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Issue Addressed: Food security is becoming increasingly difficult to achieve for many households. Research has shown that food insecurity is associated with socioeconomic disadvantage, including housing pressures, and may contribute to poor health outcomes. There is lack of data on these associations in the South Australian setting, where food security is not consistently monitored., Methods: A population health survey was administered to South Australian participants in April 2023. Descriptive analysis was conducted on data regarding food insecurity, housing circumstances, chronic and mental health conditions. Multivariate logistic regression analysis was performed to assess associations between food security and health outcomes., Results: From a sample of 3002 participants, 16.4% reported low and very low food security. These participants tended to be renting, facing housing cost pressures, and lacking infrastructure to store and prepare food. When controlling for confounders, food insecurity was found to be associated with increased likelihood of having at least one chronic condition, mental health condition, and decreased overall wellbeing., Conclusion: Food security is itself a determinant of health. Regular monitoring of the prevalence of household food insecurity and addressing the structural factors influencing food affordability and availability are required. Further research on its links to health outcomes is warranted. SO WHAT?: Evidence-based action to address food insecurity will become more pressing as the crises of cost-of-living, housing, health system pressures and environmental disasters converge., (© 2024 Australian Health Promotion Association.)

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

Competing Interests: Declaration of competing interest The authors declare no competing interests. The authors declared no conflicts of interest to the research, contribution, and publication of this article.

Aim: Cancers lacking standard screening (LSS) options account for approximately 70% of cancer-related deaths due to late-stage diagnosis. Circulating tumor DNA (ctDNA) is a promising biomarker for multi-cancer early detection. We previously developed SPOT-MAS, a multimodal ctDNA-based assay analyzing methylation and fragmentomic profiles, effective in detecting common cancers (breast, colorectal, liver, lung and gastric). This study extends the analysis to five LSS cancers: endometrial, esophageal, head and neck, ovarian and pancreatic. Methods: SPOT-MAS was applied to profile cfDNA methylation and fragmentomic patterns in 739 healthy individuals and 135 LSS cancer patients. Results: We identified 347 differentially methylated regions and observed genome-wide hypomethylation across all five LSS cancers. Esophageal and head and neck cancers showed an enrichment of short cfDNA fragments (<150 bp). Eleven 4-mer end motifs were consistently altered in cfDNA fragments across all LSS cancers. Many significant signatures were consistent with previous observations in common cancers. Notably, SPOT-MAS achieved 96.2% specificity and 74.8% overall sensitivity, with a lower sensitivity of 60.7% in early-stage cancers. Conclusion: This proof-of-concept study demonstrates that SPOT-MAS a non-invasive test trained on five common cancer types, could detect a number of LSS cancer cases, potentially complementing existing screening programs.

Efflux pumps have been reported as one of the significant mechanisms by which bacteria evade the effects of multiple antibiotics. The tripartite efflux pump MexAB-OprM in Pseudomonas aeruginosa is one of the most significant multidrug efflux systems due to its broad resistance to antibiotics such as chloramphenicol, fluoroquinolones, lipophilic β-lactam antibiotics, nalidixic acid, novobiocin, rifampicin, and tetracycline. A promising strategy to overcome this resistance mechanism is to combine antibiotics with efflux pump inhibitors (EPIs), which can increase their intracellular concentration to enhance their biological activities. Based on 143 EPIs with chemically diverse skeletons, the 3D pharmacophore and 2D-QSAR modelings were developed and used for the virtual screening on 9.2 million compounds including ZINC15, DrugBank, and Traditional Chinese Medicine databases to identify new EPIs. The molecular docking was also performed to evaluate the binding affinity of potential EPIs to the distal-binding pocket of MexB and resulted in 611 potential EPIs. The structure-activity relationship analyses suggested that nitrogen heterocyclic compounds, piperazine and pyridine scaffolds, and amide derivatives are the most favorable chemically features for MexAB inhibitory activities. The results from molecular dynamics analysis in 100 ns indicated that ZINC009296881 and ZINC009200074 were the most potential MexB inhibitors with strong binding affinity to the distal pocket and MM/GBSA ∆G bind values of - 38.97 and - 30.19 kcal mol -1 , respectively. The predicted pharmacokinetic properties and toxicity of these compounds indicated their potential oral drugs., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Issue Addressed: Intersectoral action is integral in promoting population health and health equity. In South Australia, public health partnership authorities (PHPAs) are one mechanism to promote intersectoral collaboration for addressing complex public health issues. This case study examined contemporary evidence on the critical elements of successful partnerships, explored the role of formalisation in success, and examined how identified critical elements were operationalised over time in an existing PHPA., Methods: In the first phase, a scoping review was conducted. The second phase was a retrospective longitudinal case study of a government-academic PHPA agreement, involving partnership document review and key informant interviews. Data triangulation and iterative thematic analysis were performed., Results: The critical elements of successful partnership, triangulated through multiple data sources, are mutuality, governance, communication, resources, leadership, and interactions and relationships. These elements have a high degree of interdependence. Trust supports and is reinforced by these elements, particularly during times of change or crisis. Formalisation of a partnership supports success in many ways but is insufficient on its own., Conclusion: Operating in dynamic environments, a partnership requires dedicated time and effort to be successful. Attention to the strength and interconnectedness of the critical elements over the course of a partnership is crucial. SO WHAT?: This case study describes how the elements of successful partnership can be applied to progress beyond transactional relationships towards authentic collaboration and overcome cross-border and cross-boundary public health challenges to promote population health and well-being., (© 2024 Australian Health Promotion Association.)

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (B mem ) responses. This current study reports secondary outcome data that aims to compare B mem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, B mem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, B mem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of B mem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making., (© 2024. The Author(s).)

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40-60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200-< 400, 400-< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria). Linear regression analysis was performed to examine the association between green tea consumption and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (a marker of insulin resistance) and the log-transformed homeostatic model assessment of β -cell function (HOMA- β ) (a marker of insulin secretion). The OR for prediabetes and diabetes among participants who consumed ≥ 600 ml/d v . those who did not consume green tea were 1·61 (95 % CI = 1·07, 2·42) and 2·04 (95 % CI = 1·07, 3·89), respectively. Higher green tea consumption was associated with a higher level of log-transformed HOMA-IR ( P for trend = 0·04) but not with a lower level of log-transformed HOMA- β ( P for trend = 0·75). Higher green tea consumption was positively associated with the prevalence of prediabetes, diabetes and insulin resistance in rural Vietnam. The findings of this study indicated prompting the need for further research considering context in understanding the link between green tea consumption and glucose metabolism, especially in rural settings in low- and middle-income countries.

