Microfluidic Shape Analysis of Non-spherical Graphite for Li-Ion Batteries via Viscoelastic Particle Focusing.

The size and shape of graphite, which is a popular active anode material for lithium-ion batteries (LIBs), significantly affect the electrochemical performance of LIBs and the rheological properties of the electrode slurries used in battery manufacturing. However, the accurate characterization of its size and shape remains challenging. In this study, the edge plane of graphite in a cross-slot microchannel via viscoelastic particle focusing is characterized. It is reported that the graphite particles are aligned in a direction that shows the edge plane by a planar extensional flow field at the stagnation point of the cross-slot region. Accurate quantification of the edge size and shape for both spheroidized natural and ball-milled graphite is achieved when aligned in this manner. Ball-milled graphite has a smaller circularity and higher aspect ratio than natural graphite, indicating a more plate-like shape. The effects of these differences in graphite shape and size on the rheological properties of the electrode slurry, the structure of the coated electrodes, and electrochemical performance are investigated. This method can contribute to the quality control of graphite for the mass production of LIBs and enhance the electrochemical performance of LIBs.

Encoded-Fusion-Based Quantum Computation for High Thresholds with Linear Optics.

We propose a fault-tolerant quantum computation scheme in a measurement-based manner with finite-sized entangled resource states and encoded-fusion scheme with linear optics. The encoded fusion is an entangled measurement devised to enhance the fusion success probability in the presence of losses and errors based on a quantum error-correcting code. We apply an encoded-fusion scheme, which can be performed with linear optics and active feedforwards to implement the generalized Shor code, to construct a fault-tolerant network configuration in a three-dimensional Raussendorf-Harrington-Goyal lattice based on the surface code. Numerical simulations show that our scheme allows us to achieve up to 10 times higher loss thresholds than nonencoded fusion approaches with limited numbers of photons used in fusion. Our scheme paves an efficient route toward fault-tolerant quantum computing with finite-sized entangled resource states and linear optics.

Interference-resistant gold nanoparticle assay for detecting Enterococcus in fresh and marine waters.

Enterococci are common indicators of fecal contamination and are used to assess the quality of fresh and marine water, sand, soil, and sediment. However, samples collected from these environments contain various cells and other factors that can interfere with the assays used to detect enterococci. We developed a novel assay for the sensitive and specific detection of enterococci that is resistant to interference from other cells and environmental factors. Our interference-resistant assay used 30-nm gold nanoparticles (AuNPs), streptavidin, and a biotinylated Enterococcus antibody. Enterococci inhibited the interaction between streptavidin and biotin and led to the disaggregation of AuNPs. The absence of enterococci led to the aggregation of AuNPs, and this difference was easily detected by spectrophotometry. This interference-resistant AuNP assay was able to detect whole cells of Enterococcus in the range of 10 to 107 CFU/mL within 3 h, had high specificity for enterococci, and was unaffected by the presence of other intestinal bacteria, such as Escherichia coli. Our examination of fresh and marine water samples demonstrated no interference from other cells or environmental factors. The interference-resistant AuNP assay described here has the potential to be used as a rapid, simple, and effective method for monitoring enterococci in diverse environmental samples.

Risk Factors for the Recurrence of Chronic Subdural Hematoma.

Objective: Chronic subdural hematoma (CSDH) is commonly encountered in neurosurgery, and often occurs in elderly patients following a head injury. Despite favorable postoperative prognosis, recurrence remains common. Herein, we retrospectively analyzed the clinical and radiological data of patients at our institute to identify the risk factors for CSDH recurrence. Methods: We investigated 370 patients who underwent surgery for CSDH at our institute. The following data were analyzed: sex, age, antiplatelet/anticoagulant use, preexisting diseases, radiological parameters, and surgical techniques. A univariate analysis was subsequently performed to examine the association between these variables and CSDH recurrence. Variables with a p-value of <0.05 in univariate analysis were further subjected to a multivariate logistic regression model to identify independent risk factors of CSDH. Results: Of the 370 patients, 345 (93.2%) had no recurrence and 25 (6.8%) had recurrence. Univariate and multivariate analyses revealed that male sex, advanced age, bilateral hematoma, moderate or severe brain atrophy, separation type, gradation type, and burr hole trephination were independent risk factors for CSDH recurrence. Conclusion: Sex, age, bilateral hematoma, brain atrophy, hematoma density and architecture, and surgical techniques are all associated with CSDH recurrence.

