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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.

Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy. Keywords: Akt/mTOR signaling, Hypertrophy, Myoblast differentiation, Rb1, Rb2

As COVID-19 continues to pose major risk for vulnerable populations, including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins, either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate the blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced the inhibition of pseudovirus infection by GLPG-0187. Because integrins activate transforming growth factor beta (TGF-β) signaling, we compared the plasma levels of active and total TGF-β in COVID-19+ patients. The plasma TGF-β1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-β1 levels correlated with activated TGF-β1 levels. Moreover, the inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and it may mitigate COVID-19 severity through decreased TGF-β1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.

KEYWORDS: Emily Mann, Execution of Justice, documentary drama, testimony, politics This essay presents an in-depth analysis of Emily Mann's Execution of Justice, a documentary play on the Dan White trial. The essay covers the genesis of the play, the evolution of Mann's perspective on the material, and her creative adaptation of the documentary form. Although the play owes its existence to the assassination of a prominent gay politician, the word 'homophobia' is never mentioned. A close examination reveals that Mann repeatedly brings the audience's attention to how queerness was expelled from the courtroom, She furthermore inserts queer perspectives via the chorus of uncalled witnesses. However, her politics ultimately exceed the confines of identity-based social movements, inviting the audience to work across differences toward greater social justice., THAT EMILY MANN'S PLAYS ARE political has never been in doubt. The politics of her plays, however, have been difficult to label. Does being a woman and a political playwright [...]

Automatic signature verification has been widely studied for authentication purposes in real life, but limited data availability still poses a significant challenge. To address this issue, we propose a method with a denoising diffusion probabilistic model (DDPM) to generate artificial signatures that closely resemble authentic ones. In the proposed method, we modified the noise prediction process of the DDPM to allow the generation of signatures specific to certain classes. We also employed an auxiliary classification process to ensure that the generated signatures closely resemble the originals. The model was trained and evaluated using the CEDAR signature dataset, a widely used collection of offline handwritten signatures for signature verification research. The results indicate that the generated signatures exhibited a high similarity to the originals, with an average structural similarity index (SSIM) of 0.9806 and a root mean square error (RMSE) of 0.1819. Furthermore, when the generated signatures were added to the training data and the signature verification model was retrained and validated, the model achieved an accuracy of 94.87% on the test data, representing an improvement of 0.061 percentage points compared to training on only the original dataset. These results indicate that the generated signatures reflect the diversity that original signatures may exhibit and that the generated data can enhance the performance of verification systems. The proposed method introduces a novel approach to utilizing DDPM for signature data generation and demonstrates that the auxiliary classification process can reduce the likelihood of generated data being mistaken for forged signatures.

Background and Objectives: Stroke patients often experience changes in their pelvic tilt, trunk impairments and decreased gait and balance. While various therapeutic interventions have been attempted to improve these symptoms, there is a need for interventions that are easy to apply and reduce the physical labor of physical and occupational therapists. We aimed to investigate the immediate effects of two different methods of trunk elastic taping on the pelvic inclination, trunk impairment, balance, and gait in chronic stroke patients. Materials and Methods: We performed a single-blind randomized controlled trial involving 45 patients with chronic stroke. Participants were randomly assigned to one of three groups: forward rotation with posterior pelvic tilt taping (FRPPT, n = 14), backward rotation with posterior pelvic tilt taping (BRPPT, n = 14), or placebo taping (PT = 14). This study was conducted from December 2023 to January 2024. All the measurements were performed twice: before the intervention and immediately after the intervention. The pelvic inclination was assessed using the anterior pelvic tilt angle. The trunk impairment scale (TIS) was used to measure the trunk impairment. The balance and gait were evaluated using a force plate and walkway system. Results: The pelvic inclination was significantly different in the FRPPT and BRPPT groups compared to the PT group (p < 0.05, p < 0.001). The TIS and gait were significantly increased in the FRPPT group compared to the PT group (p < 0.05). The balance significantly improved in the FRPPT and BRPPT within groups (p < 0.05). Conclusions: Two different methods of posterior pelvic tilt taping improved the anterior pelvic tilt in chronic hemiplegic stroke patients compared with PT, and the FRPPT method also improved the trunk impairment and gait. Therefore, posterior pelvic tilt taping can be used as an intervention with immediate effect.

