Galectin-3 contributes to pathogenesis of IgA nephropathy.

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis, and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.

Interstitial fibrosis increases the risk of end-stage kidney disease in patients with lupus nephritis.

OBJECTIVE: To evaluate the risk of end-stage kidney disease (ESKD) in LN patients using tubulointerstitial lesion scores. METHODS: Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions [e.g. interstitial inflammation (II), tubular atrophy (TA) and interstitial fibrosis (IF)] were analysed. RESULTS: The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n = 3, 2%), class III/IV (n = 119, 78.8%), class V (n = 23, 15.2%) and class VI (n = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, nine (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine [hazard ratio (HR): 1.7, 95% CI: 1.42-2.03, P < 0.001] and IF (HR: 3.2, 95% CI: 1.58-6.49, P = 0.001) as independent risk factors of ESKD. Kaplan-Meier analysis further confirmed a heightened risk of ESKD associated with IF. CONCLUSION: Tubulointerstitial involvement is commonly observed in the histopathological presentation of LN. However, IF, rather than II or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, the degree of IF should be reviewed.

Risk Factors and Incidence of Serious Infections in Patients With Systemic Lupus Erythematosus Undergoing Rituximab Therapy.

OBJECTIVE: To evaluate the risk and protective factors of serious infection (SI) in patients with systemic lupus erythematosus (SLE) within 180 days of rituximab (RTX) treatment. METHODS: Patients with SLE treated with RTX were analyzed. SI was defined as any infectious disease requiring hospitalization. The clinical characteristics, laboratory profiles, medications, and incidence rate (IR) are presented. Multivariate Cox proportional hazards models and Kaplan-Meier analysis for risk factors of SI were performed. RESULTS: A total of 174 patients with SLE receiving RTX treatment were enrolled. The overall IR of SIs was 51.0/100 patient-years (PYs). Pneumonia (30.4/100 PYs), followed by soft tissue infections, intra-abdominal infections, and Pneumocystis jiroveci pneumonia (all 6.1/100 PYs) were the leading types of SIs. Twelve patients died during the 180-day follow-up (crude mortality rate: 14.6/100 PYs). Chronic kidney disease (CKD), defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 (hazard ratio [HR] 2.88, 95% CI 1.30-6.38), and a background prednisolone (PSL) equivalent dosage ≥ 15 mg/day (HR 3.50, 95% CI 1.57-7.78) were risk factors for SIs among all patients with SLE. Kaplan-Meier analysis confirmed the risk of SI for patients with SLE with CKD and a background PSL equivalent dosage ≥ 15 mg/day (log-rank P = 0.001 and 0.02, respectively). Hydroxychloroquine (HCQ) reduced the risk of SIs in patients with SLE (HR 0.35, 95% CI 0.15-0.82; log-rank P = 0.003). CONCLUSION: SI was prevalent in patients with SLE after RTX treatment. Patients with SLE with CKD and high-dose glucocorticoid use required constant vigilance. HCQ may reduce the risk of SI among patients with SLE administered RTX.

Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation.

Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.

Circulating Osteocalcin Fractions are Associated with Vascular Calcification and Mortality in Chronic Hemodialysis Patients.

BACKGROUND: Vascular calcification, a component of chronic kidney disease-mineral and bone disorder (CKD-MBD), is prevalent in patients with end-stage kidney disease (ESKD) and contributes to high mortality. However, the association between the blood level of total osteocalcin (OC) and vascular calcification and mortality remains inconclusive. We, therefore, investigated whether different OC fractions can serve as biomarkers of vascular calcification and mortality in the ESKD population. METHODS: This observational cohort study enrolled patients on maintenance hemodialysis. Plasma carboxylated OC (cOC), uncarboxylated OC (ucOC), and intact parathyroid hormone (PTH) were measured. The percentage of carboxylated OC (%cOC) was calculated as dividing cOC by total OC. The vascular calcification severity was defined by an aortic calcification grade. The patients were followed for three years and one month. RESULTS: A total of 184 patients were enrolled. In the multivariable logistic regression, plasma %cOC, but not cOC or ucOC, was independently associated with the severity of vascular calcification (OR 1.019, p = 0.036). A significant U-shaped correlation was found between plasma %cOC and PTH (p = 0.002). In the multivariable Cox regression, patients with higher plasma %cOC had a higher risk of mortality (quartiles Q4 versus Q1-Q3, HR 1.991 [95% CI: 1.036-3.824], p = 0.039). CONCLUSIONS: In patients undergoing chronic hemodialysis, plasma %cOC positively correlated with vascular calcification and exhibited a U-shaped correlation with PTH. Furthermore, a higher plasma %cOC was associated with increased mortality. These findings suggest that plasma %cOC may serve as a biomarker for CKD-MBD and a predictor of clinical outcomes in chronic hemodialysis patients.

