Two different jumping mechanisms of water striders are determined by body size.

Current theory for surface tension-dominant jumps on water, created for small- and medium-sized water strider species and used in bioinspired engineering, predicts that jumping individuals are able to match their downward leg movement speed to their size and morphology such that they maximize the takeoff speed and minimize the takeoff delay without breaking the water surface. Here, we use empirical observations and theoretical modeling to show that large species (heavier than ~80 mg) could theoretically perform the surface-dominated jumps according to the existing model, but they do not conform to its predictions, and switch to using surface-breaking jumps in order to achieve jumping performance sufficient for evading attacks from underwater predators. This illustrates how natural selection for avoiding predators may break the theoretical scaling relationship between prey size and its jumping performance within one physical mechanism, leading to an evolutionary shift to another mechanism that provides protection from attacking predators. Hence, the results are consistent with a general idea: Natural selection for the maintenance of adaptive function of a specific behavior performed within environmental physical constraints leads to size-specific shift to behaviors that use a new physical mechanism that secure the adaptive function.

Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii.

Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.

A study of genetic variants associated with skin traits in the Vietnamese population.

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

Ultrasensitive and Multiplexed Protein Imaging with Clickable and Cleavable Fluorophores.

Single-cell spatial proteomic analysis holds great promise to advance our understanding of the composition, organization, interaction, and function of the various cell types in complex biological systems. However, the current multiplexed protein imaging technologies suffer from low detection sensitivity, limited multiplexing capacity, or are technically demanding. To tackle these issues, here, we report the development of a highly sensitive and multiplexed in situ protein profiling method using off-the-shelf antibodies. In this approach, the protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and cleavable fluorophores via click chemistry. Through repeated cycles of target staining, fluorescence imaging, and fluorophore cleavage, many proteins can be profiled in single cells in situ. Applying this approach, we successfully quantified 28 different proteins in human formalin-fixed paraffin-embedded (FFPE) tonsil tissue, which represents the highest multiplexing capacity among the tyramide signal amplification (TSA) methods. Based on their unique protein expression patterns and their microenvironment, ∼820,000 cells in the tissue are classified into distinct cell clusters. We also explored the cell-cell interactions between these varied cell clusters and observed that different subregions of the tissue are composed of cells from specific clusters.

Detecting and Removing Sample Contamination in Phylogenomic Data: An Example and its Implications for Cicadidae Phylogeny (Insecta: Hemiptera).

Contamination of a genetic sample with DNA from one or more nontarget species is a continuing concern of molecular phylogenetic studies, both Sanger sequencing studies and next-generation sequencing studies. We developed an automated pipeline for identifying and excluding likely cross-contaminated loci based on the detection of bimodal distributions of patristic distances across gene trees. When contamination occurs between samples within a data set, a comparison between a contaminated sample and its contaminant taxon will yield bimodal distributions with one peak close to zero patristic distance. This new method does not rely on a priori knowledge of taxon relatedness nor does it determine the causes(s) of the contamination. Exclusion of putatively contaminated loci from a data set generated for the insect family Cicadidae showed that these sequences were affecting some topological patterns and branch supports, although the effects were sometimes subtle, with some contamination-influenced relationships exhibiting strong bootstrap support. Long tip branches and outlier values for one anchored phylogenomic pipeline statistic (AvgNHomologs) were correlated with the presence of contamination. While the anchored hybrid enrichment markers used here, which target hemipteroid taxa, proved effective in resolving deep and shallow level Cicadidae relationships in aggregate, individual markers contained inadequate phylogenetic signal, in part probably due to short length. The cleaned data set, consisting of 429 loci, from 90 genera representing 44 of 56 current Cicadidae tribes, supported three of the four sampled Cicadidae subfamilies in concatenated-matrix maximum likelihood (ML) and multispecies coalescent-based species tree analyses, with the fourth subfamily weakly supported in the ML trees. No well-supported patterns from previous family-level Sanger sequencing studies of Cicadidae phylogeny were contradicted. One taxon (Aragualna plenalinea) did not fall with its current subfamily in the genetic tree, and this genus and its tribe Aragualnini is reclassified to Tibicininae following morphological re-examination. Only subtle differences were observed in trees after the removal of loci for which divergent base frequencies were detected. Greater success may be achieved by increased taxon sampling and developing a probe set targeting a more recent common ancestor and longer loci. Searches for contamination are an essential step in phylogenomic analyses of all kinds and our pipeline is an effective solution. [Auchenorrhyncha; base-composition bias; Cicadidae; Cicadoidea; Hemiptera; phylogenetic conflict.].

