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Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients.A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center.A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03).Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Diphthamide biosynthesis protein 1 (DPH1) is biochemically involved in the first step of diphthamide biosynthesis, a post-translational modification of eukaryotic elongation factor 2 (EEF2). Earlier studies showed that DPH1, also known as ovarian cancer-associated gene 1 (OVCA1), is involved in ovarian carcinogenesis. However, the role of DPH1 in hepatocellular carcinoma (HCC) remains unclear. To investigate the impact of DPH1 in hepatocellular carcinogenesis, we performed data mining from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. We found that reduced DPH1 levels were associated with advanced stages and poor survival of patients with HCC. Also, we generated hepatocyte-specific Dph1-deficient mice and showed that diphthamide-deficient EEF2 resulted in a reduced translation elongation rate in the hepatocytes and led to mild liver damage with fatty accumulation. After N-diethylnitrosamine (DEN)-induced acute liver injury, p53-mediated pericentral hepatocyte death was increased, and compensatory proliferation was reduced in Dph1-deficient mice. Consistent with these effects, Dph1 deficiency decreased the incidence of DEN-induced pericentral-derived HCC and revealed a protective effect against p53 loss. In contrast, Dph1 deficiency combined with Trp53- or Trp53/Pten-deficient hepatocytes led to increased tumor loads associated with KRT19 (K19)-positive periportal-like cell expansion in mice. Further gene set enrichment analysis also revealed that HCC patients with lower levels of DPH1 and TP53 expression had enriched gene-sets related to the cell cycle and K19-upregulated HCC. Additionally, liver tumor organoids obtained from 6-month-old Pten/Trp53/Dph1-triple-mutant mice had a higher frequency of organoid re-initiation cells and higher proliferative index compared with those of the Pten/Trp53-double-mutant. Pten/Trp53/Dph1-triple-mutant liver tumor organoids showed expression of genes associated with stem/progenitor phenotypes, including Krt19 and Prominin-1 (Cd133) progenitor markers, combined with low hepatocyte-expressed fibrinogen genes. These findings indicate that diphthamide deficiency differentially regulates hepatocellular carcinogenesis, which inhibits pericentral hepatocyte-derived tumors and promotes periportal progenitor-associated liver tumors. © 2022 The Pathological Society of Great Britain and Ireland.

AIM This study aims to investigate the effect of low molecular weight heparin (LMWH) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. METHODS Following successful thrombectomy, 66 patients with recurrent thrombosis were included in the study. The primary, assisted primary and secondary patency rates of patients who received LMWH (n = 24) were compared with those who did not receive anticoagulant (n = 42) using Kaplan-Meier analysis. Cox-regression analysis was performed to investigate potential predictors of patency rates. RESULTS The mean dose of enoxaparin used was 40 ± 13.1 mg or 0.74 ± 0.2 mg/kg daily for a median duration of 14 (IQR 7,28) days. The mean trough anti-Xa concentrations measured after two doses of LMWH was 0.17 ± 0.13 IU/mL. Kaplan-Meier analyses for mean primary, assisted primary and secondary patency rates of LMWH vs no anticoagulation groups were 149 (95% CI: 91 - 207) vs 87 (95% CI: 42-132) days (P

More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP‐glucose dehydrogenase (UGDH) was up‐regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21GHI), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G0/G1 phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH‐depletion led to the down‐regulation of epithelial‐mesenchymal transition (EMT)‐related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up‐regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.

Aim To investigate the association between specific dental therapy for periodontal disease and the risk of ischaemic stroke. Materials and methods We conducted a population-based cohort study that used data from the Taiwan National Health Insurance Research Database 2005 for the period of 2000-2013. Our observations focused on patients with the diagnoses of gingivitis or periodontitis with and without specific treatment and subsequent incidence of ischaemic stroke. Dental care services include dental scaling, intensive treatment (subgingival curettage and root planing) and tooth extraction. Multivariate Cox regression analysis was used to estimate the hazard ratios and corresponding 95% confidence intervals (95% CI). Results Compared with those in the gingivitis cohort, patients with periodontitis have a higher risk of ischaemic stroke and a lower survival rate of stroke over the 10-year follow-up period. After integrative dental care, both dental scaling and intensive treatment, the risk was reduced, especially in patients with periodontitis, while patients with periodontal disease may have an increased risk of stroke after tooth extraction therapy. Conclusions Our study showed that periodontitis is a risk factor for ischaemic stroke. Both dental scaling and intensive treatment for periodontal disease are associated with a lower risk of further ischaemic stroke events.

