Targeting optimal power consumption: Optimizing operational parameters for orchard furrowing and fertilizing machine.

In response to the problem of excessive power consumption during the furrowing operation of orchard furrowing fertilizer machines, an optimization experiment of furrowing operation parameters for orchard furrowing fertilizer machine was conducted based on discrete element simulations. This research focused on the impact of furrowing device operation parameters on furrowing power consumption under full machine operating conditions. Firstly, a kinematics analysis of the soil granules during cutting was done. The mathematical model of soil granules through three movement processes of rising, detachment, and falling was established to determine the main factors affecting the power consumption of furrowing. Secondly, in assessing the furrowing power consumption, the stability coefficient of the furrowing depth, and the percentage of soil cover, alongside the key parameters of furrowing depth, forward propulsion velocity, and furrowing blade rotation speed, a comprehensive quadratic orthogonal rotation regression experiment was meticulously conducted. It was established that test metrics and test parameters regress. Finally, the test parameters were comprehensively optimized after analyzing each factor's impact on the test metrics. The orchard furrowing fertilizer machine's optimal operating parameters were determined, and the verification test was performed. According to the field test findings, the forward propulsion velocity was 785 m/h, and the furrowing blade rotation speed was 190 r/min when the furrowing depth was 275 mm. At this point, the furrowing power consumption was 2.39 kW, the soil cover percentage was 69.06%, and the furrowing depth stability coefficient was 95.08%. These results were in line with the requirements of orchard furrowing operation. The findings of the study can be utilized as a guide for structural changes to orchard furrowing equipment and the management of furrowing operation parameters.

Integrative analysis reveals chemokines CCL2 and CXCL5 mediated shear stress-induced aortic dissection formation.

Background: Aortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. Methods: Gene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. Results: We identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. Conclusion: Through integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated "Endothelial-Monocyte-Neutrophil" axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

AdaSAM: Boosting sharpness-aware minimization with adaptive learning rate and momentum for training deep neural networks.

Sharpness aware minimization (SAM) optimizer has been extensively explored as it can generalize better for training deep neural networks via introducing extra perturbation steps to flatten the landscape of deep learning models. Integrating SAM with adaptive learning rate and momentum acceleration, dubbed AdaSAM, has already been explored empirically to train large-scale deep neural networks without theoretical guarantee due to the triple difficulties in analyzing the coupled perturbation step, adaptive learning rate and momentum step. In this paper, we try to analyze the convergence rate of AdaSAM in the stochastic non-convex setting. We theoretically show that AdaSAM admits a O(1/bT) convergence rate, which achieves linear speedup property with respect to mini-batch size b. Specifically, to decouple the stochastic gradient steps with the adaptive learning rate and perturbed gradient, we introduce the delayed second-order momentum term to decompose them to make them independent while taking an expectation during the analysis. Then we bound them by showing the adaptive learning rate has a limited range, which makes our analysis feasible. To the best of our knowledge, we are the first to provide the non-trivial convergence rate of SAM with an adaptive learning rate and momentum acceleration. At last, we conduct several experiments on several NLP tasks and the synthetic task, which show that AdaSAM could achieve superior performance compared with SGD, AMSGrad, and SAM optimizers.

Aberrant expression and regulatory role of histone deacetylase 9 in vascular endothelial cell injury in intracranial aneurysm.

