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BackgroundDual use of both e-cigarettes and cigarettes is popular among young adults and may lead to greater nicotine dependence and additive adverse health effects than single-product use. However, existing cessation programs target quitting either e-cigarettes or cigarettes, highlighting a need for interventions to help young adults quit both products (ie, dual tobacco cessation). ObjectiveThis formative study is part of a larger project to develop a smartphone intervention for dual tobacco cessation among young adults. This study aimed to (1) explore desires for and experiences with quitting both e-cigarettes and cigarettes and (2) identify needs and preferences for dual tobacco cessation intervention programming. MethodsSemistructured interviews were conducted to elicit the need for and experience with dual tobacco cessation among 14 young adults (18-29 years old) recruited through Instagram (Meta) advertisements in 2023. We conducted a thematic analysis to identify common themes related to quitting experiences and cessation needs. ResultsParticipants expressed a strong desire for dual tobacco cessation and had attempted to quit both tobacco products, mostly “cold turkey.” The priority product for quitting first varied by the individual’s perceived harm or level of consumption. Targets for dual tobacco cessation interventions included (1) highlighting the health effects of dual tobacco use compared with single product use, (2) providing cessation support to quit one prioritized product while cutting down the other product with the explicit goal to quit both, (3) emphasizing unique facilitators and barriers to quitting each product (eg, unpleasant smell of cigarettes facilitating smoking cessation and accessibility and flavors of e-cigarettes hindering vaping cessation), and (4) addressing co-use of tobacco with alcohol or cannabis. Participants wanted personalized interventions through smartphone apps that would tailor support to their tobacco use patterns and unique quitting goals and needs. They also suggested presenting intervention content in multimedia (eg, videos, graphic pictures, quizzes, and games) to increase engagement. ConclusionsThis study provides important insights into young adults’ experiences, needs, and preferences for dual tobacco product cessation. We highlight important targets for future smartphone apps to deliver personalized and tailored support to meet the heterogeneous needs and preferences of young people who want to quit using both e-cigarettes and cigarettes.

Curcuma sahuynhensis Škorničk. & N.S. Lý has been discovered recently whose antiviral potential is unknown, thus deserved for discovery-phase screening. A combination of experimental characterization, quantum calculation, molecular docking simulation, physicochemical analysis, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) was designed for the theoretical argument on the potentiality of oil-based components (1−27) against H5 hemagglutinin in influenza A virus (PDB-5E32), wild-variant SARS-CoV-2 main protease (PDB-6LU7), and SARS-CoV-2 Omicron spike protein (PDB-7T9J). Theoretical arguments based on various computational platforms specify the most promising bio-inhibitors, i.e. 23 (bio-compatibility: ground energy −966.73 a.u., dipole moment 3.708 Debye; bio-inhibitability: DS̅\bar{{\rm{DS}}} −12.5 kcal mol−1; drug-likeness: mass 304.7 amu, log P 1.31; polar-interactability: polarizability 32.8 Å3) and 26 (bio-compatibility: ground energy −1393.66109 a.u., dipole moment 5.087 Debye; bio-inhibitability: DS̅\bar{{\rm{DS}}} −11.9 kcal mol−1; drug-likeness: mass 437.5 amu, log P 4.28; polar-interactability: polarizability 45.7 Å3). The pkCSM-ADMET model confirms their favorable pharmacokinetics and pharmacology. The total essence is unsuitable for use as an antiviral source in its pure form since the most bioactive candidates are accountable for the small content. Particularly, 23 (7β-hydroxydehydroepiandrosterone) and 26 (ethyl cholate) are recommended for further experimental efforts of isolation and bioassaying trials.

Clinical imaging modalities are a mainstay of modern disease management, but the full utilization of imaging-based data remains elusive. Aortic disease is defined by anatomic scalars quantifying aortic size, even though aortic disease progression initiates complex shape changes. We present an imaging-based geometric descriptor, inspired by fundamental ideas from topology and soft-matter physics that captures dynamic shape evolution. The aorta is reduced to a two-dimensional mathematical surface in space whose geometry is fully characterized by the local principal curvatures. Disease causes deviation from the smooth bent cylindrical shape of normal aortas, leading to a family of highly heterogeneous surfaces of varying shapes and sizes. To deconvolute changes in shape from size, the shape is characterized using integrated Gaussian curvature or total curvature. The fluctuation in total curvature (δK) across aortic surfaces captures heterogeneous morphologic evolution by characterizing local shape changes. We discover that aortic morphology evolves with a power-law defined behavior with rapidly increasing δK forming the hallmark of aortic disease. Divergent δK is seen for highly diseased aortas indicative of impending topologic catastrophe or aortic rupture. We also show that aortic size (surface area or enclosed aortic volume) scales as a generalized cylinder for all shapes. Classification accuracy for predicting aortic disease state (normal, diseased with successful surgery, and diseased with failed surgical outcomes) is 92.8±1.7%. The analysis of δK can be applied on any three-dimensional geometric structure and thus may be extended to other clinical problems of characterizing disease through captured anatomic changes.

