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Microtremor horizontal-to-vertical spectral ratios (mHVSR) are frequency-dependent ratios of Fourier amplitude spectra of the horizontal to vertical components of a 3-component recording of ambient ground motions from microtremors. Results from mHVSR tests can identify the frequencies associated with site resonances at sites with large impedance contrasts, and hence have potential to provide useful parameters for predicting seismic site response. Site measurements are made by recording ground vibrations either from a temporarily deployed seismometer, typically recording for a relatively short period of time (~1-2 hrs.), or from a permanently-installed broadband seismometer. In this paper, we discuss ongoing work investigating the reliability of low frequency (< ∼0.1 Hz) mHVSR ordinates. Such low frequency ordinates are potentially useful for sites that are known to have deep basins (e.g., LA Basin, Imperial Valley, Great Salt Lake basin), where fundamental frequencies may fall in this range and direct measurements of depth to bedrock are difficult to make. We have found that low-frequency mHVSR ordinates (< ∼0.1-0.2 Hz) are for practical purposes not reliable in most cases, even when measured by high-quality temporary or permanent broadband sensors. In this paper, we discuss sensor drift and its limited impact on the reliability of mHVSR ordinates. We document the low frequency problem for multiple sites, although we do not have a solution as of this writing for how to improve the reliability of low-frequency results.

Background: Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known., Aims: Here, we present a comprehensive, international characterization of practice patterns and perspectives on the use of EVT for CVT.Methods A comprehensive 42-question survey was distributed to stroke clinicians globally from May-October 2023, asking about practice patterns and perspectives on the use of EVT for CVT., Results: The overall response rate was 31% (863 respondents of 2744 invited) across 61 countries. The majority of respondents (74%) supported the use of EVT for CVT in certain clinical situations. Key considerations for decision-making in using EVT favored clinical over radiographic/procedural factors and included worsening level of consciousness (86%) and worsening neurological deficits (76%). In the past three years, 56% of respondents used EVT for the treatment of CVT, with most (49.5%) involved in 2-5 cases. Among interventionalists, significant variability existed in the techniques used for EVT (p<0.001), with aspiration thrombectomy (56%) and stent retriever (51%) being the most used overall. Regionally, interventionalists from China predominately used intra-sinus heparin (56%), while this technique was most commonly ranked as "never indicated" throughout the rest of the world (23%). Post-procedure, low molecular weight heparin was the most used anticoagulant (83%), although North American respondents favored unfractionated heparin (37%), while imaging was primarily split between magnetic resonance (71.8%) and computed tomography (65.9%) arteriography or venography., Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, and provides a comprehensive characterization of indications, techniques and long-term management used by clinicians internationally. This resource will aid in optimizing patient selection and endovascular treatments for future trials.

The prevalence and predictors of mortality following an ischemic stroke or intracerebral hemorrhage have not been well established among patients in Vietnam. 2885 consecutive diagnosed patients with ischemic stroke and intracerebral hemorrhage at ten stroke centres across Vietnam were involved in this prospective study. Posthoc analyses were performed in 2209 subjects (age was 65.4 ± 13.7 years, with 61.4% being male) to explore the clinical characteristics and prognostic factors associated with 90-day mortality following treatment. An explainable machine learning model using extreme gradient boosting and SHapley Additive exPlanations revealed the correlation between original clinical research and advanced machine learning methods in stroke care. In the 90 days following treatment, the mortality rate for ischemic stroke was 8.2%, while for intracerebral hemorrhage, it was higher at 20.5%. Atrial fibrillation was an elevated risk of 90-day mortality in the ischemic stroke patient (OR 3.09; 95% CI 1.90-5.02, p<0.001). Among patients with intracerebral hemorrhage, there was no statistical significance in those with hypertension compared to their counterparts without hypertension (OR 0.65, 95% CI 0.41-1.03, p > 0.05). The baseline NIHSS score was a significant predictor of 90-day mortality in both patient groups. The machine learning model can predict a 0.91 accuracy prediction of death rate after 90 days. Age and NIHSS score were in the top high risks with other features, such as consciousness, heart rate, and white blood cells. Stroke severity, as measured by the NIHSS, was identified as a predictor of mortality at discharge and the 90-day mark in both patient groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This work explores strategies for electrokinetic preconcentration of extracellular vesicles (EVs) that are potential source of biomarkers for different diseases. The first approach that led to successful preconcentration of EVs is based on large volume sample stacking (LVSS), allowing an enrichment factor of 7 for CE of EVs with long-end injection (using a capillary with an effective length of 50 cm). Attempts were also made to perform multiple cycles of LVSS, field amplified sample stacking (FASS) and field amplified sample injection (FASI), to improve EVs preconcentration performance. The focus was then put on development of capillary isotachophoresis under high ionic strengths (IS) for electrokinetic enrichment of slow migrating EVs having heterogeneous mobilities. This approach relies on the use of extremely high concentrations of the terminating electrolyte (TE) to slow down the mobility of TE co-ions, rendering them slower than those of EVs. The limit of detection for intact EVs using the developed ITP-UV method reached 8.3 × 10 8 EVs/mL, allowing an enrichment of 25 folds and a linear calibration up to 4 × 10 10 EVs/mL. The ITP-UV and ITP-LIF approaches were applied to provide the electrokinetic signature of EVs of bovine milk and human plasma as well as to visualize more specifically intravesicular fluorescently labelled EVs. The investigation of these strategies shredded light into the challenges still encountered with electrokinetic preconcentration and separation of heterogeneous EVs sub-populations which are discussed herein based on our results and other attempts reported in the literature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cytochrome P450s (CYPs) regulate plant growth and stress responses by producing diverse primary and secondary metabolites. However, the function of many plant CYPs remains unknown because, despite their structural similarity, predicting the enzymatic activity of CYPs is difficult. In this study, one member of the CYP736A subfamily (CYP736A61) from tomatoes was isolated and characterized its enzymatic functions. CYP736A61 was successfully expressed in Escherichia coli through co-expression with molecular chaperones. The purified CYP736A61 showed hydroxylation activity toward 7-ethoxycoumarin, producing 7-hydroxycoumarin or 3-hydroxy 7-ethoxycoumarin. Further substrate screening revealed that dihydrochalcone and stilbene derivates (resveratrol and polydatin) are the substrates of CYP736A61. CYP736A61 also mediated the hydroxylation of resveratrol and polydatin, albeit with low activity. Importantly, CYP736A61 mediated the cleavage of resveratrol and polydatin as well as pinostilbene and pterostilbene. Interestingly, CY736A61 also converted phloretin to naringenin chalcone. These results suggest that CYP736A61 is a novel CYP enzyme with stilbene cleavage activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we review various strategies to couple sample processing in microfluidic droplets with different separation techniques, including liquid chromatography, mass spectrometry, and capillary electrophoresis. Separation techniques interfaced with droplet microfluidics represent an emerging trend in analytical chemistry, in which micro to femtoliter droplets serve as microreactors, a bridge between analytical modules, as well as carriers of target analytes between sample treatment and separation/detection steps. This allows to overcome the hurdles encountered in separation science, notably the low degree of module integration, working volume incompatibility, and cross contamination between different operational stages. For this droplet-separation interfacing purpose, this review covers different instrumental designs from all works on this topic up to May 2023, together with our viewpoints on respective advantages and considerations. Demonstration and performance of droplet-interfaced separation strategies for limited sample volumes are also discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Several glycoproteins are validated biomarkers of various diseases such as cancer, cardiovascular diseases, chronic alcohol abuse, or congenital disorders of glycosylation (CDG). In particular, CDG represent a group of more than 150 inherited diseases with varied symptoms affecting multiple organs. The distribution of glycans from target glycoprotein(s) can be used to extract information to help the diagnosis and possibly differentiate subtypes of CDG. Indeed, depending on the glycans and the proteins to which they are attached, glycans can play a very broad range of roles in both physical and biological properties of glycoproteins. For glycans in general, capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) has become a staple. Analysis of glycans with CE-LIF requires several sample preparation steps, including release of glycans from the target glycoprotein, fluorescent labeling of glycans, and purification of labeled glycans. Here, we describe the protocol for glycan sample treatment in a microfluidic droplet system prior to CE-LIF of labeled glycans. The microfluidic droplet approach offers full automation, sample, and reagent volume reduction and elimination of contamination from external environment., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Part 1 of this review provided an overview of AF in Vietnam, with a particular focus on primary and secondary stroke prevention. Part 2 explores the management of AF in special, high-risk and clinically common patient populations, including those with renal impairment, diabetes, the elderly, and those with coronary artery disease. Furthermore, Part 2 addresses the challenges posed by patients with AF who have a bioprosthetic valve, a group situated in a grey area of consideration. Managing AF in these patient groups presents unique clinical challenges that require careful consideration. Physicians are tasked with addressing specific clinical questions to identify the optimal anticoagulation strategy for each individual. To inform these decisions, subgroup analyses from pivotal studies are presented alongside real-world data derived from clinical practice. By synthesising available information and considering the nuanced clinical context, the aim is to provide informed perspectives that align with current medical knowledge and contribute to the enhancement of patient care in these challenging scenarios., Competing Interests: Disclosure: THQH has received honoraria for scientific presentations from Bayer and Pfizer. MTT, VLN and HMP have received honoraria for scientific presentations from Bayer, Pfizer, Boehringer Ingelheim and Daiichi Sankyo. SVH, NTV and TNH have received honoraria for scientific presentations from Bayer, Pfizer and Boehringer Ingelheim. TQN and LTP have received honoraria for scientific presentations from Bayer and Boehringer Ingelheim. TDM has received grants from Bayer for research and honoraria for scientific presentations from Bayer, Pfizer and Boehringer Ingelheim. Funding: The medical writing fee and the article processing charge were funded by Bayer Vietnam. The funder had no role in the design, execution, interpretation or writing of the study., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