We use a microfluidic ecology which generates non-uniform phage concentration gradients and micro-ecological niches to reveal the importance of time, spatial population structure and collective population dynamics in the de novo evolution of T4r bacteriophage resistant motile E. coli . An insensitive bacterial population against T4r phage occurs within 20 hours in small interconnected population niches created by a gradient of phage virions, driven by evolution in transient biofilm patches. Sequencing of the resistant bacteria reveals mutations at the receptor site of bacteriophage T4r as expected but also in genes associated with biofilm formation and surface adhesion, supporting the hypothesis that evolution within transient biofilms drives de novo phage resistance., Competing Interests: Additional Declarations: There is NO Competing Interest.

Automated quantification of brain tissues on MR images has greatly contributed to the diagnosis and follow-up of neurological pathologies across various life stages. However, existing solutions are specifically designed for certain age ranges, limiting their applicability in monitoring brain development from infancy to late adulthood. This retrospective study aims to develop and validate a brain segmentation model across pediatric and adult populations. First, we trained a deep learning model to segment tissues and brain structures using T1-weighted MR images from 390 patients (age range: 2-81 years) across four different datasets. Subsequently, the model was validated on a cohort of 280 patients from six distinct test datasets (age range: 4-90 years). In the initial experiment, the proposed deep learning-based pipeline, icobrain-dl, demonstrated segmentation accuracy comparable to both pediatric and adult-specific models across diverse age groups. Subsequently, we evaluated intra- and inter-scanner variability in measurements of various tissues and structures in both pediatric and adult populations computed by icobrain-dl. Results demonstrated significantly higher reproducibility compared to similar brain quantification tools, including childmetrix, FastSurfer, and the medical device icobrain v5.9 (p-value< 0.01). Finally, we explored the potential clinical applications of icobrain-dl measurements in diagnosing pediatric patients with Cerebral Visual Impairment and adult patients with Alzheimer's Disease., (© 2024. The Author(s).)

Importance: Amyloid-related imaging abnormalities (ARIA) are brain magnetic resonance imaging (MRI) findings associated with the use of amyloid-β-directed monoclonal antibody therapies in Alzheimer disease (AD). ARIA monitoring is important to inform treatment dosing decisions and might be improved through assistive software., Objective: To assess the clinical performance of an artificial intelligence (AI)-based software tool for assisting radiological interpretation of brain MRI scans in patients monitored for ARIA., Design, Setting, and Participants: This diagnostic study used a multiple-reader multiple-case design to evaluate the diagnostic performance of radiologists assisted by the software vs unassisted. The study enrolled 16 US Board of Radiology-certified radiologists to perform radiological reading with (assisted) and without the software (unassisted). The study encompassed 199 retrospective cases, where each case consisted of a predosing baseline and a postdosing follow-up MRI of patients from aducanumab clinical trials PRIME, EMERGE, and ENGAGE. Statistical analysis was performed from April to July 2023., Exposures: Use of icobrain aria, an AI-based assistive software for ARIA detection and quantification., Main Outcomes and Measures: Coprimary end points were the difference in diagnostic accuracy between assisted and unassisted detection of ARIA-E (edema and/or sulcal effusion) and ARIA-H (microhemorrhage and/or superficial siderosis) independently, assessed with the area under the receiver operating characteristic curve (AUC)., Results: Among the 199 participants included in this study of radiological reading performance, mean (SD) age was 70.4 (7.2) years; 105 (52.8%) were female; 23 (11.6%) were Asian, 1 (0.5%) was Black, 157 (78.9%) were White, and 18 (9.0%) were other or unreported race and ethnicity. Among the 16 radiological readers included, 2 were specialized neuroradiologists (12.5%), 11 were male individuals (68.8%), 7 were individuals working in academic hospitals (43.8%), and they had a mean (SD) of 9.5 (5.1) years of experience. Radiologists assisted by the software were significantly superior in detecting ARIA than unassisted radiologists, with a mean assisted AUC of 0.87 (95% CI, 0.84-0.91) for ARIA-E detection (AUC improvement of 0.05 [95% CI, 0.02-0.08]; P = .001]) and 0.83 (95% CI, 0.78-0.87) for ARIA-H detection (AUC improvement of 0.04 [95% CI, 0.02-0.07]; P = .001). Sensitivity was significantly higher in assisted reading compared with unassisted reading (87% vs 71% for ARIA-E detection; 79% vs 69% for ARIA-H detection), while specificity remained above 80% for the detection of both ARIA types., Conclusions and Relevance: This diagnostic study found that radiological reading performance for ARIA detection and diagnosis was significantly better when using the AI-based assistive software. Hence, the software has the potential to be a clinically important tool to improve safety monitoring and management of patients with AD treated with amyloid-β-directed monoclonal antibody therapies.

Chemotactic bacteria not only navigate chemical gradients, but also shape their environments by consuming and secreting attractants. Investigating how these processes influence the dynamics of bacterial populations has been challenging because of a lack of experimental methods for measuring spatial profiles of chemoattractants in real time. Here, we use a fluorescent sensor for aspartate to directly measure bacterially generated chemoattractant gradients during collective migration. Our measurements show that the standard Patlak-Keller-Segel model for collective chemotactic bacterial migration breaks down at high cell densities. To address this, we propose modifications to the model that consider the impact of cell density on bacterial chemotaxis and attractant consumption. With these changes, the model explains our experimental data across all cell densities, offering insight into chemotactic dynamics. Our findings highlight the significance of considering cell density effects on bacterial behavior, and the potential for fluorescent metabolite sensors to shed light on the complex emergent dynamics of bacterial communities., Competing Interests: Competing interests statement:The authors have patent filings to disclose, US20190376964A1.

Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from Usnea aciculifera , and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid (2) , 8' - O - methylstictic acid (5) , 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate ( 8) and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate (9) , were found by virtual screening using pharmacophore and 2D-QSAR model. Compound 8 exhibited AcrB inhibition activity in vitro with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound 8 was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound 8 interacts strongly with the residues in the distal pocket, creating a stable complex with ΔG bind of -31.51  kcal.mol-1. According to the ADMETlab 2.0 web server's predictions of pharmacokinetics and toxicities, compound 8 has the potential for drug development.Communicated by Ramaswamy H. Sarma.

Objectives: Our goal was to describe Invasive Meningococcal Disease (IMD) in Southern Vietnam over the last 10 years. We characterized 109 Neisseria meningitidis strains in Southern Vietnam isolated between 1980s to 2021, that were collected from IMD (n = 44), sexually transmitted infections (n = 2), and healthy carriage (n = 63)., Methods: IMD were confirmed by bacterial culture and/or real-time polymerase chain reaction at the national reference laboratory in Pasteur Institute of Ho Chi Minh City (PIHCM). Antimicrobial resistance was determined on 31 IMD and two sexually transmitted infection isolates with E-test for chloramphenicol (CHL), penicillin (PEN), ciprofloxacin (CIP), ceftriaxone (CRO), and rifampicin (RIF). Sequencing was performed for analyzing of multilocus-sequence-typing (MLST), porA, fetA , and antibiotic resistance genes, including gyrA, penA , and rpoB ., Results: The incidence rate during this period was 0.02 per 100,000 persons/year. Serogroup B accounted for over 90% of cases (50/54). ST-1576 were mainly responsible for IMD, 27/42 MLST profiles, and associated with CHL resistance. Resistance was prevalent among IMD isolates. Thirteen were resistant to CHL (minimum inhibitory concentration [MIC] ≥16 mg/l), 12 were intermediate to PEN (MIC between 0.19 and 0.5 mg/l), and five were CIP-resistant (MIC between 0.19 and 0.5 mg/l). Particularly, one was non-susceptible to CRO (MIC at 0.125 mg/l), belonging to ST-5571 lineage. The resistance was due to carrying resistant alleles of penA and gyrA genes, and catP gene. Notably, seven isolates were resistant/non-susceptible to two or more antibiotics., Conclusion: Our results suggest the persistence of the circulating ST-1576 in Southern Vietnam, with a spread of antimicrobial resistance across the community., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors.)