Intracranial aneurysm (IA) is one of the most challenging cerebrovascular lesions for clinicians. The aim of this study was to investigate the abnormal expression and role of histone deacetylase 9 (HDAC9) in IA-associated injury of vascular endothelial cells (VECs). First, IA tissue and normal arterial tissue were collected and VECs were isolated from IA patients. The expression levels of HDAC9, microRNA (miR)-34a-5p, and vascular endothelial growth factor-A (VEGFA) were determined. Cell viability, proliferation, apoptosis, and migration were assessed by Cell Counting Kit-8 (CCK-8) assay, EdU staining, TUNEL staining, and transwell assay. The binding of miR-34a-5p to VEGFA was analyzed by the dual-luciferase assay, and the accumulation of HDAC9 and lysine histone acetylation at H3 (H3K9, H3K14, and H3K18) on the miR-34a-5p promoter was detected by the chromatin immunoprecipitation assay. The results showed that HDAC9 and VEGFA were increased and miR-34a-5p was decreased in IA tissues and cells. Silencing of HDAC9 inhibited apoptosis and increased viability, proliferation, and migration of VECs, whereas overexpression of HDAC9 exerted the opposite functions. HDAC9 accumulated at the miR-34a-5p promoter to decrease miR-34a-5p expression by reducing H3 locus-specific acetylation and further promoted VEGFA expression. Knockdown of miR-34a-5p or VEGFA overexpression reversed the protective role of HDAC9 silencing in VECs injury. In conclusion, our study suggests that HDAC9 may be a therapeutic target for IA.

Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) often leads to sudden cardiac death. Persistent myocardial ischemia increases oxidative stress and impairs mitochondrial function, contributing significantly to postinfarction cardiac dysfunction and remodeling, and the subsequent progression to heart failure (HF). Tetrahydrocurcumin (THC), isolated from the rhizome of turmeric, has antioxidant properties and has been shown to protect against cardiovascular diseases. However, its effects on HF after MI are poorly understood. PURPOSE: The objective was the investigation of the pharmacological effects of THC and its associated mechanisms in the pathogenesis of HF after MI. METHODS: A total of 120 mice (C57BL/6, male) were used for the in vivo experiments. An MI mouse model was created by permanent ligation of the left anterior descending coronary artery. The mice received oral dose of THC at 120 mg/kg/d and the effects on MI-induced myocardial injury were evaluated by assessment of cardiac function, histopathology, myocardial oxidative levels, and mitochondrial function. Molecular mechanisms were investigated by intraperitoneal injection of 50 mg/kg of the SIRT3 selective inhibitor 3-TYP. Meanwhile, mouse neonatal cardiomyocytes were isolated and cultured in a hypoxic incubator to verify the effects of THC in vitro. Lastly, SIRT3 and Nrf2 were silenced using siRNAs to further explore the regulatory mechanism of key molecules in this process. RESULTS: The mouse hearts showed significant impairment in systolic function after MI, together with enlarged infarct size, increased myocardial fibrosis, cardiac hypertrophy, and apoptosis of cardiomyocytes. A significant reversal of these changes was seen after treatment with THC. Moreover, THC markedly reduced reactive oxygen species generation and protected mitochondrial function, thus mitigating oxidative stress in the post-MI myocardium. Mechanistically, THC counteracted reduced Nrf2 nuclear accumulation and SIRT3 signaling in the MI mice while inhibition of Nrf2 or SIRT3 reversed the effects of THC. Cell experiments showed that Nrf2 silencing markedly reduced SIRT3 levels and deacetylation activity while inhibition of SIRT3 signaling had little impact on Nrf2 expression. CONCLUSION: This is the first demonstration that THC protects against the effects of MI. THC reduced both oxidative stress and mitochondrial damage by regulating Nrf2-SIRT3 signaling. The results suggest the potential of THC in treating myocardial ischemic diseases.

The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.

OBJECTIVE: Estrogen is indispensable in health and disease and mainly functions through its receptors. The protection of the cardiovascular system by estrogen and its receptors has been recognized for decades. Numerous studies with a focus on estrogen and its receptor system have been conducted to elucidate the underlying mechanism. Although nuclear estrogen receptors, including estrogen receptor-α and estrogen receptor-ß, have been shown to be classical receptors that mediate genomic effects, studies now show that GPER mainly mediates rapid signaling events as well as transcriptional regulation via binding to estrogen as a membrane receptor. With the discovery of selective synthetic ligands for GPER and the utilization of GPER knockout mice, significant progress has been made in understanding the function of GPER. In this review, the tissue and cellular localizations, endogenous and exogenous ligands, and signaling pathways of GPER are systematically summarized in diverse physiological and diseased conditions. This article further emphasizes the role of GPER in vascular pathology and physiology, focusing on the latest research progress and evidence of GPER as a promising therapeutic target in hypertension, pulmonary hypertension, and atherosclerosis. Thus, selective regulation of GPER by its agonists and antagonists have the potential to be used in clinical practice for treating such diseases.

