Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.

Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors 1 and 2 That Disrupt Hypoxia-Response Signaling in Cancer Cells.

Hypoxia inducible factor (HIF) is a heterodimeric transcription factor composed of an oxygen-regulated α subunit and a constitutively expressed ß subunit that serves as the master regulator of the cellular response to low oxygen concentrations. The HIF transcription factor senses and responds to hypoxia by significantly altering transcription and reprogramming cells to enable adaptation to a hypoxic microenvironment. Given the central role played by HIF in the survival and growth of tumors in hypoxia, inhibition of this transcription factor serves as a potential therapeutic approach for treating a variety of cancers. Here, we report the identification, optimization, and characterization of a series of cyclic peptides that disrupt the function of HIF-1 and HIF-2 transcription factors by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1ß. These compounds are shown to bind to HIF-α and disrupt the protein-protein interaction between the α and ß subunits of the transcription factor, resulting in disruption of hypoxia-response signaling by our lead molecule in several cancer cell lines.

Novel Investigation of Higher Order Spectral Technologies for Fault Diagnosis of Motor-Based Rotating Machinery.

In the last decade, research centered around the fault diagnosis of rotating machinery using non-contact techniques has been significantly on the rise. For the first time worldwide, innovative techniques for the diagnosis of rotating machinery, based on electrical motors, including generic, nonlinear, higher-order cross-correlations of spectral moduli of the third and fourth order (CCSM3 and CCSM4, respectively), have been comprehensively validated by modeling and experiments. The existing higher-order cross-correlations of complex spectra are not sufficiently effective for the fault diagnosis of rotating machinery. The novel technology CCSM3 was comprehensively experimentally validated for induction motor bearing diagnosis via motor current signals. Experimental results, provided by the validated technology, confirmed high overall probabilities of correct diagnosis for bearings at early stages of damage development. The novel diagnosis technologies were compared with existing diagnosis technologies, based on triple and fourth cross-correlations of the complex spectra. The comprehensive validation and comparison of the novel cross-correlation technologies confirmed an important non-traditional novel outcome: the technologies based on cross-correlations of spectral moduli were more effective for damage diagnosis than the technologies based on cross-correlations of the complex spectra. Experimental and simulation validations confirmed a high probability of correct diagnosis via the CCSM at the early stage of fault development. The average total probability of incorrect diagnosis for the CCSM3 for all experimental results of 8 tested bearings, estimated via 6528 diagnostic features, was 1.475%. The effectiveness gains in the total probability of incorrect diagnosis for the CCSM3 in comparison with the CCCS3 were 26.8 for the experimental validation and 18.9 for the simulation validation. The effectiveness gains in the Fisher criterion for the CCSM3 in comparison with the CCCS3 were 50.7 for the simulation validation and 104.7 for the experimental validation.

Novel Fault Diagnosis of a Conveyor Belt Mis-Tracking via Motor Current Signature Analysis.

For the first time ever worldwide, this paper proposes, investigates, and validates, by multiple experiments, a new online automatic diagnostic technology for the belt mis-tracking of belt conveyor systems based on motor current signature analysis (MCSA). Three diagnostic technologies were investigated, experimentally evaluated, and compared for conveyor belt mis-tracking diagnosis. The proposed technologies are based on three higher-order spectral diagnostic features: bicoherence, tricoherence, and the cross-correlation of spectral moduli of order 3 (CCSM3). The investigation of the proposed technologies via comprehensive experiments has shown that technology based on the CCSM3 is highly effective for diagnosing a conveyor belt mis-tracking via MCSA.

Carbon Dot Therapeutic Platforms: Administration, Distribution, Metabolism, Excretion, Toxicity, and Therapeutic Potential.

Ultrasmall nanoparticles are often grouped under the broad umbrella term of "nanoparticles" when reported in the literature. However, for biomedical applications, their small sizes give them intimate interactions with biological species and endow them with unique functional physiochemical properties. Carbon quantum dots (CQDs) are an emerging class of ultrasmall nanoparticles which have demonstrated considerable biocompatibility and have been employed as potent theragnostic platforms. These particles find application for increasing drug solubility and targeting, along with facilitating the passage of drugs across impermeable membranes (i.e., blood brain barrier). Further functionality can be triggered by various environmental conditions or external stimuli (i.e., pH, temperature, near Infrared (NIR) light, ultrasound), and their intrinsic fluorescence is valuable for diagnostic applications. The focus of this review is to shed light on the therapeutic potential of CQDs and identify how they travel through the body, reach their site of action, administer therapeutic effect, and are excreted. Investigation into their toxicity and compatibility with larger nanoparticle carriers is also examined. The future of CQDs for theragnostic applications is promising due to their multifunctional attributes and documented biocompatibility. As nanomaterial platforms become more commonplace in clinical treatments, the commercialization of CQD therapeutics is anticipated.