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening., Competing Interests: VN VTCN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN HTN is affiliated with Gene Solutions. The author has no other competing interests to declare, ND NNTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TMQP is affiliated with Gene Solutions. The author has no other competing interests to declare, GN GTHN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN TDN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTTT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV, TP, TJ, VN, HN, TN, QD, TD, AT, VN, VN, LH, QT, TP, TH, BN, TN, TN, DP, BP, TV, TN, TT, MT, NT, TL, TT, MD, HB, VK, TP, DT, TL, TP, ML, VC, TD No competing interests declared, TN THHN is affiliated with Gene Solutions. The author has no other competing interests to declare, LH LAKH is affiliated with Gene Solutions. The author has no other competing interests to declare, TT THT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV DHV is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TMTT is affiliated with Gene Solutions. The author has no other competing interests to declare, MN MNN is affiliated with Gene Solutions. The author has no other competing interests to declare, TV TTVV is affiliated with Gene Solutions. The author has no other competing interests to declare, AN ANN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTT is affiliated with Gene Solutions. The author has no other competing interests to declare, VT VUT is affiliated with Gene Solutions. The author has no other competing interests to declare, ML MPL is affiliated with Gene Solutions. The author has no other competing interests to declare, TD TTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TVP is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HDN is affiliated with Gene Solutions. The author has no other competing interests to declare, DN DSN holds equity in Gene Solutions.DSN is affiliated with Gene Solutions. The author has no other competing interests to declare, DT DKT is affiliated with Gene Solutions. The author has no other competing interests to declare, HT HST is affiliated with Gene Solutions. The author has no other competing interests to declare, HG HG holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HG who is inventor on the patent application (USPTO 17930705).HG is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HNN holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HNN who is inventor on the patent application (USPTO 17930705).HNN is affiliated with Gene Solutions. The author has no other competing interests to declare, MP MDP holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for MDP who is inventor on the patent application (USPTO 17930705).MDP is affiliated with Gene Solutions. The author has no other competing interests to declare, LT LST holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for LST who is inventor on the patent application (USPTO 17930705).LST is affiliated with Gene Solutions. The author has no other competing interests to declare, (© 2023, Nguyen, Nguyen et al.)

We report on an outbreak of nongroupable Neisseria meningitidis-associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.

Objective: This study was performed to determine the outcomes of patients with coronavirus disease 2019 (COVID-19) who developed hypoxemic respiratory failure necessitating high-flow nasal cannula (HFNC) therapy and to identify the predictors of HFNC therapy success., Methods: This retrospective observational study involved all patients treated with HFNC therapy at a center for COVID-19 in Viet Nam from August to October 2021., Results: The study recruited 302 patients. Of these 302 patients, 171 (56.6%) underwent successful HFNC therapy, and the all-cause mortality rate was 33.44%. Non-critical COVID-19 and a higher respiratory rate-oxygenation (ROX) index at 48 hours after initiating HFNC therapy were independently correlated with HFNC therapy success. The statistically significant predictors of HFNC therapy success were younger age, non-critical COVID-19, a higher platelet count when starting HFNC therapy, and a higher ROX index at 24, 36, and 48 hours after HFNC therapy initiation., Conclusions: HFNC therapy appears to be effective in patients with COVID-19 who develop respiratory failure requiring respiratory support. Non-critical COVID-19 and a higher ROX index measured 48 hours after HFNC therapy initiation might serve as predictive factors for the success of HFNC therapy.

