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IntroductionBluetongue (BT), caused by bluetongue virus (BTV), is an important arthropod-borne livestock disease listed by the World Organization for Animal Health. Live-attenuated and inactivated vaccines have permitted to control BT but they do not simultaneously protect against the myriad of BTV serotypes. Recently, we identified the highly conserved BTV nonstructural protein NS1 and the N-terminal region of NS2 as antigens capable of conferring multiserotype protection against BTV. MethodsHere, we designed Modified Vaccinia Ankara (MVA) viral vectors that expressed BTV-4 proteins VP2 or VP7 along with NS1 and NS2-Nt as well as MVAs that expressed proteins VP2, VP7 or NS1 and NS2-Nt. ResultsImmunization of IFNAR(-/-) mice with two doses of MVA-NS1-2A-NS2-Nt protected mice from BTV-4M infection by the induction of an antigen-specific T cell immune response. Despite rMVA expressing VP7 alone were not protective in the IFNAR(-/-) mouse model, inclusion of VP7 in the vaccine formulation amplified the cell-mediated response induced by NS1 and NS2-Nt. Expression of VP2 elicited protective non-cross-reactive neutralizing antibodies (nAbs) in immunized animals and improved the protection observed in the MVA-NS1-2A-NS2-Nt immunized mice when these three BTV antigens were co-expressed. Moreover, vaccines candidates co-expressing VP2 or VP7 along with NS1 and NS2-Nt provided multiserotype protection. We assessed protective efficacy of both vaccine candidates in sheep against virulent challenge with BTV-4M.DiscussionImmunization with MVA-VP7-NS1-2A-NS2-Nt partially dumped viral replication and clinical disease whereas administration of MVA-VP2-NS1-2A-NS2-Nt promoted a complete protection, preventing viraemia and the pathology produced by BTV infection.

Summary: The Aedes aegypti midgut is crucial for blood digestion, nutrition, reproduction, and pathogen interaction. Using single-cell RNA sequencing, we explored virus infection and transcriptomic changes at the cellular level. We identified 12 distinct cell clusters in the Ae. aegypti midgut post-Zika virus infection, including intestinal stem cells, enteroblasts, enteroendocrine cells (EE), and enterocytes (ECs). The virus was found mainly in specific subsets of ECs and EE. Infection altered transcriptional profiles related to metabolism, signaling, and immune responses. Functional studies highlighted three significantly differentially expressed genes in infected cells. Notably, silencing apolipophorin III reduced virus RNA copy number in the midgut, emphasizing the role of specific genes in viral infection. These findings enhance our understanding of mosquito midgut cell processes during Zika virus infection and suggest potential targets for vector control.

La hepatitis autoinmune (HAI) es una enfermedad inflamatoria inmunomediada la cual requiere para su diagnóstico la integración de anomalías histológicas, hallazgos de laboratorio característicos, positividad de autoanticuerpos y exclusión de otras enfermedades hepáticas. Se presenta el caso de una paciente femenina de 28 años con un cuadro de ictericia generalizada de una semana de evolución asociado a dolor abdominal difuso e intermitente. Las pruebas hepáticas revelaron lesión hepatocelular (factor R= 17,6) con transaminasemia grave (aspartato-aminotransferasa [AST]: 1,502 UI/L, alanina-aminotransferasa [ALT]: 2,029 UI/L) e hiperbilirrubinemia conjugada (bilirrubina sérica total: 10,9 mg/dL, bilirrubina directa: 8,50 mg/dL). Las pruebas serológicas para virus hepatotropos fueron negativas, así como los autoanticuerpos para hepatitis autoinmune. La biopsia hepática percutánea reveló hallazgos compatibles de hepatitis autoinmune. Se calculó el puntaje revisado del Grupo Internacional de Hepatitis Autoinmune (IAIHG) de 1999 pretratamiento, en el que se obtuvo un puntaje de 16, por lo que se diagnosticó como HAI grave definitiva. La paciente fue manejada con esteroides orales y se obtuvo una mejoría clínica y bioquímica, por lo que fue egresada a los siete días de hospitalización, sin eventualidades. Mantener un alto índice de sospecha de HAI, a pesar de la negatividad inicial de los autoanticuerpos, y complementar el abordaje diagnóstico con biopsia hepática percutánea permite el diagnóstico y tratamiento oportuno de este grupo de pacientes, de modo que se previene la progresión a cirrosis avanzada y sus complicaciones.