With the rapid increase of renewable energy sources (RESs), the virtual power plant model (VPP) has been developed to integrate RESs, energy storage systems (ESSs), and local customers to overcome the RESs’ disadvantages. When the VPP’s capacity is large enough, it can participate in the electricity market as a price-maker instead of a price-taker to obtain a higher profit. This study proposes a bi-level optimization model to determine the optimal trading strategies of a price-maker VPP in the day-ahead (DA) market. The operation schedule of the components in the VPP is also optimized to achieve the highest profit for the VPP. In the bi-level optimization problem, the upper-level model is maximizing the VPP’s profit while the lower-level model is the DA market-clearing problem. The bi-level optimization problem is formulated as a Mathematical Problem with Equilibrium Constraints (MPEC), reformulated to a Mixed Integer Linear Problem (MILP), then solved by GAMS and CPLEX. This study applies the bi-level optimization model to a test VPP system, including wind plants (WP), solar plants (PV), biogas energy plants (BG), ESSs, and several customers. The maximum power outputs of WP and PV are 100MW and 90MW, respectively. The total installed capacity of BG is 70MW, while the ESS’ rated capacity is 100MWh. The local customers have the highest total consumption of 100MW. In addition to the VPP, four GENCOs and three retailers participate in the DA market. The results show that the market-clearing price varies depending on the participants’ production/consumption quantity and offering/bidding price. However, based on the optimization model, the VPP can take full advantage of WP and PV available power output, choose the right time to operate BG, then obtain the highest profit. The results also show that with the ESS’ rated capacity of 100MWh, the ESS’ rated discharging/charging power increased from 10MW to 50MW will increase VPP’s profit from 45987$ to 49464$. The obtained results show that the proposed model has practical significance

An individual's likelihood of developing non-communicable diseases is often influenced by the types, intensities and duration of exposures at work. Job exposure matrices provide exposure estimates associated with different occupations. However, due to their time-consuming expert curation process, job exposure matrices currently cover only a subset of possible workplace exposures and may not be regularly updated. Scientific literature articles describing exposure studies provide important supporting evidence for developing and updating job exposure matrices, since they report on exposures in a variety of occupational scenarios. However, the constant growth of scientific literature is increasing the challenges of efficiently identifying relevant articles and important content within them. Natural language processing methods emulate the human process of reading and understanding texts, but in a fraction of the time. Such methods can increase the efficiency of both finding relevant documents and pinpointing specific information within them, which could streamline the process of developing and updating job exposure matrices. Named entity recognition is a fundamental natural language processing method for language understanding, which automatically identifies mentions of domain-specific concepts (named entities) in documents, e.g., exposures, occupations and job tasks. State-of-the-art machine learning models typically use evidence from an annotated corpus, i.e., a set of documents in which named entities are manually marked up (annotated) by experts, to learn how to detect named entities automatically in new documents. We have developed a novel annotated corpus of scientific articles to support machine learning based named entity recognition relevant to occupational substance exposures. Through incremental refinements to the annotation process, we demonstrate that expert annotators can attain high levels of agreement, and that the corpus can be used to train high-performance named entity recognition models. The corpus thus constitutes an important foundation for the wider development of natural language processing tools to support the study of occupational exposures.

Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p

As a traditional medicinal plant in Vietnam, Myxopyrum smilacifolium has been used for a long history to treat cough, nervous disorders, numbness, rheumatism, and cephalalgia. Nevertheless, reports on the antioxidant activity and extraction of M. smilacifolium polysaccharides are still very rare. This study was designed to extract a high yield of polysaccharides from the M. smilacifolium trunk and characterize it. As a result, the maximum yield of the polysaccharides of 5.13 ± 0.05% was obtained with an extraction time of three hours, extraction temperature of 100 oC, the ratio of water to sample of 1:50 as extraction solution, extraction number of times 3, and the ratio of ethanol to extract volume 5:1 (v/v). Polysaccharides was characterized by Fourier transform infrared spectroscopy (FT-IR) and high-performance gel-permeation chromatography (HPGPC). The average molecular weight of extracted polysaccharides was around 3.78 × 105 Da. In vitro assays dan impressive antioxidant activities of the extracted polysaccharides, containing 0.2423 ± 0.0028 mg GA/g or 0.2142 ± 0.0007 μmol AS/g. The IC50 values of polysaccharides in the DPPH and ABTS methods were 0.89 mg/mL and 3.85 mg/mL, respectively. These findings exhibited the potential for application or further research and development of polysaccharides from Myxopyrum smilacifolium.