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam.

BACKGROUND AND OBJECTIVES: Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS: We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS: Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS: Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae.

A Cas9/guide RNA-based gene drive strain, AgNosCd-1, was developed to deliver antiparasite effector molecules to the malaria vector mosquito, Anopheles gambiae The drive system targets the cardinal gene ortholog producing a red-eye phenotype. Drive can achieve 98 to 100% in both sexes and full introduction was observed in small cage trials within 6 to 10 generations following a single release of gene-drive males. No genetic load resulting from the integrated transgenes impaired drive performance in the trials. Potential drive-resistant target-site alleles arise at a frequency <0.1, and five of the most prevalent polymorphisms in the guide RNA target site in collections of colonized and wild-derived African mosquitoes do not prevent cleavage in vitro by the Cas9/guide RNA complex. Only one predicted off-target site is cleavable in vitro, with negligible deletions observed in vivo. AgNosCd-1 meets key performance criteria of a target product profile and can be a valuable component of a field-ready strain for mosquito population modification to control malaria transmission.

A fair and interpretable network for clinical risk prediction: a regularized multi-view multi-task learning approach.

In healthcare domain, complication risk profiling which can be seen as multiple clinical risk prediction tasks is challenging due to the complex interaction between heterogeneous clinical entities. With the availability of real-world data, many deep learning methods are proposed for complication risk profiling. However, the existing methods face three open challenges. First, they leverage clinical data from a single view and then lead to suboptimal models. Second, most existing methods lack an effective mechanism to interpret predictions. Third, models learned from clinical data may have inherent pre-existing biases and exhibit discrimination against certain social groups. We then propose a multi-view multi-task network (MuViTaNet) to tackle these issues. MuViTaNet complements patient representation by using a multi-view encoder to exploit more information. Moreover, it uses a multi-task learning to generate more generalized representations using both labeled and unlabeled datasets. Last, a fairness variant (F-MuViTaNet) is proposed to mitigate the unfairness issues and promote healthcare equity. The experiments show that MuViTaNet outperforms existing methods for cardiac complication profiling. Its architecture also provides an effective mechanism for interpreting the predictions, which helps clinicians discover the underlying mechanism triggering the complication onsets. F-MuViTaNet can also effectively mitigate the unfairness with only negligible impact on accuracy.

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Investigating COVID-19 transmission in a tertiary hospital in Hanoi, Vietnam using social network analysis.

OBJECTIVES: In March 2020, a COVID-19 outbreak in a major referral hospital in Hanoi, Vietnam led to 7664 patients and staff being sent into lockdown for 2 weeks, and more than 52,200 persons across 49 provinces being quarantined. We assessed SARS-CoV-2 transmission patterns during this to-date largest hospital outbreak in Vietnam using social network analysis (SNA). METHODS: We constructed a directed relational network and calculated network metrics for 'degree', 'betweenness', 'closeness' and 'eigenvector' centrality to understand individual-level transmission patterns. We analysed network components and modularity to identify sub-network structures with disproportionately big effects. RESULTS: We detected 68 connections between 46 confirmed cases, of whom 27 (58.7%) were ancillary support staff, 7 (15.2%) caregivers, 6 (13%) patients and 2 (4.4%) nurses. Among the 10 most important cases selected by each SNA network metric, transmission dynamics clustered in 17 cases, of whom 12 (70.6%) cases were ancillary support staff. Ancillary support staff also constituted 71.1% of cases in the dominant sub-network and 68.8% of cases in the three largest sub-communities. CONCLUSIONS: We identified non-clinical ancillary support staff, who are responsible for room service and food distribution in hospital wards in Vietnam, as a group with disproportionally big impacts on transmission dynamics during this outbreak. Our findings call for a holistic approach to nosocomial outbreak prevention and response that includes both clinical and non-clinical hospital staff. Our work also shows the potential of SNA as a complementary outbreak investigation method to better understand infection patterns in hospitals and similar settings.

Preinvasion Assessment of Exotic Bark Beetle-Vectored Fungi to Detect Tree-Killing Pathogens.

