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Two new zinc(II) complexes, triethylammonium dichlorido[2-(4-nitrophenyl)-4-phenylquinolin-8-olato]zinc(II), (C6H16N){Zn(C21H13N2O3)Cl2] (ZnOQ), and bis(triethylammonium) {2,2′-[1,4-phenylenebis(nitrilomethylidyne)]diphenolato}bis[dichloridozinc(II)], (C6H16N)2[Zn2(C20H14N2O2)Cl4] (ZnBS), were synthesized and their structures were determined using ESI–MS spectrometry, 1H NMR spectroscopy, and single-crystal X-ray diffraction. The results showed that the ligands 2-(4-nitrophenyl)-4-phenylquinolin-8-ol (HOQ) and N,N′-bis(2-hydroxybenzylidene)benzene-1,4-diamine (H2BS) were deprotonated by triethyl-amine, forming the counter-ion Et3NH+, which interacts via an N—H...O hydrogen bond with the ligand. The ZnII atoms have a distorted trigonal–pyramidal (ZnOQ) and distorted tetrahedral (ZnBS) geometries with a coordination number of four, coordinating with the ligands via N and O atoms. The N atoms coordinating with ZnII correspond to the heterocyclic nitrogen for the HOQ ligand, while for the H2BS ligand, it is the nitrogen of the imine (CH=N). The crystal packing of ZnOQ is characterized by C—H...π interactions, while that of ZnBS by C—H...Cl interactions. The emission spectra showed that ZnBS complex exhibits green fluorescence in the solid state with a small band-gap energy, and the ZnOQ complex does exhibit non-fluorescence.

Infectious bursal disease is a highly contagious and economically devastating disease in the poultry industry worldwide caused by Infectious bursal disease virus (IBDV). However, the data on epidemiological and molecular characteristics of the IBDV outbreak in broiler flocks in the Mekong Delta of Vietnam is unclear. Herein, the epidemiological data of IBDV–positive flocks over a period of 2015–2018 were recorded and the hypervariable region of the VP2 gene of IBDV was amplified to analyze the local phylogeny. The current investigation showed that the overall morbidity and mortality rates of IBDV–positive flocks were 45% and 4.81%, respectively. The IBDV–positive birds occurred clinical signs and macroscopic findings involved with the very virulent (vv) IBDV outbreak. Epidemiological results revealed that IBDV was frequently infected in broiler flocks at 12–42 days, and birds belonging to Tau Vang and Binh Dinh breeds were more sensitive to IBDV. Also, the morbidity rate of IBDV was dramatically decreased in the open farming system. Flocks with complete vaccination significantly dropped morbidity in comparison with other groups. Regarding phylogenetic analysis, all identified IBDV sequences clustered in the same branch of vv phenotype and closely homology with prior strains circulated in Vietnam and other countries. These findings first indicated the epidemiological characteristics of the IBDV–positive broiler flocks in the Mekong Delta and highlighted the IBDV strain circulating in this region.

Abstract The phenomenon of sloshing causes a significantly negative impact on a wide range of industries. A time‐optimal flatness‐based trajectory planning and Lyapunov‐based model predictive control (LMPC) is proposed for trajectory tracking of a transmitting cylindrical container filled with liquid. Firstly, this research presents an equivalent discrete model based on a mass‐spring‐damper system. Subsequently, after the flatness of the adopted non‐linear model for 2D is established, time‐optimal trajectories are introduced. A control method called LMPC is shown to solve the problem of orbital tracking, which allows setting limits for state variables. In addition, to ensure system performance, a linear extended state observer (LESO) is integrated to cope with system uncertainties. Finally, the efficiency of the proposed approach for liquid sloshing suppression and tracking is illustrated by simulations.

The surge in digital platforms has revolutionized how consumers purchase, favoring online shopping. Despite its popularity, customer loyalty in this sphere requires enhancement. Companies are striving to augment loyalty and repurchase intention among consumers. However, the factors driving repurchase intention through shopping well-being in the online context, particularly in Vietnam, remain incompletely understood. This study examines shopping value components, including utilitarian and hedonic values, while exploring their relationships with customer trust and impulsive buying, influencing repurchase intention through customer’s shopping well-being on digital platforms. Employing a mixed-method approach, the study conducts qualitative interviews with online shoppers, marketers, and researchers to refine assessment scales for the Vietnamese context. A quantitative survey will gather data and use Covariance-based Structural Equation Modeling (CB-SEM) to test proposed hypotheses. In addition, the PRISMA model is applied in the systematic evaluation of literature reviews. This research offers a theoretical model for understanding consumer behavior in the Vietnamese online shopping landscape. Additionally, it furnishes valuable insights for digital platform sellers aiming to improve customers’ repurchase intention by refining the shopping experience and well-being.