ABSTRACTBluetongue virus (BTV) is the causative agent of the important livestock disease bluetongue (BT), which is transmitted via Culicoides bites. BT causes severe economic losses associated with its considerable impact on health and trade of animals. By reverse genetics, we have designed and rescued reporter-expressing recombinant (r)BTV expressing NanoLuc luciferase (NLuc) or Venus fluorescent protein. To generate these viruses, we custom synthesized a modified viral segment 5 encoding NS1 protein with the reporter genes located downstream and linked by the Porcine teschovirus-1 (PTV-1) 2A autoproteolytic cleavage site. Therefore, fluorescent signal or luciferase activity is only detected after virus replication and expression of non-structural proteins. Fluorescence or luminescence signals were detected in cells infected with rBTV/Venus or rBTV/NLuc, respectively. Moreover, the marking of NS2 protein confirmed that reporter genes were only expressed in BTV-infected cells. Growth kinetics of rBTV/NLuc and rBTV/Venus in Vero cells showed replication rates similar to those of wild-type and rBTV. Infectivity studies of these recombinant viruses in IFNAR(−/−) mice showed a higher lethal dose for rBTV/NLuc and rBTV/Venus than for rBTV indicating that viruses expressing the reporter genes are attenuated in vivo. Interestingly, luciferase activity was detected in the plasma of viraemic mice infected with rBTV/NLuc. Furthermore, luciferase activity quantitatively correlated with RNAemia levels of infected mice throughout the infection. In addition, we have investigated the in vivo replication and dissemination of BTV in IFNAR (−/−) mice using BTV/NLuc and non-invasive in vivo imaging systems.IMPORTANCEThe use of replication-competent viruses that encode a traceable fluorescent or luciferase reporter protein has significantly contributed to the in vitro and in vivo study of viral infections and the development of novel therapeutic approaches. In this work, we have generated rBTV that express fluorescent or luminescence proteins to track BTV infection both in vitro and in vivo. Despite the availability of vaccines, BTV and other related orbivirus are still associated with a significant impact on animal health and have important economic consequences worldwide. Our studies may contribute to the advance in orbivirus research and pave the way for the rapid development of new treatments, including vaccines.

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices—Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)—based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients.

Introduction: Bluetongue (BT), caused by bluetongue virus (BTV), is an important arthropod-borne livestock disease listed by the World Organization for Animal Health. Live-attenuated and inactivated vaccines have permitted to control BT but they do not simultaneously protect against the myriad of BTV serotypes. Recently, we identified the highly conserved BTV nonstructural protein NS1 and the N-terminal region of NS2 as antigens capable of conferring multiserotype protection against BTV. Methods: Here, we designed Modified Vaccinia Ankara (MVA) viral vectors that expressed BTV-4 proteins VP2 or VP7 along with NS1 and NS2-Nt as well as MVAs that expressed proteins VP2, VP7 or NS1 and NS2-Nt. Results: Immunization of IFNAR(-/-) mice with two doses of MVA-NS1-2A-NS2- Nt protected mice from BTV-4M infection by the induction of an antigenspecific T cell immune response. Despite rMVA expressing VP7 alone were not protective in the IFNAR(-/-) mouse model, inclusion of VP7 in the vaccine formulation amplified the cell-mediated response induced by NS1 and NS2-Nt. Expression of VP2 elicited protective non-cross-reactive neutralizing antibodies (nAbs) in immunized animals and improved the protection observed in the MVANS1-2A-NS2-Nt immunized mice when these three BTV antigens were coexpressed. Moreover, vaccines candidates co-expressing VP2 or VP7 along with NS1 and NS2-Nt provided multiserotype protection. We assessed protective efficacy of both vaccine candidates in sheep against virulent challenge with BTV-4M. Discussion: Immunization with MVA-VP7-NS1-2A-NS2-Nt partially dumped viral replication and clinical disease whereas administration of MVA-VP2-NS1-2ANS2-Nt promoted a complete protection, preventing viraemia and the pathology produced by BTV infection. [ABSTRACT FROM AUTHOR]

