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Abortive cell cycle (ACC) re-entry of apoptotic neurons is a recently characterized phenomenon that occurs after central nervous system (CNS) injury or over the course of CNS disease. Consequently, inhibiting cell cycle progression is neuroprotective in numerous CNS pathology models. Primary cilia are ubiquitous, centriole-based cellular organelles that prevent cell cycling, but their ability to modulate abortive cell cycle has not been described. Here, we show that neuronal cilia are ablated in-vitro and in-vivo following injury by hypoxia or optic nerve transection (ONT), respectively. Furthermore, forced cilia resorption sensitized neurons to these injuries and enhanced cell death. In contrast, pharmacological inhibition or shRNA knockdown of the proteins that disassemble the cilia increased neuron survival and decreased the phosphorylation of retinoblastoma (Rb), a master switch for cell cycle re-entry. Our findings show that the stabilization of neuronal primary cilia inhibits, at least transiently, apoptotic cell cycling, which has implications for future therapeutic strategies that halt or slow the progression of neurodegenerative diseases and acute CNS injuries.

We consider the well-posedness theory of the compact case of one-dimensional quantum Zakharov system with the periodic boundary condition. The global well-posedness for sufficiently regular data is shown. The semi-classical limit as is obtained on a compact time interval whereas the quantum perturbation proves to be singular on an infinite time interval.

Individuals affected by human immunodeficiency virus (HIV) have a growing demand for coronary artery bypass grafting (CABG) due to heightened risk for cardiovascular diseases and extended life expectancy. However, CABG outcomes in HIV patients are not well-established, with insights only from small case series studies. This study conducted a comprehensive, population-based examination of in-hospital CABG outcomes in HIV patients. Patients underwent CABG were identified in National Inpatient Sample from Q4 2015–2020. Patients with age < 18 years and concomitant procedures were excluded. A 1:5 propensity-score matching was used to address preoperative group differences. Among patients who underwent CABG, 613 (0.36%) had HIV and were matched to 3119 out of 167,569 non-HIV patients. For selected HIV patients, CABG is relatively safe, presenting largely similar outcomes. After matching, HIV and non-HIV patients had comparable in-hospital mortality rates (2.13% vs. 1.67%, p  = 0.40). Risk factors associated with mortality among HIV patients included previous CABG (aOR = 14.32, p  = 0.01), chronic pulmonary disease (aOR = 8.24, p  < 0.01), advanced renal failure (aOR = 7.49, p  = 0.01), and peripheral vascular disease (aOR = 6.92, p  = 0.01), which can be used for preoperative risk stratification. While HIV patients had higher acute kidney injury (AKI; 26.77% vs. 21.77%, p  = 0.01) and infection (8.21% vs. 4.18%, p  < 0.01), other complications were comparable between the groups.

There is limited data on the effect of socioeconomic status (SES) on transcatheter (TAVR) and surgical aortic valve replacement (SAVR) outcomes for aortic stenosis (AS). This study conducted a population-based analysis to assess the influence of SES on valve replacement outcomes. Patients with AS undergoing TAVR or SAVR were identified in National Inpatient Sample from Q4 2015–2020. Multivariable logistic regressions were used to compare in-hospital outcomes between patients living in neighborhoods of income at the lowest and highest quartiles. Of 613,785 AS patients, 9.77% underwent TAVR and 10.13% had SAVR. These rates decline with lower neighborhood income levels, with TAVR/SAVR ratio also declining in lower-income areas. Excluding concomitant procedures, 58,064 patients received isolated TAVR (12,355 low-income and 15,212 high-income) and 43,694 underwent isolated SAVR (10,029 low-income and 10,811 high-income). Low-income patients, in both TAVR and SAVR, were younger but had more comorbid burden. For isolated TAVR, outcomes were similar across income groups. However, for isolated SAVR, low-income patients experienced higher in-hospital mortality (aOR = 1.44, p < 0.01), pulmonary (aOR = 1.13, p = 0.01), and renal complications (aOR = 1.14, p < 0.01). They also had more transfers, longer waits for operations, and extended hospital stays. Lower-income communities had reduced access to TAVR and SAVR, with TAVR accessibility being particularly limited. When given access to TAVR, patients from lower-income neighborhoods had mostly comparable outcomes. However, patients from low-income communities faced worse outcomes in SAVR, possibly due to delays in treatment. Ensuring equitable specialized healthcare resources including expanding TAVR access in economically disadvantaged communities is crucial.