Epidermal growth factor (EGF) is a known signaling cue essential towards the development and organoid biofabrication particularly for exocrine glands. This study developed an in vitro EGF delivery platform with Nicotiana benthamiana plant-produced EGF (P-EGF) encapsulated on hyaluronic acid/alginate (HA/Alg) hydrogel to improve the effectiveness of glandular organoid biofabrication in short-term culture systems. Primary submandibular gland epithelial cells were treated with 5 - 20 ng/mL of P-EGF and commercially available bacteria-derived EGF (B-EGF). Cell proliferation and metabolic activity were measured by MTT and luciferase-based ATP assays. P-EGF and B-EGF 5 - 20 ng/mL promoted glandular epithelial cell proliferation during 6 culture days on a comparable fashion. Organoid forming efficiency and cellular viability, ATP-dependent activity and expansion were evaluated using two EGF delivery systems, HA/Alg-based encapsulation and media supplementation. Phosphate buffered saline (PBS) was used as a control vehicle. Epithelial organoids fabricated from PBS-, B-EGF-, and P-EGF-encapsulated hydrogels were characterized genotypically, phenotypically and by functional assays. P-EGF-encapsulated hydrogel enhanced organoid formation efficiency and cellular viability and metabolism relative to P-EGF supplementation. At culture day 3, epithelial organoids developed from P-EGF-encapsulated HA/Alg platform contained functional cell clusters expressing specific glandular epithelial markers such as exocrine pro-acinar (AQP5, NKCC1, CHRM1, CHRM3, Mist1), ductal (K18, Krt19), and myoepithelial (α-SMA, Acta2), and possessed a high mitotic activity (38-62% Ki67 cells) with a large epithelial progenitor population (∼70% K14 cells). The P-EGF encapsulation strikingly upregulated the expression of pro-acinar AQP5 cells through culture time when compared to others (B-EGF, PBS). Thus, the utilization of Nicotiana benthamiana in molecular farming can produce EGF biologicals amenable to encapsulation in HA/Alg-based in vitro platforms, which can effectively and promptly induce the biofabrication of exocrine gland organoids., Competing Interests: Declaration of Competing Interest Joao N. Ferreira reports financial support and equipment, drugs, or supplies were provided by National Research Council of Thailand. Joao N. Ferreira reports financial support, equipment, drugs, or supplies, and statistical analysis were provided by International Association for Dental Research. Waranyoo Phoolcharoen reports a relationship with Baiya Phytopharm Co., Ltd that includes: board membership, funding grants, and non-financial support. Supansa Yodmuang and Truc Thanh Nguyen has patent #63/240,262 pending to Chulalongkorn University. Waranyoo Phoolcharoen has patent issued to Chulalongkorn University. The authors declare the following ownership, which may be considered as potential competing interests: Dr. Waranyoo Phoolcharoen is CTO and co-founder of Baiya Phytopharm Co., Ltd, a Chulalongkorn university-based spin-off company., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The drug-eluting stent was a significant stride forward in the development of enhanced therapeutic therapy for coronary intervention, with three generations of increased advancement. VSTENT is a newly developed stent manufactured in Vietnam that aims to provide coronary artery patients with a safe, effective, and cost-efficient option. The purpose of this trial was to determine the efficacy and safety of a new bioresorbable polymer sirolimus-eluting stent called VSTENT., Methods: This is a prospective, cohort, multicenter research in 5 centers of Vietnam. A prespecified subgroup received intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging. We determined procedure success and complications during index hospitalization. We monitored all participants for a year. Six-month and 12-month rates of major cardiovascular events were reported. All patients had coronary angiography after 6 months to detect late lumen loss (LLL). Prespecified patients also had IVUS or OCT performed., Results: The rate of device success was 100% (95% CI: 98.3-100%; P<0.001). Major cardiovascular events were 4.7% (95% CI: 1.9-9.4%; P<0.001). The LLL over quantitative coronary angiography (QCA) was 0.08±0.19 mm (95% CI: 0.05-0.10; P<0.001) in the in-stent segment and 0.07±0.31 mm (95% CI: 0.03-0.11; P=0.002) in 5 mm within the two ends of the stent segment. The LLL recorded by IVUS and OCT at 6 months was 0.12±0.35 mm (95% CI: 0.01-0.22; P=0.028) and 0.15±0.24 mm (95% CI: 0.02-0.28; P=0.024), respectively., Conclusions: This study's device success rates were perfect. IVUS and OCT findings on LLL were favorable at 6-month follow-up. One-year follow-up showed low in-stent restenosis (ISR) and target lesion revascularization (TLR) rates, reflecting few significant cardiovascular events. VSTENT's safety and efficacy make it a promising percutaneous intervention option in developing nations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-522/coif). The authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Chemotactic bacteria not only navigate chemical gradients, but also shape their environments by consuming and secreting attractants. Investigating how these processes influence the dynamics of bacterial populations has been challenging because of a lack of experimental methods for measuring spatial profiles of chemoattractants in real time. Here, we use a fluorescent sensor for aspartate to directly measure bacterially generated chemoattractant gradients during collective migration. Our measurements show that the standard Patlak-Keller-Segel model for collective chemotactic bacterial migration breaks down at high cell densities. To address this, we propose modifications to the model that consider the impact of cell density on bacterial chemotaxis and attractant consumption. With these changes, the model explains our experimental data across all cell densities, offering new insight into chemotactic dynamics. Our findings highlight the significance of considering cell density effects on bacterial behavior, and the potential for fluorescent metabolite sensors to shed light on the complex emergent dynamics of bacterial communities.

Hyposalivation and severe dry mouth syndrome are the most common complications in patients with head and neck cancer (HNC) after receiving radiation therapy. Conventional treatment for hyposalivation relies on the use of sialogogues such as pilocarpine; however, their efficacy is constrained by the limited number of remnant acinar cells after radiation. After radiotherapy, the salivary gland (SG) secretory parenchyma is largely destroyed, and due to the reduced stem cell niche, this gland has poor regenerative potential. To tackle this, researchers must be able to generate highly complex cellularized 3D constructs for clinical transplantation via technologies, including those that involve bioprinting of cells and biomaterials. A potential stem cell source with promising clinical outcomes to reserve dry mouth is adipose mesenchymal stem cells (AdMSC). MSC-like cells like human dental pulp stem cells (hDPSC) have been tested in novel magnetic bioprinting platforms using nanoparticles that can bind cell membranes by electrostatic interaction, as well as their paracrine signals arising from extracellular vesicles. Both magnetized cells and their secretome cues were found to increase epithelial and neuronal growth of in vitro and ex vivo irradiated SG models. Interestingly, these magnetic bioprinting platforms can be applied as a high-throughput drug screening system due to the consistency in structure and functions of their organoids. Recently, exogenous decellularized porcine ECM was added to this magnetic platform to stimulate an ideal environment for cell tethering, proliferation, and/or differentiation. The combination of these SG tissue biofabrication strategies will promptly allow for in vitro organoid formation and establishment of cellular senescent organoids for aging models, but challenges remain in terms of epithelial polarization and lumen formation for unidirectional fluid flow. Current magnetic bioprinting nanotechnologies can provide promising functional and aging features to in vitro craniofacial exocrine gland organoids, which can be utilized for novel drug discovery and/or clinical transplantation., Competing Interests: Declaration of Competing Interests 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between red/processed meat consumption and glycaemic conditions (i.e. prediabetes (preDM) and diabetes mellitus (DM)) among middle-aged residents in rural Khánh Hòa, Vietnam., Design: In this cross-sectional study, a multinomial logistic regression model was used to examine the association between daily consumption of red/processed meat (0-99 g, 100-199 g or ≥ 200 g) and preDM/DM with adjustments for socio-demographic, lifestyle-related and health-related variables., Setting: Khánh Hòa Province, Vietnam., Participants: The study used data collected through a baseline survey conducted during a prospective cohort study on CVD among 3000 residents, aged 40-60 years, living in rural communes in Khánh Hòa Province., Results: The multinomial regression model revealed that the relative-risk ratios for DM were 1·00 (reference), 1·11 (95 % CI = 0·75, 1·62) and 1·80 (95 % CI = 1·40, 2·32) from the lowest to the highest red/processed meat consumption categories ( P trend = 0·006). The corresponding values for preDM were 1·00 (reference), 1·25 (95 % CI = 1·01, 1·54) and 1·67 (95 % CI = 1·20, 2·33) ( P trend = 0·004). We did not find any evidence of statistical significance in relation to poultry consumption., Conclusion: Increased red/processed meat consumption, but not poultry consumption, was positively associated with the prevalence of preDM/DM in rural communes in Khánh Hòa Province, Vietnam. Dietary recommendations involving a reduction in red/processed meat consumption should be considered in low- and middle-income countries.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

AcrAB-TolC tripartite efflux pump, which belongs to the RND superfamily, is a main multi-drug efflux system of Escherichia coli ( E. coli ) because of the broad resistance on various antibiotics. With the discovering of efflux pump inhibitors (EPIs), a combination between these and antibiotics is one of the most promising therapies. Therefore, building a virtual screening model with prediction capacities for the efflux pump inhibitory activities of candidates from DrugBank and ZINC15 dataset, is one of the key goals of this project. Based on the database of 170 diverse chemical structures collected from 28 research journals, two 2D-QSAR models and a 3D-pharmacophore model have been performed. On the AcrB protein (PDB 4DX7), two binding sites have been discovered that match to the hydrophobic trap in the distal pocket and the switch loop in the proximal pocket. After virtual screening processes, twenty candidate AcrAB-TolC inhibitors have been subjected to molecular dynamics simulations, binding free energy calculations and ADMET predictions. The results indicate that three compounds namely DB09233, DB02581, and DB15224 are potential inhibitors with ΔG bind of -42.30 ± 4.58, -40.76 ± 7.30 and -31.06 ± 7.63 kcal.mol -1 , respectively.Communicated by Ramaswamy H. Sarma.