Mechanotransduction of mesenchymal stem cells and hemodynamic implications.

Mesenchymal stem cells (MSCs) possess the capacity for self-renewal and multipotency. The traditional approach to manipulating MSC's fate choice predominantly relies on biochemical stimulation. Accumulating evidence also suggests the role of physical input in MSCs differentiation. Therefore, investigating mechanotransduction at the molecular level and related to tissue-specific cell functions sheds light on the responses secondary to mechanical forces. In this review, a new frontier aiming to optimize the cultural parameters was illustrated, i.e. spatial boundary condition, which recapitulates in vivo physiology and facilitates the investigations of cellular behavior. The concept of mechanical memory was additionally addressed to appreciate how MSCs store imprints from previous culture niches. Besides, different types of forces as physical stimuli were of interest based on the association with the respective signaling pathways and the differentiation outcome. The downstream mechanoreceptors and their corresponding effects were further pinpointed. The cardiovascular system or immune system may share similar mechanisms of mechanosensing and mechanotransduction; for example, resident stem cells in a vascular wall and recruited MSCs in the bloodstream experience mechanical forces such as stretch and fluid shear stress. In addition, baroreceptors or mechanosensors of endothelial cells detect changes in blood flow, pass over signals induced by mechanical stimuli and eventually maintain arterial pressure at the physiological level. These mechanosensitive receptors transduce pressure variation and regulate endothelial barrier functions. The exact signal transduction is considered context dependent but still elusive. In this review, we summarized the current evidence of how mechanical stimuli impact MSCs commitment and the underlying mechanisms. Future perspectives are anticipated to focus on the application of cardiovascular bioengineering and regenerative medicine.

An eighth note.

Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.

Evaluating the resource recovery efficiency of garbage removal and disposal in Taiwan.

All countries recognize the importance of enhancing circular resource utilization and promoting zero waste in order to achieve a circular economy. This study focuses on 22 counties (cities) in Taiwan and analyses the relationship between changes in resource recovery efficiency and productivity over an 8-year period (2011-2018) using the super efficiency directional distance function and total factor productivity. The results indicate that the average total efficiency of resource recovery in the 22 counties (cities) is 1.3951, with 17 counties (cities) exceeding 1. The average gross productivity of resource recovery is 1.0417, and only four counties have a gross productivity of less than 1. Despite having more administrative resources, municipalities directly under the central government have a slightly lower average total efficiency of resource recovery (1.1464) than non-municipalities (1.4885). To improve efficiency, the government should allocate resources rationally and upgrade technology. The study's findings can serve as a reference for the 22 counties (cities) in Taiwan and provide guidance for municipal governments worldwide in developing policies related to resource recovery.

Pentraxin 3 Predicts Arteriovenous Fistula Functional Patency Loss and Mortality in Chronic Hemodialysis Patients.