In Asia, especially Vietnam, AF is a common arrhythmia and is linked to a higher risk of stroke and systemic embolism. Anticoagulation therapy for stroke prevention in AF patients can result in bleeding complications. To effectively manage AF, adopting appropriate anticoagulation and addressing modifiable risk factors are crucial. Vietnamese clinicians are particularly interested in non-vitamin K antagonist oral anticoagulants (NOACs), a recent development in AF treatment. However, the lack of head-to-head trials comparing NOACs makes selecting a specific NOAC challenging. This review aims to provide a comprehensive overview of the available clinical evidence on NOACs for stroke prevention in AF to assist clinicians in making informed decisions and improving treatment outcomes in patients with AF. The first part of this review will present the current landscape of AF in Vietnam, focusing on AF prevalence and highlighting gaps in clinical practice. Furthermore, this part extensively discusses the anticoagulation strategy for both primary and secondary stroke prevention in AF., Competing Interests: Disclosure: THQH has received honoraria for scientific presentations from Bayer, Pfizer. MTT, VLN and HMP have received honoraria for scientific presentations from Bayer, Pfizer, Boehringer Ingelheim and Daiichi Sankyo. SVH, NTV and TNH have received honoraria for scientific presentations from Bayer, Pfizer and Boehringer Ingelheim. TQN and LTP have received honoraria for scientific presentations from Bayer and Boehringer Ingelheim. TDM has received grants from Bayer for research and honoraria for scientific presentations from Bayer, Pfizer and Boehringer Ingelheim. Funding: The medical writing fee and article processing charge were funded by Bayer Vietnam. The funder had no role in the design, execution, interpretation or writing of the study., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