This study examines the impact of low-income assistance and electrification programs on a disadvantaged community in Southern California. An urban building energy model is paired with an AC power flow and electric distribution system degradation model to evaluate how the cost of energy, carbon emissions, and pollutant emissions change after applying building weatherization, energy efficiency, and electrification measures to the community. Results show that traditional weatherization and energy efficiency measures (upgrading lighting and appliances, improving insulation to current building code standards) are the most cost-effective, reducing the cost of energy and carbon emissions by 10–20 % for the current community. Heat pump water heaters offer a 40 % average reduction in carbon emissions and almost 50 % decrease in criteria pollutant emissions, but at a cost increase of 17–22 %. Appliance electrification also reduces carbon emissions 5–10 % but increases cost by 7 % to 25 %. For reducing carbon, government programs that support building electrification are most cost-effective when they combine switching from natural gas to electricity with high efficiency system. Electrifying hot water and appliances effectively reduces emissions but must be paired with improved low-income assistance programs to prevent increased energy burden for low-income families. The urban building energy model and electrical distribution simulations used in this study can be replicated in other low-income communities.

Mangroves play an important role in coastal estuarine areas with different ecological functions, such as reducing the impact of waves and currents, accumulating biomass and sequestering carbon. However, estimation of terrestrial biomass in mangrove areas, especially in Vietnam, has not been fully studied. The application of unmanned aerial vehicles (UAV), mounted with multispectral cameras combined with field verification is an effective method for estimating terrestrial biomass for mangroves, as it reduces field survey time and allows for greater spatial range research. In this study, ground biomass was estimated for the mangrove area in the Dong Rui commune, based on multispectral image data obtained from UAV and survey results in 16 standard cells measuring actual biomass according to four regression models: Log-Log, Log-Lin, Lin-Log and Lin-Lin. The results of comparing the data from these four models show that the log-log model has the highest accuracy with a high correlation coefficient (R2 = 0.831). Based on the results of the analysis and selection of ground-based biomass estimation models, a biomass map was established for the UAV flying area in the Dong Rui mangrove forest with biomass values ranging from 20 Mg/ha to 150 Mg/ha. In summary, we present a biomass estimation method through four basic linear regression models for mangrove areas, based on multispectral image data obtained from ultrahigh-resolution UAV. The resulting research results can serve as a basis for managers to calculate and synchronise the payment of carbon services, thus contributing to effectively promoting the livelihoods of local people.

ABSTRACTLarge-molecule antibody biologics have revolutionized medicine owing to their superior target specificity, pharmacokinetic and pharmacodynamic properties, safety and toxicity profiles, and amenability to versatile engineering. In this review, we focus on preclinical antibody developability, including its definition, scope, and key activities from hit to lead optimization and selection. This includes generation, computational and in silico approaches, molecular engineering, production, analytical and biophysical characterization, stability and forced degradation studies, and process and formulation assessments. More recently, it is apparent these activities not only affect lead selection and manufacturability, but ultimately correlate with clinical progression and success. Emerging developability workflows and strategies are explored as part of a blueprint for developability success that includes an overview of the four major molecular properties that affect all developability outcomes: 1) conformational, 2) chemical, 3) colloidal, and 4) other interactions. We also examine risk assessment and mitigation strategies that increase the likelihood of success for moving the right candidate into the clinic.

Summary: Background: Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval. Methods: We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts. Findings: Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74–92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58–82%) and 49%, (95% CI 37–64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58–90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory. Interpretation: Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease. Funding: St. Baldrick's/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.

Abstract Rechargeable batteries with iodine‐based cathodes have recently been the subject of significant interest due to the moderately high theoretical specific energy (≈600 Wh kg−1) and high‐rate capability (>5 C) of the iodine cathode. Progress however has been impeded by the relatively low iodine contents of reported iodine‐based cathodes. This is likely due to high rates of poly‐iodide shuttling and cell instability that takes place at higher cell loadings. To reinforce the lithium metal anode, oxygen gas is introduced in the cells, which leads to a more robust solid‐electrolyte interphase (SEI) layer, improving cell stability. This oxygen‐assisted lithium‐iodine (OALI) battery overcomes many of the shortcomings of other reported lithium‐iodine batteries by utilizing a simple to fabricate lithium iodide (LiI) on activated carbon cathode with cell operating under an oxygen containing atmosphere to realize high‐rate capability (>50 mA cm−2) and high areal capacity (>12 mAh cm−2).

This research aimed to determine the optimal media and temperature conditions for the long-term storage of bacteriophages. In this study, the viability of Salmonella phages in 50% glycerol, 10% sodium chloride-magnesium sulfate (SM) buffer, and 5% dimethyl sulfoxide (DMSO) media at room temperature, 4oC, -20oC, and -80oC for 12 months was determined. In 50% glycerol, at the end of the experiment, no significant difference was found between four temperature conditions on phage density, ranging from 6.20-6.23 log10 PFU/mL (P>0.05). Under 10% SM medium, phage preservation at room temperature provided the optimum density at 6.31 log10 PFU/mL. In addition, phages preserved in a 5% DMSO medium were of similar density values across all temperature treatments. Still, their availability after 12 month-storage (88.0-88.5%) was significantly lower (P