Extra-anatomic revascularization and a new cannulation strategy for preoperative cerebral malperfusion due to severe stenosis or occlusion of supra-aortic branch vessels in acute type A aortic dissection.

Objectives: Acute type A aortic dissection (ATAAD) with severe stenosis or occlusion of the true lumen of aortic arch branch vessels often leads to an increased incidence of severe postsurgical neurological complications and mortality rate. In this study, we aimed to introduce our institutional extra-anatomic revascularization and cannulation strategy with improved postoperative outcomes for better management of patients with cerebral malperfusion in the setting of ATAAD. Methods: Twenty-eight patients with ATAAD complicated by severe stenosis or occlusion of the aortic arch branch vessels, as noted on combined computed tomography angiography of the aorta and craniocervical artery, between January 2021 and June 2022 were included in this study. Basic patient characteristics, surgical procedures, hospitalization stays, and early follow-up results were analyzed. Results: The median follow-up duration was 16.5 months (interquartile range: 11.5-20.5), with a 100% completion rate. The 30-day mortality rates was 7.1% (2/28 patients); two patients had multiple cerebral infarctions on preoperative computed tomography and persistent coma. Postoperative transient neurological dysfunction occurred in 10.7% (3/28) of the patients, and no new permanent neurological dysfunction occurred. Of all the patients, 3.6% (1/28) had novel acute renal failure. No other deaths, secondary surgeries, or serious complications occurred during the early follow-up period. Conclusions: Use of extra-anatomic revascularization and a new cannulation strategy before cardiopulmonary bypass is safe and feasible and may reduce the high incidence of postoperative neurological complications in patients with ATAAD and cerebral malperfusion.

Analysis of the CHD7 gene mutations in patients of congenital heart disease with extracardiac malformations.

Background: Congenital heart disease (CHD) is a common birth defect, and is frequently accompanied with extracardiac malformations (ECM). Uncovering the genetic etiology of CHD may have a meaningful impact on disease management. De novo variants have been proven to be associated with CHD. Methods: Whole exome sequencing was performed for 4 unrelated CHD families with extracardiac malformations, candidate genes were screened by using stringent bioinformatics analysis, and the obtained variants were confirmed by Sanger sequencing. RT-PCR and Sanger sequencing were used to investigate the influence of a splice variant on pre-mRNA splicing. Further targeted sequencing was conducted to investigate the association of CHD7 variants with sporadic CHD. Results: Four novel heterozygous loss-of-function CHD7 mutations were found by using stringent bioinformatics analysis: the frameshift mutation c.1951_1952delAAinsT (p.L651X) in family #1, the nonsense mutations c.2913C>G (p.Y971X) in family #2 and c.3106C>T (pA1036X) in family #3, and the splicing mutation c.4353+4_4353+12delinsGCCCA in family #4. Sanger sequencing confirmed that these were all de novo mutations and were absent in the healthy parents and siblings of the probands. Further studies revealed that the splice mutation c.4353+4_4353+12delinsGCCCA influenced CHD7 mRNA splicing in vivo. Targeted sequencing found 23 rare mutations in 1,155 sporadic CHD patients. Conclusions: The findings here confirm that de novo loss-of-function variants of the CHD7 gene are the genetic cause of familial CHD with extracardiac malformations and the spectrum of pathogenic CHD7 variants in sporadic CHD is expanded.

The shadowing effect of initial expectation on learning asymmetry.