When transfemoral (TF) access is not available during transcatheter aortic valve replacement (TAVR), transapical (TA)-TAVR can be performed. However, TA-TAVR is associated with significantly higher risk, and it is unclear whether it provides more benefit than surgical aortic valve replacement (SAVR) in non-elective cases. This study aimed to compare the in-hospital outcomes of non-elective TA-TAVR and SAVR by conducting a population-based analysis using a national registry. Patients who underwent non-elective TA-TAVR and SAVR were selected from National Inpatient Sample from Q4 2015 to 2021. Exclusion criteria included age < 18 years and concomitant procedures. Demographics, socioeconomic status, comorbidities, relevant diagnosis, transfer-in status, and hospital characteristics were matched between patients who underwent TA-TAVR and SAVR using a 1:3 propensity-score matching. In-hospital outcomes were compared. There were 130 and 10,487 patients who underwent TA-TAVR and SAVR, respectively. After the propensity-score matching, all TA-TAVR patients were matched to 341 SAVR patients. TA-TAVR and SAVR patients had comparable in-hospital mortality (7.69% vs. 7.33%, p  = 0.85), myocardial infarction (3.85% vs. 4.4%, p  = 1.00), stroke (0.77% vs. 1.76%, p  = 0.69), respiratory complications (15.38% vs. 17.6%, p  = 0.68), cardiogenic shock (14.62% vs. 12.61%, p  = 0.55), and pacemaker implantation (10% vs. 7.33%, p  = 0.35). However, TA-TAVR patients had lower hemorrhage/hematoma (38.46% vs. 68.33%, p  < 0.01), lower transfer out rate (33.08% vs. 44.87%, p  = 0.02), and shorter length of stay ( p  = 0.04). All other in-hospital outcomes were comparable. Among eligible TAVR candidates in non-elective cases and when TF access is not available, both TA-TAVR and SAVR may be equally alternative approaches considering their comparable in-hospital outcomes. Further studies should compare the long-term outcomes between TA-TAVR and SAVR.

The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogs. Plants manufacture more than 3,000 THIQ alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Here we report a yeast THIQ platform by increasing production of the central BIA intermediate ( S )-reticuline to 4.6 g L −1 , a 57,000-fold improvement over our first-generation strain. We show that gains in BIA output coincide with the formation of several substituted THIQs derived from amino acid catabolism. We use these insights to repurpose the Ehrlich pathway and synthesize an array of THIQ structures. This work provides a blueprint for building diverse alkaloid scaffolds and enables the targeted overproduction of thousands of THIQ products, including natural and semi-synthetic opioids. Plants synthesize more than 3000 tetrahydroisoquinoline (THIQ) alkaloids, but only a few of them have been produced by engineered microbes and titers are very low. Here, the authors increase ( S )-reticuline titer to 4.6 g/L and repurpose the yeast Ehrlich pathway to synthesize a diverse array of THIQ scaffolds.

This research investigates the factors influencing the capital structure of 271 non-financial firms listed on the Korean Stock Exchange (KSE) over a broad period from 1995 to 2021, encompassing both stable and crisis conditions. Employing a dynamic panel data model and the generalized method of moments (GMM) estimation, we address the endogeneity issue introduced by the inclusion of lagged dependent variables. Our research integrates firm-specific internal factors with macroeconomic external variables to provide a comprehensive understanding of the influence of varying economic environments on capital structure. Our study suggests that in times of economic stability, the capital structure decisions of a firm are more influenced by internal factors such as profitability. However, in periods of economic downturns, it is the external macroeconomic market conditions that tend to have a greater impact on these decisions. It is also noteworthy that both book leverage (BL) and market leverage (ML) exhibit quicker adjustments during stable periods as opposed to periods of crisis. This indicates a higher agility of firms in adapting their capital structures in stable, normal conditions. Our findings contribute to the existing literature by offering a holistic view of capital structure determinants in Korean firms. They underscore the necessity of adaptable financial strategies that account for both internal dynamics and external economic conditions. This study fills a gap in current research, presenting new insights into the dynamics of capital structure in Korean firms and suggesting a multifaceted approach to understanding capital structure in diverse economic contexts.