Background: WHO recommends a three-dose infant pneumococcal conjugate vaccine (PCV) schedule administered as a two-dose primary series with booster (2 + 1) or a three-dose primary series (3 + 0). Data on carriage impacts of these and further reduced PCV schedules are needed to inform PCV strategies. Here we evaluate the efficacy against carriage of four different PCV10 schedules., Methods: Participants within an open-label, randomised controlled trial in Ho Chi Minh City, Vietnam, were allocated to receive PCV10 in a 3 + 1 (2,3,4,9 months, n = 152), 3 + 0 (2,3,4 months, n = 149), 2 + 1 (2,4,9.5 months, n = 250) or novel two-dose (2,6 months, n = 202) schedule, or no infant doses of PCV (two control groups, n = 197 and n = 199). Nasopharyngeal swabs collected between 2 and 24 months were analysed (blinded) for pneumococcal carriage and serotypes. Trial registration: ClinicalTrials.gov NCT01953510., Findings: Pneumococcal carriage prevalence was low (10.6-14.1% for vaccine-type (VT) at 12-24 months in unvaccinated controls). All four PCV10 schedules reduced VT carriage compared with controls (the 2 + 1 schedule at 12, 18, and 24 months; the 3 + 1 and two-dose schedules at 18 months; and the 3 + 0 schedule at 24 months), with maximum reductions of 40.1%-64.5%. There were no differences in VT carriage prevalence at 6 or 9 months comparing three-dose and two-dose primary series, and no differences at 12, 18, or 24 months when comparing schedules with and without a booster dose., Interpretation: In Vietnamese children with a relatively low pneumococcal carriage prevalence, 3 + 1, 2 + 1, 3 + 0 and two-dose PCV10 schedules were effective in reducing VT carriage. There were no discernible differences in the effect on carriage of the WHO-recommended 2 + 1 and 3 + 0 schedules during the first two years of life. Together with the previously reported immunogenicity data, this trial suggests that a range of PCV schedules are likely to generate significant direct and indirect protection., Funding: NHMRC, BMGF., Competing Interests: The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: All authors except JB and JH received salary support from 10.13039/501100000925National Health and Medical Research Council of Australia (NHMRC) and/or 10.13039/100000865Bill & Melinda Gates Foundation grants. PCV10 vaccine doses were donated by GlaxoSmithKline Biologicals SA. KM, CS, and CN are investigators on a clinical research collaboration with Pfizer on PCV vaccination in Mongolia and are investigators on a Merck Investigator Studies Program grant funded by MSD on pneumococcal serotype epidemiology in children. JB provided a report on pneumococcal carriage in Northern Australia to MSD Australia. EMD is currently employed by Pfizer. JH receives project grant funding from 10.13039/100004319Pfizer and is co-founder and board member of BUGS Bioscience Ltd. We declare no other competing interests., (© 2022 The Author(s).)

Time-reversal symmetry breaking and entropy production are universal features of nonequilibrium phenomena. Despite its importance in the physics of active and living systems, the entropy production of systems with many degrees of freedom has remained of little practical significance because the high dimensionality of their state space makes it difficult to measure. Here we introduce a local measure of entropy production and a numerical protocol to estimate it. We establish a connection between the entropy production and extractability of work in a given region of the system and show how this quantity depends crucially on the degrees of freedom being tracked. We validate our approach in theory, simulation, and experiments by considering systems of active Brownian particles undergoing motility-induced phase separation, as well as active Brownian particles and E.coli in a rectifying device in which the time-reversal asymmetry of the particle dynamics couples to spatial asymmetry to reveal its effects on a macroscopic scale.

Experimental robobiological physics can bring insights into biological evolution. We present a development of hybrid analog/digital autonomous robots with mutable diploid dominant/recessive 6-byte genomes. The robots are capable of death, rebirth, and breeding. We map the quasi-steady-state surviving local density of the robots onto a multidimensional abstract “survival landscape.” We show that robot death in complex, self-adaptive stress landscapes proceeds by a general lowering of the robotic genetic diversity, and that stochastically changing landscapes are the most difficult to survive.

Background: At present, clinical use of MRI in Alzheimer's disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency., Methods: 20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole brain, white matter, gray matter, cortical gray matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter. DTI data was used to evaluate pairwise structural connectivity between lobar regions and the hippocampi.Logistic-Regression and Random-Forest models were trained to classify AD-status based on, respectively different isolated features and age, and feature-groups combined with age., Results: Hippocampal features, features reflecting the functional connectivity between the medial-Pre-Frontal-Cortex (mPFC) and the posterior regions of the DMN, and structural interhemispheric frontal connectivity showed the strongest differences between AD-patients and controls. Structural interhemispheric parietal connectivity, structural connectivity between the parietal lobe and hippocampus in the right hemisphere, and mPFC-DMN-features, showed only an association with AD-status (p < 0.05) but not with age. Hippocampi volumes showed an association both with age and AD-status (p < 0.05).Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.74, sensitivity:0.74, specificity:0.74) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM MD, lTPJ-mPFC connectivity and structural interhemispheric frontal connectivity) and age., Conclusions: Brain connectivity changes caused by AD are reflected in multiple MRI-biomarkers. Decline in both the functional DMN-connectivity and the parietal interhemispheric structural connectivity may assist sepparating healthy-aging driven changes from AD, complementing hippocampal volumes which are affected by both aging and AD., (© 2022 The Authors.)