Novel Diagnosis Technologies for a Lack of Oil Lubrication in Gearmotor Systems, Based on Motor Current Signature Analysis.

Due to the wide use of gearmotor systems in industry, many diagnostic techniques have been developed/employed to prevent their failures. An insufficient lubrication of gearboxes of these machines could shorten their life and lead to catastrophic failures and losses, making it important to ensure a required lubrication level. For the first time in worldwide terms, this paper proposed to diagnose a lack of gearbox oil lubrication using motor current signature analysis (MCSA). This study proposed, investigated, and experimentally validated two new technologies to diagnose a lack of lubrication of gear motor systems based on MCSA. Two new diagnostic features were extracted from the current signals of a three-phase induction motor. The effectiveness of the proposed technologies was evaluated for different gear lubrication levels and was compared for three phases of motor current signals and for a case of averaging the proposed diagnostic features over three phases. The results confirmed a high effectiveness of the proposed technologies for diagnosing a lack of oil lubrication in gearmotor systems. Other contributions were as follows: (i) it was shown for the first time in worldwide terms, that the motor current nonlinearity level increases with the reduction of the sgearbox oil level; (ii) novel experimental validations of the proposed two diagnostic technologies via comprehensive experimental trials (iii) novel experimental comparisons of the diagnosis effectiveness of the proposed two diagnostic technologies.

Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease-related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group.

INTRODUCTION: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. METHODS: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze-thawing. We measured amyloid beta (Aß)42 and 40 peptides with six assays, and Aß oligomerization-tendency (OAß), amyloid precursor protein (APP)699-711 , glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. RESULTS: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aß and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. DISCUSSION: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings.

Comparative Analysis of Antibody Titers against the Spike Protein of SARS-CoV-2 Variants in Infected Patient Cohorts and Diverse Vaccination Regimes.

The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection.

Remediation of groundwater contaminated with dye using carbon dots technology: Ecotoxicological and microbial community responses.

Groundwater pollution poses a serious threat to the main source of clean water globally. Nanoparticles have the potential for remediation of polluted aquifers; however, environmental safety concerns associated with in situ deployments of such technology include potential detrimental effects on microorganisms in terms of toxicity and functional disruptions. In this work, we evaluated a new and ecofriendly approach using carbon dots (CDs) as Fenton-like catalysts to catalyse the degradation of dye-containing groundwater samples. This investigation aimed at evaluating the efficacy of a novel remediation technology in terms of dye degradation and toxicity reduction while assessing its impacts on aquatic microorganisms. Uncontaminated Australian groundwater samples were spiked with methylene blue and incubated in the dark, at 18 °C, under slow agitation, using CDs at 0.5 mg mL-1 and H2O2 at 73.5 mM for 25 h. The dye degradation rate was determined as well as the toxicity of the treated solutions using the Microtox® bioassay. Further, to determine the changes in the groundwater microbial community, 16 S rRNA sequencing was used and evenness and diversity indices were analysed using Pielou's evenness and Simpson index, respectively. This study revealed that dye-containing groundwater were effectively treated by CDs showing a degradation rate of 78-82% and a significant 4-fold reduction in the toxicity. Characterisation of the groundwater microbiota revealed a predominance of at least 60% Proteobacteria phylum in all samples where diversity and evenness were maintained throughout the remediation process. The results showed that CDs could be an efficient approach to treat polluted groundwater and potentially have minimum impact on the environmental microbiome.

Long-term Impact of Gold and Platinum on Microbial Diversity in Australian Soils.