INTRODUCTION: Viable vascular access is the lifeline for hemodialysis patients. In the nondialysis population, emerging evidence suggests that circulating pentraxin 3 (PTX3), neutrophil gelatinase-associated lipocalin (NGAL), and chitinase-3-like protein 1 (CHI3L1) are associated with cardiovascular inflammation and endothelial injury. However, predictive values of these three biomarkers on arteriovenous fistula (AVF) outcomes are unknown. METHODS: This prospective observational cohort study enrolled 135 hemodialysis patients using AVF and then followed them for 3 years. Plasma levels of PTX3, NGAL, and CHI3L1 were measured. Patients were followed up prospectively for two clinical outcomes, including AVF functional patency loss and death. Cox proportional hazards regression models were used to analyze hazard ratios for the commencement of AVF functional patency loss and mortality. RESULTS: Among 135 patients, the mean age was 66.0 ± 15.7 years old and 48.1% were male. The plasma level of PTX3, NGAL, and CHI3L1 was 2.8 ± 2.3 ng/mL, 349.2 ± 111.4 ng/mL, and 185.5 ± 66.8 ng/mL, respectively. During a 3-year follow-up period, the plasma level of PTX3 was an independent predictor for AVF functional patency loss (per 1 ng/mL increase, HR 1.112 [95% CI: 1.001-1.235], p = 0.048). Besides, patients with higher plasma levels of PTX3 were more likely to suffer from cardiovascular mortality (per 1 ng/mL increase, HR 1.320 [95% CI: 1.023-1.703], p = 0.033), infectious mortality (per 1 ng/mL increase, HR 1.394 [95% CI: 1.099-1.769], p = 0.006), and all-cause mortality (per 1 ng/mL increase, HR 1.233 [95% CI: 1.031-1.476], p = 0.022). CONCLUSIONS: The plasma level of PTX3, not NGAL or CHI3L1, was associated with higher risks of AVF functional patency loss in chronic hemodialysis patients, showing its value in reflecting AVF endothelial dysfunction. Furthermore, PTX3 also predicts mortality in chronic hemodialysis patients.

Mechanical and chemical cues synergistically promote human venous smooth muscle cell osteogenesis through integrin ß1-ERK1/2 signaling: A cell model of hemodialysis fistula calcification.

Arteriovenous fistula (AVF) is the vascular access of choice for renal replacement therapy. However, AVF is susceptible to calcification with a high prevalence of 40%-65% in chronic hemodialysis patients. Repeated needle puncture for hemodialysis cannulation results in intimal denudation of AVF. We hypothesized that exposure to blood shear stress in the medial layer promotes venous smooth muscle cell (SMC) osteogenesis. While previous studies of shear stress focused on arterial-type SMCs, SMCs isolated from the vein had not been investigated. This study established a venous cell model of AVF using the fluid shear device, combined with a high phosphate medium to mimic the uremic milieu. Osteogenic gene expression of venous SMCs upon mechanical and chemical cues was analyzed in addition to the activated cell signaling pathways. Our findings indicated that upon shear stress and high phosphate environment, mechanical stimulation (shear stress) had an additive effect in up-regulation of an early osteogenic marker, Runx2. We further identified that the integrin ß1-ERK1/2 signaling pathway was responsible for the molecular basis of venous SMC osteogenesis upon shear stress exposure. Mitochondrial biogenesis also took part in the early stage of this venopathy pathogenesis, evident by the up-regulated mitochondrial transcription factor A and mitochondrial DNA polymerase γ in venous SMCs. In conclusion, synergistic effects of fluid shear stress and high phosphate induce venous SMC osteogenesis via the ERK1/2 pathway through activating the mechanosensing integrin ß1 signaling. The present study identified a promising druggable target for reducing AVF calcification, which deserves further in vivo investigations.

Cf-02, a novel benzamide-linked small molecule, blunts NF-κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice.

In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide-linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02) (a) reduced serum levels of IgG anti-dsDNA, IL-1ß, IL-6, and TNF-α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF-κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf-02 significantly inhibited secretion of IL-1ß in lipopolysaccharide-stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf-02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf-02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome-driven signaling.

Mortality rate of end-stage kidney disease patients in Taiwan.

BACKGROUND/PURPOSE: End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD. METHODS: We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018. RESULTS: From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally. CONCLUSION: From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.

2022 Taiwan lipid guidelines for primary prevention.

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Early control of LDL-C to prevent ASCVD later in life is important. The Taiwan Society of Lipids and Atherosclerosis in association with the other seven societies developed this new lipid guideline focusing on subjects without clinically significant ASCVD. In this guideline for primary prevention, the recommended LDL-C target is based on risk stratification. A healthy lifestyle with recommendations for foods, dietary supplements and alcohol drinking are described. The pharmacological therapies for LDL-C reduction are recommended. The aim of this guideline is to decrease the risk of ASCVD through adequate control of dyslipidemia in Taiwan.

Water reduces iron toxicity.