Efficacy of robot arm-assisted endoscopic submucosal dissection in live porcine stomach (with video).

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm2/s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety.

Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus.

Diabetes mellitus (DM) is a progressive, chronic metabolic disorder characterized by high oxidative stress, which can lead to cardiac damage. Methionine sulfoxylation (MetO) of proteins by excessive reactive oxygen species (ROS) can impair the basic functionality of essential cellular proteins, contributing to heart failure. Methionine sulfoxide reductase B2 (MsrB2) can reverse oxidation induced MetO in mitochondrial proteins, so we investigated its role in diabetic cardiomyopathy. We observed that DM-induced heart damage in diabetic mice model is characterized by increased ROS, increased protein MetO with mitochondria structural pathology, and cardiac fibrosis. In addition, MsrB2 was significantly increased in mouse DM cardiomyocytes, supporting the induction of a protective process. Further, MsrB2 directly induces Parkin and LC3 activation (mitophagy markers) in cardiomyocytes. In MsrB2, knockout mice displayed abnormal electrophysiological function, as determined by ECG analysis. Histological analysis confirmed increased cardiac fibrosis and disrupted cardiac tissue in MsrB2 knockout DM mice. We then corroborated our findings in human DM heart samples. Our study demonstrates that increased MsrB2 expression in the heart protects against diabetic cardiomyopathy.

Increasing the stability of electrolyte-gated organic synaptic transistors for neuromorphic implants.

Electrolyte-gated organic synaptic transistors (EGOSTs) can have versatile synaptic plasticity in a single device, so they are promising as components of neuromorphic implants that are intended for use in neuroprosthetic electronic nerves that are energy-efficient and have simple system structure. With the advancement in transistor properties of EGOSTs, the commercialization of neuromorphic implants for practical long-term use requires consistent operation, so they must be stable in vivo. This requirement demands strategies that maintain electronic and ionic transport in the devices while implanted in the human body, and that are mechanically, environmentally, and operationally stable. Here, we cover the structure, working mechanisms, and electrical responses of EGOSTs. We then focus on strategies to ensure their stability to maintain these characteristics and prevent adverse effects on biological tissues. We also highlight state-of-the-art neuromorphic implants that incorporate these strategies. We conclude by presenting a perspective on improvements that are needed in EGOSTs to develop practical, neuromorphic implants that are long-term useable.

IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.

Early Rhythm Control and Incident Dementia in Patients With Atrial Fibrillation and Prior Stroke.

BACKGROUND: Although early rhythm control (ERC) in patients with atrial fibrillation (AF) reduces the risk of stroke, there is no evidence thus far on whether ERC reduces the risk of developing dementia in patients with AF and prior stroke. OBJECTIVES: This study sought to evaluate whether ERC reduces the risk of developing dementia in patients with new-onset AF and prior stroke. METHODS: Using the Korean nationwide claims database, we identified patients with new-onset AF and prior stroke between 2010 and 2016. Patients who received rhythm control therapy within 1 year after AF onset were defined as the ERC group, otherwise patients were categorized as the usual care group. A propensity score weighting method was used to balance the 2 groups. Incident dementia defined by relevant diagnostic codes was evaluated. RESULTS: A total of 41,370 patients were included (mean age 70 ± 11 years; mean CHA2DS2-VASc score 5.3 ± 1.6): 10,213 in the ERC group and 31,157 in the usual care group. Compared with usual care, ERC was associated with lower risks of all dementia, Alzheimer's dementia, and vascular dementia (weighted HR: 0.825 [95% CI: 0.776-0.876], 0.831 [95% CI: 0.774-0.893], and 0.800 [95% CI: 0.702-0.913], respectively, all P < 0.001). The benefit of ERC was slightly accentuated in the younger age group (<65 years). The beneficial effect of ERC in reducing the risk of dementia was consistent regardless of the characteristics of prior stroke. CONCLUSIONS: ERC might be beneficial in the prevention of dementia in patients with AF and prior stroke. To prevent the progression of cognitive dysfunction, ERC should be considered in this population.