Landscapes play an important role in many areas of biology, in which biological lives are deeply entangled. Here we discuss a form of landscape in evolutionary biology which takes into account (1) initial growth rates, (2) mutation rates, (3) resource consumption by organisms, and (4) cyclic changes in the resources with time. The long-term equilibrium number of surviving organisms as a function of these four parameters forms what we call a success landscape, a landscape we would claim is qualitatively different from fitness landscapes which commonly do not include mutations or resource consumption/changes in mapping genomes to the final number of survivors. Although our analysis is purely theoretical, we believe the results have possibly strong connections to how we might treat diseases such as cancer in the future with a deeper understanding of the interplay between resource degradation, mutation, and uncontrolled cell growth., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Primary education is the incubator for learning academic skills that help children to become a literate, communicative, and independent person. Over this learning period, nonlinear and regional changes in the brain occur, but how these changes relate to academic performance, such as reading ability, is still unclear. In the current study, we analyzed longitudinal T1 MRI data of 41 children in order to investigate typical cortical development during the early reading stage (end of kindergarten-end of grade 2) and advanced reading stage (end of grade 2-middle of grade 5), and to detect putative deviant trajectories in children with dyslexia. The structural brain change was quantified with a reliable measure that directly calculates the local morphological differences between brain images of two time points, while considering the global head growth. When applying this measure to investigate typical cortical development, we observed that left temporal and temporoparietal regions belonging to the reading network exhibited an increase during the early reading stage and stabilized during the advanced reading stage. This suggests that the natural plasticity window for reading is within the first years of primary school, hence earlier than the typical period for reading intervention. Concerning neurotrajectories in children with dyslexia compared to typical readers, we observed no differences in gray matter development of the left reading network, but we found different neurotrajectories in right IFG opercularis (during the early reading stage) and in right isthmus cingulate (during the advanced reading stage), which could reflect compensatory neural mechanisms., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Data are scarce from low-income and middle-income countries (LMICs) to support the choice of vaccination schedule for the introduction of pneumococcal conjugate vaccines (PCV). We aimed to compare the immunogenicity of four different infant PCV10 schedules in infants in Vietnam., Methods: In this single-blind, parallel-group, open-label, randomised controlled trial, infants aged 2 months were recruited by community health staff in districts 4 and 7 of Ho Chi Minh City, Vietnam. Eligible infants had no clinically significant maternal or prenatal history and were born at or after 36 weeks' gestation. Participants were randomly assigned (3:3:5:4:5:4) using block randomisation, stratified by district, to one of six PCV10 or PCV13 vaccination schedules. Here we report results for four groups: group A, who were given PCV10 at ages 2, 3, 4, and 9 months (a 3 + 1 schedule); group B, who were vaccinated at ages 2, 3, and 4 months (3 + 0 schedule); group C, who were vaccinated at ages 2, 4, and 9·5 months (2 + 1 schedule); and group D, who were vaccinated at ages 2 and 6 months (two-dose schedule). Laboratory-based assessors were masked to group allocation. Blood samples were collected at different prespecified timepoints between ages 3-18 months depending on group allocation, within 27-43 days after vaccination, and these were analysed for serotype-specific IgG and opsonophagocytic responses. Participants were followed-up until age 24 months. The primary outcome was the proportion of infants with serotype-specific IgG levels of 0·35 μg/mL or higher at age 5 months, analysed as a non-inferiority comparison (10% margin) of the two-dose and three-dose primary series (group C vs groups A and B combined). We also compared responses 4 weeks after two doses administered at either ages 2 and 4 months (group C) or at ages 2 and 6 months (group D). The primary endpoint was analysed in the per-protocol population. Reactogenicity has been reported previously. This study is registered with ClinicalTrials.gov, NCT01953510, and is now closed to accrual., Findings: Between Sept 30, 2013, and Jan 9, 2015, 1201 infants were enrolled and randomly assigned to group A (n=152), group B (n=149), group C (n=250), group D (n=202), or groups E (n=251) and F (n=197). In groups A-D, 388 (52%) of 753 participants were female and 365 (48%) were male. 286 (95%) participants in groups A and B combined (three-dose primary series) and 237 (95%) in group C (two-dose primary series) completed the primary vaccination series and had blood samples taken within the specified time window at age 5 months (per-protocol population). At this timepoint, a two-dose primary series was non-inferior to a three-dose primary series for eight of ten vaccine serotypes; exceptions were 6B (84·6% [95% CI 79·9-88·6] of infants had protective IgG concentrations after three doses [groups A and B combined] vs 76·8% [70·9-82·0] of infants after two doses [group C]; risk difference 7·8% [90% CI 2·1-13·6]) and 23F (90·6% [95% CI 86·6-93·7] vs 77·6% [71·8-82·2]; 12·9% [90% CI 7·7-18·3]). Two doses at ages 2 and 6 months produced higher antibody levels than two doses at ages 2 and 4 months for all serotypes except 5 and 7F., Interpretation: A two-dose primary vaccination series was non-inferior to a three-dose primary vaccination series while two doses given with a wider interval between doses increased immunogenicity. The use of a two-dose primary vaccination schedule using a wider interval could be considered in LMIC settings to extend protection in the second year of life., Funding: Australian National Health and Medical Research Council, and The Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: This study investigated the immunogenicity and impact on nasopharyngeal carriage of a single dose of PCV10 given to 18-month-old Vietnamese children. This information is important for countries considering catch-up vaccination during PCV introduction and in the context of vaccination during humanitarian crises., Methods: Two groups of PCV-naïve children within the Vietnam Pneumococcal Project received PCV10 (n=197) or no PCV (unvaccinated; n=199) at 18 months of age. Blood samples were collected at 18, 19, and 24 months of age, and nasopharyngeal swabs at 18 and 24 months of age. Immunogenicity was assessed by measuring serotype-specific IgG, opsonophagocytosis (OPA) and memory B cells (Bmem). Pneumococci were detected and quantified using real-time PCR and serotyped by microarray., Findings: At 19 months of age, IgG and OPA responses were higher in the PCV10 group compared with the unvaccinated group for all PCV10 serotypes and cross-reactive serotypes 6A and 19A. This was sustained out to 24 months of age, at which point PCV10-type carriage was 60% lower in the PCV10 group than the unvaccinated group. Bmem levels increased between 18 and 24 months of age in the vaccinated group., Interpretation: We demonstrate strong protective immune responses in vaccinees following a single dose of PCV10 at 18 months of age, and a potential impact on herd protection through a substantial reduction in vaccine-type carriage. A single dose of PCV10 in the second year of life could be considered as part of catch-up campaigns or in humanitarian crises to protect children at high-risk of pneumococcal disease., Competing Interests: Funding for this study was provided by grants from National Health and Medical Research Council of Australia (NHMRC) and/or Bill & Melinda Gates Foundation grants. Non-financial support (in the form of PCV10 vaccine doses) and funding for opsonophagocytic assays were provided by GSK Biologicals SA. KM, CS and CDN have received grant funding for a collaborative study on PCV impact on adult pneumonia from Pfizer. None of the authors have any other competing interests to declare., (© 2021 The Author(s). Published by Elsevier Ltd.)

We reinvestigate a simple model used in the literature concerning the thermodynamic analysis of protein cold denaturation. We derive an exact thermodynamic expression for cold denaturation and give a better approximation than exists in the literature for predicting cold denaturation temperatures in the two-state model. We discuss the "dark-side" implications of this work for previous temperature-dependent protein dynamics experiments and discuss microfluidic experimental technologies, which could explore the thermal stability range of proteins below the bulk freezing point of water.