The effects of platinum (Pt) and gold (Au) and on the soil bacterial community was evaluated in four different Australian soil types (acidic Burn Grounds (BGR), organic matter-rich Fox Lane, high silt/metal Pinpinio (PPN), and alkali Minnipa (MNP) spiked with either Pt or Au at 1, 25, and 100 mg kg-1 using a next-generation sequencing approach (amplicon-based, MiSeq). Soil type and metal concentrations were observed to be key drivers of Pt and Au effects on soil microbial community structure. Different trends were therefore observed in the response of the bacterial community to Pt and Au amendments; however in each soil type, Pt and Au amendment caused a detectable shift in community structure that in most samples was positively correlated with increasing metal concentrations. New dominant groups were only observed in BGR and PPN soils at 100 mg kg-1 (Kazan-3B-28 and Verrucomicrobia groups (BGR, Pt) and Firmicutes and Caldithrix groups (PPN, Pt) and WS2 (BGR, Au). The effects of Pt on soil microbial diversity were largely adverse at 100 mg kg-1 and were pronounced in acidic, basic, and metal/silt-rich soils. However, this effect was concentration-related; Au appeared to be more toxic to soil bacterial communities than Pt at 25 mg kg-1 but Pt was more toxic at 100 mg kg-1. More bacterial groups such as those belonging to Burkholderiales/Burkholderiaceae, Alicyclobacillaceae, Rubrobacteraceae, Cytophagaceae, Oxalobacteraceae were selectively enriched by Pt compared to Au (Sphingomonadaceae and Rhodospirillaceae) amendments irrespective of soil type. The research outcomes have important implications in the management (remediation) of Pt- and Au-contaminated environments.

Qualitative Examination of Voting Empowerment and Participation Among People Living With Traumatic Brain Injury.

OBJECTIVE: To examine political participation after traumatic brain injury (TBI). DESIGN: Qualitative, participatory research via interviews and observations. Each participant was interviewed to discuss their experience of voting in 2007 or 2008. Data were coded using Grounded Theory to develop themes, metacodes, and theories. SETTING: Community. PARTICIPANTS: A total of 57 individuals with history of TBI and 28 family members (N=85). MAIN OUTCOME MEASURES: Not applicable. RESULTS: Four themes emerged from the data: (1) people with TBI have barriers to voting; (2) the voting process can be improved for people with TBI; (3) voting is the responsibility of members of society; and (4) voting is one way we have a voice in society. CONCLUSIONS: The data support the importance of voting as an American right regardless of the presence of disability. While persons with TBI report voting represents their freedom and voice, there may be barriers that can threaten or limit their voice.

Novel Prediction of Diagnosis Effectiveness for Adaptation of the Spectral Kurtosis Technology to Varying Operating Conditions.

In this paper, two novel consistency vectors are proposed, which when combined with appropriate machine learning algorithms, can be used to adapt the Spectral Kurtosis technology for optimum gearbox damage diagnosis in varying operating conditions. Much of the existing research in the field is limited to test apparatus run in constant and carefully controlled operating conditions, and the authors have previously publicised that the Spectral Kurtosis technology requires adaptation to achieve the highest possible probabilities of correct diagnosis when a gearbox is run in non-stationary conditions of speed and load. However, the authors' previous adaptation has been computationally heavy using a brute-force approach unsuited to online use, and therefore, created the requirement to develop these two newly proposed vectors and allow computationally lighter techniques more suited to online condition monitoring. The new vectors are demonstrated and experimentally validated on vibration data collected from a gearbox run in multiple combinations of operating conditions; for the first time, the two consistency vectors are used to predict diagnosis effectiveness, with the comparison and proof of relative gains between the traditional and novel techniques discussed. Consistency calculations are computationally light and thus, many combinations of Spectral Kurtosis technology parameters can be evaluated on a dataset in a very short time. This study shows that machine learning can predict the total probability of correct diagnosis from the consistency values and this can quickly provide pre-adaptation/prediction of optimum Spectral Kurtosis technology parameters for a dataset. The full adaptation and damage evaluation process, which is computationally heavier, can then be undertaken on a much lower number of combinations of Spectral Kurtosis resolution and threshold.

First Report of CRISPR/Cas9 Mediated DNA-Free Editing of 4CL and RVE7 Genes in Chickpea Protoplasts.

The current genome editing system Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR/Cas9) has already confirmed its proficiency, adaptability, and simplicity in several plant-based applications. Together with the availability of a vast amount of genome data and transcriptome data, CRISPR/Cas9 presents a massive opportunity for plant breeders and researchers. The successful delivery of ribonucleoproteins (RNPs), which are composed of Cas9 enzyme and a synthetically designed single guide RNA (sgRNA) and are used in combination with various transformation methods or lately available novel nanoparticle-based delivery approaches, allows targeted mutagenesis in plants species. Even though this editing technique is limitless, it has still not been employed in many plant species to date. Chickpea is the second most crucial winter grain crop cultivated worldwide; there are currently no reports on CRISPR/Cas9 gene editing in chickpea. Here, we selected the 4-coumarate ligase (4CL) and Reveille 7 (RVE7) genes, both associated with drought tolerance for CRISPR/Cas9 editing in chickpea protoplast. The 4CL represents a key enzyme involved in phenylpropanoid metabolism in the lignin biosynthesis pathway. It regulates the accumulation of lignin under stress conditions in several plants. The RVE7 is a MYB transcription factor which is part of regulating circadian rhythm in plants. The knockout of these selected genes in the chickpea protoplast using DNA-free CRISPR/Cas9 editing represents a novel approach for achieving targeted mutagenesis in chickpea. Results showed high-efficiency editing was achieved for RVE7 gene in vivo compared to the 4CL gene. This study will help unravel the role of these genes under drought stress and understand the complex drought stress mechanism pathways. This is the first study in chickpea protoplast utilizing CRISPR/Cas9 DNA free gene editing of drought tolerance associated genes.