Exotic diseases and pests of trees have caused continental-scale disturbances in forest ecosystems and industries, and their invasions are considered largely unpredictable. We tested the concept of preinvasion assessment of not yet invasive organisms, which enables empirical risk assessment of potential invasion and impact. Our example assesses fungi associated with Old World bark and ambrosia beetles and their potential to impact North American trees. We selected 55 Asian and European scolytine beetle species using host use, economic, and regulatory criteria. We isolated 111 of their most consistent fungal associates and tested their effect on four important southeastern American pine and oak species. Our test dataset found no highly virulent pathogens that should be classified as an imminent threat. Twenty-two fungal species were minor pathogens, which may require context-dependent response for their vectors at North American borders, while most of the tested fungi displayed no significant impact. Our results are significant in three ways; they ease the concerns over multiple overseas fungus vectors suspected of heightened potential risk, they provide a basis for the focus on the prevention of introduction and establishment of species that may be of consequence, and they demonstrate that preinvasion assessment, if scaled up, can support practical risk assessment of exotic pathogens.

Assessing the mental effects of COVID-19-related work on depression among community health workers in Vietnam.

BACKGROUND: Community health workers (CHWs) involved in the COVID-19 response might be at increased risk of developing depression, though evidence is scarce. We investigated effects of COVID-19-related work on changes in depression levels among CHWs in Vietnam and identified sub-groups among CHWs who are at particular risk of developing severe depression. METHODS: We conducted a cross-sectional online survey among 979 CHWs who were involved in the COVID-19 response in Vietnam, in particular during the 2021 Tet holiday outbreak between January and March 2021. Respondents were asked to report depression symptoms at two-time points, before the start of the COVID-19 pandemic (average June to December 2019) and during the 2021 Tet holiday outbreak using the PHQ-9 mental health questionnaire. We estimated depression levels at both time points and developed univariate and multivariable logistic regression models to estimate odds ratios and 95% confidence intervals (95% CIs) to explore the association between deterioration to high depression levels and selected risk factors. RESULTS: Median depression levels among CHWs in Vietnam doubled from 3 (IQR = 2-7) before COVID-19 to 6 (IQR = 3-9) on the PHQ-9 scale during the Tet holiday outbreak. The proportion with normal/minimal levels decreased from 77.1% (95% CI = 74.4-79.7) to 50.9% (95% CI = 47.7-54) (p-value < 0.001), while the proportion of CHWs with moderate, moderately severe, and severe depression levels increased 4.3, 4.5, and five-fold, respectively. Less sleep and poor sleep quality, working in unfavorable work environments, and being involved in contact tracing and the organization of quarantine for suspected cases were associated with an increased risk of deterioration to high depression levels. CONCLUSIONS: We found a substantial increase in overall depression levels among CHWs in Vietnam due to their COVID-19 related work and a particularly worrisome rise in CHWs suffering from severe depression. CHWs are an indispensable yet often overlooked cadre of work in many low- and middle-income countries and shoulder a heavy psychological burden during the COVID-19 pandemic. Targeted psychological support for CHWs is needed to improve their mental health and to ensure the sustainability of community-based health interventions during COVID-19 and future epidemics.

The Veteran Affair Surgical Quality Improvement Program Calculator is a Poor Predictor of Morbidity and Mortality in Octogenarian and Nonagenarian Veterans Undergoing Major Lower Extremity Amputations.

BACKGROUND: Morbidity and mortality for major (above the ankle) lower extremity amputation (LEA) is high in veteran patients and age is a predictor of mortality. The Veteran Affair Surgical Quality Improvement Program (VASQIP) risk assessment tool has been validated for several operations but not for elderly patients undergoing LEA. The present study interrogated the accuracy for the VASQIP calculator for a medium/high-risk operation in a high-risk veteran population (octogenarians and nonagenarians). METHODS: Variables required from input for the VASQIP calculator were retrospectively obtained for 57 octogenarians and 11 nonagenarians submitting to LEA at our institution from 2009 to 2021. The six-outcome variables provided by the VASQIP calculator (30-day mortality, 180-day mortality, 30-day morbidity, 30-day surgical site infection risk, probability of intensive care unit stay, and probability of hospital stay) were compared to observed morbidity and mortality. The accuracy of the calculator was assessed by area under the receiver operating characteristic curve and reported by the area under the curve (AUC) as previously described. RESULTS: In the 68 patients included in this analysis, the time to death from the last index operation was 422.0 ± 604.9 days for octogenarians and 65.6 ± 89.3 days for nonagenarians. Predicted versus observed 30-day mortality for octogenarians and nonagenarians was 8.46 vs. 24.56 [AUC = 0.739; 95% confidence interval (0.581 to 0.898)] and 24.46 vs. 45.45 [AUC = 0.600 (0.171 to 1.000)], respectively. Predicted versus observed 180-day mortality for the same cohorts was 25.22 vs. 47.37 [AUC = 0.578 (0.427 to 0.728)] and 45.34 vs. 90.91 [AUC = 0.100 (0.000 to 0.286)], respectively. Thirty-day morbidity, 30-day surgical site infection, probability of intensive care unit, and probability of in-hospital stay produced an AUC less than 0.600 for all these outcomes. CONCLUSIONS: The VASQIP risk calculator is a poor predictor of short-term outcomes in octogenarians and nonagenarians undergoing major LEA. Most octogenarian and nonagenarian veterans died within 1 year, and the mean survival for nonagenarians was less than 3 months after LEA. The decision for major LEA in octogenarian and nonagenarian veterans warrants an informed discussion with the patient and family.