Abstract: With COVID-19 affecting millions of people around the globe, quarantine of international arrivals is a critical public health measure to prevent further disease transmission in local populations. This measure has also been applied in the repatriation of citizens, undertaken by several countries as an ethical obligation and legal responsibility. This article describes the process of planning and preparing for the repatriation operation in South Australia during the COVID-19 pandemic. Interagency collaboration, development of a COVID-19 testing and quarantining protocol, implementing infection prevention and control, and building a specialised health care delivery model were essential aspects of the repatriation operational planning, with a focus on maintaining dignity and wellbeing of the passengers as well as on effective prevention of COVID-19 transmission. From April 2020 to mid-February 2021, more than 14,000 international arrivals travellers have been repatriated under the South Australian repatriation operations. This paper has implications to inform ongoing repatriation efforts in Australia and overseas in a pandemic situation., (© Commonwealth of Australia CC BY-NC-ND.)

ABCG2 is an ABC membrane protein reverse transport pump, which removes toxic substances such as medicines out of cells. As a result, drug bioavailability is an unexpected change and negatively influences the ADMET (absorption, distribution, metabolism, excretion, and toxicity), leading to multi-drug resistance (MDR). Currently, in spite of promising studies, screening for ABCG2 inhibitors showed modest results. The aim of this study was to search for small molecules that could inhibit the ABCG2 pump. We first used the WISS MODEL automatic server to build up ABCG2 homology protein from 655 amino acids. Pharmacophore models, which were con-structed based on strong ABCG2 inhibitors (IC 50 < 1 μM), consist of two hydrophobic (Hyd) groups, two hydrogen bonding acceptors (Acc2), and an aromatic or conjugated ring (Aro|PiR). Using molecular docking method, 714 substances from the DrugBank and 837 substances from the TCM with potential to inhibit the ABCG2 were obtained. These chemicals maybe favor synthesized or extracted and bioactivity testing.

The overexpression of ABCC2/MRP2, an ATP-binding cassette transporter, contributes to multidrug resistance in cancer cells. In this study, a quantitative structure-activity relationship (QSAR) analysis on ABCC2 inhibitors has been carried out, aiming to establish a computational prediction model for ABCC2 modulators. Seven classification models and two regression models were built by SONNIA 4.2, and two other regression models were built by MOE 2008.10 based on a data set comprising 372 compounds collected from 16 relevant publications. The CPG-C iABCC2 model for classifying ABCC2 inhibitors has total accuracy of 0.88 and Matthews correlation coefficient MCC = 0.75. The CPG-C iEG model for classifying ABCC2 inhibitors (substrate EG: β-estradiol 17-β-D-glucuronide) has total accuracy of 0.91 and MCC = 0.82. The regression model PLS EG-IC 50 for predicting ABCC2 inhibitors (substrate EG) gave root-mean-square error RMSE = 0.26, Q 2  = 0.73 and [Formula: see text]. The regression model PLS CDCF-IC 50 for predicting ABCC2 inhibitors [substrate CDCF: 5(6)-carboxy-2',7'-dichlorofluorescein] gave RMSE = 0.31, Q 2  = 0.74 and [Formula: see text]. Four 2D-QSAR models were applied to 1661 compounds, with results indicating 369 compounds having the ability to reverse the efflux of both EG and CDCF by ABCC2, 152 among them having IC 50  < 100 µM.

Background: Pneumococcal conjugate vaccines (PCVs) generate herd protection by reducing nasopharyngeal (NP) carriage. Two PCVs, PCV10 and PCV13, have been in use for over a decade, yet there are few data comparing their impact on carriage. Here we report their effect on carriage in a 2+1 schedule, compared with each other and with unvaccinated controls., Methods: Data from four groups within a parallel, open-label randomised controlled trial in Ho Chi Minh City contribute to this article. Three groups were randomised to receive a 2+1 schedule of PCV10 (n = 250), a 2+1 schedule of PCV13 (n = 251), or two doses of PCV10 at 18 and 24 months (controls, n = 197). An additional group (n = 199) was recruited at 18 months to serve as controls from 18 to 24 months. NP swabs collected at 2, 6, 9, 12, 18, and 24 months were analysed (blinded) for pneumococcal carriage. This study aimed to determine if PCV10 and PCV13 have a differential effect on pneumococcal carriage, a secondary outcome of the trial. We also describe the serotype distribution among unvaccinated participants., Trial Registration: ClinicalTrials.gov NCT01953510., Findings: Compared with unvaccinated controls, a 2+1 schedule of PCV10 reduced PCV10-type carriage by 45-62% from pre-booster through to 24 months of age, and a 2+1 schedule of PCV13 reduced PCV13-type carriage by 36-49% at 12 and 18 months of age. Compared directly with each other, there were few differences between the vaccines in their impact on carriage. Vaccine serotypes accounted for the majority of carriage in unvaccinated participants., Interpretation: Both PCV10 and PCV13 reduce the carriage of pneumococcal vaccine serotypes. The introduction of either vaccine would have the potential to generate significant herd protection in this population., Funding: National Health and Medical Research Council of Australia, Bill & Melinda Gates Foundation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors except JB and JH received salary support from National Health and Medical Research Council of Australia (NHMRC) and/or Bill & Melinda Gates Foundation grants. KM has received grant funding for a collaborative study on PCV impact on adult pneumonia from Pfizer. PCV10 vaccine doses were donated by GlaxoSmithKline Biologicals SA. We declare no other competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We present an ecology-inspired form of active matter consisting of a robot swarm. Each robot moves over a planar dynamic resource environment represented by a large light-emitting diode array in search of maximum light intensity; the robots deplete (dim) locally by their presence the local light intensity and seek maximum light intensity. Their movement is directed along the steepest local light intensity gradient; we call this emergent symmetry breaking motion "field drive." We show there emerge dynamic and spatial transitions similar to gas, crystalline, liquid, glass, and jammed states as a function of robot density, resource consumption rates, and resource recovery rates. Paradoxically the nongas states emerge from smooth, flat resource landscapes, not rough ones, and each state can directly move to a glassy state if the resource recovery rate is slow enough, at any robot density.

Acute Hepatopancreatic Necrosis Disease (AHPND) is a newly emerging shrimp disease with mortality up to 100 percent caused by Vibrio parahaemolyticus which carries a plasmid encoding for two toxins, ToxA and ToxB. In 2013, the Global Aquaculture Alliance (GAA) estimated shrimp farming decline in Asia accounted for 1-billion US dollar lost. Currently, diagnosis using PCR method does not meet the demand of in situ detection, which is based on antigen-antibody interaction, has not been developed yet. In this present study, we proceeded to create the toxin and its antibody for lateral flow development. First, recombinant toxin ToxA was generated by gene manipulation. After that, purified ToxA was used to immunize rabbits. Finally, antisera from rabbits and protein-A purified antibodies were evaluated for titer, specificity, and detection threshold. Results showed that recombinant ToxA was overexpressed in soluble fraction at 37 o C with 1mM IPTG. Purification by affinity chromatography was able to isolate recombinant ToxA with the purity up to 94.49%. In ELISA experiment, the immunized antisera reached a titer of up to 1/5,210,000 with 1µg/ml of antigen, and detection threshold was 100ng recombinant toxin. After purification, the detection threshold of purified polyclonal antibodies was 25ng toxin per dot. These results laid a groundwork for the development of AHPND detection kit based on antigen - antibody interactions.