An 86-year-old man presented to the emergency room with vomiting and melena. The patient was hemodynamically stable and remained alert and orientated. According to his family, ingestion of a pack of disposable hand warmers, which he mistook for black sesame powder, occurred 17 h prior to admission. Before ingestion, he mixed the powder with warm water. Physical examination revealed no thermal injury of the oral mucosa with no abdominal pain or tenderness. An abdominal plain film showed multiple scattered radiopaque material with zonal distribution over the right abdomen. An intravenous 500-mg deferoxamine challenge test showed no vin rosé urine discoloration. Serial serum iron levels remained within the normal range. The patient remained clinically stable with no medical complications. He was discharged 3 days after admission. The hand warmers consisted of iron powder (50% w/w), sodium chloride, activated charcoal, and nontoxic vermiculite: a potential risk for intestinal thermal injury. In this case, the water added beforehand rapidly terminated the iron oxidation reaction. This explained the lack of thermal injury. Ferric oxide is poorly absorbed by the digestive tract and explained the absence of iron intoxication. Therefore, clinicians should clarify the method of ingestion. If a hand warmer has been premixed with water, less mucosa injury can be expected with a lower risk of iron intoxication. This report also provided evidence that abdominal plain films can be used to confirm the ingestion of iron and monitor its elimination.

Inverse Relationship between Mean Corpuscular Volume and T-Score in Chronic Dialysis Patients.

Background and Objectives: Osteoporosis and anemia are prevalent among chronic kidney disease stage 5D (CKD stage 5D) patients. Osteoblasts are known as the niche cells of hematopoietic stem cells (HSCs) and stimulate HSCs to form blood-cell lineages within bone marrow microenvironments. We hypothesized that an inverse correlation may exist between mean corpuscular volume (MCV), a surrogate for ineffective hematopoiesis, and bone mineral density (BMD) in the CKD stage 5D population. Materials and Methods: This is a cross-sectional designed cohort study evaluating CKD stage 5D patients who have received dialysis therapy for over three months. Baseline clinical characteristics and laboratory data were prospectively collected. The dual-energy X-ray absorptiometry (DXA) method was used to measure BMD at five sites, which were bilateral femoral neck, total hip, and lumbar spine 1-4. The Pearson correlation test was initially adopted, and a multivariate linear regression model was further applied for potential confounder adjustments. Results: From September 2020 to January 2021, a total of 123 CKD stage 5D patients were enrolled. The Pearson correlation test revealed a significant inverse association between MCV and BMD at bilateral femoral neck and lumbar spine. The lowest T-score of the five body sites was determined as the recorded T-score. After adjustments for several potential confounding factors, the multivariate linear regression model found consistent negative associations between T-score and MCV. Conclusions: The present study found significant inverse correlations between MCV and BMD at specific body locations in patients on dialysis. A decreased T-score was also found to be associated with macrocytosis after adjustments for confounding variables. However, direct evidence for the causative etiology was lacking.

IgM mesangial deposition as a risk factor for relapses of adult-onset minimal change disease.

BACKGROUND: Immunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive. METHODS: In this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups. RESULTS: Analysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116-0.784, p = 0.010). CONCLUSIONS: Our findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.

Machine Learning Analysis of Time-Dependent Features for Predicting Adverse Events During Hemodialysis Therapy: Model Development and Validation Study.

BACKGROUND: Hemodialysis (HD) therapy is an indispensable tool used in critical care management. Patients undergoing HD are at risk for intradialytic adverse events, ranging from muscle cramps to cardiac arrest. So far, there is no effective HD device-integrated algorithm to assist medical staff in response to these adverse events a step earlier during HD. OBJECTIVE: We aimed to develop machine learning algorithms to predict intradialytic adverse events in an unbiased manner. METHODS: Three-month dialysis and physiological time-series data were collected from all patients who underwent maintenance HD therapy at a tertiary care referral center. Dialysis data were collected automatically by HD devices, and physiological data were recorded by medical staff. Intradialytic adverse events were documented by medical staff according to patient complaints. Features extracted from the time series data sets by linear and differential analyses were used for machine learning to predict adverse events during HD. RESULTS: Time series dialysis data were collected during the 4-hour HD session in 108 patients who underwent maintenance HD therapy. There were a total of 4221 HD sessions, 406 of which involved at least one intradialytic adverse event. Models were built by classification algorithms and evaluated by four-fold cross-validation. The developed algorithm predicted overall intradialytic adverse events, with an area under the curve (AUC) of 0.83, sensitivity of 0.53, and specificity of 0.96. The algorithm also predicted muscle cramps, with an AUC of 0.85, and blood pressure elevation, with an AUC of 0.93. In addition, the model built based on ultrafiltration-unrelated features predicted all types of adverse events, with an AUC of 0.81, indicating that ultrafiltration-unrelated factors also contribute to the onset of adverse events. CONCLUSIONS: Our results demonstrated that algorithms combining linear and differential analyses with two-class classification machine learning can predict intradialytic adverse events in quasi-real time with high AUCs. Such a methodology implemented with local cloud computation and real-time optimization by personalized HD data could warn clinicians to take timely actions in advance.