This study reports the development of a Taylor Dispersion Analysis (TDA) method for the size characterization of Extracellular Vesicles (EVs), which are highly heterogeneous nanoscale cell-derived vesicles (30-1000 nm). Here, we showed that TDA, conducted in uncoated fused silica capillaries (50 µm i.d.) using a conventional Capillary Electrophoresis instrument, is able to provide absolute sizing (requiring no calibration) of bovine milk-derived EVs in a small sample volume (∼ 7 nL) and over their entire size range, even the smallest ones (< 70 nm) not accessible via other techniques that provide nanoparticle sizing in suspension. TDA size measurements were repeatable (RSD < 10%) and the average EV sizes were found in the range of 120-210 nm, in very good agreement with those measured with Nanoparticle Tracking Analysis, commonly used for EV characterization. TDA allowed quantitative estimation of EVs for concentrations ≥ 2 × 10 11 EVs/mL. Furthermore, TDA was able to detect minor changes in EV size (i.e. by ∼25 nm upon interaction with specific anti-CD9 antibodies of ∼150 kDa), and to highlight the impact of extraction methods (i.e. milk pretreatment: freezing, acid precipitation or centrifugation; the type of size-exclusion chromatography column) and of fluorescent labeling (i.e. intravesicular or surface labeling) on the isolated EV population size. In parallel to EV sizing, TDA allowed to detect molecular contaminants (average sizes ∼1-13 nm) present within the sample, rendering this method a valuable tool to assess the quality and quantity of EV isolates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH., Methods: From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome., Results: Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROC<0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5; PAUROC<0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5; PAUROC<0.001) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001)., Conclusions: In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study reports on the development of a new concept of on-line dual preconcentration stages for capillary electrophoresis (CE), in which two completely different preconcentration approaches can be realized in the same capillary. In the first stage, a dynamic magneto-extraction of target analytes on circulating magnetic beads is implemented within the capillary. In the second one, electrokinetic preconcentration of eluted analytes via large volume sample stacking is carried out to focus them into a nano band, prior to CE separation of enriched analytes. To implement the dual-stage preconcentration operation, a purpose-made instrument was designed, combining electrophoretic and microfluidic modules to allow precise control of the movement of magnetic beads and analyte's flow. The potential of this new enrichment principle and its associated instrument was demonstrated for CE separation with light-emitting-diode-induced fluorescent (LEDIF) detection of target double-stranded DNA (ds-DNA). The workflow consists of purification and preconcentration of a target DNA fragment (300 bp) on negatively charged magnetic beads, followed by in-capillary elution and fluorescent labelling of the enriched DNA. Large volume sample stacking of the DNA eluent was then triggered to further preconcentrate the labelled DNA before its analysis by CE-LEDIF. An enrichment factor of 125 was achieved for the target DNA fragment. With our new approach, dual-stage sample pretreatment and CE separation can now be performed in-capillary without any mismatch of working volumes, nor any waste of pretreated samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This multicentre prospective cohort study aimed to compare the accuracy of the PAASH, WFNS, and Hunt and Hess (H&H) scales in predicting the outcomes of adult patients with aneurysmal SAH presented to three central hospitals in Hanoi, Vietnam, from August 2019 to June 2021. Of 415 eligible patients, 32.0% had a 90-day poor outcome, defined as an mRS score of 4 (moderately severe disability) to 6 (death). The PAASH, WFNS and H&H scales all have good discriminatory abilities for predicting the 90-day poor outcome. There were significant differences in the 90-day mean mRS scores between grades I and II (p = 0.001) and grades II and III (p = 0.001) of the PAASH scale, between grades IV and V (p = 0.026) of the WFNS scale, and between grades IV and V (p < 0.001) of the H&H scale. In contrast to a WFNS grade of IV-V and an H&H grade of IV-V, a PAASH grade of III-V was an independent predictor of the 90-day poor outcome. Because of the more clearly significant difference between the outcomes of the adjacent grades and the more strong effect size for predicting poor outcomes, the PAASH scale was preferable to the WFNS and H&H scales., (© 2023. The Author(s).)

Objectives: To investigate the impact of intracerebral haematoma (ICH) on the outcomes and the factors related to an ICH in patients with aneurysmal subarachnoid haemorrhage (aSAH) in a low- and middle-income country., Design: A multicentre prospective cohort study., Setting: Three central hospitals in Hanoi, Vietnam., Participants: This study included all patients (≥18 years) presenting with aSAH to the three central hospitals within 4 days of ictus, from August 2019 to June 2021, and excluded patients for whom the admission Glasgow Coma Scale was unable to be scored or patients who became lost at 90 days of follow-up during the study., Outcome Measures: The primary outcome was ICH after aneurysm rupture, defined as ICH detected on an admission head CT scan. The secondary outcomes were 90-day poor outcomes and 90-day death., Results: Of 415 patients, 217 (52.3%) were females, and the median age was 57.0 years (IQR: 48.0-67.0). ICH was present in 20.5% (85/415) of patients with aSAH. There was a significant difference in the 90-day poor outcomes (43.5% (37/85) and 29.1% (96/330); p=0.011) and 90-day mortality (36.5% (31/85) and 20.0% (66/330); p=0.001) between patients who had ICH and patients who did not have ICH. The multivariable regression analysis showed that systolic blood pressure (SBP) ≥140 mm Hg (adjusted odds ratio (AOR): 2.674; 95% CI: 1.372 to 5.214; p=0.004), World Federation of Neurosurgical Societies (WFNS) grades II (AOR: 3.683; 95% CI: 1.250 to 10.858; p=0.018) to V (AOR: 6.912; 95% CI: 2.553 to 18.709; p<0.001) and a ruptured middle cerebral artery (MCA) aneurysm (AOR: 3.717; 95% CI: 1.848 to 7.477; p<0.001) were independently associated with ICH on admission., Conclusions: In this study, ICH was present in a substantial proportion of patients with aSAH and contributed significantly to a high rate of poor outcomes and death. Higher SBP, worse WFNS grades and ruptured MCA aneurysms were independently associated with ICH on admission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic left its unique mark on the twenty-first century as one of the most significant disasters in history, triggering governments all over the world to respond with a wide range of interventions. However, these restrictions come with a substantial price tag. It is crucial for governments to form anti-virus strategies that balance the trade-off between protecting public health and minimizing the economic cost. This work proposes a probabilistic programming method to quantify the efficiency of major initial non-pharmaceutical interventions. We present a generative simulation model that accounts for the economic and human capital cost of adopting such strategies, and provide an end-to-end pipeline to simulate the virus spread and the incurred loss of various policy combinations. By investigating the national response in 10 countries covering four continents, we found that social distancing coupled with contact tracing is the most successful policy, reducing the virus transmission rate by 96% along with a 98% reduction in economic and human capital loss. Together with experimental results, we open-sourced a framework to test the efficacy of each policy combination., Competing Interests: T-DM was employed by the company Samsung Electronics, but this work was done when he was an undergraduate student at KAIST/IBS Data Science Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhunis, Mai and Kim.)

In this study, we present a novel microfluidic droplet-based strategy for high performance isolation of extracellular vesicles (EVs). For EVs capture and release, a magnetic bead-based approach without having recourse to any antibody was optimized in batch and then adapted to the microfluidic droplet system. This antibody-free capture approach relies on the presence of a water-excluding polymer, polyethylene glycol (PEG), to precipitate EVs on the surface of negatively charged magnetic beads. We significantly improved the reproducibility of EV recovery and avoided positive false bias by including a washing step and optimizing the protocol. Well-characterized EV standards derived from pre-purified bovine milk were used for EVs isolation performance evaluation. An EVs recovery of up to 25% estimated with nanoparticle tracking analysis (NTA) was achieved for this batchwise PEG-based approach. The confirmation of isolated EVs identity was also made with our recently developed method using capillary electrophoresis (CE) coupled with laser-induced fluorescent (LIF) detection. In parallel, a purpose-made droplet platform working with magnetic tweezers was developed for translation of this PEG-based method into a droplet microfluidic protocol to further improve the performance in terms of EVs capture efficiency and high throughput. The droplet-based protocol offers a significant improvement of recovery rate (up to 50%) while reducing sample and reagent volumes (by more than 10 folds) and operation time (by 3 folds) compared to the batch-wise mode., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, we present a new approach for in-capillary fluorescent labeling of N-glycans prior to their analysis with CE coupled with laser-induced fluorescent detection. This integrated approach allows using a CE capillary as a microreactor to perform several steps required for labeling glycans with 8-aminopyrene-1,3,6 trisulfonic acid and at the same time as a separation channel for CE of fluorescently labeled glycans. This could be achieved through careful optimization of all different steps, including sequential injections of fluorescent dye and glycan plugs, mixing by transverse diffusion of laminar flow profiles, incubation in a thermostatic zone, and finally separation and detection with CE. Such a complex sample treatment protocol for glycan labeling that is feasible thus far only in batchwise mode can now be converted into an automated and integrated protocol. Our approach was applied successfully to analyze fluorescently labeled N-linked oligosaccharides released from human immunoglobulin G and rituximab, a monoclonal antibody used for cancer treatment. We demonstrated the superiority of this in-capillary approach over the conventional in-tube protocol, with fourfold less reagent consumption and full automation without remarkable degradation of the glycan separation profile obtained by capillary electrophoresis., (© 2022 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)

