The association between low serum calcium level and new-onset atrial fibrillation after coronary artery bypass grafting.

OBJECTIVES: This study aims to investigate the relationship between serum calcium (SC) levels and the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass graft surgery. METHODS: This retrospective, observational cohort study consecutively enrolled patients undergoing isolated coronary artery bypass grafting in Beijing Anzhen Hospital from January 2018 to December 2021. Patients with a previous history of atrial fibrillation or atrial flutter or requiring concomitant cardiac surgery were excluded. A logistic regression model was used to determine predictors of POAF. Multivariable adjustment, inverse probability of treatment weighting and propensity score matching were used to adjust for confounders. Moreover, we conducted univariable and multivariable logistic regression analyses on preoperative and postoperative SC and ionized SC levels. RESULTS: The analysis encompassed 12 293 patients. The POAF rate was significantly higher in patients with low SC level than those without (1379 [33.9%] vs 2375 [28.9%], P < 0.001). Low SC level was associated with an increased odds ratio of POAF (odds ratio [95% confidence interval]: 1.27 [1.18-1.37], P < 0.001). Inverse probability of treatment weighting and propensity score matching analyses confirmed the results. The increased POAF rate in low SC level group still existed among subgroup analysis based on different age, sex, body mass index, hypertension, hyperlipidaemia, CHA2DS2-VASc and magnesium. CONCLUSIONS: Low SC level indicates elevated POAF risk in patients undergoing isolated coronary artery bypass graft surgery even after the adjustment for age, sex, cardiovascular risk factors, echocardiographic parameters and laboratory markers.

Quantitative comparison of the renal pelvic urine and bladder urine to examine modifications of the urine proteome by the lower urinary tract.

PURPOSE: Urine proteome is a valuable reservoir of biomarkers for disease diagnosis and monitoring. Following formation as the plasma filtrate in the kidney, urine is progressively modified by the active reabsorption and secretion of the urinary tract. However, little is known about how the urine proteome changes as it passes along the urinary tract. EXPERIMENTAL DESIGN: To investigate this, we compared the proteome composition of the renal pelvis urine (RPU) and individually self-voided bladder urine (BU) collected from seven unilateral urinary tract obstruction male patients by LC-MS/MS screening. To our knowledge, this is the first proteomic comparison of RPU and BU samples from the same individual. RESULTS: Overall, RPU and BU proteomes did not exhibit proteins that were exclusively present in all samples of one urine type while in none of the other type. Nonetheless, BU had more overrepresented proteins that were observed at a higher frequency than RPU. Label-free quantitative analyses revealed BU-RPU differential proteins that are enriched in exosomes and extracellular proteins. However, the differences were not significant after corrections for multiple testing. Interestingly, we observed a significant increase of collagen peptides with hydroxyproline modifications in the BU samples, suggesting differences in protein modifications. CONCLUSIONS AND CLINICAL RELEVANCE: Our study revealed no substantial differences at the protein level between the BU and RPU samples. Future investigations with expanded cohorts would provide more insights about the urothelial-urinary interactions.

MPTN: A message-passing transformer network for drug repurposing from knowledge graph.

Drug repurposing (DR) based on knowledge graphs (KGs) is challenging, which uses knowledge graph reasoning models to predict new therapeutic pathways for existing drugs. With the rapid development of computing technology and the growing availability of validated biomedical data, various knowledge graph-based methods have been widely used to analyze and process complex and novel data to discover new indications for given drugs. However, existing methods need to be improved in extracting semantic information from contextual triples of biomedical entities. In this study, we propose a message-passing transformer network named MPTN based on knowledge graph for drug repurposing. Firstly, CompGCN is used as precoder to jointly aggregate entity and relation embeddings. Then, to fully capture the semantic information of entity context triples, the message propagating transformer module is designed. The module integrates the transformer into the message passing mechanism and incorporates the attention weight information of computing entity context triples into the entity embedding to update the entity embedding. Next, the residual connection is introduced to retain information as much as possible and improve prediction accuracy. Finally, MPTN utilizes the InteractE module as the decoder to obtain heterogeneous feature interactions in entity and relation representations and predict new pathways for drug treatment. Experiments on two datasets show that the model is superior to the existing knowledge graph embedding (KGE) learning methods.