Evidence for positivity and optimism bias abounds in high-level belief updates. However, no consensus has been reached regarding whether learning asymmetries exist in more elementary forms of updates such as reinforcement learning (RL). In RL, the learning asymmetry concerns the sensitivity difference in incorporating positive and negative prediction errors (PE) into value estimation, namely the asymmetry of learning rates associated with positive and negative PEs. Although RL has been established as a canonical framework in characterizing interactions between agent and environment, the direction of learning asymmetry remains controversial. Here, we propose that part of the controversy stems from the fact that people may have different value expectations before entering the learning environment. Such a default value expectation influences how PEs are calculated and consequently biases subjects' choices. We test this hypothesis in two learning experiments with stable or varying reinforcement probabilities, across monetary gains, losses, and gain-loss mixed environments. Our results consistently support the model incorporating both asymmetric learning rates and the initial value expectation, highlighting the role of initial expectation in value updating and choice preference. Further simulation and model parameter recovery analyses confirm the unique contribution of initial value expectation in accessing learning rate asymmetry.

The prognostic and biology of tumour-infiltrating lymphocytes in the immunotherapy of cancer.

Tumour immunotherapy has achieved remarkable clinical success in many different types of cancer in the past two decades. The outcome of immune checkpoint inhibitors in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell within the tumour microenvironment, suggesting that the immune landscape of a tumour is highly connected to patient response and prognosis. It is critical to understanding tumour immune microenvironments for identifying immune modifiers of cancer progression and developing cancer immunotherapies. The infiltration of solid tumours by immune cells with anti-tumour activity is both a strong prognostic factor and a therapeutic goal. Recent approaches and applications of new technologies, especially single-cell mRNA analysis in dissecting tumour microenvironments have brought important insights into the biology of tumour-infiltrating immune cells, revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune response. In this review, we will discuss recent advances in the understanding of tumour infiltrated lymphocytes, their prognostic benefit, and predictive value for immunotherapy.

Resilience, Insight, Self-Compassion, and Empowerment (RISE): A Randomized Controlled Trial of a Psychoeducational Group Program for Nurses.

BACKGROUND: Nurses tend to be vulnerable to burnout and compassion fatigue due to constant workplace stressors. There is a need to provide advocacy, education, programming, and resources in the areas of positive coping and self-care to reduce burnout symptoms and promote well-being. RISE is an 8-week psychoeducational group intervention for nurses with four themes: resilience, insight, self-compassion, and empowerment. AIMS: This randomized controlled trial examined the effects of RISE on mental well-being. METHODS: The sample included 75 registered nurses who work in a hospital-based setting. Outcomes included resilience, insight, self-compassion, empowerment, stress mind-set, perceived stress, and burnout. Independent-samples t tests were conducted to compare outcomes between intervention and wait-list control groups at baseline and 1-month follow-up, as well as at 3-month follow-up. Supplemental analyses included paired-samples t tests and linear mixed models to compare the outcomes of the intervention group participants at baseline to 1-month follow-up, as well as at 3-month and 6-month follow-ups. RESULTS: Participants in the intervention group showed improved levels of insight (i.e., engagement in self-reflection), perceived stress, and burnout (i.e., emotional exhaustion) when compared with the control group and improved levels of resilience, self-compassion, stress mind-set, and perceived stress when compared with their baseline. CONCLUSIONS: This study informs how RISE affects nurse well-being and may be an effective intervention for reducing burnout and stress. This type of whole-person intervention can support nurses to improve their well-being and ability to cope amid the complex interplay of factors at the individual, unit, and organizational levels.

Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

INTRODUCTION: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation. METHOD: We modulated the PI3K-AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or AKT2, and characterized their effects on TIL phenotype and effector function. Mechanistic study was further performed with RNA-seq analysis of AKT1/2 KO TIL in comparison to control TIL. RESULT: The inhibition of either PI3K or AKT led to an increase in the population of effector CD8+ T cells with upregulation of activation markers, elevated CD39- CD69- memory T cells, and significantly enhanced cytotoxicity when cocultured with tumor cell lines and patient-derived tumor samples. Moreover, dual knockout of AKT1 and AKT2 largely phenocopies the functional impact of AKT or PI3K inhibition on TIL. This result was further validated by RNA-seq analysis indicating that AKT1/2 ablation primarily regulates T cell differentiation and function-related programs. CONCLUSION: Modulation of PI3K-AKT signaling represents a promising strategy to enhance TIL stemness and cytotoxicity and improve the clinical outcome of current TIL-based therapy to treat solid tumors.

The role of primary cilia in thyroid diseases.

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PC-mediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study.

Clinical implications of respiratory ciliary dysfunction in heterotaxy patients with congenital heart disease: elevated risk of postoperative airway complications.

Objective: Cardiac surgery in Congenital Heart Disease-Heterotaxy (CHD-HTX) patients often leads to increased postoperative airway complications. Abnormal respiratory ciliary function, resembling primary ciliary dyskinesia, has been observed. We expanded the sample size by retrospectively reviewing Ciliary Dysfunction (CD) in CHD-HTX patients to verify the increased risk of post-surgical respiratory complications. Methods: We conducted a retrospective review of 69 CHD-HTX patients undergoing cardiac surgery, assessing abnormal respiratory function using nasal nitric oxide (nNO) levels and nasal ciliary motion observed in video microscopy. Data collected included demographics, surgical details, postoperative complications, length of stay, ICU hours, salvage procedures, intubation duration, and mortality. Results: The CD and no-CD cohorts exhibited notable similarities in risk adjustment in Congenital Heart Surgery-1 (RACHS-1) risk categories, age at the time of surgery, and the duration of follow-up evaluations. We observed a trend toward an increased length of post-operative stay in the CD group (15.0 vs. 14.0; P = 0.0017). CHD-HTX patients with CD showed significantly higher rates of respiratory complications (70% vs. 44.4%; P = 0.008). There were no notable variances observed in postoperative hospitalization duration, mechanical ventilation period, or surgical mortality. Conclusion: Our findings suggest that CHD-HTX patients with CD may face an elevated risk of respiratory complications. These results offer guidance for perioperative management and serve as a reference for further pathological studies.

Traumatic blunt thoracic aortic injury: a 10-year single-center retrospective analysis.

BACKGROUND: Approximately 80% of patients with blunt thoracic aortic injury (BTAI) die before reaching the hospital. Most people who survive the initial injury eventually die without appropriate treatment. This study analyzed and reported the treatment strategy of a single center for BTAI in the last 10 years and the early and middle clinical results. METHODS: This retrospective study included patients diagnosed with BTAI at Xijing Hospital from 2013 to 2022. All inpatients with BTAI aged ≥ 18 years were included in this study. The clinical data, imaging findings, and follow-up results were retrospectively collected and analyzed. The Kaplan-Meier curve and multivariate logistic regression were used to compare survivors and nonsurvivors. RESULTS: A total of 72 patients (57% men) were diagnosed with BTAI, with a mean age of 54.2 ± 9.1 years. The injury severity score was 24.3 ± 18, with Grade I BTAI1 (1.4%), Grade II 17 (23.6%), Grade III 52 (72.2%), and Grade IV 2 (2.8%) aortic injuries. Traffic accidents were the main cause of BTAI in 32 patients (44.4%). Most patients had trauma, 37 had rib fractures (51.4%), Sixty patients (83.3%) underwent thoracic endovascular aortic repair (TEVAR) surgery, eight (11.1%) underwent conservative treatment, and only four (5.6%) underwent open surgery. The overall hospitalization mortality was 12.5%. In multivariate logistic regression, elevated creatinine levels (P = 0.041) and high Glasgow coma scale (GCS) score (P = 0.004) were the predictors of hospital mortality. The median follow-up period was 57 (28-87) months. During the follow-up period, all-cause mortality was 5.6% and no aortic-related deaths were reported. Three patients (4.2%) needed secondary surgery and two of them underwent endovascular repair. CONCLUSION: Although TEVAR surgery may be associated with intra- or postoperative dissection rupture or serious complications in the treatment of Grade III BTAI, the incidence rate was only 8.9%. Nevertheless, TEVAR surgery remains a safe and feasible approach for the treatment of Grade II or III BTAI, and surgical treatment should be considered first,. A high GCS score and elevated creatinine levels in the emergency department were closely associated with hospital mortality. Younger patients need long-term follow-up after TEVAR.