We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The cytokine interleukin 6 (IL-6) is involved in the pathogenesis of different inflammatory diseases, including cancer, and its monitoring could help diagnosis, prognosis of relapse-free survival and recurrence. Here, we report an innovative microfluidic approach that uses the fluidization of magnetic beads to specifically extract, preconcentrate and fluorescently detect IL-6 directly on-chip. We assess how the physical properties of the beads can be tuned to improve assay performance by enhancing mass transport, reduce non-specific binding and multiply the detection signal threefold by transitioning between packed and fluidization states. With the integration of a full ELISA protocol in a single microfluidic chamber, we show a twofold reduction in LOD compared to conventional methods along with a large dynamic range (10 pg/mL to 2 ng/mL). We additionally demonstrate its application to IL-6 detection in undiluted serum samples., (© 2022. The Author(s).)

Ascorbate is an essential antioxidant substance for humans. Due to the lack of ascorbate biosynthetic enzyme, a human must intake ascorbate from the food source. Tomato is one of the most widely consumed fruits, thus elevation of ascorbate content in tomato fruits will improve their nutritional value. Here we characterized Solanum lycopersicum ASCORBATE PEROXIDASE 4 ( SlAPX4 ) as a gene specifically induced during fruit ripening. In tomatoes, ascorbate accumulates in the yellow stage of fruits, then decreases during later stages of fruit ripening. To investigate whether SlAPX is involved in the decrease of ascorbate, the expression of SlAPX s was analyzed during fruit maturation. Among nine SlAPX s, SlAPX4 is the only gene whose expression was induced during fruit ripening. Mutation of SlAPX4 by the CRISPR/Cas9 system increased ascorbate content in ripened tomato fruits, while ascorbate content in leaves was not significantly changed by mutation of SlAPX4 . Phenotype analysis revealed that mutation of SlAPX4 did not induce an adverse effect on the growth of tomato plants. Collectively, we suggest that SlAPX4 mediates a decrease of ascorbate content during the later stage of fruit ripening, and mutation of SlAPX4 can be used for the development of genome-edited tomatoes with elevated ascorbate content in fruits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Do, Park, Park, Kim, Ma, Mai, Shim and Joung.)

We present in this study a novel strategy to drastically improve the detection sensitivity and peak capacity for capillary electrophoresis with laser induced fluorescent detection (CE-LIF) of glucose oligomers and released glycans. This is based on a new approach exploiting a polymer-free background electrolyte (BGE) for CE-LIF of glycans. The best performance in terms of sample stacking and suppression of electroosmotic flow (EOF) was found for a BGE composed of triethanolamine/citric acid and triethanolamine/acetic acid at elevated ionic strengths (IS up to 200 mM). Compared to the conventional protocols for CE-LIF of glucose-oligosaccharides and released glycans, our polymer-free strategy offered up to 5-fold improvement of detection sensitivity and visualization of higher degree of polymerization (DP) of glucose oligomers (18 vs 15). To further improve the detection sensitivity, a new electrokinetic preconcentration strategy via large volume sample stacking with electroosmotic modulation without having recourse to neutrally coated capillaries is proposed, offering a 200-fold signal enhancement. This approach is based on variation of the buffer's IS, rather than pH adjustment as in conventional methods, for EOF modulation or quasi-total reduction. This strategy allows selecting with high flexibility the best pH conditions to perform efficient preconcentration and separation. The new approach was demonstrated to be applicable for the analysis of N-linked oligosaccharides released from a model glycoprotein (Human Immunoglobulin G) and applied to map N-glycans from human serum for congenital disorders of glycosylation (CDG) diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of magnetic beads bio-functionalized by antibodies (Ab) is constantly increasing with a wide range of biomedical applications. However, despite an urgent need for current methods to monitor Ab's grafting process and orientation, existing methods are still either cumbersome and/or limited. In this work, we propose a new simple and rapid analytical approach to evaluate antibody orientation and density on magnetic beads. This approach relies on the cleavage by IdeS, a highly specific protease for human immunoglobulin G (hIgG), of immobilized antibodies. The F(ab) 2 and Fc fragments could be then accurately quantified by size exclusion chromatography (SEC)-coupled to fluorescent detection (FLD), and the ratio of these fragments was used to give insight on the IgG orientation at the bead surface. Four different commercially available magnetic beads, bearing carboxyl groups, tosyl groups, streptavidin, or protein G on their surface have been used in this study. Results obtained showed that this approach ensures reliable information on hIgG orientation and bead surface coverage. Protein G magnetic beads demonstrated an optimal orientation of antibodies for antigen capture (75% of accessible F(ab) 2 fragment) compared to tosylactivated, carboxylated, and streptavidin ones. Capture efficiency of the different functionalized beads towards human TNF-α immunocapture, a biomarker of inflammation, has been also compared. Protein G beads provided a more efficient capture compared to other beads. In the future, this approach could be applied to any type of surface and beads to assess hIgG coverage and orientation after any type of immobilization. A rapid and simple approach to evaluate orientation and density of antibodies immobilized on magnetic beads., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The prevalence of risk factors for poor outcomes from aneurysmal subarachnoid hemorrhage (SAH) varies widely and has not been fully elucidated to date in Vietnam. Understanding the risk and prognosis of aneurysmal SAH is important to reduce poor outcomes in Vietnam. The aim of this study, therefore, was to investigate the rate of poor outcome at 90 days of ictus and associated factors from aneurysmal SAH in the country., Methods: We performed a multicenter prospective cohort study of patients (≥18 years) presenting with aneurysmal SAH to three central hospitals in Hanoi, Vietnam, from August 2019 to August 2020. We collected data on the characteristics, management, and outcomes of patients with aneurysmal SAH and compared these data between good (defined as modified Rankin Scale (mRS) of 0 to 3) and poor (mRS, 4-6) outcomes at 90 days of ictus. We assessed factors associated with poor outcomes using logistic regression analysis., Results: Of 168 patients with aneurysmal SAH, 77/168 (45.8%) were men, and the median age was 57 years (IQR: 48-67). Up to 57/168 (33.9%) of these patients had poor outcomes at 90 days of ictus. Most patients underwent sudden-onset and severe headache (87.5%; 147/168) and were transferred from local to participating central hospitals (80.4%, 135/168), over half (57.1%, 92/161) of whom arrived in central hospitals after 24 hours of ictus, and the initial median World Federation of Neurological Surgeons (WFNS) grading score was 2 (IQR: 1-4). Nearly half of the patients (47.0%; 79/168) were treated with endovascular coiling, 37.5% (63/168) were treated with surgical clipping, the remaining patients (15.5%; 26/168) did not receive aneurysm repair, and late rebleeding and delayed cerebral ischemia (DCI) occurred in 6.1% (10/164) and 10.4% (17/163) of patients, respectively. An initial WFNS grade of IV (odds ratio, OR: 15.285; 95% confidence interval, CI: 3.096-75.466) and a grade of V (OR: 162.965; 95% CI: 9.975-2662.318) were independently associated with poor outcomes. Additionally, both endovascular coiling (OR: 0.033; 95% CI: 0.005-0.235) and surgical clipping (OR: 0.046; 95% CI: 0.006-0.370) were inversely and independently associated with poor outcome. Late rebleeding (OR: 97.624; 95% CI: 5.653-1686.010) and DCI (OR: 15.209; 95% CI: 2.321-99.673) were also independently associated with poor outcome., Conclusions: Improvements are needed in the management of aneurysmal SAH in Vietnam, such as increasing the number of aneurysm repairs, performing earlier aneurysm treatment by surgical clipping or endovascular coiling, and improving both aneurysm repairs and neurocritical care., Competing Interests: The authors have declared that no competing interests exist.

