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(1) Background: Klotho is a multifunctional protein, but its biophysiological roles during fish early development are unclear. (2) Methods: We carried out anti-sense Klotho morpholino injection and whole-mount in situ hybridization experiments in this study. (3) Results: Our results showed that in the Klotho MO1-injected group, embryos displayed longitudinal shapes and swelling yolks compared to those of the un-injected groups. Their length/width ratio by 9 hpf for the uninfected group is 1 ± 0.1; but for 0.1 mM-, 0.2 mM-, and 0.5 mM-MO-injected are 1.1 ± 0.1, 1.2 ± 0.1, and 1.3 ± 0.1, respectively, suggesting that the klotho knockdown-induced length/width ratio changes are in a dose-dependent manner. Whole-mount in situ hybridization showed that several cell migration-related gene expressions, including goosecoid, floating head, bone morphogenetic protein 4, and even-skipped-liked 1 were affected in the Klotho MO-injected embryos. (4) Conclusions: We suggest that knockdown of klotho leads to cell movement impairment during zebrafish gastrulation. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) and cloud technologies have significantly facilitated healthcare. In such a context, medical data are collected by the terminals from the patients, manipulated, and stored on the cloud by hospitals (doctors). This brings asymmetry problems in medical data access control, processing, and storage between doctors and patients, which results in medical data sharing face many challenges such as privacy leakage and malicious feedback from cloud servers on queries. To solve these asymmetry problems, this paper proposes a medical data sharing scheme with cloud-chain cooperation and policy fusion in the IoT. Regarding asymmetrical access control rights, a conflict resolution and fusion algorithm that enables co-authorization of medical data by the doctor and the patient is introduced. To balance the symmetry of medical data storage and processing, a cloud-chain cooperation ciphertext retrieval method is proposed by means of two-stage joint searching from cloud servers and the blockchain, which can not only detect malicious medical data feedback from cloud servers, but also improve the data search efficiency. The security analysis showed that this scheme satisfies the confidentiality and verifiability of the retrieved information, and the feasibility of the proposed scheme was demonstrated through experiments. [ABSTRACT FROM AUTHOR]

Background: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. Methods: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. Results: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. Conclusions: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects. [ABSTRACT FROM AUTHOR]

Background: Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. Previous studies have shown that KDM4C may also play a role in mediating stress responses. The purpose of this study was to examine the roles of KDM4C in kidney development and acute kidney injury (AKI). Methods: The effect of KDM4C on kidney development was assessed by comparing the kidney phenotype between 96 zebrafish embryos treated with kdm4c-morpholino oligonucleotide and 96 untreated zebrafish embryos. We further examined whether KDM4C is essential for maintaining cell survival in AKI. Cultured human renal tubular cells were used for the in vitro study. Wild-type and Kdm4c knockout mice (C57BL/6NTac-Kdm4ctm1a(KOMP)Wtsi) were divided into a sham group and model group, and then subjected to ischemic reperfusion kidney injury (IRI-AKI). Blood samples and kidneys were collected at different time points (day 3, day 7, day 14, and day 28) and were processed for in vivo studies (n = 8 in each group). Results: Kdm4c knockdown significantly decreased zebrafish embryo survival and impaired kidney development. The in vitro study showed that KDM4C inhibition by JIB04 significantly increased cellular apoptosis under oxidative stress conditions. KDM4C knockdown cells had impaired autophagy function under stress conditions. The IRI-AKI mice study showed that KDM4C protein levels dynamically changed and were significantly correlated with HIF-1α levels in AKI. Kdm4c−/− mice had significantly more severe renal impairment and increased kidney fibrosis than the wild-type mice. Cytokine array results also indicated that the kidneys of Kdm4c−/− mice had increased inflammation in AKI compared with the wild-type mice. Further RNA sequence analysis revealed that KDM4C may regulate transcription factors related to mitochondrial dynamics and function. Conclusions: Our study suggests that KDM4C may play a critical role in regulating mitochondria, which is related to a protective effect on maintaining cell survival in AKI. [ABSTRACT FROM AUTHOR]

Background: Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. Methods: This prospective observational cohort study enrolled 261 patients with CKD stages 1–5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. Results: The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (β ± SE: 24.298 ± 8.616, p = 0.005; 60.316 ± 21.875, p = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both p < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, p = 0.019). Conclusion: Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival. [ABSTRACT FROM AUTHOR]

Background: Clinical decisions regarding the appropriate timing of weaning off renal replacement therapy (RRT) in critically ill patients are complex and multifactorial. The aim of the current study was to identify which critical patients with acute kidney injury (AKI) may be more likely to be successfully weaned off RRT using consensus cluster analysis. Methods: In this study, critically ill patients who received RRT at three multicenter referral hospitals at several timepoints from August 2016 to July 2018 were enrolled. An unsupervised consensus clustering algorithm was used to identify distinct phenotypes. The outcomes of interest were the ability to wean off RTT and 90-day mortality. Results: A total of 124 patients with AKI requiring RRT (AKI-RRT) were enrolled. The 90-day mortality rate was 30.7% (38/124), and 49.2% (61/124) of the patients were successfully weaned off RRT for over 90 days. The consensus clustering algorithm identified three clusters from a total of 45 features. The three clusters had distinct features and could be separated according to the combination of urinary neutrophil gelatinase-associated lipocalin to creatinine ratio (uNGAL/Cr), Sequential Organ Failure Assessment (SOFA) score, and estimated glomerular filtration rate at the time of weaning off RRT. uNGAL/Cr (hazard ratio [HR] 2.43, 95% confidence interval [CI]: 1.36–4.33) and clustering phenotype (cluster 1 vs. 3, HR 2.7, 95% CI: 1.11–6.57; cluster 2 vs. 3, HR 44.5, 95% CI: 11.92–166.39) could predict 90-day mortality or re-dialysis. Conclusions: Almost half of the critical patients with AKI-RRT could wean off dialysis for over 90 days. Urinary NGAL/Cr and distinct clustering phenotypes could predict 90-day mortality or re-dialysis. [ABSTRACT FROM AUTHOR]