Postoperative acute kidney injury increases short- and long-term death risks in elderly patients (≥ 75 years old) undergoing coronary artery bypass graft surgery.

PURPOSE: To explore the incidence of postoperative acute kidney injury (AKI) after coronary artery bypass grafting (CABG) in elderly Chinese patients (≥ 75 years old) and its impacts on the short- and long-term prognosis. METHODS: A total of 493 patients aged 75-88 years old who underwent CABG from two medical centers between January 2006 and October 2021 were involved. Perioperative (preoperative and 7 days after operation) serum creatinine (Scr) levels were measured in all the enrolled patients. Univariate and multivariate logistic regression analyses were conducted to explore the independent risk factors of postoperative in-hospital mortality. Kaplan-Meier curves and COX model were used to test the risk factors of all-cause death during follow-up. Propensity score matching was used to balance differences between AKI and control groups. The primary outcome event was in-hospital death, and the secondary outcome was all-cause death during follow-up. RESULTS: The 198 patients were diagnosed with postoperative AKI. Intra-aortic balloon pump (IABP), cardiopulmonary bypass, and postoperative AKI were independent risk factors of in-hospital death. Gender, New York Heart Association Classification, preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI, and postoperative renal function all impacted long-term prognosis. After 1:1 matching, 190 patients were included in the AKI and control groups. Use of IABP, use of cardiopulmonary bypass, and occurrence of postoperative AKI were still independent risk factors of in-hospital death. Preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI and postoperative renal function all impacted long-term prognosis. CONCLUSION: The incidence of postoperative AKI in elderly patients undergoing CABG is high, and postoperative AKI is an independent risk factor of both short- and long-term postoperative prognosis.

Double-layer horizontal cross sutures for intra-atrial mitral valve implantation: An effective surgical method for severe mitral annular calcification.

Objective: Severe mitral annular calcification (MAC) can make prosthetic implantation extremely difficult. Although intra-atrial mitral valve prosthesis implantation without annular decalcification offers a simpler approach, it poses a potential rupture risk due to high left ventricular pressure. We developed a double-layer (DL) horizontal cross-suture technique, which ensures close proximity of the valve prosthesis to the calcified annulus and segregates the left atrial wall from the left ventricle. The aim of this study was to compare the outcomes of DL suture with conventional single-layer (SL) suture in patients with severe MAC. Methods: This retrospective cohort study consecutively enrolled patients with severe MAC undergoing mitral valve replacement at Beijing Anzhen Hospital from May 2018 to December 2022. A detailed description of the DL suture method is described. Follow-up medical evaluations, including transthoracic echocardiography measurements, were obtained through outpatient chart reviews. Results: The study included 10 patients in the DL suture group and 20 in the SL suture group. All patients in the DL group and all but 3 in the SL group achieved technical success. Compared with the SL group, the DL suture technique was associated with lower rates of perivalvular leakage, stroke, new-onset atrial fibrillation, reoperation, and 30-day mortality. Follow-up was complete, with 1 late mortality in the DL group due to stroke and 4 cardiovascular deaths in the SL group. Conclusions: The DL horizontal cross-suture technique offers a more effective and safer approach for intra-atrial mitral valve implantation in severe MAC cases than the conventional SL suture method.

Hypertonicity induces mitochondrial extracellular vesicles (MEVs) that activate TNF-α and ß-catenin signaling to promote adipocyte dedifferentiation.