The application of Marinobacter hydrocarbonoclasticus as a bioaugmentation agent for the enhanced treatment of non-sterile fish wastewater.

Wastewaters generated by fish processing are characterised by salt concentrations similar to or greater than that of seawater together with high nutrient concentrations (e.g. organic carbon and total nitrogen) due to the presence of blood, oil, and fish tissues. Fish processing wastewater entering rivers and oceans have become a key factor leading to the pollution of receiving waters; the adequate treatment of this wastewater is, therefore, crucial to a sustainable fish industry. The present study aimed to determine whether augmentation of fish wastewater with either Marinirhabdus sp., Marinobacter hydrocarbonoclasticus or a consortium of the two halobacteria, could successfully enhance the removal of both chemical oxygen demand (COD) and total nitrogen (TN) from fish wastewater. Following 9 days of incubation, the bioaugmentation treatment resulted in a significant reduction in COD, 88%, 91%, and 92% in fish wastewater augmented with either Marinirhabdus sp., Marinobacter hydrocarbonoclasticus respectively, or a consortium of the two halobacteria compared with the control (non-bioaugmented) treatment (77% removal). In tall bioaugmentation treatments (79-88%) TN removal was also significantly greater than the control treatment (57%). After 9 days of incubation, the COD and TN in bioaugmentation reached the European Union's (EU) wastewater discharge standard (Level B, COD < 120 mg L-1, TN < 70 mg L-1). The addition of monoculture was effective in enhancing the removal of COD, while co-culture significantly improved TN removal. Results of 16S rDNA sequence analysis investigating the survival of these introduced bacteria showed that only Marinobacter hydrocarbonoclasticus was detected at the end of the treatment, constituting 36% of the total bacterial population when added alone to the wastewater. This study confirms the effectiveness of bioaugmentation in removing COD and TN in saline fish wastewater. The ability of Marinobacter hydrocarbonclasticus to enhance the treatment and dominate the bacterial community suggests the commercial potential of this organism for bioaugmentation of aquaculture wastewater without the need for further bioaugmentation.

Dynamic Effect of Operational Regulation on the Mesophilic BioMethanation of Grape Marc.

Wine production annually generates an estimated 11 million metric tonnes of grape marc (GM) worldwide. The diversion of this organic waste away from landfill and towards its use in the generation of renewable energy has been investigated. This study aimed to evaluate the effectiveness of operational parameters relating to the treatment regime and inoculum source in the extraction of methane from GM under unmixed anaerobic conditions at 35 °C. The study entailed the recirculation of a previously acclimated sludge (120 days) as downstream inoculum, an increased loading volume (1.3 kg) and a low substrate-to-inoculum ratio (10:3 SIR). The results showed that an incorporation of accessible operational controls can effectively enhance cumulative methane yield (0.145 m3 CH4 kg-1 VS), corresponding to higher amounts of digestible organics converted. The calculated average volumetric methane productivity equalled 0.8802 L CH4 LWork-1 d-1 over 33.6 days whilst moderate pollutant removal (43.50% COD removal efficiency) was achieved. Molecular analyses identified Firmicutes and Bacteroidetes phyla as core organisms for hydrolytic and fermentative stages in trophic relationships with terminal electron acceptors from the methane-producing Methanosarcina genus. Economic projections established that the cost-effective operational enhancements were sustainable for valorisation from grape marc by existing wineries and distilleries.

Application of Co-Culture Technology to Enhance Protease Production by Two Halophilic Bacteria, Marinirhabdus sp. and Marinobacter hydrocarbonoclasticus.