It is reported in this study a new approach for modulation and even suppression of the electroosmotic flow (EOF) to achieve better electrokinetic preconcentration in capillary electrophoresis. This is based on the augmentation of the buffer's concentrations to very high levels (more than a thousand of mM) without recourse to any dynamic/permanent coating nor viscous gel. The use of large weakly charged molecules as background electrolyte's constituents allows working at extreme concentration ranges without penalty of high electric currents and Joule heating. By this way, the electroosmotic mobility could be modulated over a wide range (2-60 × 10 -5  cm 2  V -1  s -1 under alkaline conditions), and suppressed to levels equivalent to those obtained with several neutral coatings. The highest buffer concentrations, and the lowest EOF magnitudes, accordingly, were achieved with diethanolamine/3-(Cyclohexylamino)-1-propanesulfonic acid (ionic strength (IS) of 250 mM, pH 9.5), Tris(hydroxymethyl)aminomethane (Tris)/2-(Cyclohexylamino)ethanesulfonic acid (CHES) (IS of 280 mM, pH 8.7) and triethanolamine/2-(Cyclohexylamino)ethanesulfonic acid (IS of 250 mM, pH 8.5). For demonstration, this new approach was applied for sensitive determination of core-shell magnetic nanoparticles (CSMNPs) having high potential for healthcare applications such as imaging agents for diagnostics and controllable cargos for nanomedicine. Different profiles were achieved for purpose-made and commercial magnetic nanoparticles using CE coupled with light-emitting-diode induced fluorescence (LEDIF) detection. The best performance for EOF-assisted preconcentration and CE-LEDIF of CSMNPs was achieved with these nanoparticles prepared in TRIS/CHES (IS 10 mM, pH 8.4) for preconcentration, and separation under BGE of TRIS/CHES (IS 100 mM, pH 8.4). Compared to the conventional capillary electrophoresis (CE-UV) method for characterization of magnetic nanoparticles, our proposed approach with fluorescent detection and EOF-assisted preconcentration offers almost 350-fold sensitivity improvement. Furthermore, our scheme can be used for monitoring the interaction between CSMNPs and target pharmaceutical molecules, serving for drug delivery development. A preliminary study with two antibiotics using this approach revealed that kanamycin interacts better with the target nanoparticles than amikacin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Key Message: The thylakoid transit peptide of tobacco oxygen-evolving enhancer protein contains a minimal ten amino acid sequences for thylakoid lumen transports. This ten amino acids do not contain twin-arginine, which is required for typical chloroplast lumen translocation. Chloroplasts are intracellular organelles responsible for photosynthesis to produce organic carbon for all organisms. Numerous proteins must be transported from the cytosol to chloroplasts to support photosynthesis. This transport is facilitated by chloroplast transit peptides (TPs). Four chloroplast thylakoid lumen TPs were isolated from Nicotiana tabacum and were functionally analyzed as thylakoid lumen TPs. Typical chloroplast stroma-transit peptides and thylakoid lumen transit peptides (tTPs) are found in N. tabacum transit peptides (NtTPs) and the functions of these peptides are confirmed with TP-GFP fusion proteins under fluorescence microscopy and chloroplast fractionation, followed by Western blot analysis. During the functional analysis of tTPs, we uncovered the minimum 10 amino acid sequence is sufficient for thylakoid lumen transport. These ten amino acids can efficiently translocate GFP protein, even if they do not contain the twin-arginine residues required for the twin-arginine translocation (Tat) pathway, which is a typical thylakoid lumen transport. Further, thylakoid lumen transporting processes through the Tat pathway was examined by analyzing tTP sequence functions and we demonstrate that the importance of hydrophobic core for the tTP cleavage and target protein translocation.

In this study, for the first time we report on a comprehensive overview of different strategies to hyphenate droplet-based sample handling and preparation with electrophoretic separation in different formats (i.e. microchip and capillary electrophoresis). Droplet-interfaced electrophoresis is an emerging technique in which micro/nanometric droplets are used as a bridge and carrier of target analytes between sample treatment and electrokinetic separation steps, thus being expected to overcome the challenges of working dimension mismatch and low degree of module integration. This review covers all works on this topic from 2006 (the year of the first communication) up to 2020, with focus being given to three principal interfacing strategies, including droplets in immiscible phases, digital microfluidics with electrowetting-on-dielectric principle and inkjet droplet generation. Different instrumental developments for such purpose, the viewpoints on pros and cons of these designs as well as application demonstrations of droplet-interfaced electrokinetic strategies are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Among all neurodegenerative diseases, Alzheimer's Disease (AD) is the most prevalent worldwide, with a huge burden to the society and no efficient AD treatment so far. Continued efforts have been being made towards early and powerful diagnosis of AD, in the hope for a successful set of clinical trials and subsequently AD curative treatment. Towards this aim, detection and quantification of amyloid beta (Aβ) peptides in cerebrospinal fluid (CSF) and other biofluids, which are established and validated biomarkers for AD, have drawn attention of the scientific community and industry over almost two decades. In this work, an overview on our major contributions over 15 years to develop different electrokinetic and microfluidic strategies for Aβ peptides detection and quantification is reported. Accordingly, discussions and viewpoints on instrumental and methodological developments for microscale electrophoresis, microfluidic designs and immuno-enrichment / assays on magnetic beads in microchannels for tracing Aβ peptides in CSF are given in this review., (© 2020 The Chemical Society of Japan & Wiley-VCH GmbH.)