BACKGROUND: Recent studies demonstrated that elevated osmolarity could induce adipocyte dedifferentiation, representing an appealing procedure to generate multipotent stem cells. Here we aim to elucidate the molecular mechanisms that underlie osmotic induction of adipocyte reprogramming. METHODS: To induce dedifferentiation, the 3T3-L1 or SVF adipocytes were cultured under the hypertonic pressure in 2% PEG 300 medium. Adipocyte dedifferentiation was monitored by aspect ratio measurement, Oil Red staining and qPCR to examine the morphology, lipid droplets, and specific genes of adipocytes, respectively. The osteogenic and chondrogenic re-differentiation capacities of dedifferentiated adipocytes were also examined. To investigate the mechanisms of the osmotic stress-induced dedifferentiation, extracellular vesicles (EVs) were collected from the reprograming cells, followed by proteomic and functional analyses. In addition, qPCR, ELISA, and TNF-α neutralizing antibody (20 ng/ml) was applied to examine the activation and effects of the TNF-α signaling. Furthermore, we also analyzed the Wnt signaling by assessing the activation of ß-catenin and applying BML-284, an agonist of ß-catenin. RESULTS: Hypertonic treatment induced dedifferentiation of both 3T3-L1 and the primary stromal vascular fraction (SVF) adipocytes, characterized by morphological and functional changes. Proteomic profiling revealed that hypertonicity induced extracellular vesicles (EVs) containing mitochondrial molecules including NDUFA9 and VDAC. Functionally, the mitochondrial EVs (MEVs) stimulated TNF-α signaling that activates Wnt-ß-catenin signaling and adipocyte dedifferentiation. Neutralizing TNF-α inhibited hypertonic dedifferentiation of adipocytes. In addition, direct activation of Wnt-ß-catenin signaling using BML-284 could efficiently induce adipocyte dedifferentiation while circumventing the apoptotic effect of the hypertonic treatment. CONCLUSIONS: Hypertonicity prompts the adipocytes to release MEVs, which in turn enhances the secretion of TNF-α as a pro-inflammatory cytokine during the stress response. Importantly, TNF-α is essential for the activation of the Wnt/ß-catenin signaling that drives adipocyte dedifferentiation. A caveat of the hypertonic treatment is apoptosis, which could be circumvented by direct activation of the Wnt/ß-catenin signaling using BML-284.

Electrostatic Self-Assembled Synthesis of Amorphous/Crystalline g-C3N4 Homo-Junction for Efficient Photocatalytic H2 Production with Simultaneous Antibiotic Degradation.

g-C3N4 has been regarded as a promising photocatalyst for photo-reforming antibiotics for H2 production but still suffers from its high charge recombination, which has been proven to be solvable by constructing a g-C3N4 homo-junction. However, those reported methods based on uncontrollable calcination for preparing a g-C3N4 homo-junction are difficult to reproduce. Herein, an amorphous/crystalline g-C3N4 homo-junction (ACN/CCN) was successfully synthesized via the electrostatic self-assembly attachment of negatively charged crystalline g-C3N4 nanorods (CCN) on positively charged amorphous g-C3N4 sheets (ACN). All the ACN/CCN samples displayed much higher photo-reforming of antibiotics for H2 production ability than that of pristine ACN and CCN. In particular, ACN/CCN-2 with the optimal ratio exhibited the best photocatalytic performance, with a H2 evolution rate of 162.5 µmol·g-1·h-1 and simultaneous consecutive ciprofloxacin (CIP) degradation under light irradiation for 4 h. The UV-vis diffuse reflectance spectra (DRS), photoluminescence (PL), and electrochemical results revealed that a homo-junction is formed in ACN/CCN due to the difference in the band arrangement of ACN and CCN, which effectively suppressed the charge recombination and then led to those above significantly enhanced photocatalytic activity. Moreover, H2 was generated from the water reduction reaction with a photogenerated electron (e-), and CIP was degraded via a photogenerated hole (h+). ACN/CCN exhibited adequate photostability and reusability for photocatalytic H2 production with simultaneous CIP degradation. This work provides a new idea for rationally designing and preparing homo-junction photocatalysts to achieve the dual purpose of chemical energy production and environmental treatment.

Proteomic profile of the germinating seeds reveals enhanced seedling growth in Arabidopsis rpp1a mutant.

Ribosomal phosphoprotein P1 (RPP1) is an integral component of the P-protein stalk in the 60S subunit of eukaryotic ribosomes and is required for the efficient elongation of translation. Previously, Arabidopsis RPP1A was revealed to be involved in the regulation of seed size and seed storage protein accumulation. In this work, the seedling growth analysis shows that the knockout mutation of Arabidopsis RPP1A significantly promoted seedling growth, particularly in the shoots. The label-free quantitative proteomic analysis demonstrated that a total of 593 proteins were differentially accumulated between the germinating seeds of the wild-type Col-0 and rpp1a mutant. And these proteins were significantly enriched in the intracellular transport, nitrogen compound transport, protein transport, and organophosphate metabolic process. The abundance of proteins involved in the RNA and protein processing processes, including ncRNA processing and protein folding, were significantly increased in the rpp1a mutant. Mutation in RPP1A highlighted the effects on the ribosome, energy metabolism, and nitrogen metabolism. The abundance of enzymes involved in glycolysis and pyruvate mechanism was decreased in the germinating seeds of the rpp1a mutant. Whereas the processes of amino acid biosynthesis, protein processing in endoplasmic reticulum, and biosynthesis of cofactors were enhanced in the germinating seeds of the rpp1a mutant. Taken together, the lack of RPP1A triggered changes in other ribosomal proteins, and the higher amino acid contents in the seedlings of the rpp1a mutant probably contributed to enhanced biosynthesis, processing, and transport of proteins, resulting in accelerated growth. Our results show the novel role of a P-protein and shed new light on the regulatory mechanism of seedling growth.

Preoperative prognostic nutritional index is an independent indicator for perioperative prognosis in coronary artery bypass grafting patients.

OBJECTIVES: The prognostic nutritional index is widely used for surgery prognosis, but the association between preoperative prognostic nutritional index and short-term prognosis for coronary artery bypass grafting surgery and the profiles of perioperative prognostic nutritional index remain unclear. METHODS: This study retrospectively enrolled a total of 879 adult patients undergoing coronary artery bypass grafting surgery in the Shanghai Chest Hospital from 2006 to 2022. The prognostic nutritional index was calculated based on serum albumin and peripheral lymphocyte count. In-hospital mortality, demographic characteristics, blood biochemistry parameters, cardiovascular medical history, and physical examination results were collected from the hospital information system. The propensity score matching method and multivariate logistic regression were used to detect the association between preoperative prognostic nutritional index and in-hospital mortality. RESULTS: Patients were divided into a high-prognostic nutritional index group (n = 500) and a low-prognostic nutritional index group (n = 379), using a cutoff value of 48.1 according to receiver operating characteristic curve analysis. The propensity score matching-adjusted mean prognostic nutritional index levels decreased from 48.35 before the operation to 34.04 an in ≤24 h after the operation and rebounded to 43.36 before discharge. High preoperative prognostic nutritional index was inversely associated with in-hospital mortality for coronary artery bypass grafting surgery (odds ratio = 0.86; 95% CI, 0.77-0.97) in propensity score matching-adjusted multivariate logistic regression. CONCLUSIONS: Preoperative prognostic nutritional index is an independent indicator for in-hospital mortality of for coronary artery bypass grafting surgery, and the variation trend of prognostic nutritional index during perioperation tends to be U-shaped.

Vitamin D status in hospitalized COVID­19 patients is associated with disease severity and IL-5 production.

BACKGROUND: There are many studies on the relationship between vitamin D and coronavirus disease 2019 (COVID-19), while the results are matters of debate and the mechanisms remain unknown. The present study was performed to assess the impact of serum 25-hydroxyvitamin D [25(OH)D] levels on the severity of disease in hospitalized COVID-19 patients and identify potential mechanisms of 25(OH)D alterations. METHODS: A total of 399 hospitalized COVID-19 patients were recruited from three centers between December 19, 2022, and February 1, 2023. Medical history, laboratory examination, and radiologic data were retrospectively collected. The patients were divided into four groups based on disease severity. Serum 25(OH)D levels in the patients were determined by the electrochemiluminescence method and cytokines were detected by flow cytometry. The relationship between serum 25(OH)D status and the severity of COVID-19, and the correlation between 25(OH)D levels and cytokines in COVID-19 patients were assessed. RESULTS: Levels of 25(OH)D were significantly lower in the deceased group than in the other three groups (P < 0.05), and lower in the critical group than in the general group (P < 0.05). There were no significant differences in the 25(OH)D levels between the general and severe groups (P > 0.05). The levels of 25(OH)D (odds ratio = 0.986, 95% confidence interval: 0.973-0.998, P = 0.024) and IL-5 (odds ratio = 1.239, 95% confidence interval: 1.104-1.391, P = 0.04) were independent risk factors for the severity of COVID-19 disease upon admission. Serum 25(OH)D levels were able to predict the mortality of patients with COVID-19, and the predictive value was even higher when combined with IL-5 levels and eosinophil (Eos) count. Circulating 25(OH)D status correlated negatively with the expression of IL-5 (r=-0.262, P < 0.001) and was positively linked with CD8+ T cell counts (r=-0.121, P < 0.05) in patients with COVID-19. CONCLUSIONS: This study found that the serum 25(OH)D status combined with IL-5 levels and Eos counts could be identified as a predictive factor for recognizing the risk of COVID-19 mortality. The serum 25(OH)D status in COVID-19 patients correlated negatively with the expression of IL-5. The potential mechanism for this relationship is worth further exploration.

