Search

Influenza is one of the leading causes of disease-related mortalities worldwide. Several strategies have been implemented during the past decades to hinder the replication cycle of influenza viruses, all of which have resulted in the emergence of resistant virus strains. The most recent example is baloxavir marboxil, where a single mutation in the active site of the target endonuclease domain of the RNA-dependent-RNA polymerase renders the recent FDA approved compound ∼1000-fold less effective. Raltegravir is a first-in-class HIV inhibitor that shows modest activity to the endonuclease. Here, we have used structure-guided approaches to create rationally designed derivative molecules that efficiently engage the endonuclease active site. The design strategy was driven by our previously published structures of endonuclease-substrate complexes, which allowed us to target functionally conserved residues and reduce the likelihood of resistance mutations. We succeeded in developing low nanomolar equipotent inhibitors of both wild-type and baloxavir-resistant endonuclease. We also developed macrocyclic versions of these inhibitors that engage the active site in the same manner as their 'open' counterparts but with reduced affinity. Structural analyses provide clear avenues for how to increase the affinity of these cyclic compounds.

Introduction: This study aims to evaluate parental acceptance of dental treatment with silver diamine fluoride (SDF) in children with cerebral palsy (CP). Methods: The present study is a case‐control study with 80 children in the age range of 6–11 years. Group I consisted of children diagnosed with CP and Group II consisted of children without any Special Health Care Needs and systemic conditions. Preoperative and postoperative behavior assessment was done using Frankl's behavior Rating Scale. 38 % SDF application was done in any one primary molar with occlusal dentinal caries. A well‐designed validated structured questionnaire with 10 questions was developed to assess the parental acceptance of dental treatment with SDF. The questionnaire comprised 10 close‐ended questions with subdivisions on socio‐demographic details, the reason for the previous and current dental visit, and acceptance of dental treatment with SDF. The data were analyzed using SPSS (version 26, IBM, Chicago, USA). Continuous variables were expressed as mean ± standard deviation (M ± SD). Categorical variables were expressed as frequency (n) and percentage (%). The chi‐square test was used for qualitative analysis. The level of significance was set at 5%. Results: The number of children showing positive behavior on Frankl's behavior Rating Scale increased from 55% to 70% after dental treatment with SDF and this difference was statistically significant in Group I (p‐value < 0.001). 87.5% of parents in Group I had accepted the discoloration caused after dental treatment with SDF compared to 80% in Group II. In Group I, 95% of parents agreed strongly, while in Group II, 82.5% agreed strongly that SDF can be done on un‐cooperative and special health care needs children. This difference in agreement seen between parents of Group I and Group II was found to be statistically significant (p‐value = 0.02). Also, the acceptance of SDF was found to be higher in parents who were educationally more qualified in Group I. This difference in the acceptance level of SDF seen based on the educational status of parents was statistically significant (p‐value < 0.001). Conclusion: Parental acceptance of SDF for dental treatment was higher in Group I (children with CP) as a greater number of parents accepted dental treatment despite discoloration with the modality being noninvasive and less time‐consuming. Improved behavior rating was observed among children in both groups after dental treatment with SDF. [ABSTRACT FROM AUTHOR]

In the current era, the environmental component of ESG is recognized as a major driver due to the pressing challenges posed by climate change, population growth, global warming, and shifting weather patterns. The environment must be considered a critical factor, and as evidenced by existing research, it is regarded as the dominant component within ESG. In this study, the ESG score is derived primarily from the environmental score. The increasing importance of the environmental, social, and governance (ESG) factors in financial markets, along with the growing need for sentiment analysis in sustainability, has necessitated the development of advanced sentiment analysis techniques. A predictive model has been introduced utilizing a nested sentiment analysis framework, which classifies sentiments towards eco-friendly and non-eco-friendly products, as well as positive and negative sentiments, using FinBERT. The model has been optimized with the AdamW optimizer, L2 regularization, and dropout to assess how sentiments related to these product types influence ESG metrics. The "black-box" nature of the model has been addressed through the application of explainable AI (XAI) to enhance its interpretability. The model demonstrated an accuracy of 91.76% in predicting ESG scores and 99% in sentiment classification. The integration of XAI improves the transparency of the model's predictions, making it a valuable tool for decision-making in making sustainable investments. This research is aligned with the United Nations' Sustainable Development Goals (SDG 12 and SDG 13), contributing to the promotion of sustainable practices and fostering improved market dynamics. [ABSTRACT FROM AUTHOR]

In constrained IoT networks, Stateless Address Autoconfiguration (SLAAC) utilizes the Duplicate Address Detection (DAD) protocol to ensure the uniqueness of IPv6 addresses. However, the DAD employed in SLAAC is susceptible to various security vulnerabilities, including issues related to confidentiality, conflicting addresses, and spoofing attacks. Malicious nodes can exploit these weaknesses to perform Denial of Service (DoS) attacks by consistently claiming a tentative address, joining with conflicting address, or disclosing assigned address. Existing measures against DAD attacks have limitations, e.g. high computation, communication overhead, energy consumption, and major protocol modification. To address these challenges, this paper presents an innovative Optimized DAD (O-DAD) that is robust, scalable, and compliant with standard specifications. In O-DAD, the uniqueness of tentative IPv6 addresses is ensured in a way that neither new nor existing nodes have knowledge of each other's exact assigned addresses. O-DAD also hampers the ability of malicious nodes to spoof new/existing nodes. Experimental results demonstrate that the proposed solution effectively mitigates these attacks and exhibits superior performance in terms of Address Success Ratio (ASR), computational complexity, overhead, and energy consumption. When compared to Secure, Improved, and Standard DAD, the proposed scheme reduces overhead and energy by approximately 6%, 8%, and 15%, respectively. [ABSTRACT FROM AUTHOR]

Summary: The fusion of drones with the Internet, termed the Internet of Drones (IoD), resembles the Internet of Things (IoT) paradigm. In IoD, drones necessitate unique identifiers similar to IPv6 addresses. This paper presents a novel approach for securing the duplicate address detection (DAD) process in the IoD environment. This paper focuses on addressing the security challenges posed by malicious drones in the DAD process. The proposed solution introduces a hidden DAD (H‐DAD) process, to mitigate attacks on the DAD process. In this scheme, drones transmit a transformed portion of their interface identifier (IID) while concealing the full IID, thus thwarting potential disruptions by malicious entities. We evaluated the effectiveness of the H‐DAD scheme through experimental analysis using Python with SimPy, comparing it with the Improved DAD, Secure DAD, and Standard DAD schemes. Our results demonstrate a notable improvement, with the Hidden DAD scheme achieving a 100% address success rate under attack. Moreover, it exhibits approximately 5% and 12% lower overhead and energy consumption, respectively, compared to the other schemes. [ABSTRACT FROM AUTHOR]