Molecular Mechanisms of Mesenchymal Stem Cell-Based Therapy in Acute Kidney Injury.

Acute kidney injury (AKI) causes a lot of harm to human health but is treated by only supportive therapy in most cases. Recent evidence shows that mesenchymal stem cells (MSCs) benefit kidney regeneration through releasing paracrine factors and extracellular vesicles (EVs) to the recipient kidney cells and are considered to be promising cellular therapy for AKI. To develop more efficient, precise therapies for AKI, we review the therapeutic mechanism of MSCs and MSC-derived EVs in AKI and look for a better understanding of molecular signaling and cellular communication between donor MSCs and recipient kidney cells. We also review recent clinical trials of MSC-EVs in AKI. This review summarizes the molecular mechanisms of MSCs' therapeutic effects on kidney regeneration, expecting to comprehensively facilitate future clinical application for treating AKI.

Evaluating the energy, health efficiency, and productivity in OECD.

In the past, energy and environmental research focused on the performance of individual efficiencies. In order to make up for the research deficiencies, this research uses SBM (slack-based measures) dynamic network DEA (DN-SBM) to assess energy, health efficiency, and DN-TFP productivity changes from 2011 to 2015. This research uses forest area as the carryover that can objectively measure the performance of OECD energy, health, and total efficiency, and calls for the importance of forest protection and planting. The empirical results show that Estonia, Finland, Hungary, Iceland, Mexico, New Zealand, Portugal, Slovenia, Sweden, and Turkey have the best overall efficiency performance, while Ireland (0.4469), Israel (0.4179), and the Netherlands (0.3697) are the three worst. In total, 29 economies show progress in terms of productivity. Moreover, Chile (0.9706), Mexico (0.9995), Slovak Republic (0.9942), Turkey (0.9815), and the UK (0.9886) exhibit a slight decline. The overall efficiency value of 20 countries is greater than the average, and their productivity is showing an upward trend. Only the UK (0.5081, 0.9886) has an overall efficiency value that is less than the overall average with productivity that is showing a drop. About research method, this study utilizes dynamic intertemporal data to evaluate the changes in the overall efficiency and productivity of OECD members with DN-SBM and DN-TFP indices in order to offer more objective research results for various economies that are useful for formulating policies related to energy, national health, and forest conservation.

Aggregation Temperature of Escherichia coli Depends on Steepness of the Thermal Gradient.

Bacterial chemotaxis, the directed migration of bacteria in a gradient of chemoattractant, is one of the most well-studied and well-understood processes in cell biology. On the other hand, bacterial thermotaxis, the directed migration of bacteria in a gradient of temperature, is understood relatively poorly, with somewhat conflicting reports by different groups. One of the reasons for that is the relative technical difficulty of the generation of well-defined gradients of temperature that are sufficiently steep to elicit readily detectable thermotaxis. Here, we used a specially designed microfluidic device to study thermotaxis of Escherichia coli in a broad range of thermal gradients with a high rate of data collection. We found that in shallow temperature gradients with narrow temperature ranges, E. coli tended to aggregate near a sidewall of the gradient channel at either the lowest or the highest temperature. On the other hand, in sufficiently steep gradients with wide temperature ranges, E. coli aggregated at intermediate temperatures, with maximal cell concentrations found away from the sidewalls. We observed this intermediate temperature aggregation in a motility buffer that did not contain any major chemoattractants of E. coli, in contradiction to some previous reports, which suggested that this type of aggregation required the presence of at least one major chemoattractant in the medium. Even more surprisingly, the aggregation temperature strongly depended on the gradient steepness, decreasing by ∼10° as the steepness was increased from 27 to 53°C/mm. Our experiments also highlight the fact that assessments of thermal gradients by changes in fluorescence of temperature-sensitive fluorescent dyes need to account for thermophoresis of the dyes.