Objective: Fragments of fibrillin-1 and fibrillin-2 will be detectable in the plasma of patients with aortic dissections and aneurysms. We sought to determine whether the plasma fibrillin fragment levels (PFFLs) differ between patients with thoracic aortic pathology and those presenting with nonaortic chest pain. Methods: PFFLs were measured in patients with thoracic aortic aneurysm (n = 27) or dissection (n = 28). For comparison, patients without aortic pathology who had presented to the emergency department with acute chest pain (n = 281) were categorized into three groups according to the cause of the chest pain: ischemic cardiac chest pain; nonischemic cardiac chest pain; and noncardiac chest pain. The PFFLs were measured using a sandwich enzyme-linked immunosorbent assay. Results: Fibrillin-1 fragments were detectable in all patients and were lowest in the ischemic cardiac chest pain group. Age, sex, and the presence of hypertension were associated with differences in fibrillin-1 fragment levels. Fibrillin-2 fragments were detected more often in the thoracic aneurysm and dissection groups than in the emergency department chest pain group (P < .0001). Patients with aortic dissection demonstrated a trend toward increased detectability (P = .051) and concentrations (P = .06) of fibrillin-2 fragments compared with patients with aortic aneurysms. Analysis of specific antibody pairs identified fibrillin-1 B15-HRP26 and fibrillin-2 B205-HRP143 as the most informative in distinguishing between the emergency department and aortic pathology groups. Conclusions: Patients with thoracic aortic dissections demonstrated elevated plasma fibrillin-2 fragment levels (B205-HRP143) compared with patients presenting with ischemic or nonischemic cardiac chest pain and increased fibrillin-1 levels (B15-HRP26) compared with patients with ischemic cardiac chest pain. Investigation of fibrillin-1 and fibrillin-2 fragment generation might lead to diagnostic, therapeutic, and prognostic advances for patients with thoracic aortic dissection. : Clinical Relevance: Differentiating between thoracic aortic dissection and other causes of acute chest pain is clinically important. Investigating the clinical and mechanistic processes that contribute to higher fibrillin fragment concentrations in patients with thoracic aortic dissection compared with patients with cardiac chest pain could lead to diagnostic, prognostic, and therapeutic improvements in the care of patients with thoracic aortic dissections.

Deep learning-based intrusion detection systems have advanced due to their technological innovations such as high accuracy, automation, and scalability to develop an effective network intrusion detection system (NIDS). However, most of the previous research has focused on model generation through intensive analysis of feature engineering instead of considering real environments. They have limitations to applying the previous methods for a real network environment to detect real-time network attacks. In this paper, we propose a new flexible and robust NIDS based on Recurrent Neural Network (RNN) with a multi-classifier to generate a detection model in real time. The proposed system adaptively and intelligently adjusts the generated model with given system parameters that can be used as security parameters to defend against the attacker’s obfuscation techniques in real time. In the experimental results, the proposed system detects network attacks with a high accuracy and high-speed model upgrade in real-time while showing robustness under an attack.

Fingerprinting techniques, which utilize the unique chemical and physical properties of food samples, have emerged as a promising approach for food authentication and traceability. Recent studies have demonstrated significant advancements in food authentication through the use of fingerprinting methods, such as multivariate statistical analysis techniques applied to trace elements and isotope ratios. However, further research is required to optimize these methods and ensure their validity and reliability in real-world applications. In this study, the inductively coupled plasma mass spectrometry (ICP-MS) analytical method was employed to determine the content of 21 elements in 300 cashew nut (Anacardium occidentale L.) samples from 5 brands. Multivariate statistical methods, such as principal components analysis (PCA), were employed to analyze the data obtained and establish the provenance of the cashew nuts. While cashew nuts are widely marketed in many countries, no universal method has been utilized to differentiate the origin of these nuts. Our study represents the initial step in identifying the geographical origin of commercial cashew nuts marketed in Vietnam. The analysis showed significant differences in the means of 21 of the 40 analyzed elements among the cashew nut samples from the 5 brands, including 7Li, 11B, 24Mg, 27Al, 44Ca, 48Ti, 51V, 52Cr, 55Mn, 57Fe, 60Ni, 63Cu, 66Zn, 93Nb, 98Mo, 111Cd, 115In, 121Sb, 138Ba, 208Pb, and 209Bi. The PCA analysis indicated that the cashew nut samples can be accurately classified according to their original locations. This research serves as a prerequisite for future studies involving the combination of elemental composition analysis with statistical classification methods for the accurate establishment of cashew nut provenance, which involves the identification of key markers for the original discrimination of cashew nuts.

BackgroundJob satisfaction is an important factor affecting job performance and turnover of healthcare workers, especially hospital pharmacists. Nevertheless, limited studies have reported this issue in the context of Vietnam.ObjectivesTo help maintain the quality and size of the limited hospital pharmacy workforce in Vietnam, especially in the Mekong Delta area, this study investigated the job satisfaction of hospital pharmacists, and the associated factors, in Vinh Long province, a representative province in the central Mekong Delta.MethodsA cross-sectional survey was conducted, recruiting hospital pharmacists working in all 17 province/district-affiliated healthcare facilities across Vinh Long province, Vietnam, between August and September 2022.ResultsAmong the 235 survey participants (representing a response rate of 97.1%), 189 pharmacists (80.4%) reported that they were satisfied with their job. Working conditions, leadership styles, and benefits were factors found to significantly influence job satisfaction. Pharmacists who had worked in the field for 3-5 years (OR = 3.752, 95% CI = 1.036-13.595), more than 5 years (OR = 6.361, 95% CI = 2.264-17.875), did not have additional duties besides their primary responsibilities (OR = 2.046, 95% CI = 1.005-4.163), and worked in a private healthcare facility (OR = 12.021, 95% CI = 1.470-98.316), were significantly more likely to be satisfied with their job.ConclusionsMost hospital pharmacists were satisfied with their current job. To further improve job satisfaction in this population, further improvements to working conditions are necessary.