Background: Immune response assessed by the quantification of neutralizing antibodies (nAbs) and predictors associated with immunogenicity after the prime-boost ChAdOx1 (Oxford–AstraZeneca) COVID-19 vaccine in hemodialysis (HD) patients remains unclear. Methods: This prospective study enrolled 174 HD patients and 67 healthy subjects to evaluate antibodies against the spike protein 1 and receptor-binding domain of severe acute respiratory syndrome coronavirus type 2 after prime-booster vaccination, by using enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict 50% neutralization titer (NT50). The correlation between HD parameters and NT50 was analyzed. Results: NT50 was lower in HD patients compared with healthy controls after the prime-boost dose (p < 0.001). The geometric mean titer ratios were higher in first-dose seronegative than in the seropositive subgroup in HD patients and healthy controls (6.96 vs. 2.36, p = 0.002, and 9.28 vs. 1.26, p = 0.011, respectively). After two doses of ChAdOx1, one-way ANOVA showed that Ca × P was positively associated with NT50 (p trend = 0.043) and multiple linear regression showed the similar results (p = 0.021). Kt/V (a quantification of dialysis adequacy) (OR = 20.295, p = 0.005) could independently predict seroconversion (NT50 ≥ 35.13 IU/mL). Conclusion: Adequacy of hemodialysis could independently predict seroconversion in HD subjects vaccinated with prime-boost doses of ChAdOx1. [ABSTRACT FROM AUTHOR]

Background: Data are lacking regarding predictors of quantification of neutralizing antibodies (nAbs) based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 50% neutralization titer (NT50) after a single dose of COVID-19 vaccine in hemodialysis (HD) patients. Methods: This prospective single-center study enrolled 200 HD patients and 82 healthy subjects to estimate antibodies against the SARS-CoV-2 viral spike protein 1 and receptor-binding domain after a first dose of a COVID-19 vaccine (ChAdOx1 or mRNA-1273), measured by enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict NT50 converted to international units. Results: After the first dose of ChAdOx1, multiple linear regression showed that age (p = 0.011) and cardiothoracic ratio (p = 0.002) were negatively associated with NT50. Older age (OR = 0.958, p = 0.052) and higher cardiothoracic ratio (OR < 0.001, p = 0.037) could predict negative humoral response (NT50 < 35.13 IU/mL). NT50 was lower in HD patients compared with healthy controls receiving ChAdOx1 (10.68 vs. 43.01 IU/m, p < 0.001) or mRNA-1273 (36.39 vs. 262.2 IU/mL, p < 0.001). ChAdOx1 elicited lower GMTs than mRNA-1273 in the HD cohort (10.68 vs. 36.39 IU/mL, p < 0.001) and in healthy controls (43.01 vs. 262.22 IU/mL, p < 0.001). Conclusion: High cardiothoracic ratio and old age could independently predict a decline in nAb titers in an HD cohort vaccinated with a single dose of ChAdOx1. [ABSTRACT FROM AUTHOR]

Background: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. Methods: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. Results: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75–27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). Conclusions: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients. [ABSTRACT FROM AUTHOR]

Fabrication of dense aluminum (Al-1100) parts (>99.3% of relative density) by our recently developed laser-foil-printing (LFP) additive manufacturing method was investigated as described in this paper. This was achieved by using a laser energy density of 7.0 MW/cm2 to stabilize the melt pool formation and create sufficient penetration depth with 300 μm thickness foil. The highest yield strength (YS) and ultimate tensile strength (UTS) in the LFP-fabricated samples reached 111 ± 8 MPa and 128 ± 3 MPa, respectively, along the laser scanning direction. These samples exhibited greater tensile strength but less ductility compared to annealed Al-1100 samples. Fractographic analysis showed elongated gas pores in the tensile test samples. Strong crystallographic texturing along the solidification direction and dense subgrain boundaries in the LFP-fabricated samples were observed by using the electron backscattered diffraction (EBSD) technique. [ABSTRACT FROM AUTHOR]

In this study, waste cotton fibers were environmentally reused. First, they were milled into fine powders with particle sizes of around 30 µm and dyed for use as pigments. Dyeing properties of the cellulose powder were explored by determining the dye uptake, K/S value, and bath ratio. Among the various samples, powders with owf (on weight of fabric) of 0% dye (pristine cellulose powder), and 10% and 50% dyed powders were selected; and these powders were characterized by several methods to compare the properties of dyed and undyed cellulose. The surface morphologies of the powders were observed with a scanning electron microscope (SEM). Combining the SEM images with the Brunauer–Emmet–Teller (BET) data, it was found that the smaller the particle size, the larger is the surface area. In addition, the X-ray photoelectron spectroscopy (XPS) results revealed that with increasing dye concentration, the intensity of the C peak reduced, while those of O and S increased. Moreover, the main components of the dyed and undyed cellulose powders were found to be almost the same from the Fourier-transform infrared spectroscopy (FTIR) results. Finally, the dynamic mechanical analysis (DMA) data revealed that the loss modulus was significantly larger than the storage modulus, demonstrating that the material mainly undergoes viscous deformation. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study., Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD., Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD., Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.