Randomized controlled trials conducted in Mediterranean countries have shown that the Mediterranean diet lowers adverse cardiovascular events. In the American population, diet remains the biggest uncontrolled risk factor for cardiovascular disease. This study aimed to test the hypothesis that asynchronous dietary counseling supplied through a custom smartphone app results in better adherence to a Mediterranean diet in a non-Mediterranean population than traditional standard-of-care (SOC) counseling. In total, 100 patients presenting to the cardiology clinic of an academic medical center were randomized to either the SOC or smartphone app-based experimental (EXP) Mediterranean diet intervention after informed consent and 1 hour of individual face-to-face dietary counseling with a registered dietitian. Participants in EXP received a custom smartphone app that reinforced the Mediterranean diet, whereas participants in SOC received 2 additional sessions of in-person dietary counseling with the registered dietitian-30 min at 1 month and 30 min at 3 months. Preexisting knowledge of a Mediterranean diet was measured by the validated Mediterranean Diet Score (MDS) instrument. Baseline height, weight, blood pressure (BP), and laboratory biomarkers were collected. At 1, 3, and 6 months, participants presented for a follow-up appointment to assess compliance to the Mediterranean diet using the MDS as well as a patient satisfaction survey, BP, and weight. Repeat laboratory biomarkers were performed at 3 and 6 months. Enrolled participants had a mean age with SE of 56.6 (SD 1.7) for SOC and 57.2 (SD 1.8) for EXP; 65.3% of SOC and 56.9% of EXP were male, and 20.4% of SOC and 35.3% of EXP had coronary artery disease. There were no significant differences between EXP and SOC with regard to BP, lipid parameters, hemoglobin A , or C-reactive protein (CRP). Participants in EXP achieved a significantly greater weight loss on average of 3.3 pounds versus 3.1 pounds for participants in SOC, P=.04. Adherence to the Mediterranean diet increased significantly over time for both groups (P<.001), but there was no significant difference between groups (P=.69). Similarly, there was no significant difference in diet satisfaction between EXP and SOC, although diet satisfaction increased significantly over time for both groups. The proportion of participants with high Mediterranean diet compliance (defined as the MDS ≥9) increased significantly over time (P<.001)-from 18.4% to 57.1% for SOC and 27.5% to 64.7% for EXP; however, there was no significant difference between the groups. Both traditional SOC counseling and smartphone-based counseling were effective in getting participants to adhere to a Mediterranean diet, and these dietary changes persisted even after counseling had ended. However, neither method was more effective than the other. This pilot study demonstrates that patients can change to and maintain a Mediterranean diet with either traditional or smartphone app-based nutrition counseling. ClinicalTrials.gov NCT03897426;https://clinicaltrials.gov/ct2/show/NCT03897426.

The demographics of authors in manuscript publications have been investigated in many specialties but not yet cardiology. We explored the authorship trends in The American Journal of Cardiology, a fundamental journal in this field, to uncover the historical demographic patterns in the field. Manuscripts published in 1958 (the first year of publication), 1966, 1976, 1986, 1996, 2006, and 2016 were analyzed. Parameters used were gender of first and last authors, number of authors per article, the authors’ qualifications and country of corresponding authors. A total of 4,329 articles were analyzed. We hypothesized an increase in authors per article, variety of authors’ degrees, countries contributing to authorship, and an increase in female authorship over time. We found that the mean number of authors per article increased from 1.8 in 1958 to 8.6 in 2016. Qualification varieties of first and last authors also increased, particularly first and last authors holding degrees in MD/PhD and first authors holding masters degrees. Female first and last authorship showed an increase. In 1958, female first authors comprised of 3.0% of all the publications compared with 23% in 2016. Similarly, female last authors accounted for 5.2% of all publications in 1958 compared with 20% in 2016. There was also an increase in articles originating from Europe and Asia. In conclusion, there has been a significant increase in authors per article, variety of author degrees, and contribution from international authors. Despite the relative lack of increase in female cardiologists compared to physicians in other specialties in the United States, female authors in The American Journal of Cardiology have increased significantly over this 58-year time period, surpassing the 13% overall female representation within this specialty.