In this study, the development of our purpose-made capacitively coupled contactless conductivity detection (C 4 D) for CE is reported. These systems have been employed as a simple, versatile, and cost-effective analytical tool. CE-C 4 D devices, whose principle is based on the control of the ion movements under an electrical field, can be constructed even with a modest financial budget and limited infrastructure. A featured application was developed for quality control of antimicrobial drugs using CE-C 4 D, with most recent work on determination of aminoglycoside and glycopeptide antibiotics being communicated. For aminoglycosides, the development of CE-C 4 D methods was adapted to two categories. The first one includes drugs (liquid or powder form) for intravenous injection, containing either amikacin, streptomycin, kanamycin A, or kanamycin B. The second one covers drugs for eye drops (liquid or ointment form), containing either neomycin, tobramycin, or polymyxin. The CE-C 4 D method development was also made for determination of some popular glycopeptide antibiotics in Vietnam, including vancomycin and teicoplanin. The best detection limit achieved using the developed CE-C 4 D methods was 0.5 mg/L. Good agreement between results from CE-C 4 D and the confirmation method (HPLC- Photometric Diode Array ) was achieved, with their result deviations less than 8% and 13% for aminoglycoside and glycopeptide antibiotics, respectively., (© 2020 Wiley-VCH GmbH.)

This study reports on the development of a novel instrument for capillary electrophoresis (CE) coupled with laser induced fluorescence (LIF) detection that is inspired by the Lego-toy concept. The Lego CE-LIF design is an evolution of purpose-made CE instrumentation, allowing the users to construct their own analytical device with a high degree of standardization (i.e. a "standard" setup) without requirement of mechanical and electronic workshop facilities. To allow instrument reproduction outside the original fabrication laboratory, which is not trivial for in-house-built CE systems, the new design is based on unprecedent 'plugging' hyphenation of various off-the-shelf parts available for microfluidics, optics and electrophoresis. To render the operation with Lego CE-LIF optimal, we developed a new background electrolyte (BGE), using for the first time extremely high concentrations of zwitterionic and large weakly charged species for much improvement of detection sensitivity. The Lego CE-LIF was demonstrated for separation and detection of oligosaccharides labelled with 8-aminopyrene-1,3,6-trisulfonic acid (APTS). The new gel-free BGE for oligosaccharide analysis also allowed simplification of the conventional CE-LIF protocol used with commercial instruments while keeping satisfactory separation performances. Furthermore, the new BGE is fully compatible with a non-thermostatted Lego CE instrument thanks to low current and therefore low heat generation under application of a high voltage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Glycosylation is one of the most complex post-translational modifications of proteins and lipids, notably requiring many glycosyltransferases, glycosidases and sugar transporters encoded by about 1-2% of all human genes. Deleterious variants in any of them may result in improper protein or lipid glycosylation, thus yielding the so-called 'congenital disorders of glycosylation' or CDG., Scope of Review: We first review the current state of knowledge on the common blood and cellular glycoproteins used in the biochemical screening of CDG, as well as the emerging ones for an improved diagnosis. We then provide an overview of the current state-of-the-art methodologies ranging from gel electrophoresis to mass spectrometry to measure improper glycosylation. Finally, we discuss how additional tools such as metabolomics and microfluidics can be added to the current toolbox to better diagnose and delineate CDG., Major Conclusions: Combining several biochemical indicators and related methods is often required to cope with the large clinical heterogeneity of CDG and establish a definitive diagnosis., General Significance: This review aims to critically present current available CDG biochemical biomarkers and dedicated methods in the context of highly diverse glycosylation pathways and related inherited diseases., Competing Interests: Declaration of Competing Interest No competing interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This work reports on the development of the first capillary electrophoresis methodology for the elucidation of extracellular vesicles' (EVs) electrokinetic distributions. The approach is based on capillary electrophoresis coupled with laser-induced fluorescent (LIF) detection for the identification and quantification of EVs after their isolation. Sensitive detection of these nanometric entities was possible thanks to an 'inorganic-species-free' background electrolyte. This electrolyte was made up of weakly charged molecules at very high concentrations to stabilize EVs, and an intra-membrane labelling approach was used to prevent EV morphology modification. The limit of detection for EVs achieved using the developed CE-LIF method reached 8 × 10 9  EV/mL, whereas the calibration curve was acquired from 1.22 × 10 10 to 1.20 × 10 11  EV/mL. The CE-LIF approach was applied to provide the electrokinetic distributions of various EVs of animal and human origins, and visualize different EV subpopulations from our recently developed high-yield EV isolation method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, the employment of a purpose-made capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C 4 D) as a simple and cost-effective approach for simultaneous determination of different carbapenem antibiotics is reported. The developed CE-C 4 D approach was for the first time applied for quality control of various pharmaceutical formulations in Vietnam, as well as for therapeutic monitoring of these antibiotics in plasma samples from patients under intensive care. Four of the most popular carbapenems in Vietnam, doripenem, meropenem, imipenem and ertapenem, were determined using an electrolyte composed of 10 mM Tris adjusted to pH 8.0 with acetic acid. The best detection limits achieved using the developed CE-C 4 D method were 0.36 mg/L and 0.45 mg/L for pharmaceutical and plasma samples, respectively. Good agreement between results from CE-C 4 D and the confirmation method (HPLC-PDA) was achieved, with a coefficient of determination (r 2 ) for the two pairs of data of 0.9967., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that requires immediate treatment. Allergic reaction to insulin is rare, especially when using recombinant human insulin. The clinical presentation of insulin allergy can range from minor local symptoms to a severe generalized allergic reaction such as anaphylaxis. A limited number of cases have been reported on the treatment of severe DKA in patients with type 2 diabetes with insulin allergy. Here, we describe a patient with type 2 diabetes with insulin allergy in which severe DKA resolved after the initiation of continuous intravenous (IV) recombinant human insulin infusion., Case Presentation: A 58-year-old man with type 2 diabetes initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic treatment. Symptoms of an allergic reaction developed, including pruritic wheals appearing within 10 min of injection and lasting over 24 h. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms and then experienced weakness and upper abdominal pain. On admission, he was in severe metabolic acidosis with a pH of 6.984 and bicarbonate of 2.5 mmol/litre. The blood glucose level was 20.79 mmol/litre, BUN 4.01 mmol/litre, creatinine 128 μmol/litre, and urinary ketone 11.44 mmol/litre. Over 24 h, metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as haemodialysis. Ultimately, he received continuous IV recombinant human insulin infusion at a rate of 0.1 units/kg/hour, in combination with haemodiafiltration, and no further allergic reactions were observed. On day 5, ketonaemia and metabolic acidosis completely resolved. He had transitioned from IV insulin infusion to SIA on day 14. He was discharged on day 21 with SIA treatment. Three months later, he had good glycaemic control but still had allergic symptoms at the insulin injection sites., Conclusions: In this patient, SIA caused an allergic reaction, in contrast to continuous IV insulin infusion for which allergic symptoms did not appear. Continuous IV recombinant human insulin infusion in combination with haemodiafiltration could be an option for the treatment of severe DKA in patients with diabetes with insulin allergy.