Introduction. The peroneus longus tendon is used in many orthopedic surgeries to regenerate the external ligaments of the knee. This study aims to evaluate some anatomical, biomechanical, and load-bearing properties of the peroneus longus tendon for use in cruciate ligament reconstruction. Materials and Methods. The study design is a cross-sectional description. The study subjects were 20 samples of the peroneus longus tendon from fresh carcasses. The leg is still intact, not crushed, is well preserved, and it has never been used in research. Results. The average length of the peroneus longus tendon was 29.25 ± 2.1 cm, and the average distance from the peroneus longus tendon to the deep peroneal nerve was 71.1 ± 8.63 mm. The peroneus longus tendon did not have an accessory ligament, the maximum tension of the peroneus longus tendon was 1170.4 ± 203 N, and the maximum length at break was 14.29 ± 3.88 mm. Conclusion. Removing the peroneus longus tendon will not affect the surrounding anatomical components. The maximum breaking force and the diameter of the peroneus longus tendon are similar to other graft materials, such as the hamstring tendon and patellar tendon.

Abstract Background Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. Methods Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. Results There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). Conclusions Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

Life cycle strategies for traction batteries, such as remanufacturing, reuse, and recycling of retired automotive lithium-ion batteries (LIBs), have received growing attention, as large volumes of LIBs will retire in the near future and the demand for LIBs continues to grow. At the same time, the relevance of the sustainability of a battery system over its entire life cycle is increasing as factors such as the EU Battery Regulation provide greater market and product transparency. As a result, research and industry require forecasts in order to assess the future market situation and to make well-founded decisions. Therefore, this paper provides forecasts of the return volumes of battery systems from BEVs and PHEVs up to 2035. Additionally, a representative European battery pack for PHEVs and BEVs was evaluated for each year since 2013, based on the ten vehicles with the largest market share in each year until 2021. In addition, the battery return streams are divided into three different 3R strategies based on expert interviews in order to evaluate the upcoming workload in these areas. The term “3R” refers to the sum of the currently existing pathways around reuse, remanufacturing, and recycling. In 2030, about 38.8 GWh will return and enter the recycling process annually. For battery reuse, about 13 GWh will return every year from 2030 onwards, ready to be used in stationary storage for energy transition. Compared to this, battery remanufacturing is expected to be supplied with a slightly lower volume of approximately 11 GWh per year.

In this study, the effect of dimethyl ether enriched air (DMEA) on pollutants and performance characteristics a diesel engine was evaluated. The combustion parameters have been evaluated by simulation method. Simulation results show that the in-cylinder pressure increases slightly while the combustion duration is shorter for DMEA-engine compared to the original case. In addition, a comparative test on DMEA-engine was carried out, in which DME was supplied into the intake manifold at a constant concentration to the mass of intake air. The results show that, when operating with DMEA, the brake specific energy consumption (BSEC) reduces slightly at full load condition by 2.20%. While, at a speed of 1600 rpm, the BSEC increases from 2.6% to 7.7% at low load and slides from 3.1% to 5.5% at high load condition. The smoke level reduces moderately when the test engine operating with DMEA by 6.25% on average at full load and 2.0% to 8.2% as load increases at intermediate speed condition. The CO emission reduces 5.28% while NOx and HC emission increase 5.62% and 7.1% on average at full load condition. At the speed of 1600 rpm, CO reduces 5.9% while NOx and HC increase by 7.1% and 27.5% on average.

The lives and learning experiences of high school students are increasingly intertwined with online activities. With the global trend of Education 4.0, equipping students with digital skills is essential, including the capacity for online social-emotional skills. Someone with social-emotional skills knows how to turn social media into a useful tool, providing opportunities for personal development. This study focuses on developing social-emotional competence for high school students in the context of the Education 4.0 trend. The project has developed a learning program consisting of 6 common social-emotional skill themes for both virtual and real environments and implemented a test on 34 students. Using experimental evaluation methods, classroom observation, and quantitative methods were employed to assess the effectiveness of the program. The results indicate a significant improvement in students' social-emotional competence, with an average score post-experiment of 3.7397. Our experimental model also achieved 63.6% of CASEL criteria for organizing social-emotional competence. Therefore, the study has strengthened the findings and achievements in the development of social-emotional competence training in the fields of educational psychology in Vietnam.

Abstract Background Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. Methods We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. Results 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. Conclusions The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.

This paper conducted an experimental study on the performance and emission characteristics of bi-fuel gasoline-liquefied petroleum gas (LPG) for in-used fuel-injected motorcycles. By using an electric bi-fuel controller, the original engine can operate smoothly on either conventional fuel or alternative one. The performance was evaluated by comparing the brake power at the wheel of the test motorcycle with a different kind of fuel. The carbon balance method was used to determine the fuel consumption from instantaneous emission levels measured by the constant volume sampler system. The pollutant level was measured following the driving cycle test ECE R40. The exhaust emission of HC, CO, and NOx of the test vehicle fueled by LPG reduces 69.94%, 47.89%, and 46.48% compared to gasoline. The average fuel (kg/100 km) and energy (MJ/100 km) consumption were reduced by 14.78% and 12.84%, respectively. In contrast, average fuel consumption in l/100 km increased by 11.10%. The degradation in engine performance was observed. The best brake power at the wheel was reduced by 19.42% on average. The developed bi-fuel system could be a feasible solution for environmental protection, fuel economy and guarantee the long life of currently used motorcycles in Vietnam’s current context.

Introduction BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysis This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and dissemination Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registration ClinicalTrials.gov NCT04327206

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StanEx1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.

Summary: Alterations in cardiac energy metabolism after a myocardial infarction contribute to the severity of heart failure (HF). Although fatty acid oxidation can be impaired in HF, it is unclear if stimulating fatty acid oxidation is a desirable approach to treat HF. Both immediate and chronic malonyl coenzyme A decarboxylase inhibition, which decreases fatty acid oxidation, improved cardiac function through enhancing cardiac efficiency in a post–myocardial infarction rat that underwent permanent left anterior descending coronary artery ligation. The beneficial effects of MCD inhibition were attributed to a decrease in proton production due to an improved coupling between glycolysis and glucose oxidation. Key Words: fatty acid oxidation, heart failure, glucose oxidation, uncoupling of glycolysis

The in situ observation of electrochemical reactions is challenging due to a constantly changing electrode surface under highly sensitive conditions. This study reports the development of an in situ atomic force microscopy (AFM) technique for electrochemical systems, including the design, fabrication, and successful performance of a sealed AFM cell operating in a controlled atmosphere. Documentation of reversible physical processes on the cathode surface was performed on the example of a highly reactive lithium–oxygen battery system at different water concentrations in the solvent. The AFM data collected during the discharge–recharge cycles correlated well with the simultaneously recorded electrochemical data. We were able to capture the formation of discharge products from correlated electrical and topographical channels and measure the impact of the presence of water. The cell design permitted acquisition of electrochemical impedance spectroscopy, contributing information about electrical double layers under the system’s controlled environment. This characterization method can be applied to a wide range of reactive surfaces undergoing transformations under carefully controlled conditions.

In recent years, due to the ubiquitous presence of WiFi access points in buildings, the WiFi fingerprinting method has become one of the most promising approaches for indoor positioning applications. However, the performance of this method is vulnerable to changes in indoor environments. To tackle this challenge, in this paper, we propose a novel WiFi fingerprinting method that uses the valued tolerance rough set theory–based classification method. In the offline phase, the conventional received signal strength (RSS) fingerprinting database is converted into a decision table. Then a new fingerprinting database with decision rules is constructed based on the decision table, which includes the credibility degrees and the support object set values for all decision rules. In the online phase, various classification levels are applied to find out the best match between the RSS values in the decision rules database and the measured RSS values at the unknown position. The experimental results compared the performance of the proposed method with those of the nearest-neighbor-based and the random statistical methods in two different test cases. The results show that the proposed method greatly outperforms the others in both cases, where it achieves high accuracy with 98.05% of right position classification, which is approximately 50.49% more accurate than the others. The mean positioning errors at wrong estimated positions for the two test cases are 1.71 m and 1.99 m, using the proposed method.

BackgroundHepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains.MethodsWe analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined.Results92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively.ConclusionStrains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.

We investigated changes in some laboratory indices and the liver histology of chronic hepatitis patients who were exposed to dioxin. In 2014, we collected liver biopsy samples for histopathological examination from 33 chronic hepatitis patients living around the Da Nang Airbase, which is a dioxin-contaminated area due to the herbicide spraying in Vietnam. Dioxin exposure was measured by its levels in the blood. METAVIR classification was used to clarify the liver fibrosis stage. Laboratory tests included ten biochemical and six hematological indices that were measured in the blood. A regression linear model and binary logistic regression were used for data analysis. The observed alterations in the liver at the histological level mainly comprised hydropic degenerative hepatocytes, lymphocytes and polynuclear leukocytes surrounding the liver cells and granular and lipoic degeneration. In addition, increased TCDD levels were associated with increasing aminotransferase (AST), alanine aminotransferase, protein and total bilirubin levels and liver fibrosis stage. Similarly, increased TEQ-PCDD/Fs levels were associated with higher levels of AST and protein and liver fibrosis stage. In conclusion, dioxin exposure altered the liver histology and increased some biochemical marker indices and the liver fibrosis stage of chronic hepatitis patients living in dioxin-contaminated areas in Da Nang, Vietnam.