BackgroundAlthough left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI.MethodsIn a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated.ResultsAmong the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p

Abstract Aims Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large‐scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. Methods and results From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF)

Summary: Background: The impact of titrated versus fixed intensity statin therapy in patients with coronary artery disease (CAD) and diabetes mellitus (DM) remains to be elucidated. Methods: This was a pre-specified analysis of patients with and without DM from the LODESTAR trial. Patients with CAD were randomly assigned to receive either a treat-to-target strategy with a target LDL-C level of 50–70 mg/dL or a high-intensity statin treatment. Primary outcome was the 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. Secondary outcomes were safety endpoints. This trial is registered with ClinicalTrials.gov, NCT02579499. Findings: Between September 9, 2016 and November 27, 2019, 4400 patients with CAD were enrolled in the LODESTAR trial. The median age was 65 years (interquartile range, 59–73 years), 3172 (72%) were male, and 1468 (33%) had DM at baseline. There was no significant difference in the occurrence of the primary outcome between the treat-to-target group and high-intensity statin group among patients with DM (10.5% versus 11.1%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69–1.29, p = 0.70) and those without DM (6.9% versus 7.5%, HR 0.93, 95% CI 0.71–1.21, p = 0.58). Among patients without DM, there was a trend towards a lower risk of new-onset DM in the treat-to-target group (8.4% versus 10.4% in the high-intensity statin group, HR 0.79, 95% CI 0.62–1.01; p = 0.06). Interpretation: In patients with CAD, a treat-to-target LDL-C strategy of 50–70 mg/dL as the goal was comparable to high-intensity statin therapy in terms of 3-year clinical efficacy and safety outcomes regardless of the presence of DM. Funding: Sam Jin Pharmaceutical, Seoul, Korea and Chong Kun Dang Pharmaceutical, Seoul, Korea.

PURPOSE The purpose of this study was to demonstrate differences in cardiovascular and autonomic nerve function among physical activity levels and associations between physical activity level and cardiovascular and autonomic nerve function. METHODS Sixty-six healthy young adults voluntarily participated in this cross-sectional study. Physical activity levels were assessed using triaxial accelerometers for 7 consecutive days. Central hemodynamics and arterial stiffness were measured using the Sphygomo-Cor Xcel system. Autonomic nerve function was assessed by heart rate variability. RESULTS The highest tertile group of the total quantity of physical activity had higher lnRMSSD than did the lowest tertile group (p=0.047). The augmentation index adjusted for heart rate at 75 beats per min (AIx@75) was lower in the highest tertile group of vig-orous-intensity physical activity than in the lowest tertile group (p=0.012). Moreover, AIx@75 was negatively associated with vigorous-intensity physical activity (r=-0.27, p=0.028). CONCLUSIONS High levels of physical activity contribute to the dominance of parasympathetic nerve activity at rest. Increased engagement in vigorous-intensity physical activity can help reduce arterial pulse wave reflection, an independent risk factor for cardiovascular diseases, even in healthy young adults.

Abstract Background It is an important strategy for healthcare providers to support heart failure patients with comprehensive aspects of self-management. A practical alternative to a comprehensive and user-friendly self-management program for heart failure patients is needed. This study aimed to develop a mobile self-management app program for patients with heart failure and to identify the impact of the program. Methods We developed a mobile app, called Heart Failure-Smart Life. The app was to provide educational materials using a daily health check-up diary, Q & A, and 1:1 chat, considering individual users’ convenience. An experimental study was employed using a randomized controlled trial to evaluate the effects of the program in patients with heart failure from July 2018 to June 2019. The experimental group (n = 36) participated in using the mobile app that provided feedback on their self-management and allowed monitoring of their daily health status by cardiac nurses for 3 months, and the control group (n = 38) continued to undergo their usual care. The differences in the physical, psychosocial, and behavioral factors between the two groups over time were analyzed using the analysis of covariance. Results After 3 months of intervention, significant differences between experimental and control groups were shown in the New York Heart Association functional class (p = 0.003) and cardiac diastolic function (p = 0.024). The improvements over time in the experimental group tended to be higher than those in the control group in considered variables. However, no changes in psychosocial and behavioral variables were observed between the groups over time. Conclusions This study provides evidence that the mobile app program may provide benefits to its users, specifically improvements of symptom and cardiac diastolic function in patients with heart failure. Healthcare providers can effectively and practically guide and support patients with heart failure using comprehensive and convenient self-management tools such as smartphone apps.

Automatic signature verification has been widely studied for authentication purposes in real life, but limited data availability still poses a significant challenge. To address this issue, we propose a method with a denoising diffusion probabilistic model (DDPM) to generate artificial signatures that closely resemble authentic ones. In the proposed method, we modified the noise prediction process of the DDPM to allow the generation of signatures specific to certain classes. We also employed an auxiliary classification process to ensure that the generated signatures closely resemble the originals. The model was trained and evaluated using the CEDAR signature dataset, a widely used collection of offline handwritten signatures for signature verification research. The results indicate that the generated signatures exhibited a high similarity to the originals, with an average structural similarity index (SSIM) of 0.9806 and a root mean square error (RMSE) of 0.1819. Furthermore, when the generated signatures were added to the training data and the signature verification model was retrained and validated, the model achieved an accuracy of 94.87% on the test data, representing an improvement of 0.061 percentage points compared to training on only the original dataset. These results indicate that the generated signatures reflect the diversity that original signatures may exhibit and that the generated data can enhance the performance of verification systems. The proposed method introduces a novel approach to utilizing DDPM for signature data generation and demonstrates that the auxiliary classification process can reduce the likelihood of generated data being mistaken for forged signatures. [ABSTRACT FROM AUTHOR]