IMA peptides function in iron homeostasis and cadmium resistance.

Iron (Fe), an essential micronutrient, participates in photosynthesis, respiration, and many other enzymatic reactions. Cadmium (Cd), by contrast, is a toxic element to virtually all living organisms. Both Fe deficiency and Cd toxicity severally impair crop growth and productivity, finally leading to human health issues. Understanding how plants control the uptake and homeostasis of Fe and combat Cd toxicity thus is mandatory to develop Fe-enriched but Cd-cleaned germplasms for human beings. Recent studies in Arabidopsis and rice have revealed that IRON MAN (IMA) peptides stand out as a key regulator to respond to Fe deficiency by competitively interacting with a ubiquitin E3 ligase, thus inhibiting the degradation of IVc subgroup bHLH transcription factors (TFs), mediated by 26 S proteasome. Elevated expression of IMA confers tolerance to Cd stress in both Arabidopsis and wheat by activating the iron deficiency response. Here, we discuss recent breakthroughs that IMA peptides function in the Fe-deficiency response to attain Fe homeostasis and combat Cd toxicity as a potential candidate for phytoremediation.

A Novel Thermal Tactile Sensor Based on Micro Thermoelectric Generator for Underwater Flow Direction Perception.

Underwater vehicles can operate independently in the exploitation of marine resources. However, water flow disturbance is one of the challenges underwater vehicles must face. The underwater flow direction sensing method is a feasible way to overcome the challenges but faces difficulties such as integrating the existing sensors with underwater vehicles and high-cost maintenance fees. In this research, an underwater flow direction sensing method based on the thermal tactility of the micro thermoelectric generator (MTEG) is proposed, with the theoretical model established. To verify the model, a flow direction sensing prototype is fabricated to carry out experiments under three typical working conditions. The three typical flow direction conditions are: condition No. 1, in which the flow direction is parallel to the x-axis; condition No. 2, in which the flow direction is at an angle of 45° to the x-axis; and condition No. 3, which is a variable flow direction condition based on condition No. 1 and condition No. 2. According to the experimental data, the variations and orders of the prototype output voltages under three conditions fit the theoretical model, which means the prototype can identify the flow direction of three conditions. Besides, experimental data show that in the flow velocity range of 0~5 m/s and the flow direction variation range of 0~90°, the prototype can accurately identify the flow direction in 0~2 s. The first time utilizing MTEG on underwater flow direction perception, the underwater flow direction sensing method proposed in this research is cheaper and easier to be applied on the underwater vehicles than traditional underwater flow direction sensing methods, which means it has great application prospects in underwater vehicles. Besides, the MTEG can utilize the waste heat of the underwater vehicle battery as the energy source to achieve self-powered work, which greatly enhances its practical value.

Advances of Liquid Biopsy for Diagnosis of Atrial Fibrillation and Its Recurrence After Ablation in Clinical Application.

Atrial fibrillation (AF) is a common arrhythmia disease with high morbidity in clinical practice and leads to stroke, heart failure, peripheral embolism, and other severe complications. With aging of the society, AF has become one of the biggest public health challenges. Effective treatments including antiarrhythmic drugs, electrical cardioversion, and ablation (with or without catheters) can alleviate the symptoms of AF. Ablation is the most effective method for the treatment of persistent AF, but cannot cure all patients. Recurrence of AF is a realistic and unavoidable problem. For early predicting and warning of AF and its recurrence, liquid biopsy for accurate molecular analysis of biofluids is a new strategy with potential value and easy sampling and can detect genetic and epigenetic polymorphisms, especially microRNAs. In this review, liquid biopsy is constructed as a new powerful way for diagnosing AF and predicting its recurrence, contributing to the treatment of AF.