In recent years, with the rapid increase in renewable energy sources (RESs), a Virtual Power Plant (VPP) concept has been developed to integrate many small-scale RESs, energy storage systems (ESSs), and customers into a unified agent in the electricity market. Optimal coordination among resources within the VPP will overcome their disadvantages and enable them to participate in both energy and balancing markets. This study considers a VPP as an active agent in reserve provision with an upward reserve capacity contract pre-signed in the balancing capacity (BC) market. Based on the BC contract’s requirements and the forecasted data of RESs and demand, a two-stage stochastic optimization model is presented to determine the VPP’s optimal scheduling in the day-ahead (DA) and balancing energy (BE) markets. The probability of reserve activation in the BE market is considered in this model. The ESS’s reserve provision model is proposed so as not to affect its schedule in the DA market. The proposed optimal scheduling model is applied to a test VPP system; then, the effects of the BC contract and the probability of reserve activation on the VPP’s trading schedule are analyzed. The results show that the proposed model has practical significance.

Background and Aims: Thalassemia is a hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner which affected 1.5% of the population. Clinically, there are two major forms: [Formula: see text]-thalassemia and [Formula: see text]-thalassemia. Palliative treatment of the severe forms by blood transfusion is eventually compromised by the concomitant problems of iron overload, alloimmunization, and bloodborne infections. In Vietnam, there are approximately 13.8% cases of thalassemia carriers in the entire population. PGT-M aims to characterize the genetic status of embryos resulting from in vitro fertilization (IVF) cycles. Herein, we report the clinical outcome of using PGT-M in couples who are thalassemia carriers. Methods: This was a case series report conducted at IVFMD, My Duc Hospital, Vietnam between April 2019 and April 2022. A total of 38 couples who underwent IVF cycle in combination with PGT-M were enrolled in this study. Trophectoderm biopsy samples undergone whole-genome amplification, followed by next-generation sequencing (NGS) via the MiSeq platform for aneuploidy screening. Specific-targeted genes were performed for thalassemia detection in the next step. Results: PGT-M was performed on a total of 128 blastocysts from 38 couples. Among 128 blastocysts, 92 (71.9%) were euploid. The rate of unaffected blastocysts was 38.0% and heterozygous blastocysts was 27.2% among euploid blastocysts. Single blastocyst transfer was performed in 30 couples and underwent 34 cycles. The clinical pregnancy rate was 50.0% and the overall live birth rate was 41.2%. Conclusion: Data from this study showed a favorable live birth rate after PGT-M for thalassemia. We should encourage carrier couples to undergo PGT-M to eliminate the transfer of this disorder through the next generation.

Objectives Trying to adapt to a new culture, Vietnamese (expectant) mothers in the USA gathered in few Facebook groups with thousands of members discussing pregnancy, health, and child caring issues. However, there is little research exploring how social support was given/taken among these (expectant) mothers. This empirical research aims at shedding light on how such mothers use social media groups for social support seeking/providing regarding health utilization during their acculturation process. Methods Drawing from Andersen's Behavioral Model of Health Utilization, acculturation, and online social support conceptual frameworks, this study analyzes 18 in-depth interviews with immigrant Vietnamese (expectant) mothers in the United States on the use of social media in navigating health acculturation during their pregnancy and motherhood. Results Results show that these mothers give and take all forms of social support including informational, emotional, relational, and instrumental ones. Facebook groups do not provide the best environment for improving “bonding” social capital for its members. However, these groups provide a platform where “strangers help strangers” overcome various barriers to sufficiently understand and independently access and use the official healthcare system. The groups, hence, aid these women's pregnancy and their child(ren)'s health. The informational and emotional support provided by Facebook groups among (soon-to-be) mothers helped them tremendously in overcoming acculturative stress. Moreover, with better language skills, knowledge, and experience in using health and social security systems, help-seekers tend to be transformed into help providers to deliver support for those “newcomers.” Conclusions This research provides insights into personal experience on the uses of social media in navigating health behavior in the process of acculturation among Vietnamese immigrant (expectant) mothers in the United States. The research seeks to contribute to the conceptual frameworks and practical experience of behavioral model of health utitlization among immigrant Vietnamese ethnic immigrant pregnant women and mothers of babies and toddlers in navigating health during acculturation process in the United States. The limitations and future research suggestions are also discussed.

Khan et al. use human blood and a macaque model of tuberculosis (TB) to assess whether macrophage heterogeneity contributes to TB immunity. They demonstrate that human macrophages show unique patterns of gene expression that enable differential control of TB after infection.