Empowering powdered activated carbon (PAC) with 3D printing: Achieving highly efficient and reusable cationic dye removal.

Powdered activated carbon (PAC) has been extensively used as an effective adsorbent. Despite its excellent adsorption ability, PAC has drawbacks, including difficulty in filtration and reactivation after use, limitations of mass transfer in deeper areas because of its aggregated powder form, and limited applicability in high-flow systems. To overcome these limitations, we used a three-dimensional (3D) printing system to fabricate PAC into a 3D structure. Spectral and microscopic analyses indicated that PAC was embedded into 3D monolith and exhibited high porosity suitable for facile mass transfer. The designed 3D PAC filter effectively removed 200 ppm-methylene blue (MB) within 8 h and showed an adsorption efficiency of 93.4 ± 0.9%. The adsorption of MB onto the 3D PAC filter was described by the pseudo-first-order kinetic and Freundlich isotherm models. The negatively charged 3D PAC filter might attract the positively charged MB, thus favoring the physical adsorption of MB onto the 3D PAC filter. The adsorption performance of the 3D PAC filter was tested at various pH levels of 4-10 and against MB spiked in seawaters and freshwaters to evaluate its feasibility for use in real environments. Finally, the reproducibility and reusability of the 3D PAC filter were demonstrated through repeated adsorption and desorption processes against MB.

Clinical Impact of Early Rhythm Control and Healthy Lifestyles in Patients With Atrial Fibrillation.

BACKGROUND: There are limited data regarding the combined effect of early rhythm control (ERC) and healthy lifestyle (HLS) behaviors on the risk of ischemic stroke in patients with atrial fibrillation (AF). OBJECTIVES: This study sought to evaluate how the combination of ERC and HLS behaviors affects the risk of ischemic stroke in patients with AF. METHODS: Using the Korean National Health Insurance database, we included patients with new-onset AF between 2009 and 2016 (n = 208,662). Patients who received rhythm control therapy within 2 years after AF diagnosis were defined as the ERC group. Patients with ≥2 HLS behaviors were defined as the HLS group. Patients were categorized into 4 groups: group 1, without ERC and without HLS (n = 46,972); group 2, with HLS alone (n = 110,479); group 3, with ERC alone (n = 15,133); and group 4, with both ERC and HLS (n = 36,078). The primary outcome was ischemic stroke. RESULTS: Compared to group 1, group 2 and group 3 were associated with a lower risk of stroke (HR: 0.769 [95% CI: 0.728-0.881] and HR: 0.774 [95% CI: 0.703-0.852], respectively). Group 4 showed the lowest risk of stroke (HR: 0.575; 95% CI: 0.536-0.617). After propensity score weighting, the incorporation of additional ERC alongside HLS was associated with a relative risk reduction of 22% for stroke, and additional HLS alongside ERC were associated with a relative risk reduction of 27% for stroke. CONCLUSIONS: Each of ERC and HLS might reduce the risk of ischemic stroke in patients with new-onset AF. The presence of both ERC and HLS is associated with an enhanced benefit for stroke prevention in this population.

Metabolic dysfunction-associated steatotic liver disease and risk of esophageal cancer in patients with diabetes mellitus: a nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Combination of early rhythm control and healthy lifestyle on the risk of stroke in elderly patients with new-onset atrial fibrillation: a nationwide population-based cohort study.