AIM Dysfunctional arteriovenous (AV) access remains a significant cause of morbidity and hospital admission for patients with end stage renal failure on haemodialysis. This study was performed to evaluate the impact of paclitaxel-coated Balloon (PCB) on the patency of AV access with recurrent stenoses. METHODS We retrospectively studied haemodialysis patients who presented to our centre with recurrent AV access dysfunction and compared intervention-free patency using plain balloon versus PCB. RESULTS A total of 147 patients were followed up longitudinally. Intervention-free patency was better following PCB compared to previous intervention using plain balloons (6.4 ± 5.8 versus 4.0 ± 3.7, P

Aim Formation of autogenous arteriovenous fistula (AVF) in patients with chronic kidney disease (CKD) is complicated by a high primary failure rate. We hypothesized that early (months to years before AVF creation) Venous Preservation Scan (VPS) followed by vasculature preservation is effective in protecting the patient's best 'for fistula' vasculature. This study was performed to evaluate the impact of VPS on AVF outcomes. Methods The case records of 123 patients who underwent ultrasound mapping for AVF creation in a district hospital were reviewed. Ninety-seven were VPS and 26 were Routine Pre-Operative Planning Scan (RPOPS) performed immediately prior to surgery. Outcomes of 21 patients who went onto AVF creation in the VPS group were compared to 23 patients in the RPOPS group. Results Success and complication rates for AVF placement in patients who underwent VPS versus RPOPS were 100% versus 91.3% (P = 0.27) and 0 versus 8.7% (P = 0.23). A greater proportion of AVF created following RPOPS required intervention before maturation (47.6% vs 19%, P = 0.05). The median primary patency of AVF created following VPS versus RPOPS was 492 (IQR 222, 1219) versus 169 (IQR 116, 414) days (P = 0.02). The cumulative patency did not differ between the two groups (median = 807 (IQR 499, 1308) versus 1059 (IQR 331, 1263) days, P = 0.26). Conclusions This small study suggests that VPS may favourably influence the survival of primary AVF and reduce the need for assisted interventions. However, confirmation with larger randomized controlled trial is warranted.

Field measurements were conducted to study the influence of aquatic vegetation on flow structures in floodplains under combined currents and wind‐driven waves. Wave and turbulent velocities were decomposed from the time series of instantaneous velocity and analysed separately. In the present study, the wind waves were small, leading to the ratios of wave excursion (Ew) to stem spacing (S) for all cases tested here were less than 0.5. This caused the vertical distributions of time‐averaged velocity (Uₕₒᵣᵢz) and turbulent kinetic energy (TKE) impacted by vegetation similar with the vegetated flow structures under pure current conditions. For emergent vegetation, Uₕₒᵣᵢz and TKE distributed uniformly through the entire water column or increased slightly from bed to water surface. Similar distributions were present in the lower part of submerged vegetation. In the upper part of submerged vegetation, Uₕₒᵣᵢz and TKE increased rapidly toward water surface and TKE reached its maximum near the top of vegetation. The measured wave orbital velocity (Uw) fitted linear wave theory well through the entire water depth for both the emergent and submerged cases, so that with small Ew/S the wave velocity was not attenuated within vegetation and Uw within canopy can be predicted by the linear wave theory under combined currents and waves. However, wind‐driven waves made the turbulence generated near the top of canopy penetrate a deeper depth into vegetation than predictions under pure current conditions.

Aim Traditional apprenticeship model (AM) of teaching in invasive procedures such as temporary haemodialysis catheter (THDC) insertion can result in propagation of errors and complications. Simulation-based learning (SBL) offers standardization of skills and allows trainees to repeatedly practice invasive procedures prior to performing them on actual patient. Methods Retrospective cohort study of first-, second- and third-year Nephrology Fellows from a tertiary teaching hospital from September 2008 to September 2015. The intervention group (n = 9) received simulation training in ultrasound-guided THDC placement. The historical control group (n = 12) received training through traditional AM. The primary and secondary outcomes were the immediate complications and success rates of THDC insertion. Results A total of 2481 THDCs were placed in 1787 patients. Success rate of internal jugular THDC placement for AM vs. SBL Fellow was 99.8% versus 100% (P = 0.90), while the success rate for femoral THDC placement was 99.6% versus 99.2% (P = 0.53). SBL Fellows reported fewer overall peri-procedure complications (8.3% vs. 11.2%, P = 0.02) and mechanical complications (1% vs. 2.4%, P = 0.02) compared to AM Fellows. The rate of reported technical difficulty was similar (7.5% vs. 9.2%, P = 0.17). After adjusting for side and site of THDC placement, body mass index and laboratory indices, THDC inserted by AM Fellows were independently associated with increased overall peri-procedure complications (OR = 1.396, 95% CI: 1.052-1.854, P = 0.02) and mechanical complications (OR = 2.481, 95% CI: 1.178-4.810, P = 0.02). Conclusions Simulation-based learning was associated with lower procedure related complications and should be an integral component in the teaching of procedural skills in Nephrology.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.