A simple and inexpensive approach for determination of various antimicrobial drugs using a purpose-made compact capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C 4 D) is reported. The objective of the work is to propose an affordable and easily-implemented tool for quality control and detection of counterfeiting of antibiotic formulations in resource constrained developing countries. The design of the purpose-made CE-C 4 D system was improved according to the feedback from over 10 years of use of our previous instrument. CE-C 4 D methods were for the first time developed to analyze β-lactam-based antibiotics commonly used in Vietnam, including single- β-lactam antibiotics (i.e. Cephalexin, Cefotaxime Sodium, Cefixime and Sulbactam) as well as β-lactams co-formulated with Sulbactam (i.e. Amoxicillin, Ampicillin, Cefoperazone and Sulbactam). Single β-lactam antibiotics were analyzed using a background electrolyte (BGE) composed of Tris/Ace (10 mM, pH 7.8) whereas β-lactam - Sulbactam combinations were simultaneously separated using a BGE containing Tris/Ace (10 mM, pH 7.5). The best achieved detection limits were 2.0 mg/L and 1.0 mg/L for these two groups, respectively. Good agreement between results obtained from CE-C 4 D and standard confirmation methods (LCMS) was achieved, with a coefficient of determination, r 2 , of 0.9991. The applicability of the developed CE-C 4 D method was demonstrated for quality control of 24 β-lactam-based antimicrobial drugs available in Vietnam., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study reports a reinvestigation of background electrolyte selection strategy for performance improvement in CE-LIF of peptides and proteins. This strategy is based on the employment of high concentrations of organic species in BGE possessing high buffer capacity and low specific conductivity in order to ensure excellent stacking preconcentration and separation resolution of fluorescently tagged peptides and proteins. Unlike universal UV detection, the use of such BGEs at high concentrations does not lead to degradation of LIF detection signals at the working excitation and emission wavelengths. At the same buffer ionic strength, pH and electric field, an "inorganic-species-free" BGE (or ISF BGE) for CE-LIF of fluorescently labeled beta amyloid peptide Aβ 1-42 (a model analyte) offered a signal intensity and peak efficiency at least three-times higher than those obtained with a conventional BGE normally used for CE-LIF, while producing an electric current twice lower. Good peak performance (in terms of height and shape) was maintained when using ISF BGEs even with samples prepared in high-conductivity phosphate buffer saline matrix. The advantageous features of such BGEs used at high concentrations over conventional ones in terms of high separation resolution, improved signal intensities, tuning of EOF magnitudes and minimization of protein adsorption on an uncoated fused silica capillary are demonstrated using Alexa-488-labelled trypsin inhibitor. Such BGE selection approach was applied for investigation of separation performance for CE-LIF of ovalbumin labelled with different fluorophores., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study reports on the conception of magneto-Capillary Electrophoresis (magneto-CE), an approach integrating immuno-capture on circulating bio-functionalized magnetic beads into a unique capillary for preconcentration and electrokinetic separation. This hybrid mode is an evolution of in-capillary magnetic bead-based operation from static cluster format to dynamic configuration where beads are allowed to controllably circulate inside a CE capillary for interaction improvement. To implement the magneto-CE operation, a purpose-made instrument was constructed, allowing visual observation of the movement of the magnetic beads. We applied a new methodological strategy for determination of the amyloid β peptide (Aβ 1-42), which is as an established biomarker for molecular diagnosis of Alzheimer's disease (AD). The methodology is based on magneto-immuno-capture of fluorescently labeled Aβ 1-42 followed by a chemical elution with a basic solution prior to CE separation with laser induced fluorescent (LIF) detection. The superiority of this dynamic configuration of magneto-CE was demonstrated for this target analyte, with sample pretreatment and separation being performed in-capillary without any delay in between and without any waste of pretreated sample, which otherwise would not be the case with offline/batch-wise operation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study is reported a simple and inexpensive method for concurrent determination of taurine and choline in different supplementary nutrient samples using dual-channeled capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C 4 D). The objective of the work is to propose a tool for food control activities that allows screening of different target compounds (having different characteristics) in a single run for high throughput and can be realizable even with modest infrastructure. Taurine was analyzed in the first CE channel using the background electrolyte (BGE) composed of 150 mM tris(hydroxymethyl)aminomethane/lactic acid (pH 8.96) whereas choline was simultaneously separated in the second CE channel using a BGE containing 150 mM tris(hydroxymethyl)aminomethane/acetic acid (pH 9.5). The best achieved detection limit was 0.27 mg/L and 0.45 mg/L for taurine and choline, respectively, using the developed CE-C 4 D method. Good agreement between results obtained from CE-C 4 D and those with the standard confirmation methods (HPLC-DAD for taurine and LC/MS for choline) was achieved, with the result deviation for the two pairs of data being less than 12%., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Intraventricular haemorrhage (IVH) patients with acute obstructive hydrocephalus (AOH) who require external ventricular drainage (EVD) are at high risk for poor outcomes. Intraventricular fibrinolysis (IVF) with low-dose recombinant tissue plasminogen activator (rtPA) can be used to improve patient outcomes. Here, we evaluated the impact of IVF on the risk of death and the functional outcomes in IVH patients with AOH., Methods: This prospective cohort study included IVH patients with hypertensive intracranial haemorrhage complicated by AOH who required EVD. We evaluated the risk of death and the functional outcomes at 1 and 3 months, with a specific focus on the impact of combined EVD with IVF by low-dose rtPA., Results: Between November 30, 2011 and December 30, 2014, 80 patients were included. Forty-five patients were treated with EVD alone (EVD group) and 35 received IVF (EVD+IVF group). The 30- and 90-day mortality rates were lower in the EVD+IVF group than in the EVD group (42.2 vs. 11.4%, p = 0.003, and 62.2 vs. 20%, p < 0.001, respectively). The Graeb scores were significantly lower in the EVD+IVF group than in the EVD group (p ≤ 0.001) during the first 3 days and on day 7 after assignment. The 30-day good functional outcome (modified Rankin Scale [mRS] score 0-3) was also higher in the EVD+IVF group than in the EVD group (6.7 vs. 28.6%, p = 0.008). However, the 90-day good functional outcome (mRS score 0-3) did not significantly increase in the EVD+IVF group (30.8% in the EVD group vs. 51.6% in the EVD+IVF group, p = 0.112)., Conclusions: In our prospective observational study, EVD+IVF was associated with a lower risk of death in IVH patients. EVD+IVF improved the chance of having a good functional outcome at 1 month; however, this result was no longer observed at 3 months., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

A novel electrokinetic preconcentration approach, so-called multiple pressure-assisted large-volume sample stacking with an electroosmotic flow pump (M-PA-LVSEP), was developed to allow in-capillary enrichment and separation of analytes from unlimited sample volumes. With this approach, the inherent limitation of in-capillary electrokinetic preconcentrations to the separation capillary volume can be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure-assisted electroosmotic pumping and injection of extremely large sample volumes for analyte stacking and sample matrix removal. This technique was developed to address the challenge of sensitive and simultaneous determination of several amyloid β (Aβ) peptides, which are biomarkers for the molecular diagnosis of Alzheimer's disease (AD). For the first time, reliable quantification of different species of fluorescently derivatized Aβ peptides, that is, Aβ 1-42, Aβ 1-40, and Aβ 1-38 down to subnanomolar ranges in cerebrospinal fluids (CSF) from AD and non-demented patients (healthy controls) was made possible without recourse to immunoassay, immunoprecipitation, or mass spectrometry approaches. Based on the stacking from a sample plug representing up to 400% of the total capillary volume, sensitive enhancement factors up to 170 could be achieved with this "antibody free" approach. Quantification limits for these Aβ peptides down to 0.05 nM with capillary electrophoresis coupled with laser-induced fluorescent detection could be obtained. Excellent agreement between results from M-PA-LVSEP and the gold standard ELISA method was achieved for measurements of Aβ 1-42 in CSF, with a determination correlation (r 2 ) better than 0.993.

The employment of a purpose-made capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C 4 D) as a simple and cost-effective solution for clinical screening of paraquat in plasma samples for early-stage diagnosis of acute herbicide poisoning is reported. Paraquat was determined using an electrolyte composed of 10mM histidine adjusted to pH 4 with acetic acid. A detection limit of 0.5mg/L was achieved. Good agreement between results from CE-C 4 D and the confirmation method (HPLC-UV) was obtained, with relative errors for the two pairs of data better than 20% for 31 samples taken from paraquat-intoxicated patients. The results were used by medical doctors for identification and prognosis of acute paraquat poisoning cases. The objective of the work is the deployment of the developed approach in rural areas in Vietnam as a low-cost solution to reduce the mortality rate due to accidental or suicidal ingestion of paraquat., (Copyright © 2017. Published by Elsevier B.V.)

Globally, transgender women have higher risk for HIV than the general population and men who have sex with men, but there is little data on this population in Vietnam. In 2015 we conducted a biological and behavioral survey of 205 transgender women in Ho Chi Minh City, Vietnam. Factors associated with HIV and syphilis infection were assessed through multivariable logistic regression models. Median age was 25 years (range 18-64). Overall prevalence was 18.0 % for HIV and 17.6 % for syphilis. Factors independently associated with HIV infection included risky alcohol use [adjusted Odds Ratio (aOR) 3.55, 95 % confidence interval (CI) 1.53-8.21], amphetamine stimulant use (aOR 2.90, 95 % CI 1.27-6.61), sex with male sex workers (aOR 4.73, 95 % CI 1.72-13.0), and history of sex with an adult before the age of 18 years (aOR 2.97, 95 % CI 1.06-8.34). Two factors associated with syphilis infection were HIV infection (aOR 2.37, 95 % CI 1.03-5.45) and condomless anal sex with casual partners (aOR 2.27, 95 % CI 1.03-5.00). In order to address the HIV and syphilis epidemics in Vietnamese transgender women, interventions are needed to make HIV and sexually transmitted infection screening and treatment more accessible.

In this study, the employment of purpose-made dual-channel compact capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C(4)D) as a simple and inexpensive solution for screening determination of various pharmaceutical pollutants frequently occurring in surface water and hospital wastewater in Hanoi, Vietnam is reported. Five negatively charged pharmaceutically active compounds, namely ibuprofen, diclofenac, bezafibrate, ketoprofen and mefenamic acid were determined using the first channel whereas three positively charged ones, namely diphenhydramine, metoprolol and atenolol were determined with the second channel of the CE-C(4)D instrument. Two different background electrolytes (BGEs) were used in these two CE channels independently. The best detection limits achieved were in the range of 0.2-0.8mg/L without sample pre-concentration. Enrichment factors up to 200 were obtainable with the inclusion of a solid phase extraction step. Good agreement between results obtained from CE-C(4)D and those with the standard confirmation method (HPLC-DAD) was achieved, with correlation coefficients higher than 0.98., (Copyright © 2016 Elsevier B.V. All rights reserved.)

From the fruit of Pandanus tectorius Parkinson ex Du Roi, one new dihydrofurocoumarin, named pandanusin A (1) and 15 known compounds, including one furanocoumarin (2), two coumarins (3, 4), four lignans (5-8), one neolignan (9), two flavonoids (10, 11), three phenolics (12-14), one monoglyceride (15) and one monosaccharide (16) were isolated by various chromatography methods. Among them, compounds (3-5) were obtained from the Pandanus genus for the first time and compounds (9-14, 16) were reported from this species for the first time. Their structures were elucidated by HR-ESI-MS, NMR 1D and 2D experiments and comparison with previous reported data. The α-glucosidase inhibitory activity of all compounds was measured. The isolated compounds (1-12, 14) showed better α-glucosidase inhibitory activity (IC50 = 42.2, 36.5, 84.7, 73.2, 40.8, 26.7, 76.5, 33.8, 68.1, 14.4, 22.1, 81.5, 43.8 μM, respectively) than the standard drug acarbose (IC50 = 214.5 μM).

A CE with contactless conductivity detection methodology using a novel background electrolyte for the separation and determination of 17 metal cations (Cs + , Rb + , K + , Ca 2+ , Na + , Mg 2+ , Mn 2+ , Sr 2+ , Li + , Ba 2+ , Fe 2+ , Pb 2+ , Cd 2+ , Zn 2+ , Co 2+ , Cu 2+ and Ni 2+ ) and ammonium has been investigated. The buffer, based on lactic acid and β-alanine, was experimentally compared with other two commonly used electrolytes, showing important improvements, such as shorter analysis times (<11 min), better electrophoretic resolutions and higher detectabilities for certain analytes, such as Fe 2+ and Pb 2+ . The inclusion of other additives such as 18-Crown-6 and α-hydroxyisobutyric acid was studied in order to obtain the best separation of the analytes of interest. The optimised method was applied to the analysis of 11 water-based pen inks and the determination of their metal composition. The methodology was demonstrated for the comparison and differentiation of pen inks., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)