Background: The impact of early rhythm control (ERC) combined with healthy lifestyle (HLS) on the risk of ischemic stroke in elderly patients with atrial fibrillation (AF) remains unaddressed. Objective: To evaluate the impact of combined ERC and HLS on the risk of stroke in elderly patients with new-onset AF. Methods: Using the Korean National Health Insurance Service database, we included patients aged ≥75 years with new-onset AF from January 2009 to December 2016 (n = 41,315). Patients who received rhythm control therapy within 2 years of AF diagnosis were defined as the ERC group. Non-smoking, non-to-mild alcohol consumption (<105 g/week), and regular exercise were defined as HLS. Subjects were categorized into four groups: group 1 (without ERC and HLS, n = 25,093), 2 (HLS alone, n = 8,351), 3 (ERC alone, n = 5,565), and 4 (both ERC and HLS, n = 2,306). We assessed the incidence of ischemic stroke as the primary outcome, along with admissions for heart failure, all-cause death, and the composite of ischemic stroke, admission for heart failure, and all-cause death. Results: Median follow-up duration of the study cohort was 3.4 years. After adjusting for multiple variables, groups 2 and 3 were associated with a lower stroke risk (adjusted hazard ratio [aHR]: 95% confidence interval [CI]: 0.867, 0.794-0.948 and 0.713, 0.637-0.798, respectively) than that of group 1. Compared to Group 1, group 4 showed the lowest stroke risk (aHR: 0.694, 95% CI: 0.586-0.822) among all groups, followed by group 3 (0.713, 0.637-0.798) and group 2 (0.857, 0.794-0.948), respectively. Group 4 was associated with the lowest risk of all-cause death (aHR: 0.680, 95% CI: 0.613-0.754) and the composite outcome (aHR: 0.708, 95% CI: 0.649-0.772). Conclusion: ERC and HLS were associated with a lower risk of ischemic stroke in elderly patients with new-onset AF. Concurrently implementing ERC and maintaining HLS was associated with the lowest risk of death and the composite outcome, with a modest synergistic effect on stroke prevention.

Harnessing the Power of IL-7 to Boost T Cell Immunity in Experimental and Clinical Immunotherapies.

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

Distributed quantum sensing of multiple phases with fewer photons.

Distributed quantum metrology has drawn intense interest as it outperforms the optimal classical counterparts in estimating multiple distributed parameters. However, most schemes so far have required entangled resources consisting of photon numbers equal to or more than the parameter numbers, which is a fairly demanding requirement as the number of nodes increases. Here, we present a distributed quantum sensing scenario in which quantum-enhanced sensitivity can be achieved with fewer photons than the number of parameters. As an experimental demonstration, using a two-photon entangled state, we estimate four phases distributed 3 km away from the central node, resulting in a 2.2 dB sensitivity enhancement from the standard quantum limit. Our results show that the Heisenberg scaling can be achieved even when using fewer photons than the number of parameters. We believe our scheme will open a pathway to perform large-scale distributed quantum sensing with currently available entangled sources.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Impact of Unhealthy Lifestyles on Patients with Atrial Fibrillation at Low Risk of Stroke: A Nationwide Cohort Study.

BACKGROUND: The impact of unhealthy lifestyles on clinical outcomes among patients with atrial fibrillation (AF) who are at low risk of stroke remains uncertain. The study objective was to evaluate the association between unhealthy lifestyles and clinical outcomes among low-risk AF patients with 0-1 non-sex risk factor of the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack [TIA], Vascular disease, Age 65-74 years, female Sex;) score. METHODS: A total of 52,451 low-risk AF patients (mean age 51.6 ± 10.4 years) were evaluated with the National Health Insurance Service of the Republic of Korea database between 2009 and 2016. Using the survey on health habits, an unhealthy lifestyle score (ULS) was calculated by adding one point each if a respondent had a sedentary lifestyle, drinking, or smoking. The primary outcome was the composite of myocardial infarction, ischemic stroke, heart failure, and all-cause death. Multivariable Cox regression analysis was used to estimate the risk of the study outcome according to the ULS. RESULTS: There was a total of 12,792 (24.4%), 24,785 (47.3%), 11,602 (22.1%), and 3272 (6.2%) low-risk AF patients with 0 to 3 points of the ULS, respectively. The median follow-up period was 4.1 (2.1-6.1) years. Compared with the healthiest-lifestyle group (ULS 0), the other groups were associated with significantly higher risks of the primary outcome, with a gradually increasing trend according to the ULS (adjusted hazard ratio [95% confidence interval] =1.17 [1.05-1.31], 1.37 [1.21-1.56], 1.82 [1.53-2.17], for the groups with ULS 1, 2, and 3, respectively). CONCLUSION: Unhealthy lifestyles, including a sedentary lifestyle, drinking, and smoking, may synergistically impact poor clinical outcomes in AF patients who are deemed to be at low risk of stroke.