Utilizing facial recognition technology, the current study has attempted to predict the likelihood of student conceptual change with decision tree models based on the facial micro‐expression states (FMES) students exhibited when they experience conceptual conflict. While conceptual change through conceptual conflicts in science education is a well‐studied field, there is little research done on conceptual change through conceptual conflict in terms of students' facial expressions. As facial expressions are one of the most direct and immediate responses one can get during instruction and that facial expressions are often representations student's emotions, a link between students' FMES and learning was explored. Facial data was collected from 90 tenth graders. Only data from the 72 students who made incorrect predictions were analyzed in this study. The concept taught was the relationship between boiling point and air pressure. Through facial recognition software analysis and decision tree models, the current study found Surprised, Sad and Disgusted to be key FMES that could be used to predict student conceptual change in a conceptual conflict‐based scenario. [ABSTRACT FROM AUTHOR]

Aim and Methods Post-donation kidney function has not been well characterized in the Southeast Asian population. We studied a retrospective cohort of 174 living kidney donors at Singapore General Hospital between 1976 and 2012, evaluated patterns of change in kidney function using quantile regression analysis and investigated for predictors of low estimated glomerular filtration rate (eGFR) 6 months to

The aim of this study is to investigate whether use of cyclooxygenase-2 (COX-2) inhibitors as auxiliary drug in colorectal cancer (CRC) patients will lead to better survival outcome. This population-based retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. The cohort consisted of newly diagnosed CRC adult patients during 2003–2010 with at least one prescription of nonsteroidal anti-inflammation drugs. Analysis groups were defined as users or nonusers of COX-2 inhibitors based on their usage prior to or 1 year after diagnosis of CRC. The outcome measurement was overall survival. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Subgroup analyses included stratification of different cancer site, treatment modalities, and first chemotherapy regimens. Kaplan–Meier estimates and Cox regressions were used to compare survival outcome. We identified 14,688 patients with newly diagnosed CRC. The adjusted hazard ratio (HR) with IPTW was 0.91 [95% confidence interval (CI), 0.86–0.96] in patients using COX-2 inhibitors in before and after diagnosis groups, and statistical significance was not reached for usages at only prior to or only after diagnosis. In subgroup analyses, patients with rectal cancer (adjusted HR with IPTW=0.86; 95% CI, 0.79–0.94) who received surgery followed by chemoradiation (adjusted HR with IPTW=0.57; 95% CI, 0.47–0.77) and with adjuvant chemotherapy of FOLFOX regimen (adjusted HR with IPTW=0.81; 95% CI, 0.67–0.99) had survival benefits in using COX-2 inhibitors both prior to and after diagnosis. Use of COX-2 inhibitors was found to be associated with reduction in mortality for CRC patients when taken both prior to and after cancer diagnosis.

Aim Vascular access in haemodialysis is critical for effective therapy. We aim to evaluate the outcomes of arteriovenous fistula (AVF) creation in incident haemodialysis patients, impact of preoperative vein mapping and predictors of successful AVF maturation in our centre. Methods Data of End-stage Renal Disease (ESRD) patients initiated on haemodialysis from January 2010 to December 2012 in our centre were retrospectively obtained from electronic medical records and clinical notes. Demographic characteristics, medical comorbidities, perioperative details were collected, and patients were followed up until 1 January 2014. Results A total of 708 patients (median age 64, IQR 55-72) were included with mean duration of follow up of 2.3 ± 1.2 years, with access of AVF and arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight patients were lost to follow-up. Successful AVF maturation was achieved in 542 patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis revealed male gender, upper arm AVF and good postoperative thrill and pulse as predictors of successful AVF maturation. Preoperative vein mapping was performed in 42.5% (295/694) of patients, with mean vein diameter of 2.44 ± 0.82 mm. Maturation rates with and without vein mapping were 72.2% and 82.4%, respectively, (P = 0.001). In patients with vein diameters of

Rationale The deduction of useful information from the mass spectra of a complex mixture like coals remains difficult, which limits the clean and efficient utilization of coals. It is necessary to explore the data interpretation methods for mass spectra and visualize the analytical data of coals for industrial utilization such as feedstock selection. Methods Coal sample and methanol were mixed and heated to 310 °C and kept at that temperature for 2 h. The solvent was under supercritical state at 310 °C and the solubility for the solid mixture increased. Soluble products from thermal dissolution of two Chinese coals were analyzed by high-performance liquid chromatography/atmospheric pressure chemical ionization orbitrap mass spectrometry. Results The iso-abundance plot for molecules in coals was upgraded to display the distributions of isomers which are indicated as concentric circles or triangles with the same carbon number and value of double-bond equivalent. The concentration ratio was introduced from economics to describe the content inequality of organic species within the same class of coal molecules. Conclusions Interpretation methods for mass spectra visualize and simplify the understanding of complex components in coals for industrial utilization. Coals with a high concentration ratio for a specific class should take priority as a feedstock for chemicals and receive more attention. Copyright © 2016 John Wiley & Sons, Ltd.