Although axenic microbial cultures form the basis of many large successful industrial biotechnologies, the production of single commercial microbial strains for use in large environmental biotechnologies such as wastewater treatment has proved less successful. This study aimed to evaluate the potential of the co-culture of two halophilic bacteria, Marinirhabdus sp. and Marinobacter hydrocarbonoclasticus for enhanced protease activity. The co-culture was significantly more productive than monoculture (1.6-2.0 times more growth), with Marinobacter hydrocarbonoclasticus being predominant (64%). In terms of protease activity, enhanced total activity (1.8-2.4 times) was observed in the co-culture. Importantly, protease activity in the co-culture was found to remain active over a much broader range of environmental conditions (temperature 25 °C to 60 °C, pH 4-12, and 10-30% salinity, respectively). This study confirms that the co-culturing of halophilic bacteria represents an economical approach as it resulted in both increased biomass and protease production, the latter which showed activity over arange of environmental conditions.

The Impacts of Different Biological Treatments on the Transformation of Explosives Waste Contaminated Sludge.

The dinitrotoluene isomers 2,4 and 2,6-dinitrotoluene (DNT) represent highly toxic, mutagenic, and carcinogenic compounds used in explosive manufacturing and in commercial production of polyurethane foam. Bioremediation, the use of microbes to degrade residual DNT in industry wastewaters, represents a promising, low cost and environmentally friendly alternative technology to landfilling. In the present study, the effect of different bioremediation strategies on the degradation of DNT in a microcosm-based study was evaluated. Biostimulation of the indigenous microbial community with sulphur phosphate (2.3 g/kg sludge) enhanced DNT transformation (82% transformation, from 300 g/L at Day 0 to 55 g/L in week 6) compared to natural attenuation over the same period at 25 °C. The indigenous microbial activity was found to be capable of transforming the contaminant, with around 70% transformation of DNT occurring over the microcosm study. 16S rDNA sequence analysis revealed that while the original bacterial community was dominated by Gammaproteobacteria (30%), the addition of sulphur phosphate significantly increased the abundance of Betaproteobacteria by the end of the biostimulation treatment, with the bacterial community dominated by Burkholderia (46%) followed by Rhodanobacter, Acidovorax and Pseudomonas. In summary, the results suggest biostimulation as a treatment choice for the remediation of dinitrotoluenes and explosives waste.

AT-CuAAC Synthesis of Mechanically Interlocked Oligonucleotides.

We present a simple strategy for the synthesis of main chain oligonucleotide rotaxanes with precise control over the position of the macrocycle. The novel DNA-based rotaxanes were analyzed to assess the effect of the mechanical bond on their properties.

A lanthipeptide library used to identify a protein-protein interaction inhibitor.

In this article we describe the production and screening of a genetically encoded library of 106 lanthipeptides in Escherichia coli using the substrate-tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, which is a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle-budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing substantial structural diversity. Such libraries may be combined with any cell-based assay to identify lanthipeptides with new biological activities.

Cost-Effectiveness of Testing and Treatment for Hepatitis B Virus and Hepatitis C Virus Infections: An Analysis by Scenarios, Regions, and Income.

OBJECTIVES: Testing and treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are highly effective, high-impact interventions. This article aims to estimate the cost-effectiveness of scaling up these interventions by scenarios, regions, and income groups. METHODS: We modeled costs and impacts of hepatitis elimination in 67 low- and middle-income countries from 2016 to 2030. Costs included testing and treatment commodities, healthcare consultations, and future savings from cirrhosis and hepatocellular carcinomas averted. We modeled disease progression to estimate disability-adjusted life-years (DALYs) averted. We estimated incremental cost-effectiveness ratios (ICERs) by regions and World Bank income groups, according to 3 scenarios: flatline (status quo), progress (testing/treatment according to World Health Organization guidelines), and ambitious (elimination). RESULTS: Compared with no action, current levels of testing and treatment had an ICER of $807/DALY for HBV and -$62/DALY (cost-saving) for HCV. Scaling up to progress scenario, both interventions had ICERs less than the average gross domestic product/capita of countries (HBV: $532/DALY; HCV: $613/DALY). Scaling up from flatline to elimination led to higher ICERs across countries (HBV: $927/DALY; HCV: $2528/DALY, respectively) that remained lower than the average gross domestic product/capita. Sensitivity analysis indicated discount rates and commodity costs were main factors driving results. CONCLUSIONS: Scaling up testing and treatment for HBV and HCV infection as per World Health Organization guidelines is a cost-effective intervention. Elimination leads to a much larger impact though ICERs are higher. Price reduction strategies are needed to achieve elimination given the substantial budget impact at current commodity prices.