Insights into brain anatomy are important for the early detection of neurodevelopmental disorders, such as dyslexia. FreeSurfer is one of the most frequently applied automatized software tools to study brain morphology. However, quality control of the outcomes provided by FreeSurfer is often ignored and could lead to wrong statistical inferences. Additional manual editing of the data may be a solution, although not without a cost in time and resources. Past research in adults on comparing the automatized method of FreeSurfer with and without additional manual editing indicated that although editing may lead to significant differences in morphological measures between the methods in some regions, it does not substantially change the sensitivity to detect clinical differences. Given that automated approaches are more likely to fail in pediatric-and inherently more noisy-data, we investigated in the current study whether FreeSurfer can be applied fully automatically or additional manual edits of T1-images are needed in a pediatric sample. Specifically, cortical thickness and surface area measures with and without additional manual edits were compared in six regions of interest (ROIs) of the reading network in 5-to-6-year-old children with and without dyslexia. Results revealed that additional editing leads to statistical differences in the morphological measures, but that these differences are consistent across subjects and that the sensitivity to reveal statistical differences in the morphological measures between children with and without dyslexia is not affected, even though conclusions of marginally significant findings can differ depending on the method used. Thereby, our results indicate that additional manual editing of reading-related regions in FreeSurfer has limited gain for pediatric samples., (Copyright © 2020 Beelen, Phan, Wouters, Ghesquière and Vandermosten.)

Brain volumes computed from magnetic resonance images have potential for assisting with the diagnosis of individual dementia patients, provided that they have low measurement error and high reliability. In this paper we describe and validate icobrain dm, an automatic tool that segments brain structures that are relevant for differential diagnosis of dementia, such as the hippocampi and cerebral lobes. Experiments were conducted in comparison to the widely used FreeSurfer software. The hippocampus segmentations were compared against manual segmentations, with significantly higher Dice coefficients obtained with icobrain dm (25-75th quantiles: 0.86-0.88) than with FreeSurfer (25-75th quantiles: 0.80-0.83). Other brain structures were also compared against manual delineations, with icobrain dm showing lower volumetric errors overall. Test-retest experiments show that the precision of all measurements is higher for icobrain dm than for FreeSurfer except for the parietal cortex volume. Finally, when comparing volumes obtained from Alzheimer's disease patients against age-matched healthy controls, all measures achieved high diagnostic performance levels when discriminating patients from cognitively healthy controls, with the temporal cortex volume measured by icobrain dm reaching the highest diagnostic performance level (area under the receiver operating characteristic curve = 0.99) in this dataset., Competing Interests: Declaration of Competing Interest The following authors are employed (or have been employed at the time of performing the work relevant for this paper) by icometrix: Hanne Struyfs, Diana M. Sima, Annemie Ribbens, Nuno Pedrosa de Barros, Thanh Vân Phan, Lene Claes, Maria Ines Ferraz Meyer, Wim Van Hecke, Dirk Smeets. Melissa Wittens and Ellis Niemantsverdriet have no competing interests. Sebastiaan Engelborghs has received unrestricted research grants from Janssen Pharmaceutica NV and ADx Neurosciences (paid to institution)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Bacteria under external stress can reveal unexpected emergent phenotypes. We show that the intensely studied bacterium Escherichia coli can transform into long, highly motile helical filaments poized at a torsional buckling criticality when exposed to minimum inhibitory concentrations of several antibiotics. While the highly motile helices are physically either right- or left-handed, the motile helices always rotate with a right-handed angular velocity [Formula: see text], which points in the same direction as the translational velocity [Formula: see text] of the helix. Furthermore, these helical cells do not swim by a "run and tumble" but rather synchronously flip their spin [Formula: see text] and thus translational velocity-backing up rather than tumbling. By increasing the translational persistence length, these dynamics give rise to an effective diffusion coefficient up to 20 times that of a normal E. coli cell. Finally, we propose an evolutionary mechanism for this phenotype's emergence whereby the increased effective diffusivity provides a fitness advantage in allowing filamentous cells to more readily escape regions of high external stress., Competing Interests: The authors declare no conflict of interest.

Background: Vietnam is endemic for taeniasis and T. solium cysticercosis. Despite this, information on the epidemiological characteristics of the diseases in the Central Highlands of Vietnam are poorly described. The aims of this study were to determine the epidemiological characteristics of taeniasis (Taenia spp.) and T. solium cysticerci exposure in humans in Dak Lak province in the Central Highlands, Vietnam., Methods: This cross-sectional study was carried out in six villages in three districts of Dak Lak. A total of 190 households were visited. From each household, between one and five individuals were asked to donate a single faecal and blood sample and respond to a questionnaire. Serum samples were subjected to lentil lectin purified glycoprotein enzyme-linked immunoelectrotransfer blot assay to detect antibodies against T. solium cysticerci. Multiplex real-time PCR was used to detect Taenia spp. infection in faecal samples. A fixed-effects logistic regression model was developed to identify factors associated with the probability of Taenia spp. infection or T. solium cysticerci exposure risk. The contribution of each of identified factor was quantified using population attributable fractions., Results: The prevalence of seroexposure to T. solium in Dak Lak was 5% (95% CI 3% to 8%). Consumption of raw vegetables, sourcing drinking water from lakes, streams or ponds and the practice of outdoor defaecation were identified as primary risk factors for the prevalence of T. solium cysticerci exposure, while consuming undercooked pork and beef, pork tongue and observing Taenia proglottids in stool were associated with Taenia spp. infection. Consumption of raw vegetables attributed to 74% of T. solium cysticerci exposure-positive cases and consumption of undercooked beef attributed to 77% of taeniasis cases in these communities., Conclusions: The prevalence of T. solium seroexposure in Dak Lak is consistent with those reported in other regions of Vietnam. The identified risk factors associated with the prevalence of T. solium seroexposure and taeniasis infection in Dak Lak are modifiable and thus advocate for targeted community intervention programs to mitigating these risks.

The structure of the brain is subject to very rapid developmental changes during early childhood. Pediatric studies based on Magnetic Resonance Imaging (MRI) over this age range have recently become more frequent, with the advantage of providing in vivo and non-invasive high-resolution images of the developing brain, toward understanding typical and atypical trajectories. However, it has also been demonstrated that application of currently standard MRI processing methods that have been developed with datasets from adults may not be appropriate for use with pediatric datasets. In this review, we examine the approaches currently used in MRI studies involving young children, including an overview of the rationale for new MRI processing methods that have been designed specifically for pediatric investigations. These methods are mainly related to the use of age-specific or 4D brain atlases, improved methods for quantifying and optimizing image quality, and provision for registration of developmental data obtained with longitudinal designs. The overall goal is to raise awareness of the existence of these methods and the possibilities for implementing them in developmental neuroimaging studies., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)