BackgroundCo-use of tobacco and cannabis is highly prevalent among young US adults. Same-day co-use of tobacco and cannabis (ie, use of both substances on the same day) may increase the extent of use and negative health consequences among young adults. However, much remains unknown about same-day co-use of tobacco and cannabis, in part due to challenges in measuring this complex behavior. Nuanced understanding of tobacco and cannabis co-use in terms of specific products and intensity (ie, quantity of tobacco and cannabis use within a day) is critical to inform prevention and intervention efforts. ObjectiveWe used a daily-diary data collection method via smartphone to capture occurrence of tobacco and cannabis co-use within a day. We examined (1) whether the same route of administration would facilitate co-use of 2 substances on the same day and (2) whether participants would use more tobacco on a day when they use more cannabis. MethodsThis smartphone-based study collected 2891 daily assessments from 147 cigarette smokers (aged 18-26 years, n=76, 51.7% female) during 30 consecutive days. Daily assessments measured type (ie, cigarette, cigarillo, or e-cigarette) and intensity (ie, number of cigarettes or cigarillos smoked or number of times vaping e-cigarettes per day) of tobacco use and type (ie, combustible, vaporized, or edible) and intensity (ie, number of times used per day) of cannabis use. We estimated multilevel models to examine day-level associations between types of cannabis use and each type of tobacco use, as well as day-level associations between intensities of using cannabis and tobacco. All models controlled for demographic covariates, day-level alcohol use, and time effects (ie, study day and weekend vs weekday). ResultsSame-day co-use was reported in 989 of the total 2891 daily assessments (34.2%). Co-use of cigarettes and combustible cannabis (885 of the 2891 daily assessments; 30.6%) was most commonly reported. Participants had higher odds of using cigarettes (adjusted odds ratio [AOR] 1.92, 95% CI 1.31-2.81) and cigarillos (AOR 244.29, 95% CI 35.51-1680.62) on days when they used combustible cannabis. Notably, participants had higher odds of using e-cigarettes on days when they used vaporized cannabis (AOR 23.21, 95% CI 8.66-62.24). Participants reported a greater intensity of using cigarettes (AOR 1.35, 95% CI 1.23-1.48), cigarillos (AOR 2.04, 95% CI 1.70-2.46), and e-cigarettes (AOR 1.48, 95% CI 1.16-1.88) on days when they used more cannabis. ConclusionsTypes and intensities of tobacco and cannabis use within a day among young adult smokers were positively correlated, including co-use of vaporized products. Prevention and intervention efforts should address co-use and pay attention to all forms of use and timeframes of co-use (eg, within a day or at the same time), including co-use of e-cigarettes and vaporized cannabis, to reduce negative health outcomes.

BackgroundLittle is known about whether people who use both tobacco and cannabis (co-use) are more or less likely to have mental health disorders than single substance users or non-users. We aimed to examine associations between use of tobacco and/or cannabis with anxiety and depression.MethodsWe analyzed data from the COVID-19 Citizen Science Study, a digital cohort study, collected via online surveys during 2020-2022 from a convenience sample of 53,843 US adults (≥ 18 years old) nationwide. Past 30-day use of tobacco and cannabis was self-reported at baseline and categorized into four exclusive patterns: tobacco-only use, cannabis-only use, co-use of both substances, and non-use. Anxiety and depression were repeatedly measured in monthly surveys. To account for multiple assessments of mental health outcomes within a participant, we used Generalized Estimating Equations to examine associations between the patterns of tobacco and cannabis use with each outcome.ResultsIn the total sample (mean age 51.0 years old, 67.9% female), 4.9% reported tobacco-only use, 6.9% cannabis-only use, 1.6% co-use, and 86.6% non-use. Proportions of reporting anxiety and depression were highest for the co-use group (26.5% and 28.3%, respectively) and lowest for the non-use group (10.6% and 11.2%, respectively). Compared to non-use, the adjusted odds of mental health disorders were highest for co-use (Anxiety: OR = 1.89, 95%CI = 1.64-2.18; Depression: OR = 1.77, 95%CI = 1.46-2.16), followed by cannabis-only use, and tobacco-only use. Compared to tobacco-only use, co-use (OR = 1.35, 95%CI = 1.08-1.69) and cannabis-only use (OR = 1.17, 95%CI = 1.00-1.37) were associated with higher adjusted odds for anxiety, but not for depression. Daily use (vs. non-daily use) of cigarettes, e-cigarettes, and cannabis were associated with higher adjusted odds for anxiety and depression.ConclusionsUse of tobacco and/or cannabis, particularly co-use of both substances, were associated with poor mental health. Integrating mental health support with tobacco and cannabis cessation may address this co-morbidity.

Palte et al provide cryo-EM structures of five potent and inhibitory monoclonal antibodies bound to human Arginase 1, a T-cell modulating metalloenzyme and a cancer drug target. They provide structural insights that will aid in the evaluation of these antibodies as therapeutic inhibitors of arginasemediated T-cell suppression.

Rationale: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. Measurements and Main Results: Among 2,255 participants with 6,978 plasma samples, pyrazinamide displayed sevenfold exposure variability (151-1,053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in therapeutic windows of 231-355 mg · h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1,000 mg would have permitted an additional 13.1% (n = 96) of participants allocated to the control and 9.2% (n = 70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared with the current weight-banded dosing. Conclusions: Flat dosing of pyrazinamide at 1,000 mg/d would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registered with www.clinicaltrials.gov (NCT02410772).

Background: Endovascular aortic repair is the common approach for abdominal aortic aneurysms, but endoleaks remain a significant problem with long-term success. Endoanchors have been found to reduce the incidence of type 1A endoleaks and can treat intraoperative type 1a endoleaks. However, little is known about the optimal number and position of endoanchors to achieve the best outcome. Methods: Using image segmentation and a computational model derived from a reconstructed native patient abdominal aortic aneurysm geometry, the stability of the proximal seal zone was examined through finite element analysis in Abaqus (Dassault Systèmes, Providence, RI). The biomechanical parameter of contact area was compared for varying numbers (0, 2, 4, 8) and positions (proximal, medial, distal) of endoanchors under different adhesion strengths and physiologic pressure conditions. Results: In every simulation, an increase in adhesion strength is associated with maintenance of proximal seal. For biologically plausible adhesion strengths, under conditions of normal blood pressure (120 mm Hg), the addition of any number of endoanchors increases the stability of the endograft-wall interface at the proximal seal zone by approximately 10% compared with no endoanchors. At hypertensive pressures (200 mm Hg), endoanchors increase the stability of the interface by 20% to 60% compared with no endoanchors. The positioning of endoanchors within the proximal seal zone has a greater effect at hypertensive pressures, with proximal positioning increasing stability by 15% compared with medial and distal positioning and 30% compared with no endoanchors. Conclusions: Endoanchors improve fixation within the proximal seal zone particularly under conditions of high peak systolic pressure. Seal zone stabilization provides a mechanism through which endoanchor addition may translate into lower rates of type 1a endoleaks for patients. : Clinical Relevance: Endovascular aortic repairs are commonly used to treat abdominal aortic aneurysms. Type 1a endoleaks threaten the long-term durability of repairs. Endoanchors have been found to reduce the incidence of this complication. Herein, we examine parameters surrounding optimal endoanchor number and positioning to reduce endovascular aortic repair failure. The computational modeling allowed for testing of endoanchors in varied adhesion strength between the endograft and the aorta, as well as hemodynamic conditions to mimic normotension vs hypertension. The results of the finite element analysis suggest that the addition of any number of endoanchors in the proximal seal zone is beneficial, especially with hypertensive loading.

This paper studies the bidding strategy of a Virtual Power Plant (VPP) in a market of energy and regulation service. The operation of distributed energy resources (DER) and battery energy storage inside the VPP is analyzed. A bidding strategy of the VPP including the spinning reserve contract and day-ahead offering/bidding contract is investigated. A two-stage robust optimization model is proposed to determine the VPP’s purchasing/sell power in each contract to maximize the VPP’s profit. The uncertainty in the DER and demand is considered in the optimization framework. The proposed model is applied to a small VPP including the photovoltaic (PV) system, battery energy storage (BESS) equipped in a customer. Keywords: Electricity market, Energy storage, Robust optimization, Spinning reserve, Virtual Power Plant

Cannabis vaping may increase susceptibility to COVID-19 infection and related outcomes; however, little is known about the impact of the pandemic on cannabis vaping among US young populations. This study examined self-reported changes in cannabis vaping since the pandemic and factors associated with changes. A national, cross-sectional survey was conducted among 4,351 US adolescents and young adults (13–24 years old) in May 2020. Of those, 1,553 participants who reported ever vaping cannabis were included in the analytic sample. Binary outcome was self-reported increase in cannabis vaping (more hours/times of vaping in a day) vs. no change/quitting/reducing/switching. Weighted logistic regression examined associations between independent variables (i.e., risk perceptions of vaping, cannabis dependence, and stress/anxiety) and the outcome, controlling for sociodemographic factors. Overall, 6.8% reported increasing cannabis vaping since the pandemic, 37.0% quitting or reducing vaping in general, and 42.3% no change. Participants were more likely to report increased cannabis vaping if they perceived “Vaping is safer than smoking cigarettes” (Adjusted Odds Ratio [AOR] = 3.66; 95%CI = 1.43–9.38), reported more dependence on cannabis vaping (AOR = 1.59; 95%CI = 1.11–2.27), and were female (AOR = 2.80; 95%CI = 1.23–6.36). Those perceiving “Vaping cannabis can cause lung injuries” were less likely to increase cannabis vaping (AOR = 0.37; 95%CI = 0.18–0.76). Findings indicate that adolescent and young adult ever-cannabis vapers were more likely to report decreasing vaping generally than increasing cannabis vaping and most did not change use during the early pandemic. Educational campaigns should address potential health risks of cannabis vaping and focus on lung health to reduce use among young people during and following the pandemic.

Background Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.Methods A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs’ referral.Results In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan.Conclusions Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

The pyridinedicarboxylate-Tb(III) complexes, TbPDC and Tb(PDC)3, as luminescent probes for ATP monitoring have been conveniently prepared and characterized by FT-IR, 1H-NMR, ESI-MS, UV-Vis, excitation, and emission spectroscopy. Interestingly, these two Tb(III) complexes were quenched by ATP by a similar mechanism via π-π stacking interaction between the chelating ligand and adenine moiety. The ability of luminescent probes applied for the determination of ATP in aqueous solution has been investigated. The dynamic ranges for the quantification of ATP are within 10−90 μM and 10−100 μM with detection limits of 7.62 and 11.20 μM for TbPDC and Tb(PDC)3, respectively. The results demonstrated that these luminescent probes would be a potential candidate assay for ATP monitoring in hygiene assessment.

The New Zealand Certificate in Early Childhood Education and Care Level 4 programme was designed and developed in the context of a Level 4 early childhood education qualification becoming a requirement for educators in home-based sector, and the Open Polytechnic transformation. The programme is delivered fully online. This paper is to share our stories of designing and developing the programme. The stories focus on pedagogy that empowers learners in an online flexible distance learning environment, our innovative of team work, and initial feedback from stakeholders. The pedagogy is underpinned by the integration of sociocultural and constructivist theories with information communication technology (ICT), specified by the CSI Model (The Pedagogic Model of Integrating Constructivist and Sociocultural Learning Principles with Information Communication Technology), the key educational design principles and the assessment approach. Based on the pedagogy, the programme was created in two phases: Design and development. The work of the first phase was on designing at a programme level while the work of the second phase was on developing the three courses of the programme. With the pedagogy and innovative team work, initial feedback from stakeholders was very positive. It is recommended that feedback from stakeholders is formally collected later this year and in the new year.

Background Species occurrence records are very important in the biodiversity domain. While several available corpora contain only annotations of species names or habitats and geographical locations, there is no consolidated corpus that covers all types of entities necessary for extracting species occurrence from biodiversity literature. In order to alleviate this issue, we have constructed the COPIOUS corpus—a gold standard corpus that covers a wide range of biodiversity entities. Results Two annotators manually annotated the corpus with five categories of entities, i.e. taxon names, geographical locations, habitats, temporal expressions and person names. The overall inter-annotator agreement on 200 doubly-annotated documents is approximately 81.86% F-score. Amongst the five categories, the agreement on habitat entities was the lowest, indicating that this type of entity is complex. The COPIOUS corpus consists of 668 documents downloaded from the Biodiversity Heritage Library with over 26K sentences and more than 28K entities. Named entity recognisers trained on the corpus could achieve an F-score of 74.58%. Moreover, in recognising taxon names, our model performed better than two available tools in the biodiversity domain, namely the SPECIES tagger and the Global Name Recognition and Discovery. More than 1,600 binary relations of Taxon-Habitat, Taxon-Person, Taxon-Geographical locations and Taxon-Temporal expressions were identified by applying a pattern-based relation extraction system to the gold standard. Based on the extracted relations, we can produce a knowledge repository of species occurrences. Conclusion The paper describes in detail the construction of a gold standard named entity corpus for the biodiversity domain. An investigation of the performance of named entity recognition (NER) tools trained on the gold standard revealed that the corpus is sufficiently reliable and sizeable for both training and evaluation purposes. The corpus can be further used for relation extraction to locate species occurrences in literature—a useful task for monitoring species distribution and preserving the biodiversity.

Tuberculosis (TB) remains a leading cause of death from an infectious disease worldwide, partly due to a lack of effective strategies to screen and triage individuals with potential TB. Whole blood RNA signatures have been tested as biomarkers for TB, but have failed to meet the World Health Organizations (WHO) optimal target product profiles (TPP). Here, we use RNA sequencing and machine-learning to investigate the utility of plasma cell-free RNA (cfRNA) as a host-response biomarker for TB in cohorts from Uganda, Vietnam and Philippines. We report a 6-gene cfRNA signature, which differentiates TB-positive and TB-negative individuals with AUC = 0.95, 0.92, and 0.95 in test, training and validation, respectively. This signature meets WHO TPPs (sensitivity: 97.1% [95% CI: 80.9-100%], specificity: 85.2% [95% CI: 72.4-100%]) regardless of geographic location, sample collection method and HIV status. Overall, our results identify plasma cfRNA as a promising host response biomarker to diagnose TB.