Polarity- and Pressure-Induced Emission from a Benzophenone-Based Luminophore.

Since strong polarity usually causes emission quenching, materials with polarity-induced emission (PIE) are rarely reported despite their important applications in polar environments. Herein, an N-phenylcarbazole-substituted benzophenone derivative (BP-3-Cz) with a twisted electron donor-acceptor (D-A) structure is synthesized. The incorporation of heteroatoms into the twisted π-conjugated D-A backbone simultaneously endows BP-3-Cz with obvious polarity- and pressure-induced emission. Spectral analysis, X-ray diffraction, differential scanning calorimetry, and quantum chemical calculation results confirm that BP-3-Cz has special optical features related to the molecular conformation change and excited state turning to planarized intramolecular charge transfer with an increase in polarity or applied pressure. These findings contribute to the understanding of the PIE mechanism and the design of new PIE materials.

Employment Status of Nurses After a Psychoeducational Group Intervention: A Matched Case-Control Study.

OBJECTIVE: This matched case-control study compared the long-term employment status of direct care nurses based on participation in a psychoeducational group intervention and calculated the estimated cost savings. BACKGROUND: Chronic stress, in addition to lack of support and low autonomy, can lead to burnout among nurses. Burnout is a common reason for job dissatisfaction and turnover. Interventions combining education with therapeutic processing and peer support may lead to healing and growth in nurses already experiencing the effects of chronic stress and burnout. The COVID-19 pandemic also contributed to stress among nurses. METHODS: Fifty-four direct care nurses who participated in the intervention were paired with 54 direct care nurses who did not participate, matched on the following variables: age, gender, race, work setting, and campus. RESULTS: This study found a higher percentage of direct care nurses who participated in the intervention remained employed compared with the matched control subjects who did not participate. CONCLUSION: At a relatively low cost compared with the cost of turnover by each nurse, the psychoeducational group intervention may provide an opportunity to improve retention among nurses.

Incremental cost-effectiveness of extracorporeal membranous oxygenation as a bridge to cardiac transplant or left ventricular assist device placement in patients with refractory cardiogenic shock.

Objective: Emerging literature has described using venoarterial extracorporeal membranous oxygenation (ECMO) as a bridge to transplant or left ventricular assist device (LVAD) placement. We sought to identify the incremental cost-effectiveness ratio (ICER) of ECMO used as a bridge to cardiac transplant or LVAD. Methods: Patients with refractory cardiogenic shock who received venoarterial ECMO and were bridged to either cardiac transplant (n = 7) or a HeartMate 3 LVAD (n = 6) placement were included. Markov modeling was used, comparing ECMO bridging with non-ECMO-bridged patients. Cohorts entered the model alive and at every 1-year cycle, were exposed to risk of death, and ran forward for 20 years after transplant or LVAD. Results: Patients bridged with ECMO to cardiac transplant were stratified as group 1 whereas those bridged with ECMO to LVAD were stratified as group 2. The average ECMO run was 3 days in group 1 versus 11 days in group 2. Among group 1 patients, the ICER was $246,629 but was paired with a longer life expectancy. The ICER of group 2 patients was -$107,088 and was not paired with a longer life expectancy. The average inpatient cost for group 1 was found to be $636,023 versus $769,471 for group 2 patients. The average inpatient costs for patients not bridged to ECMO who received cardiac transplant or LVAD was $538,928 and $325,242, respectively. Conclusions: Using ECMO to bridge to transplant or LVAD placement is not cost effective. However, patients bridged to transplant are paired with longer life expectancy in contrast to patients bridged to LVAD.