Background and Objectives: Stroke patients often experience changes in their pelvic tilt, trunk impairments and decreased gait and balance. While various therapeutic interventions have been attempted to improve these symptoms, there is a need for interventions that are easy to apply and reduce the physical labor of physical and occupational therapists. We aimed to investigate the immediate effects of two different methods of trunk elastic taping on the pelvic inclination, trunk impairment, balance, and gait in chronic stroke patients. Materials and Methods: We performed a single-blind randomized controlled trial involving 45 patients with chronic stroke. Participants were randomly assigned to one of three groups: forward rotation with posterior pelvic tilt taping (FRPPT, n = 14), backward rotation with posterior pelvic tilt taping (BRPPT, n = 14), or placebo taping (PT = 14). This study was conducted from December 2023 to January 2024. All the measurements were performed twice: before the intervention and immediately after the intervention. The pelvic inclination was assessed using the anterior pelvic tilt angle. The trunk impairment scale (TIS) was used to measure the trunk impairment. The balance and gait were evaluated using a force plate and walkway system. Results: The pelvic inclination was significantly different in the FRPPT and BRPPT groups compared to the PT group (p < 0.05, p < 0.001). The TIS and gait were significantly increased in the FRPPT group compared to the PT group (p < 0.05). The balance significantly improved in the FRPPT and BRPPT within groups (p < 0.05). Conclusions: Two different methods of posterior pelvic tilt taping improved the anterior pelvic tilt in chronic hemiplegic stroke patients compared with PT, and the FRPPT method also improved the trunk impairment and gait. Therefore, posterior pelvic tilt taping can be used as an intervention with immediate effect. [ABSTRACT FROM AUTHOR]

BackgroundDue to increased needs to reduce non-fatal as well as fatal cardiac events, preoperative echocardiography remains part of routine clinical practice in many hospitals. Data on the role of preoperative echocardiography in low-risk non-cardiac surgery (NCS) other than ambulatory surgeries do not exist. We aimed to investigate the role of preoperative echocardiography in predicting postoperative adverse cardiovascular events (CVEs) in asymptomatic patients undergoing low-risk NCS.MethodsThe study population was derived from a retrospective cohort of 1,264 patients who underwent elective low-risk surgery at three tertiary hospitals from June 1, 2021, to June 30, 2021. Breast, distal bone, thyroid, and transurethral surgeries were included. Preoperative examination data including electrocardiography, chest radiography, and echocardiography were collected. The primary outcome was a composite of postoperative adverse CVEs including all-cause death, myocardial infarction, cerebrovascular events, newly diagnosed or acutely decompensated heart failure (HF), lethal arrhythmia such as sustained ventricular tachycardia/fibrillation, and new-onset atrial fibrillation within 30 days after the index surgery.ResultsPreoperative echocardiography was performed in 503 patients (39.8%), most frequently in patients with breast surgery (73.5%), followed by transurethral (37.7%), distal bone (21.6%), and thyroid surgeries (11.9%). Abnormal findings were observed in 5.0% of patients with preoperative echocardiography. Postoperative adverse CVEs occurred in 10 (0.79%) patients. Although a history of previous HF was an independent predictor of postoperative CVE occurrence (adjusted odds ratio, aOR: 17.98; 95% confidence interval, CI: 1.21–266.71, P = 0.036), preoperative echocardiography did not significantly predict CVE in multivariate analysis (P = 0.097). However, in patients who underwent preoperative echocardiography, the presence of abnormal echocardiographic findings was independently associated with development of CVE after NCS (aOR: 23.93; 95% CI: 1.2.28–250.76, P = 0.008). In particular, the presence of wall motion abnormality was a strong predictor of postoperative adverse CVE.ConclusionIn real-world clinical practice, preoperative echocardiography was performed in substantial number of patients with potential cardiac risk even in low-risk NCS, and abnormal findings were independently associated with postoperative CVE. Future studies should identify patients undergoing low-risk NCS for whom preoperative echocardiography would be helpful to predict adverse CVE.

Ventricular hypertrophy is associated with diastolic dysfunction, resulting in increased left atrial (LA) pressure, enlargement, fibrosis, and decreased LA function. Hypertrophic cardiomyopathy (HCM) is characterized by myocyte disarray, myocardial fibrosis, and hypertrophy. Notably, a thickened and noncompliant LV results in the impairment of diastolic function. These conditions promote LA remodeling and enlargement, which contribute to developing and maintaining atrial fibrillation (AF). AF is an atrial arrhythmia that occurs frequently in HCM, and evaluating the morphology and physiology of the atrium and ventricle is important for treatment and prognosis determination in HCM patients with AF. In addition, it provides a clue that can predict the possibility of new AF, even in patients not previously diagnosed with AF. Cardiac magnetic resonance (CMR), which can overcome the limitations of transthoracic echocardiography (TTE), has been widely used traditionally and even enables tissue characterization; moreover, it has emerged as an essential imaging modality for patients with HCM. Here, we review the role of multimodal imaging in patients with HCM and AF.