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices—Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)—based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory disease that requires the integration of histological abnormalities, characteristic laboratory findings, autoantibody positivity, and exclusion of other liver diseases for diagnosis. The case of a 28-year-old female patient with a week-long history of generalized jaundice associated with diffuse and intermittent abdominal pain is presented. Liver tests revealed hepatocellular injury (R factor = 17.6) with severe transaminitis (aspartate aminotransferase [AST]: 1.502 IU/L, alanine aminotransferase [ALT]: 2.029 IU/L) and conjugated hyperbilirubinemia (total serum bilirubin: 10.9 mg/dL, direct bilirubin: 8.50 mg/dL). Serological tests for hepatotropic viruses were negative, as were autoantibodies for autoimmune hepatitis. Percutaneous liver biopsy revealed findings compatible with autoimmune hepatitis. The revised 1999 International Autoimmune Hepatitis Group (IAIHG) score was calculated pretreatment, resulting in a score of 16, thus diagnosing it as definitive severe AIH. The patient was treated with oral steroids, obtaining clinical and biochemical improvement, so she was discharged after seven days of hospitalization without incidents. Maintaining a high index of suspicion for AIH, despite the initial negativity of autoantibodies, and complementing the diagnostic approach with percutaneous liver biopsy allow the timely diagnosis and treatment of this group of patients, thus preventing progression to advanced cirrhosis and its complications. [ABSTRACT FROM AUTHOR]

Based on the “brakes” model of self-control, this study sought to analyze if psychopathy traits are related to Artificial Intelligence use, and whether low levels of self-control mediate this hypothetical relation. A cross-sectional study involving 1687 undergraduate students was conducted. Psychopathy traits predicted more use of artificial intelligence, as well as using these tools to do academic work instead of the student and to create fake content. However, self-control just mediated the link between psychopathy traits and the frequency of Artificial Intelligence use, suggesting that the misuse of Artificial Intelligence tools might be planned rather than impulsive behavior. [ABSTRACT FROM AUTHOR]

The Aedes aegypti mosquito plays a critical role in the transmission of viral diseases, including Zika virus, which poses significant public health challenges. Understanding the complex interactions between mosquitoes and viruses is paramount for the development of effective control strategies. In this study, we demonstrate that silencing the A. aegypti adiponectin receptor-like protein (AaARLP) results in a reduction of Zika virus infection. Transcriptomic analysis identified alterations in several trypsin genes and further revealed that AaARLP -knockdown mosquitoes had diminished trypsin activity. Moreover, silencing of selected trypsins resulted in a similar delay in Zika virus infection in mosquitoes, further highlighting the connection between the AaARLP and trypsin. Overall, our findings demonstrate that AaARLP signaling is important for Zika virus infection of A. aegypti ., Importance: Arboviruses pose a significant threat to public health, with mosquitoes, especially Aedes aegypti , being a major vector for their transmission. Gaining insight into the complex interaction between mosquitoes and viruses is essential to build successful control strategies. In this study, we identified a novel pathway connecting the A. aegypti adiponectin receptor-like protein and its association with trypsin, key enzymes involved in blood digestion. Furthermore, we demonstrated the significance of signaling via the adiponectin receptor-like protein in virus infection within the mosquito. Together, our discoveries illuminate mosquito metabolic pathways essential in viral infection.