Dietary Magnesium Intake Level Modifies the Association Between Vitamin D and Insulin Resistance: A Large Cross-Sectional Analysis of American Adults.

Background: Previous clinical studies and randomized controlled trials have revealed that low serum vitamin D levels are associated with the risk of developing insulin resistance. Magnesium has been reported to be a protective factor for insulin resistance, and magnesium has been considered an important co-factor for vitamin D activation. However, the effect of dietary magnesium intake on the relationship between vitamin D and the risk of developing insulin resistance has not been comprehensively investigated. Therefore, we designed this cross-sectional analysis to assess whether dietary magnesium intake modifies the association of vitamin D and insulin resistance. Methods: A total of 4,878 participants (male: 48.2%) from 4 consecutive cycles of the National Health and Nutrition Examination Survey (2007-2014) were included in this study after a rigorous screening process. Participants were stratified by their dietary magnesium intake into low-intake (<267 mg/day) and high-intake (≥267 mg/day) groups. We assessed differences between serum vitamin D levels and the risk of developing insulin resistance (interaction test), using a weighted multivariate logistic regression to analyze differences between participants with low and high magnesium intake levels. Results: There was a negative association between vitamin D and insulin resistance in the US adult population [OR: 0.93 (0.88-0.98)], P < 0.001. Dietary magnesium intake strengthened the association (P for interaction < 0.001). In the low dietary magnesium intake group, vitamin D was negatively associated with the insulin resistance [OR: 0.94 (0.90-0.98)]; in the high dietary magnesium intake group, vitamin D was negatively associated with insulin resistance [OR: 0.92 (0.88-0.96)]. Conclusion: Among adults in the United States, we found an independent association between vitamin D level and insulin resistance, and this association was modified according to different levels of magnesium intake.

CpG site hypomethylation at ETS1­binding region regulates DLK1 expression in Chinese patients with Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation accounting for ~10% of cases. Although the pathogenesis of TOF is complex and largely unknown, epigenetics plays a huge role, specifically DNA methylation. The protein δ like non­canonical Notch ligand 1 (DLK1) gene encodes a non­canonical ligand of the Notch signaling pathway, which is involved in heart development. However, the epigenetic mechanism of DLK1 in the pathogenesis of TOF is yet to be elucidated. Therefore, the present study aimed to clarify its specific mechanism. In this study, immunohistochemistry was used to detect the protein expression of DLK1 and the methylation status of the DLK1 promoter was measured via bisulfite sequencing PCR. Dual­luciferase reporter assays were performed to examine the influence of transcription factor ETS proto­oncogene 1 (ETS1) on DLK1 gene expression. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay, both in vivo and in vitro, were used to verify the binding of the ETS1 transcription factor to the DLK1 promoter as well as the influence of methylation status of DLK1 promoter on this binding affinity. The expression of DLK1 in the right ventricular outflow tract was significantly lower in patients with Tetralogy of Fallot (TOF) than that in controls (P<0.001). Moreover, the methylation level of CpG site 10 and CpG site 11 in the DLK1_R region was significantly decreased in TOF cases compared with controls (P<0.01). The integral methylation levels of DLK1_R and the methylation status of the CpG site 11 were both positively associated with DLK1 protein expression in TOF cases. ETS1 was found to inhibit DLK1 transcriptional activity by binding to the CpG site 11 and this affinity could be influenced by the methylation level of the DLK1 promoter. These findings demonstrated that the hypomethylation of the DLK1 promoter could increase the binding affinity of ETS1 transcription factor, which in turn inhibited DLK1 gene transcriptional activity and contributed to the development of TOF.