Genetic Characterization of Two Novel Insect-Infecting Negative-Sense RNA Viruses Identified in a Leaf Beetle, Aulacophora indica.

Herbivorous insects harbor a variety of insect-specific viruses (ISVs) some of which are considered to be valuable biological agents for potential applications in biological defense and control strategies. Leaf beetles with chewing mouthparts are particularly known for their capacity to disrupt plant tissue while feeding, often creating openings that can act as entry points for plant pathogens. In this study, we have identified two new negative-sense RNA viruses infecting the leaf beetle Aulacophora indica, an important member of the Chrysomelidae family. These recently discovered viruses belong to the viral families Nyamiviridae and Chuviridae and have been preliminarily named Aulacophora indica nyami-like virus 1 (AINlV1) and Aulacophora indica chu-like virus 1 (AIClV1), respectively. The complete genomic sequences of these viruses were obtained using rapid amplification of cDNA ends (RACE) techniques. Detailed analysis of their genomic structures has confirmed their similarity to other members within their respective families. Furthermore, analysis of virus-derived small interfering RNA (vsiRNA) demonstrated a high abundance and typical vsiRNA pattern of AINlV1 and AIClV1, offering substantial evidence to support their classification as ISVs. This research enhances our understanding of viral diversity within insects.

Light-regulated soliton dynamics in liquid crystals.

Electrically powered solitons are particle-like field configurations in out-of-equilibrium nematics that have garnered significant interest. However, their random generation and lack of controllable motion have limited their application. Here, we present a reconfigurable optoelectronic approach capable of regulating the entire lifecycle of solitons by utilizing multi-strategy digital light projection to construct delicate patterning of virtual electrode. We demonstrate that optically actuated domains with diverse geometry enable the generation of multiple solitons and further allow in-situ formation of individual soliton by matching the light pattern to its dimension. Exquisitely engineered light intensity of patterns facilitates modulation of soliton velocity and transformation of propagating direction. The utilization of a light-guided channel enables the on-demand control of soliton trajectories along customized paths. Furthermore, dynamic light patterns that vary in space and time allow for collective motion such as migration, mimicking phototaxis in biological systems. This reconfigurable manipulation strategy, grounded in the photoconductive effect, proves highly versatile and effective in directing soliton dynamics, heralding the potential for their programmable control and offering a significant advantage in multitasking scenarios.

Highly Efficient Peroxymonosulfate Electroactivation on Co(OH)2 Nanoarray Electrode for Pefloxacin Degradation.

The activation of PMS to produce active species is an attractive technique for antibiotic degradation but is restricted to the low reaction kinetics and high costs. In this work, a cobalt-based catalyst was prepared by in situ electrodeposition to enhance the electrically activated PMS process for the degradation of antibiotics. Almost 100% of pefloxacin (PFX) was removed within 10 min by employing Co(OH)2 as the catalyst in the electrically activated peroxymonosulfate (PMS) process, and the reaction kinetic constant reached 0.52 min-1. The redox processes of Co2+ and Co3+ in Co(OH)2 catalysts were considered to be the main pathways for PMS activation, in which 1O2 was the main active species. Furthermore, this strategy could also achieve excellent degradation efficiency for other organic pollutants. This study provides an effective and low-cost strategy with no secondary pollution for pollutant degradation.

Targeted lipidomics-based study of radiation-induced metabolite profiles changes in plasma of total body irradiation cases.

PURPOSE: Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification. METHODS: Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed. RESULTS: In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model. CONCLUSION: This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship.

Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT. AIM OF THE STUDY: The purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests. MATERIALS AND METHODS: Network pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established. RESULTS: PPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging. CONCLUSION: The research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications.

Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

SLC38A2 promotes cell proliferation and invasion by promoting glutamine metabolism in adenomyosis.

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.

Molecular and biological characterization of a bunyavirus infecting the brown planthopper (Nilaparvata lugens).

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.

Dietary E. coli promotes age-dependent chemotaxis decline in C. elegans.

An animal's ability to sense odors declines during aging, and its olfactory drive is tuned by internal states such as satiety. However, whether internal states modulate an age-dependent decline in odor sensation is unknown. To address this issue, we utilized the nematode Caenorhabditis elegans and compared their chemotaxis abilities toward attractive odorants when aged under different dietary conditions. Feeding with the standard laboratory diet, Escherichia coli attenuated the chemotaxis ability toward diacetyl, isoamyl alcohol, and benzaldehyde when aged. On the other hand, feeding with either the lactic acid bacteria Lactobacillus reuteri or food deprivation selectively maintained the chemotaxis ability toward diacetyl. Our results suggest that ingestion of E. coli causes age-dependent chemotaxis decline. The changes in the chemotaxis behavior are attributed to the different expressions of diacetyl receptor odr-10, and the chemotaxis behavior of aged animals under food deprivation is shown to be dependent on daf-16. Our study demonstrates the molecular mechanism of how diet shapes the trajectory of age-dependent decline in chemosensory behaviors.