Solution assembly of heterocyclic disulfide ligand, 4-ppds {4-ppds = bis[4-(pyridin-4-yl)pyrimidinyl]disulfide}, with Cu(OAc)2 and ZnI2 resulted in two 1D (one-dimensional) coordination polymers 1 and 2, which were well characterized by infrared spectroscopy, elemental analysis, powder X-ray diffraction, single-crystal X-ray diffraction, diffuse-reflectance UV/Vis as well as photoluminescence spectroscopy. Single crystal X-ray crystallography discloses that 1 shows an achiral zigzag chain structure built up by alternate linking of paddlewheel Cu2(OAc)4 dicopper unit and 4-ppds ligand with opposite configurations, whereas 2 exhibits a helical chain structure constructed by alternate linkage of tetrahedral zinc atom and 4-ppds ligand with the same chirality (P- or M-configuration). It is supposed that the flexible coordination environment around the tetrahedral ZnII ion might be beneficial to homochiral arrangement of 4-ppds ligand.

A new organic building block, TEPB, has been synthesized that comprises three 2-ethylthio-substituted pyrimidine groups coupled to one central phenyl ring at the 1-, 3- and 5-positions. TEPB exhibits a quasi-planar conformation due to its intramolecular C–H···N hydrogen bonds. The assembly of TEPB with CuI and CuCl2 produced two flat coordination chains 1 and 2, both exhibiting similar assembly hierarchies from chain through 2D layer to 3D architecture. It was found that extensive S···S and C–H···S contacts exist in the 2D layers of 1 and 2, respectively. Between the 2D layers of 2, there are O–H···Cl hydrogen-bonding interactions between water molecules and coordinated Cl atoms that provide a proton-transfer network. Complex 2 exhibits a smaller optical band gap (1.11 eV) than 1 (1.93 eV), which has been attributed to d-electron transition in the copper(II) ion. The d.c. conductivities of 1 and 2 at room temperature were measured to be 2.84 × 10–12 and 2.42 × 10–10 S cm–1, respectively. The a.c. conductivity of 2 obtained at room temperature by the complex impedance technique is about 5.90 × 10–9 S cm–1, which can be attributed largely to proton conduction. Moreover, the a.c. conductivity of 2 decreases almost linearly with increasing temperature, presumably as a result of its temperature-sensitive O–H···Cl hydrogen-bonding network that allows for proton conduction.

The self-assembly of 4-MTPP [4-MTPP = 2-(methylthio)-4-(pyridin-4-yl)pyrimidine] with Cu(NO3)2 and AgNO3 was structurally investigated. For Cu(NO3)2, a discrete mononuclear CuII coordination compound, [Cu(4-MTPP)2(NO3)2] (1), resulted that is exclusively based on Cu–N coordination. For AgNO3, a unique one-dimensional double-chain structure (2) was obtained with the Ag–N distances varying from 2.181(9) to 2.223(9) A, and the average Ag–S distance being 2.98 A. Compared to zero-dimensional 1, the extension to one-dimensional 2 is considered to result from the specific affinity between Ag+ and the ligand 4-MTPP that is attributed to the strong coordinating tendency of silver for aromatic nitrogen and thioether sulfur atoms.

A computer-assisted method is described for optimization of multi-component, mobile phase selection for separation of five phosphoamidothioate enantiomers with a series of silica and chiral columns in normal phase HPLC. The method is based on the triangular solvent selection concept using a statistical scanning method. The optimization of the separation over the experimental region is based on a special polynomial estimation from seven experimental runs, and resolution (Rs) is used as the selection criterion. Excellent agreement was obtained between predicted and experimental data.

The enantiomers of a series of fourteen O-ethyl O-(substituted) phenyl N-isopropyl-phosphoroamidothioates have been separated by high performance liquid chromatography (HPLC) on the Pirkle-type chiral stationary phase. Seven molecular descriptors were calculated and four significant descriptors were chosen to correlate against the experimental lnk' values in order to form the quantitative structure-enantioselectivity retention relationships (QSERRs). Through the QSERRs, the retention and enantioselectivity mechanism were examined.

Three computer-assisted statistical scanning methods, the monofactor optimization system (MOS), multicomponent solvent optimization system (MSOS), and difactor optimization system (DOS) for optimizing HPLC separations, have been integrated to produce the optimization system of HPLC (OS-L). The method proposes the complementary use of these techniques, maximizing their strengths while compensating for their weaknesses. The result of OS-L is a method development strategy which obtains simple solutions for simple separation problems and reserves the more complex solutions for difficult separations.