Experimental population modification of the malaria vector mosquito, Anopheles stephensi.

Small laboratory cage trials of non-drive and gene-drive strains of the Asian malaria vector mosquito, Anopheles stephensi, were used to investigate release ratios and other strain properties for their impact on transgene spread during simulated population modification. We evaluated the effects of transgenes on survival, male contributions to next-generation populations, female reproductive success and the impact of accumulation of gene drive-resistant genomic target sites resulting from nonhomologous end-joining (NHEJ) mutagenesis during Cas9, guide RNA-mediated cleavage. Experiments with a non-drive, autosomally-linked malaria-resistance gene cassette showed 'full introduction' (100% of the insects have at least one copy of the transgene) within 8 weeks (≤ 3 generations) following weekly releases of 10:1 transgenic:wild-type males in an overlapping generation trial design. Male release ratios of 1:1 resulted in cages where mosquitoes with at least one copy of the transgene fluctuated around 50%. In comparison, two of three cages in which the malaria-resistance genes were linked to a gene-drive system in an overlapping generation, single 1:1 release reached full introduction in 6-8 generations with a third cage at ~80% within the same time. Release ratios of 0.1:1 failed to establish the transgenes. A non-overlapping generation, single-release trial of the same gene-drive strain resulted in two of three cages reaching 100% introduction within 6-12 generations following a 1:1 transgenic:wild-type male release. Two of three cages with 0.33:1 transgenic:wild-type male single releases achieved full introduction in 13-16 generations. All populations exhibiting full introduction went extinct within three generations due to a significant load on females having disruptions of both copies of the target gene, kynurenine hydroxylase. While repeated releases of high-ratio (10:1) non-drive constructs could achieve full introduction, results from the 1:1 release ratios across all experimental designs favor the use of gene drive, both for efficiency and anticipated cost of the control programs.

Exchange transfusion in the management of critical pertussis in young infants: a case series.

BACKGROUND AND OBJECTIVES: It is proposed that severe leucocytosis mainly contributes to pulmonary hypertension by blocking pulmonary capillaries and restricting blood flow. Exchange transfusion (ET) in pertussis has been demonstrated as a safe and useful technique for depleting the leucocyte mass. We aim to discuss four cases of pertussis-induced respiratory distress and the effectiveness of ET in such a setting. MATERIALS AND METHODS: We conducted a retrospective case series at the Infectious Disease Department of Children's Hospital 2 in Ho Chi Minh City, Vietnam, and included four pertussis patients that were confirmed by PCR tests on respiratory secretions, presented with severe leucocytosis and respiratory distress and required mechanical ventilation. RESULTS: Among the included patients, three underwent a double volume ET for leucodepletion, two of whom were discharged after the procedure with proper vitals and laboratory test results. On the other hand, one patient died despite ET, performed late in the course of the disease. Exchange transfusion was not performed in the last patient who died as well. CONCLUSION: Early ET may be a useful and rapid life-saving treatment in children with critical pertussis and severe leucocytosis before cardiopulmonary complications appear.

Timeliness of contact tracing among flight passengers during the COVID-19 epidemic in Vietnam.