With the increasing share of variable and limitedly predictable renewable energy in power systems worldwide, ensuring reserve capacity to maintain the balance of supply and demand becomes more important. On the other hand, the development of the virtual power plant model (VPP) allows renewable sources and energy storage to participate in reserve service. This paper addresses the optimal reserve bidding strategy problem of a VPP comprising of renewable energy resources (RESs), energy storage systems (ESSs), and several customers. The VPP participates in balance capacity (BC), day-ahead (DA), and intra-day (ID) markets. The scheduling problem is formulated as a two-stage chance-constrained optimization model taking the uncertainty of RESs production, load consumption, and probability of reserve activation into account. The response of VPP after its reserve capacity is called and generated is also considered to increase the operational flexibility of VPP. The proposed model is implemented on a test VPP system, and the effects of RESs sizing, ESSs sizing, and the probability of reserve activation are analyzed. Results indicate that the proposed model can perform well under real-world conditions.

Abstract Background Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method. Results On the basis of three existing phylogenetic inference algorithms, we built an integrated pipeline for inferring the evolutionary history of a given gene family; this pipeline can model gene sequence evolution, gene duplication-loss, gene transfer and multispecies coalescent processes. As a case study, we applied this pipeline to the STIMATE (TMEM110) gene family, which has recently been reported to play an important role in store-operated Ca2+ entry (SOCE) mediated by ORAI and STIM proteins. We inferred their phylogenetic trees in 69 sequenced chordate genomes. Conclusions By integrating three tree reconstruction algorithms with diverse evolutionary models, a pipeline for inferring the evolutionary history of a gene family was developed, and its application was demonstrated.

This paper presents a case study of a teacher’s experience in implementing an inquiry approach to his teaching over a period of two years with two different classes. His focus was on using a range of information technologies to support student inquiry learning. The study demonstrates the need to consider the characteristics of students when implementing an inquiry approach, and also the influence of the teachers level of understanding and related confidence in such an approach. The case also indicated that a range of technologies can be effective in supporting student inquiry learning.

Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term ‘developability’ encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties include the tendency for self-interaction and aggregation, thermal stability, colloidal stability, and optimization of their properties through sequence engineering. Selection of the best antibody molecule based on biological function, efficacy, safety, and developability allows for a streamlined and successful CMC phase. An efficient and practical high-throughput developability workflow (100 s-1,000 s of molecules) implemented during early antibody generation and screening is crucial to select the best lead candidates. This involves careful assessment of critical developability parameters, combined with binding affinity and biological properties evaluation using small amounts of purified material (

Objective. Ascorbic acid (AA) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative, pluripotency, and differentiation attributes of gingival mesenchymal stem/progenitor cells (G-MSCs). The current study’s objective was to explore and compare for the first time the impact of the major inflammatory cytokines (IL-1β/TNF-α/IFN-γ), AA, or their combination on multipotency/pluripotency, proliferative, and differentiation characteristics of G-MSCs. Design. Human G-MSCs (n=5) were isolated and cultured in basic medium (control group), in basic medium with major inflammatory cytokines; 1 ng/ml IL-1β, 10 ng/ml TNF-α, and 100 ng/ml IFN-γ (inflammatory group), in basic medium with 250 μmol/l AA (AA group) and in inflammatory medium supplemented by AA (inflammatory/AA group). All media were renewed three times per week. In stimulated G-MSCs intracellular β-catenin at 1 hour, pluripotency gene expression at 1, 3, and 5 days, as well as colony-forming units (CFUs) ability and cellular proliferation over 14 days were examined. Following a five-days stimulation in the designated groups, multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression. Results. β-Catenin significantly decreased intracellularly in all experimental groups (p=0.002, Friedman). AA group exhibited significantly higher cellular counts on days 3, 6, 7, and 13 (p

BackgroundNon-sputum-based triage tests for tuberculosis are a priority for ending tuberculosis. We aimed to evaluate the diagnostic accuracy of the late-prototype Xpert MTB Host Response (Xpert HR) blood-based assay.MethodsWe conducted a prospective diagnostic accuracy study among outpatients with presumed tuberculosis in outpatient clinics in Viet Nam, India, the Philippines, Uganda, and South Africa. Eligible participants were aged 18 years or older and reported cough lasting at least 2 weeks. We excluded those receiving tuberculosis treatment in the preceding 12 months and those who were unwilling to consent. Xpert HR was performed on capillary or venous blood. Reference standard testing included sputum Xpert MTB/RIF Ultra and mycobacterial culture. We performed receiver operating characteristic (ROC) analysis to identify the optimal cutoff value for the Xpert HR to achieve the target sensitivity of 90% or more while maximising specificity, then calculated diagnostic accuracy using this cutoff value. This study was prospectively registered with ClinicalTrials.gov, NCT04923958.FindingsBetween July 13, 2021, and Aug 15, 2022, 2046 adults with at least 2 weeks of cough were identified, of whom 1499 adults (686 [45·8%] females and 813 [54·2%] males) had valid Xpert HR and reference standard results. 329 (21·9%) had microbiologically confirmed tuberculosis. Xpert HR had an area under the ROC curve of 0·89 (95% CI 0·86-0·91). The optimal cutoff value was less than or equal to -1·25, giving a sensitivity of 90·3% (95% CI 86·5-93·3; 297 of 329) and a specificity of 62·6% (95% CI 59·7-65·3; 732 of 1170). Sensitivity was similar across countries, by sex, and by subgroups, although specificity was lower in people living with HIV (45·1%, 95% CI 37·8-52·6) than in those not living with HIV (65·9%, 62·8-68·8; difference of 20·8%, 95% CI 13·0-28·6; p