“Polynia” and “Covehithe” are two short stories from China Miéville’s 2015 collection Three Moments of an Explosion. Present in both is an “ecosystem” of spectacular violence that the author builds through, first, the graphic description of violence, second, the encapsulation of eye-witnessed violence in visual objects that resemble what the Marxist philosopher Guy Debord terms “spectacles” and, third, the manipulation of textual spectatorship. To construct a chilling and eerie atmosphere for his narratives, Miéville can be said to have drawn heavily on HP Lovecraft’s weird tales. Nonetheless, behind the spectacles of violence represented in “Polynia” and “Covehithe” is not the cosmic horror typical of Lovecraft but a different kind of horror, heavily anchored in our reality, possessing new and increasing urgency: the horror of global warming and environmental degradation, or, as in the words of Rob Nixon, of “slow violence.” Consequently, there happens in “Polynia” and “Covehithe” what is similar to an act of translation, of the slow into the spectacular. I argue that this translation provides a potential answer to Nixon’s pressing question about how to surmount the representational challenges created by slow violence in order to render it more urgent and engaging. This argument is furthermore related to broader discussions about the relationship between literature and the media, fiction’s engagement with the environmental crisis, as well as the differences between Old Weird and New Weird.

(1) Background: Antibiotic resistance (ABR) has been escalating to seriously high levels worldwide, accelerated by the misuse and overuse of antibiotics, especially in Vietnam. In this work, we investigated the Vietnamese public socio-demographic and knowledge factors associated with inappropriate practices of antibiotics to better understand the country’s antibiotic use and ABR. (2) Methods: To this end, a cross-sectional survey was conducted among Vietnamese people aged 18–60 years via Computer Assisted Telephone Interviews (CATIs) from May 2019 to November 2019. (3) Results: Among 3069 responses distributed equally in all 63 provinces in Vietnam, 1306 respondents completed the survey (response rate of 42.5%). Socio-demographically, most participants were male (56.4%), 18–25 years old (40.4%), located in Southern Vietnam (67.1%), highly educated (93.7%), and possessed medical insurance (95.3%). Respondents with higher education levels (college and above) had 2.663 times higher knowledge scores than those with lower education levels (p < 0.001). High-income respondents possessed more knowledge than low-income respondents (OR = 1.555, CI 95% 0.835–2.910, p = 0.024). Students, non-skilled workers, skilled workers, and professionals and managers had 0.052, 0.150, 0.732, and 0.393 times lower practice scores than the unemployed group, respectively (p < 0.001). Furthermore, respondents with higher/adequate knowledge scores had higher practice scores than those with inadequate knowledge scores (p < 0.05). (4) Conclusions: The findings indicate that socio-demographic differences in knowledge and practices exist, and focusing on these issues should be the priority in forthcoming interventions. The research data also provide information for policy makers to raise the community’s awareness of ABR.

Sodium and sulfate ions are among the suggested abundant ions on Europa, a moon of Jupiter. In order to investigate the potential habitability of Europa, we study the effects of sodium sulfate (Na2SO4) on a non-halophilic bacterium by subjecting Escherichia coli (E. coli) to a wide range of Na2SO4 concentrations (0–1.0 m). We discover that, as the concentration of sodium sulfate increases, the biomass doubling time increases and the cell growth is completely inhibited at 1.0 m Na2SO4. Furthermore, we find that E. coli exhibits three distinct morphological phenotypes—(i) shortened, (ii) normal, and (iii) elongated/filamented cells at 0.6 m and 0.8 m Na2SO4. We have examined the expression of different genes involved in sodium and sulfate transport (nhaA, nhaB, cysZ, sbp), osmotically driven transport of water (aqpZ), sulfate metabolism (cysN), fatty acid production (fabA), and a global transcriptional regulator (osmZ). Our results suggest that the expression of these genes is not affected significantly at high concentrations of sodium sulfate in the exponential growth phase. Using our experimental data and the existing data in the literature, we show that the osmotic pressure difference may play a major role in determining the growth inhibition of E. coli and B. subtilis at high concentrations of salt.

Abstract Background Endoplasmic reticulum (ER) stress and its consequent unfolded protein response (UPR) are believed to be associated with progression, survival and chemoresistance of a variety of tumor cells through multiple cellular processes, including autophagy. Therefore, the ER stress-autophagy pathway presents a potential molecular target for therapeutic intervention. The objective of this study was to evaluate the therapeutic efficacy of ER stress and autophagy modulators in the context of pancreatic ductal adenocarcinoma (PDAC). Methods We first targeted IRE1α, an important regulator of the UPR, through STF-083010 treatment in PDAC cell lines in vitro. Chloroquine was then used to target autophagy and an optimal combination treatment was developed using chloroquine, sunitinib and gemcitabine. Apoptosis was analyzed using TUNEL assay, autophagy was estimated using lysotracker staining and electron microscopy, and UPR was analyzed using anti-GRP78 immunostaining and XBP1 splicing. Transplantation of PDAC derived KPCP1 and Panc02 cells in mouse pancreas were performed to study treatment efficacy in vivo. Results Suppression of the IRE1α by STF-083010 alone resulted in increased lysosomes and reduced viability of PDAC cells. Chloroquine treatment alone inhibited downstream autophagy but was insufficient in reducing PDAC cell growth. However, combining STF-083010 and chloroquine had additive anti-tumor efficacy when used with gemcitabine. Sunitinib alone caused abnormal maturation of the autolysosomes with increased intracellular multivesicular bodies and increased apoptosis evident in PDAC cells. Sunitinib showed a synergistic effect with chloroquine in reducing in vitro PDAC cell viability and significantly increased the efficacy of gemcitabine in human and murine PDAC cell lines. The anti-proliferative effect of gemcitabine was significantly increased when used in combination with sunitinib and/or chloroquine in both in vitro and in vivo PDAC models. The addition of sunitinib and/or chloroquine to gemcitabine, resulted in a significantly increased survival of the animals without noticeably increased toxicity. Sunitinib, gemcitabine and chloroquine treated mice showed a significant reduction of GRP78 expression, reduced cell proliferation and increased apoptosis in pancreas, compatible with a tumor response. Conclusions Sunitinib combined with chloroquine reduces tumor growth through suppression of autophagy and increased apoptosis. Co-administration of modulators of ER stress-mediated autophagy with chemotherapy presents a novel therapeutic approach in PDAC.

Abstract Background Non-technical skills are emerging as an important component of postgraduate medical education. Between 2013 and 2016, a new blended training program incorporating non-technical skills was introduced at an Australian university affiliated hospital. Program participants were medical officers in years 1 and 2 of postgraduate training. Methods An interdisciplinary faculty trained in simulation-based education led the program. The blended approach combined open access online resources with multiple opportunities to participate in simulation-based learning. The aim of the study was to examine the value of the program to the participants and the effects on the wider hospital system. The mixed methods evaluation included data from simulation centre records, hospital quality improvement data, and a post-hoc reflective survey of the enrolled participants (n = 68). Results Over 30 months, 283 junior doctors were invited to participate in the program. Enrolment in a designated simulation-based course was completed by 169 doctors (59.7%). Supplementary revision sessions were made available to the cohort with a median weekly attendance of five participants. 56/68 (82.4%) of survey respondents reported increased confidence in managing deteriorating patients. During the period of implementation, the overall rate of hospital cardiac arrests declined by 42.3%. Future objectives requested by participants included training in graded assertiveness and neurological emergencies. Conclusions Implementation of a non-technical skills program was achieved with limited simulation resources and was associated with observable improvements in clinical performance. The participants surveyed reported increased confidence in managing deteriorating patients, and the program introduction coincided with a significant reduction in the rate of in-hospital cardiac arrests.

Standard cancer treatments involve surgery, radiotherapy, chemotherapy, and immunotherapy. In clinical practice, the respective drugs are applied orally or intravenously leading to their systemic circulation in the whole organism. For chemotherapeutics or immune modulatory agents, severe side effects such as immune depression or autoimmunity can occur. At the same time the intratumoral drug doses are often too low for effective cancer therapy. Since monotherapies frequently cannot cure cancer, due to their synergistic effects multimodal therapy concepts are applied to enhance treatment efficacy. The targeted delivery of drugs to the tumor by employment of functionalized nanoparticles might be a promising solution to overcome these challenges. For multimodal therapy concepts and individualized patient care nanoparticle platforms can be functionalized with compounds from various therapeutic classes (e.g. radiosensitizers, phototoxic drugs, chemotherapeutics, immune modulators). Superparamagnetic iron oxide nanoparticles (SPIONs) as drug transporters can add further functionalities, such as guidance or heating by external magnetic fields (Magnetic Drug Targeting or Magnetic Hyperthermia), and imaging-controlled therapy (Magnetic Resonance Imaging).

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The bridge between classical continuum plasticity and crystal plasticity is becoming narrower with continuously improved computational power and with engineers’ desire to obtain more information and better accuracy from their simulations, incorporating at the same time more effects about the microstructure of the material. This paper presents a short overview of the main current techniques employed in crystal plasticity formulations for finite element analysis, as to serve as a point of departure for researchers willing to incorporate microstructure effects in elastoplastic simulations. We include both classical and novel crystal plasticity formulations, as well as the different approaches to model dislocations in crystals.

Abstract In this paper, we present a mixture of support vector data descriptions (mSVDD) for one-class classification or novelty detection. A mixture of optimal hyperspheres is automatically discovered to characterize data. The model includes two parts: log likelihood to control the fit of data to model (i.e., empirical risk) and regularization quantizer to control the generalization ability of model (i.e., general risk). Expectation maximization (EM) principle is employed to train our proposed mSVDD. We demonstrate the advantage of the proposed model: if learning mSVDD in the input space, it simulates learning a single hypersphere in the feature space and the accuracy is thus comparable, but the training time is significantly shorter.