BACKGROUND: International air travel plays an important role in the global spread of SARS-CoV-2, and tracing of close contacts is an integral part of the public health response to COVID-19. We aimed to assess the timeliness of contact tracing among airline passengers arriving in Vietnam on flights containing COVID-19 cases and investigated factors associated with timeliness of contact tracing. METHODS: We included data from 2228 passengers on 22 incoming flights between 2 and 19 March 2020. Contact tracing duration was assessed separately for the time between the date of index case confirmation and date of contact tracing initiation (interval I), and the date of contact tracing initiation and completion (interval II). We used log-rank tests and multivariable Poisson regression models to identify factors associated with timeliness. RESULTS: The median duration of interval I and interval II was one (IQR: 1-2) and 3 days (IQR: 2-5), respectively. The contact tracing duration was shorter for passengers from flights where the index case was identified through mandatory testing directly upon arrival (median = 4; IQR: 3-5) compared to flights with index case detection through self-presentation at health facilities after arrival (median = 7; IQR: 5-8) (p-value = 0.018). Cumulative hazards for successful tracing were higher for Vietnamese nationals compared to non-Vietnamese nationals (p < 0.001). CONCLUSIONS: Contact tracing among flight passengers in the early stage of the COVID-19 epidemic in Vietnam was timely though delays occurred on high workload days. Mandatory SARS-CoV-2 testing at arrival may reduce contact tracing duration and should be considered as an integrated screening tool for flight passengers from high-risk areas when entering low-transmission settings with limited contact tracing capacity. We recommend a standardized risk-based contact tracing approach for flight passengers during the ongoing COVID-19 epidemic.

Ultrasensitive and Multiplexed Protein Imaging with Cleavable Fluorescent Tyramide and Antibody Stripping.

Multiplexed single-cell analysis of proteins in their native cellular contexts holds great promise to reveal the composition, interaction and function of the distinct cell types in complex biological systems. However, the existing multiplexed protein imaging technologies are limited by their detection sensitivity or technical demands. To address these issues, here, we develop an ultrasensitive and multiplexed in situ protein profiling approach by reiterative staining with off-the-shelf antibodies and cleavable fluorescent tyramide (CFT). In each cycle of this approach, the protein targets are recognized by antibodies labeled with horseradish peroxidase, which catalyze the covalent deposition of CFT on or close to the protein targets. After imaging, the fluorophores are chemically cleaved, and the antibodies are stripped. Through continuous cycles of staining, imaging, fluorophore cleavage and antibody stripping, a large number of proteins can be quantified in individual cells in situ. Applying this method, we analyzed 20 different proteins in each of ~67,000 cells in a human formalin-fixed paraffin-embedded (FFPE) tonsil tissue. Based on their unique protein expression profiles and microenvironment, these individual cells are partitioned into different cell clusters. We also explored the cell-cell interactions in the tissue by examining which specific cell clusters are selectively associating or avoiding each other.

Multiplexed In Situ Protein Profiling with High-Performance Cleavable Fluorescent Tyramide.

Understanding the composition, function and regulation of complex cellular systems requires tools that quantify the expression of multiple proteins at their native cellular context. Here, we report a highly sensitive and accurate protein in situ profiling approach using off-the-shelf antibodies and cleavable fluorescent tyramide (CFT). In each cycle of this method, protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and CFT. Subsequently, the fluorophores are efficiently cleaved by mild chemical reagents, which simultaneously deactivate HRP. Through reiterative cycles of protein staining, fluorescence imaging, fluorophore cleavage, and HRP deactivation, multiplexed protein quantification in single cells in situ can be achieved. We designed and synthesized the high-performance CFT, and demonstrated that over 95% of the staining signals can be erased by mild chemical reagents while preserving the integrity of the epitopes on protein targets. Applying this method, we explored the protein expression heterogeneity and correlation in a group of genetically identical cells. With the high signal removal efficiency, this approach also enables us to accurately profile proteins in formalin-fixed paraffin-embedded (FFPE) tissues in the order of low to high and also high to low expression levels.

Water quality and climate variability of urban and tourism areas in Thailand and northern Vietnam: correlations and possible influences on nearby coastal shrimp farms.

This research explored the long-term relationships of climate parameters and coastal water quality nearby shrimp farms in two countries. In Thailand, two sampling points in canals located in Bangkok and Trang provinces were selected as the urban and tourism areas, respectively. In northern Vietnam, the canals located in Thai Binh and Quang Ninh provinces were used as the urban and tourism areas, respectively. The diurnal monitoring of water quality and weather was performed at each site to evaluate the relationships between climate and water quality, pollution load, and risk analysis. A questionnaire was also used to assess the climate and water exposure, vulnerability, and adaptability of each site. All data were ranked on a scale of 1 to 5 to integrate each factor. It was determined that the main water quality problem was fecal pollution. Notably, aquaculture farming in northern Vietnam is more vulnerable than in Thailand; however, Vietnam farmers were adaptable for climate variability.

Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.

Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila.