is also found in the endocrine system and digestive system, and then involves in the occurrence of the related endocrine diseases, digestive system diseases, and cancer. Understanding the function of HAP1 could help elucidate the pathogenesis that HTT plays in the disease process. Therefore, this article attempts to summarize the latest research progress of the role of HAP1 and its application for diseases in recent years, aiming to clarify the functions of HAP1 and its interacting proteins, and provide new research ideas and new therapeutic targets for the treatment of cancer and related diseases.

In this manuscript we present a nonlinear site amplification model for ground-motion prediction equations (GMPEs) in Japan, using a site period-based site class and a site impedance ratio as site parameters. We used a large number of shear-wave velocity profiles from the Kiban-Kyoshin network (KiK-net) and the Kyoshin network (K-NET) to construct the one-dimensional (1D) numerical models. The strong-motion records from rock-sites in Japan with different earthquake categories and taken from the Pacific Earthquake Engineering Research Center dataset were used in this study. We fit a set of 1D site amplification models using the spectral amplification ratios derived from 1D equivalent linear analyses. Parameters of site impedance ratios for both linear and nonlinear site response were included in the 1D model. The 1D model could be implemented into GMPEs using a new proposed adjustment method. The adjusted site amplification ratios retain the nonlinear characteristics of the 1D model for strong motions and match the linear amplification ratio in GMPE for weak motions. The nonlinearity of the present site model is reasonably similar to that of the historical models, and the present site model could satisfactorily capture the nonlinear site response in empirical data.

This study presents a fully explicit closed-form solution for axisymmetric electro-osmotic consolidation considering smear effects. Different soil properties within and outside the smear zone are fully considered. The analytical solution is obtained through the method of separation of variables based on the orthogonal relationship of the eigenfunction. Subsequently, the solution is verified by comparing the proposed degraded solution with the existing analytical solution and finite element simulation. Both sets of verifications demonstrate the great agreement of the proposed analytical solution with the established solution. Moreover, a parametric study is performed to illustrate the smear effects on electro-osmotic consolidation. The radial distribution of excess pore water pressure shows a bilinear pattern due to the smear effects. The smaller the electro-osmosis conductivity in the smear zone, the larger the excess pore pressure. Meanwhile, the larger the water permeability coefficient in the smear zone, the larger the excess pore pressure. If the smear effects of the water permeability coefficient within the smear zone are ignored, the calculated pore water pressure is overestimated. Besides, the coefficient of volume compressibility within the smear zone has fewer influences on the excess pore pressure. It is acceptable to ignore the smear effects of compressibility in the analytical model for axisymmetric electro-osmotic consolidation.

We examine whether managers provide more voluntary disclosure when GAAP limits their reporting discretion in financial statements. We find managers are more likely to disclose non-GAAP earnings, issue more management forecasts, and provide longer yet more readable MD&A disclosures when GAAP limits their discretion. These effects are stronger when there is greater demand for information and better monitoring. In contrast, these effects are weaker when managers have incentives to manage earnings. Difference-in-differences analyses around standard changes provide further evidence that managers make more non-GAAP adjustments and are more likely to discuss the standard and its underlying transaction in the MD&A when a new standard limits their discretion more than its predecessor. Collectively, our results suggest managers use voluntary disclosure channels to convey information when GAAP limits their ability to recognize such information in financial statements.

BACKGROUND: Innate lymphoid cells type 2 (ILC2s) play critical homeostatic functions in peripheral tissues. ILC2s reside in perivascular niches and limit atherosclerosis development. OBJECTIVES: ILC2s also reside in the pericardium but their role in postischemic injury is unknown. METHODS: We examined the role of ILC2 in a mouse model of myocardial infarction (MI), and compared mice with or without genetic deletion of ILC2. We determined infarct size using histology and heart function using echocardiography. We assessed cardiac ILC2 using flow cytometry and RNA sequencing. Based on these data, we devised a therapeutic strategy to activate ILC2 in mice with acute MI, using exogenous interleukin (IL)-2. We also assessed the ability of low-dose IL-2 to activate ILC2 in a double-blind randomized clinical trial of patients with acute coronary syndromes (ACS). RESULTS: We found that ILC2 levels were increased in pericardial adipose tissue after experimental MI, and genetic ablation of ILC2 impeded the recovery of heart function. RNA sequencing revealed distinct transcript signatures in ILC2, and pointed to IL-2 axis as a major upstream regulator. Treatment of T-cell-deficient mice with IL-2 (to activate ILC2) significantly improved the recovery of heart function post-MI. Administration of low-dose IL-2 to patients with ACS led to activation of circulating ILC2, with significant increase in circulating IL-5, a prototypic ILC2-derived cytokine. CONCLUSIONS: ILC2s promote cardiac healing and improve the recovery of heart function after MI in mice. Activation of ILC2 using low-dose IL-2 could be a novel therapeutic strategy to promote a reparative response after MI.

It is of great significance to study the influence of evaporation on the protection and management of regional water resources. In this study, water samples have been collected from a typical enclosed water body, Liuxi, a small brook in the campus of Suzhou University in May and June, and then analyzed for their hydrogen and oxygen stable isotopes. The results indicate that the samples collected in June have higher d18O and dD values relative to the samples collected in May, and both of them have d18O and dD values plotted at the right of the meteoric line, in combination with their lower deuterium excess (d-excess) values relative to the meteoric line, implying that the water has been influenced by evaporation. Moreover, the d-excess values showed decreasing and increasing in different sampling sites, which was demonstrated to be influenced by different extents of evaporation. Based on the calculation, the residual water quantities were 70–75% and 51–70% for May and June relative to the initial water, which indicates that about 10% of the water had evaporated during May and June.

The effect of prior coronary artery bypass graft (CABG) on the outcomes of transcatheter aortic valve replacement (TAVR) remains incompletely characterized. In this meta-analysis, we investigated the impact of prior CABG on TAVR outcomes.A systematic search was conducted in PubMed, Google Scholar, and Cochrane databases from inception to 24 July 2022, using the search terms 'TAVR', 'CABG', 'peri-procedural complications', and 'mortality'. The major outcomes were peri-procedural complications, intraprocedural mortality, 30-day mortality, and 30-day cardiac mortality. We used random-effects models to aggregate data and to calculate pooled incidence and risk ratios with 95% confidence intervals (CIs).Among 116 results from the systematic search, a total of 8 studies (5952 patients) were included. Compared to patients without previous CABG, patients with prior CABG undergoing TAVR were younger, predominantly male sex, had more comorbidities, higher rates of peri-procedural myocardial infarction (MI) [relative risk (RR) 1.93; 95% CI, 1.09-3.43; P = 0.03], but lower rates of stroke (RR 0.71; 95% CI, 0.51-0.99; P = 0.04), major vascular complications (RR 0.70; 95% CI, 0.51-0.95; P = 0.02), and major bleeding (RR 0.70; 95% CI, 0.56-0.88; P = 0.002). There were no significant differences between the two cohorts in rates of pacemaker implantation, cardiac tamponade, acute kidney injury, intra-procedural mortality, 30-day mortality, and 30-day cardiac mortality.Among patients undergoing TAVR, a history of prior CABG was not associated with an increased risk of periprocedural complications (except for acute MI) or short-term mortality compared to those without CABG.

With the in-depth research on treatment drugs of rheumatoid arthritis (RA), a variety of disease modifying anti-rheumatic drugs (DMARDs) have been approved for the treatment of RA. By now methotrexate (MTX) is still the anchor drug for RA treatment. The 2019 European League Against Rheumatism (EULAR) and 2021 American College of Rheumatology (ACR) recommendations for RA management both point out that for newly diagnosed RA patients, MTX monotherapy should be used as the first choice, which shows the importance of MTX monotherapy in DMARDs naïve RA. This paper mainly reviews the relevant researches on MTX in the treatment of RA in recent years, especially the relevant literature on the use of MTX monotherapy in initial treatment of RA. We summarize the development history, efficacy, treatment and adverse reactions of MTX to recognize the importance of MTX in the treatment of RA and the feasibility of MTX monotherapy.随着对类风湿关节炎（RA）治疗药物研究的深入，多种改善病情抗风湿药（DMARDs）被批准用于治疗RA，但甲氨蝶呤（MTX）仍是RA治疗的基础药物。2019年欧洲抗风湿病联盟（EULAR）及2021年美国风湿病学会（ACR）关于RA的治疗推荐意见均指出对于初治RA患者，MTX单药治疗仍应作为首选方案，由此可见MTX单药治疗的重要性。本文主要回顾了近年来关于MTX治疗RA的相关研究，尤其是单药方案用于RA初始治疗的相关文献，对MTX治疗RA的发展历程、疗效、治疗方式、不良反应等进行总结，更全面地认识MTX在RA治疗中的重要性及MTX单药治疗的可行性。.

Background Conducting an apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variable approaches for determining brain death (BD), also known as death by neurologic criteria (DNC). This study aims to describe the diagnostic criteria and barriers for DNC in a high-volume ECMO center with an emphasis on the role of AT. Methods A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016-March 2022. Brain death was defined according to the 2010American Academy of Neurologyguidelines. AT for DNC in this study was performed in accordance with the 2020 Journal of the American Medical Association BD/DNC criteria recommendations for ECMO patients, including a period of pre-oxygenation, setting ECMO sweep to 0.5-1 L/min, and measuring serial blood gases. Results During the study period, 15 of 300 (5%) patients underwent testing for DNC. Eight (2.7%) ECMO patients (median age = 44 years, 75% male, and 50% VA-ECMO) were diagnosed with BD, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (TCD and EEG) were consistent with BD and the patients were declared BD on the basis of those findings. An additional seven (2.3%) patients (median age = 55 years, 71% male, and 86% VA ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment due to family wishes before a full evaluation was completed. Six (86%) of these patients with unconfirmed BD had at least one ancillary test performed that were not consistent with BD despite either neurological exam findings and/or AT results supporting a BD diagnosis. In the seventh patient, although absent brainstem reflexes were noted on the neurological exam with explanatory findings on imaging, there was no AT or ancillary testing done. Conclusion AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with BD, though providers were more confident using AT with ancillary tests. AT was always consistent with the neurological exam and imaging findings suggesting BD. However, there are limitations to ancillary tests for BD assessments when used without AT and we recommend performing at least two ancillary tests to confirm brain death if AT cannot be performed or is inconclusive in ECMO patients.

This study sought to compare the impact of additional anticoagulation or thrombolytic therapy in patients with cardiac arrest without ST-segment-elevation on electrocardiography and not receiving percutaneous coronary intervention. Three studies (two randomized controlled studies and one observational study) were included, which demonstrated that use of anticoagulation or thrombolytic therapy was associated with higher risk of bleeding, without improvements in time to return of spontaneous circulation or in-hospital mortality.

Aims Recent research reported that lower low-density lipoprotein cholesterol (LDL-C) is associated with more in-hospital bleeding in acute coronary syndrome (ACS) patients. However, the association between lower LDL-C levels and long-term bleeding in percutaneous coronary intervention (PCI) patients remains unclear. Methods A total of 10724 patients treated with PCI enrolled in ourhospital from January 2013 to December 2013. The primary endpoint was the Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding at 5 years. The secondary endpoint was intracranial hemorrhage. Taking the LDL-C value of 1.8 mmol/L (70 mg/dL) or 1.4 mmol/L (55 mg/dL) as cut-off points, patients were grouped to analyse, respectively. Results Among 9697 PCI patients treated with dual antiplatelet therapy finally enrolled, a total of 411 BARC type 2, 3 or 5 bleedings and 42 intracranial hemorrhage were recorded during a follow-up of 5 years. With LDL-C value of 1.8 mmol/L as cut-off point, multivariate Cox regression showed that lower LDL-C level was not associated with the risk for bleeding [hazard ratio (HR): 1.166, 95% confidence interval (CI): 0.879–1.549]. The result was consistent (HR: 1.185; 95% CI: 0.713–1.968) in a 1:4 propensity-score matching cohort (n=1285). For further study, we performed subgroup analysis which showed that lower LDL-C was not associated with the risk for bleeding in ACS (HR: 1.140; 95% CI: 0.846–1.535) or non-ACS patients (HR: 1.284; 95% CI: 0.909–1.813). With LDL-C value of 1.4 mmol/L as cut-off point, Cox regression showed that lower LDL-C level was not associated with the risk for bleeding in total population, ACS or non-ACS patients (P>0.05). The result was consistent in a 1:4 propensity-score matching cohort (n=760) (P>0.05). As for secondary endpoint, lower LDL-C level was not associated with the risk for intracranial hemorrhage whether the LDL-C value is 1.8 or 1.4 mmol/L as the cut-off point (P>0.05). Conclusions To the best of our knowledge, we firstly report lower LDL-C level (whether the LDL-C value is 1.8 or 1.4 mmol/L as the cut-off point) was not the independent risk factor of long-term bleeding in PCI population and ACS or non-ACS subgroup populations. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CAMS Innovation Fund for Medical Sciences (CIFMS); Young and middle-aged talents in the XPCC Science and Technology Project

Real Clifford algebras play a fundamental role in the eight real Altland-Zirnbauer symmetry classes and the classification tables of topological phases. Here, we present another elegant realization of real Clifford algebras in the $d$-dimensional spinless rectangular lattices with $\pi$ flux per plaquette. Due to the $T$-invariant flux configuration, real Clifford algebras are realized as projective symmetry algebras of lattice symmetries. Remarkably, $d$ mod $8$ exactly corresponds to the eight Morita equivalence classes of real Clifford algebras with eightfold Bott periodicity, resembling the eight real Altland-Zirnbauer classes. The representation theory of Clifford algebras determines the degree of degeneracy of band structures, both at generic $k$ points and at high-symmetry points of the Brillouin zone. Particularly, we demonstrate that the large degeneracy at high-symmetry points offers a rich resource for forming novel topological states by various dimerization patterns, including a $3$D higher-order semimetal state with double-charged bulk nodal loops and hinge modes, a $4$D nodal surface semimetal with $3$D surface solid-ball zero modes, and $4$D M\"{o}bius topological insulators with a eightfold surface nodal point or a fourfold surface nodal ring. Our theory can be experimentally realized in artificial crystals by their engineerable $\mathbb{Z}_2$ gauge fields and capability to simulate higher dimensional systems., Comment: 8 pages, 6 figures

ObjectiveCerebral microbleeds (CMB) are small accumulations of hemosiderin associated with cerebrovascular risk factors, but whether they are associated with atrial cardiopathy is not known. The goal of this study is to determine, among ischemic stroke patients, the association between study-defined atrial cardiopathy and CMB presence, location, and number.MethodsIschemic stroke patients admitted to Johns Hopkins (2015–2019) with transthoracic echocardiography and electrocardiography were included. Cerebral microbleeds were defined as small, round hypo-intensities on T2* susceptibility weighted imaging or gradient recalled echo magnetic resonance imaging sequences. Atrial cardiopathy was defined as the presence of ≥1: left atrium diameter >4.0 cm (males) or >3.8 cm (females), PR interval >200 ms, or N-terminal pro-B-type natriuretic peptide >250 pg/ml. Binary/Ordinal logistic regression models were used to determine the association between atrial cardiopathy, and cerebral microbleed presence, location (lobar/deep), or number, each, adjusted for potential confounders.ResultsPatients (N = 120) were mean age 60 years (range 22–98), 46% female, 62% black, and 39% were on anti-thrombotic medication at time of admission. 39 (32%) participants had ≥1 cerebral microbleeds. Forty-six (38%) patients had atrial cardiopathy. Atrial cardiopathy was associated with higher odds of having cerebral microbleeds (OR 2.50, 95% CI 1.02–6.15). Atrial cardiopathy was associated with lobar cerebral microbleeds (OR 2.33, 95% CI 1.01–5.37) in univariate analysis but not with deep cerebral microbleeds (OR 0.45, 95% CI 0.13–1.54), with neither association significant after adjustment. There was no difference in risk of having 1 vs. no cerebral microbleeds (RRR 2.51, 95% CI 0.75–8.37) and >1 cerebral microbleed vs none (RRR 2.57, 95% CI 0.87–7.60) among those with atrial cardiopathy.ConclusionsAtrial cardiopathy is associated with the presence, but not burden, of cerebral microbleeds in ischemic stroke patients. We cautiously suggest that atrial cardiopathy, either directly or through shared vascular risk, may contribute to the presence of CMB.