Label-Free Quantitative Proteomics in Plant.

Label-free quantitation (LFQ) proteomics, mainly based on the extraction of the peptide (precursor) intensity at the MS1 (mass spectrum 1) level, enables to quantify the relative amount of the proteins among samples. In an LFQ proteomics study, all samples are scanned individually on an advanced mass spectrometer and the chromatographic features of each run are extracted to generate consensus patterns among various runs in the experiment. Here, we describe the LFQ proteomics experimental protocol adapted for plant research, such as plant iron homeostasis.

Comparative physiological and proteomic response to phosphate deficiency between two wheat genotypes differing in phosphorus utilization efficiency.

Genetic variation in phosphorus utilization efficiency (PUE) widely exists among wheat genotypes. However, the underlying mechanisms are still unclear. Two contrasting wheat genotypes, Heng4399 (H4399) and Tanmai98 (TM98), were screened out from 17 bread wheat genotypes based on shoot soluble phosphate (Pi) concentrations. The TM98 had a significantly higher PUE than the H4399, especially under Pi deficiency. The induction of genes in the PHR1-centered Pi signaling pathway was significantly higher in TM98 than in H4399. Collectively, through a label-free quantitative proteomic analysis, 2110 high-confidence proteins were identified in shoots of the two wheat genotypes. Among them, 244 and 133 proteins were differentially accumulated under Pi deficiency in H4399 and TM98, respectively. The abundance of proteins related to nitrogen and phosphorus metabolic processes, small molecule metabolic process, and carboxylic acid metabolic process weas significantly affected by Pi deficiency in the shoots of the two genotypes. The abundance of proteins in energy metabolism, especially photosynthesis, was decreased by Pi deficiency in the shoots of H4399. Inversely, the PUE-efficient genotype TM98 could maintain protein abundance in energy metabolism. Moreover, the proteins involved in pyruvate metabolism, glutathione metabolism, and sulfolipid biosynthesis were significantly accumulated in TM98, which probably contributed to its high PUE. SIGNIFICANCE: Improving the PUE of wheat is urgent and crucial for sustainable agriculture. Genetic variation among wheat genotypes provides materials for exploring the underlying mechanisms for high PUE. This study selected two wheat genotypes with contrasting PUE to reveal the differences in the physiological and proteomic responses to phosphate deficiency. The PUE-efficiency genotype TM98 greatly induced the expression of genes in the PHR1-centered Pi signaling pathway. Subsequently, the TM98 could maintain the abundance of proteins related to energy metabolism and enhance the abundance of proteins involved in pyruvate metabolism, glutathione metabolism, and sulfolipid biosynthesis to increase PUE under Pi deficiency. The differentially expressed genes or proteins between the genotypes with contrasting PUE would provide potential and basis for breeding wheat varieties with improved phosphorus use efficiency.

Prognostic significance of the CRAFITY score in hepatocellular carcinoma treated with immunotherapy: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the performance of the CRAFITY (CRP and AFP in immunotherapy) score as a prognostic factor in hepatocellular carcinoma (HCC) treated with immunotherapy. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched for published studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) outcomes were pooled using fixed- and random-effects models. Odds ratios (ORs) with 95% CI were used to measure the association of individual CRAFITY scores with the disease control rate (DCR). RESULTS: Four eligible studies comprising 786 patients were included. The results indicate that a lower CRAFITY score is a significant predictor of better OS (HR = 0.22, 95% CI: 0.10-0.50) and PFS (HR = 0.36, 95% CI: 0.23-0.55) outcomes. In addition, the DCR was significantly higher in patients with lower CRAFITY scores (OR = 3.16, 95% CI: 2.00-4.99). A significant positive association between low CRAFITY scores and favorable prognoses was also observed in Barcelona Clinic Liver Cancer stage B/C/D patients. CONCLUSION: In this study, a low CRAFITY score was associated with better overall outcomes in HCC patients treated with immunotherapy. However, this finding requires further investigation.