Low but highly geographically structured genomic diversity of East Asian Eurasian otters and its conservation implications.

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

SPOP negatively regulates mTORC1 activity by ubiquitinating Sec13.

The mammalian target of rapamycin complex1 (mTORC1) can response to amino acid to regulate metabolism and cell growth. GATOR2 act as important role in amino acid mediated mTORC1 signaling pathway by repressing GTPase activity (GAP) of GATOR1. However, it is still unclear how GATOR2 regulates mTORC1 signaling pathway. Here, we found that K63-ubiquitination of Sce13, one component of GATOR2, suppresses the mTORC1 activity by lessening the inter-interaction of GATOR2. Mechanistically, the ubiquitination of Sec13 was mediated by SPOP. Subsequently, the ubiquitination of Sec13 attenuated its interaction with the other component of GATOR2, thus suppressing the activity of mTORC1. Importantly, the deficiency of SPOP promoted the faster proliferation and migration of breast cancer cells, which was attenuated by knocking down of Sec13. Therefore, SPOP can act as a tumor suppressor gene by negatively regulating mTORC1 signaling pathway.

Electrical tuning of branched flow of light.

Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Endoscopic transgastric fenestration versus percutaneous drainage for management of (peri)pancreatic fluid collections adjacent to gastric wall (with video).

BACKGROUND: Percutaneous drainage (PCD) and endoscopic approaches have largely replaced surgical drainage as the initial approach for (peri) pancreatic fluid collections (PFC)s, while complications associated with endoscopic stent implantation are common. AIM: To introduce a novel endoscopic therapy named endoscopic transgastric fenestration (ETGF), which involves resection of tissue by endoscopic accessory between gastric and PFCs without stent implantation, and to evaluate its efficacy and safety compared with PCD for the management of PFCs adjacent to the gastric wall. METHODS: Patients diagnosed with PFCs adjacent to the gastric wall and who subsequently received ETGF or PCD were restrospectively enrolled. Indications for intervention were consistent with related guidelines. We analyzed patients baseline characteristics, technical and clinical success rate, recurrence and reintervention rate, procedure-related complications and adverse events. RESULTS: Seventy-two eligible patients were retrospectively identified (ETGF = 34, PCD = 38) from October 2017 to May 2021. Patients in the ETGF group had a significantly higher clinical success rate than those in the PCD group (97.1 vs 76.3%, P = 0.01). There were no statistically significant differences regarding recurrence, reintervention and incidence of complication between the two groups. While long-term catheter drainage was very common in the PCD group. CONCLUSION: Compared with PCD, ETGF has a higher clinical success rate in the management of PFCs adjacent to the gastric wall. ETGF is an alternative effective strategy for the treatment of PFCs adjacent to the gastric wall.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Clinical value of [18F]F-FDG PET/CT in patients with suspected paraneoplastic dermatoses: Diagnostic performance and impact on clinical management.

PURPOSE: We retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). MATERIALS AND METHODS: From an institutional PET/CT database (2014-2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. RESULTS: We analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. CONCLUSIONS: This study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients.

Assessment of the Cepheid 3-gene Host Response Fingerstick Blood Test (MTB-HR) on rapid diagnosis of tuberculosis.

ABSTRACTThe World Health Organization has identified high-priority target product profiles for new TB diagnostics which include rapid biomarker-based, non-sputum-based diagnostic testing, using an easily accessible sample. The Cepheid 3-gene Host Response Fingerstick Blood Prototype Test (MTB-HR) quantifies relative mRNA levels of a 3-gene signature (GBP5, DUSP3, and KLF2) from a whole-blood sample on the GeneXpert platform. The objective of the present study was to evaluate the performance of the MTB-HR to distinguish between active tuberculosis (ATB), latent Mycobacterium tuberculosis infection (LTBI), other pulmonary diseases, and healthy volunteers at a tertiary care centre. Among 653 participants enrolled in this study, 192 were diagnosed as having ATB, and the remaining 461 were classified as non-ATB, including 137 cases of LTBI, 224 cases of other pulmonary diseases, and 100 healthy volunteers. The corresponding AUCs of the MTB-HR in distinguishing untreated ATB from non-ATB, LTBI, other pulmonary diseases, and healthy volunteers were 0.814 (95% CI, 0.760-0.868, sensitivity 76.1%, specificity 71.6%), 0.739 (95% CI, 0.667-0.812, sensitivity 59.7%, specificity 78.1%), 0.825 (95% CI, 0.770-0.880, sensitivity 82.1%, specificity 65.6%), 0.892 (95% CI, 0.839-0.945, sensitivity 76.1%, specificity 88.0%), respectively. When only samples with TAT of less than 1 h were included, the AUC of the MTB-HR in distinguishing untreated ATB from non-ATB was largest, 0.920 (95% CI, 0.822-1.000, sensitivity 81.3%, specificity 87.7%). In conclusion, the MTB-HR assay shows potential as a rapid, blood-based screening and triage test for ATB, especially for untreated ATB, with the advantage of increased diagnostic yield since blood is more readily available.