Engineering drawing is valuable in capturing geometric features, conveying engineering ideas, and creating a blueprint of the intended product. Engineering students usually perform orthographic projections, imagining a 3D situation and sketching its 2D representation. That requires imagination and mental visualization, determined by the learner's spatial ability. This study proposes the infusion of an AR stereogram mobile application into an engineering drawing course to establish how it influences learning outcomes among students with different spatial abilities. The quantitative experimental study involved two mechanical engineering classes in northern Taiwan, N = 69 first-year vocational high schoolers. Statistical analysis revealed that the experimental group with high spatial ability recorded better results and excellent drawing skills. Bloom's taxonomy categorization reported that spatial ability influenced "understanding" and "applying" levels, with the strongest effect on "understanding." Although no significant interaction existed, learning outcomes were highly affected by spatial ability in "understanding" and "applying" levels and AR in the overall performance. The findings and discussions show AR holds great potential to enhance students' spatial ability for real-time visualization and enables better concept comprehension by improving their understanding of engineering topics. Future studies should consider these implications in creating effective and immersive learning environments for different courses in engineering education.

An augmented reality (AR)-integrated gamification learning approach in an electronics course was developed in this study to help students better understand the concepts while simultaneously increasing their motivation. An experimental study was conducted to examine the effectiveness of the AR-integrated gamification approach on students' learning outcomes and motivation. A total of 29 vocational high school students was divided into two groups. The experimental group experienced AR-integrated gamification while the control group adopted conventional gamification. The results indicated that students in the AR-integrated gamification approach outperformed the conventional gamification group in the psychomotor learning outcomes, but no significant difference was found in cognitive and affective domains between the two groups. Concerning learning motivation, the experimental group only performed better intrinsic goal orientation than the control group while the other categories of motivation were insignificant. To compare the pretest and posttest in each group, the experimental group gained higher posttest scores in all domains of learning outcomes than the pretest scores after the intervention, but the control group only improved cognitive and psychomotor domains. Regarding learning motivation, the proposed approach pointed out the better posttest scores in all components compared to the pretest scores in the experimental group while only the posttest scores of extrinsic goal orientation, task value, and control beliefs about learning were higher than the pretest scores in the control group. The practical implications and recommendations for future work are presented.

Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired as well. This limits the administered dose and eventually allows tumor cells to escape treatment. In order to increase intratumoral drug concentration and simultaneously reduce systemic side effects, nanoparticles have come into focus as drug carriers. The functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with chemotherapeutics such as mitoxantrone (MTO) enables targeted drug transport by using magnetic forces. Here, we investigate SPIONs consisting of individual iron oxide cores of 10 nm in diameter and a total hydrodynamic diameter of 53 ± 0.8 nm as a transporting system for MTO. Comparing the killing efficacy in monolayer cell culture and multicellular tumor spheroids of HT-29 cells, we show that spheroids tolerate considerably higher doses of nanoparticle-loaded MTO. Therefore, dose predictions from conventional monolayer cell cultures are often misleading for in vivo applications. This was true for both soluble and nanoparticle-bound MTO. Using flow chambers mimicking in vivo blood flow, we furthermore demonstrate that SPIONs can magnetically accumulate MTO. We conclude that SPIONs can function as an effective delivery platform to increase local drug concentrations, thereby potentially overcoming chemotherapy resistance of cells.

In this study, waste cooking oil (WCO) was used to successfully manufacture catalyst cracking biodiesel in the laboratory. This study aims to evaluate and compare the influence of waste cooking oil synthetic diesel (WCOSD) with that of commercial diesel (CD) fuel on an engine’s operating characteristics. The second goal of this study is to compare the engine performance and temperature characteristics of cooling water and lubricant oil under various engine operating conditions of a test engine fueled by waste cooking oil and CD. The results indicated that the engine torque of the engine running with WCOSD dropped from 1.9 Nm to 5.4 Nm at all speeds, and its brake specific fuel consumption (BSFC) dropped at almost every speed. Thus, the thermal brake efficiency (BTE) of the engine fueled by WCOSD was higher at all engine speeds. Also, the engine torque of the WCOSD-fueled engine was lower than the engine torque of the CD-fueled engine at all engine speeds. The engine’s power dropped sequentially through 0.3 kW, 0.4 kW, 0.6 kW, 0.9 kW, 0.8 kW, 0.9 kW, 1.0 kW and 1.9 kW.

Many solutes have been reported to remain at higher plasma levels relative to normal than the standard index solute urea in hemodialysis patients. Untargeted mass spectrometry was employed to compare solute levels in plasma and plasma ultrafiltrate of hemodialysis patients and normal subjects. Quantitative assays were employed to check the accuracy of untargeted results for selected solutes and additional measurements were made in dialysate and urine to estimate solute clearances and production. Comparison of peak areas indicated that many solutes accumulated to high levels in hemodialysis patients, with average peak areas in plasma ultrafiltrate of dialysis patients being more than 100 times greater than those in normals for 123 features. Most of these mass spectrometric features were identified only by their mass values. Untargeted analysis correctly ranked the accumulation of 5 solutes which were quantitatively assayed but tended to overestimate its extent. Mathematical modeling showed that the elevation of plasma levels for these solutes could be accounted for by a low dialytic to native kidney clearance ratio and a high dialytic clearance relative to the volume of the accessible compartment. Numerous solutes accumulate to high levels in hemodialysis patients because dialysis does not replicate the clearance provided by the native kidney. Many of these solutes remain to be chemically identified and their pathogenic potential elucidated.