BACKGROUND:Although QuantiFERON-TB Gold Plus (QFT-Plus), a new interferon-gamma release assay, has shown good performance in adults, little data is available in children. METHODS:De-identified data from TB-suspected patients age

To improve tuberculosis (TB) care among individuals attending a private tertiary care hospital in Vietnam, an innovative private sector engagement model was implemented from June to December 2018. This included: (i) Active facility-based screening of all adults for TB symptoms (and chest x-ray (CXR) for those with symptoms) by trained and incentivized providers, with on-site diagnostic testing or transport of sputum samples, (ii) a mobile application to reduce dropout in the care cascade and (iii) enhanced follow-up care by community health workers. We conducted a cohort study using project and routine surveillance data for evaluation. Among 52,078 attendees, 368 (0.7%) had symptoms suggestive of TB and abnormalities on CXR. Among them, 299 (81%) were tested and 103 (34.4%) were diagnosed with TB. In addition, 195 individuals with normal CXR were indicated for TB testing by attending clinicians, of whom, seven were diagnosed with TB. Of the 110 TB patients diagnosed, 104 (95%) were initiated on treatment and 97 (93%) had a successful treatment outcome. Given the success of this model, the National TB Programme is considering to scale it up nationwide after undertaking a detailed cost-effectiveness analysis.

Nowadays, the hybrid wind–diesel system is widely used on small islands. However, the operation of these systems faces a major challenge in frequency control due to their small inertia. Furthermore, it is also difficult to maintain the power balance when both wind power and load are uncertain. To solve these problems, energy storage systems (ESS) are usually installed. This paper demonstrates the effectiveness of using ESS to provide Fast Frequency Response (FFR) to ensure that the frequency criteria are met after the sudden loss of a generator. An optimal day-ahead scheduling problem is implemented to simultaneously minimize the operating cost of the system, take full advantage of the available wind power, and ensure that the ESS has enough energy to provide FFR when the wind power and demand are uncertain. The optimization problem is formulated in terms of two-stage chance-constrained programming, and solved using a Modified Sample Average Approximation (MSAA) algorithm—a combination of the traditional Sample Average Approximation (SAA) algorithm and the k-means approach. The proposed method is tested with a realistic islanded power system, and the effects of the ESS size and its response time is analyzed. Results indicate that the proposed model should perform well under real-world conditions.

We investigate factors from firm side that determine their financing pattern for new investment projects and their decision to choose formal, informal credit, or both. For financing pattern of new investment project, we use Random-effect model while Unordered-Multinomial Logistic is used to estimate probability of choosing any of four choices to access to finance, say, formal credit, informal credit, both of them, or none of them. Our analysis is based on a panel of around 2200 small and medium sized enterprises with 7900 observations extracted from the “Survey of small and medium scale manufacturing enterprises in Vietnam” in 2005, 2007, and 2009.

Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB). Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved. Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. Measurements and Main Results: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 wk). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure. Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.

To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people most affected by TB - including those who have increased exposure to TB, limited access to services, and/or are at increased risk for TB - into new tools and strategies to improve screening and diagnosis. This perspective emphasizes the importance of preference research among people most affected by TB, provides an overview of qualitative preference exploration and quantitative preference elicitation research methods, and outlines how preferences can be applied to improve the acceptability, accessibility, and appropriateness of TB screening and testing services via four key opportunities. These include the following: (1) Defining the most preferred features of novel screening, triage, and diagnostic tools, (2) exploring and prioritizing setting-specific barriers and facilitators to screening and testing, (3) understanding what features of community- and facility-based strategies for improving TB detection and treatment are most valued, and (4) identifying the most relevant and resonant communication strategies to increase individual- and community-level awareness and demand. Preference research studies and translation of their findings into policy/guidance and operationalization have enormous potential to close the existing gaps in detection in high burden settings by enhancing the people-centeredness and reach of screening and diagnostic services to people most affected by TB who are currently being missed and left behind.