A Self-Propagating c-Met-SOX2 Axis Drives Cancer-Derived IgG Signaling That Promotes Lung Cancer Cell Stemness.

SIGNIFICANCE: Sialylated cancer IgG activates c-Met-SOX2 signaling to promote stemness properties in cancer cells and can be targeted to suppress tumor growth.

Metabolic signatures in pericardial fluid and serum are associated with new-onset atrial fibrillation after isolated coronary artery bypass grafting.

Postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass grafting (CABG) procedures. However, the molecular mechanism of POAF remains poorly understood, hence the absence of effective prevention strategies. Here we used targeted metabolomics on pericardial fluid and serum samples from CABG patients to investigate POAF-associated metabolic alterations and related risk prediction of new-onset AF. Nine differential metabolites in various metabolic pathways were found in both pericardial fluid and serum samples from patients with POAF and without POAF. By using machine learning algorithms and regression models, a 4-metabolite (aceglutamide, ornithine, methionine, and arginine) risk prediction model was constructed and showed accurate performance in predicting POAF in both discovery and validation sets. This work extends the metabolic insights of the cardiac microenvironment and blood in patients with POAF and paves the way for the use of targeted metabolomics for predicting POAF in patients with CABG surgery.

Costs and Effects of School-Based Licensed Practical Nurses on Elementary Student Attendance and Chronic Absenteeism.

Despite increasing reliance on licensed practical nurses (LPNs) to provide health services in schools, we do not know whether this is a cost-effective prevention strategy against student absenteeism. Therefore, we evaluated the costs and effectiveness of an LPN-based school nursing program for improving attendance and chronic absenteeism at a large, urban school district in the southeastern USA. We first identified a matched set of 46 elementary schools (23 nurse, 23 no-nurse) by using an optimal multilevel matching algorithm based on student- and school-level characteristics. We then conducted a cost-effectiveness analysis on the matched set, using the ingredients method to estimate societal costs and multilevel regression to estimate effects. The results indicated that despite substantial incremental costs of $68,228 per school, the presence of a full-time LPN was associated with at best negligible improvements, and at worst slight disimprovements, in attendance and chronic absenteeism. We recommend a careful review of the theory of change for LPN-based school nursing programs to clarify the specific inputs and activities that are expected to lead to improved student outcomes. Education agencies should develop explicit assignment, training, monitoring, and auditing plans to ensure LPNs are equitably distributed and that their activities are aligned with the theory of change. Education agencies should also explore whether expanded Medicaid billing can reduce their share of the nursing cost burden.

Prediction of bronchodilation test in adults with chronic cough suspected of cough variant asthma.

Background: Many patients with cough variant asthma (CVA) are underdiagnosed and undertreated due to the atypical symptoms, low diagnostic sensitivity of bronchodilator response (BDR), and limited application of bronchial challenge test. Objective: To investigate whether airway reversibility in BDR can predict CVA diagnosis in patients with chronic cough and negative BDR. Methods: This open-label, prospective cohort study included patients with chronic cough, nearly normal chest CT scan, and negative BDR results. Inhaled corticosteroids and long-acting ß2 agonists were given for 4 weeks. The confirmed diagnosis of CVA was defined as improved symptoms and an increase of forced expiratory volume in 1 s (FEV1) by >12% and >200 mL after 4 weeks of treatment. Results: Of 155 patients recruited, 140 completed the study. Patients in the CVA positive diagnosis group had greater absolute (Δ) and percent (Δ%) improvements in FEV1 and forced expiratory flows (FEFs), and higher fractional exhaled nitric oxide (FENO) than in the CVA negative diagnosis group. The area under the receiver operating characteristic curves (AUCs) of ΔFEV1%, FEF25-75%pred (percentage of predicted forced expiratory flow at 25% to 75%) and FENO for CVA positive diagnosis was 0.825, 0.714, and 0.637, with cutoff values of 5.90%, 61.99% and 41.50 ppb, respectively. A joint model of ΔFEV1% combined with FEF25-75%pred or FENO increased the AUC to 0.848 and 0.847, respectively. Conclusion: ΔFEV1% in BDR can predict a CVA diagnosis and response to anti-asthma treatment in patients with chronic cough and negative BDR. Clinical trial registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2000029065].