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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]

Background: Calcium channel blockers, including the recently developed cilnidipine, are widely used as first-line medications for treating newly diagnosed cases of primary essential hypertension. Cilnidipine has a unique advantage compared to amlodipine, another common calcium channel blocker. While amlodipine only targets L-type calcium channels, cilnidipine can target both L and N-type channels. This study aimed to compare the effectiveness and safety of these two medications in patients with essential hypertension. Methods: A total of n=80 cases of mild to moderate hypertension were randomly allocated to two groups. Group I n=40 received a daily dose of Amlodipine 5mg, whereas those in Group II n=40 received Cilnidipine 10mg once daily, 30 minutes after breakfast, for 8 weeks. Participants were prohibited from using any other medications during the study period. Each patient underwent three visits: a baseline visit (Visit 0) on recruitment day, visit 1 after 30 days of medication, and Visit 2 after 60 days of treatment. Systolic and diastolic blood pressures, as well as heart rate, were measured at each visit. Clinical and laboratory parameters were reassessed at the end of the 8 weeks. Results: Both medications significantly reduced Systolic and Diastolic Blood Pressure (SBP and DBP) and heart rate in both groups over 8 weeks. While Group II (Cilnidipine) consistently showed slightly lower blood pressure and heart rate, these differences were statistically insignificant, suggesting similar effectiveness between the two medications in this study. Both groups reported mild/moderate adverse events, with Group I having a consistently higher number and wider range of events compared to Group II. The most common events were fatigue and headache, with Group I experiencing additional events like headache + GI upset, vomiting, and ankle edema. Conclusion: Both the calcium channel blockers amlodipine and cilnidipine exhibit equivalent efficacy in reducing systolic and diastolic blood pressure in patients with mild to moderate essential hypertension. Cilnidipine, as a fourth-generation calcium channel blocker, offers a promising pharmacological profile. In addition to its blood pressure-lowering effects, cilnidipine demonstrates notable safety and provides additional benefits including renoprotective, cardioprotective, and neuroprotective effects. [ABSTRACT FROM AUTHOR]

Feeding attributes of phytophagous insects are greatly influenced by abiotic and biotic factors. Therefore, we assessed the combined effect of temperature, age and sex on food consumption and utilization efficiencies of Zygogramma bicolorata Pallister. This Mexican beetle is known as one of the most promising candidates for the biocontrol of Parthenium hysterophorus Linnaeus, a noxious weed of barren, grazing and farming lands. Temperature, age and sex influenced food consumption, its utilization and ecological efficiencies of the beetle. Temperature between 27°C and 30°C was found optimal for 20-day-old adults of Z. bicolorata to convert and utilize the food biomass to body mass. Above and below the optimal temperature and age, the feeding attributes declined. Young females kept at 27°C consumed more food and laid more number of eggs compared to other females at different temperatures. This study reveals that females are more voracious feeders than the males regardless of temperature regimes. The present findings can be helpful to mass-multiply Z. bicolorata in the laboratory for the biocontrol of Parthenium weed in fields and agricultural farms. The results also suggest that global climate change may affect the biocontrol potential of the insect, but field investigations are needed to support the present findings. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) is going to create a heterogeneous network of billions or trillions of connected things with self-aware, self-configuration capabilities that will exchange data with each other. This heterogeneous IoT network requires standard protocols, secure and energy-efficient wireless communication, and the allocation of unique identities such as IPv6 addresses. One of the key challenges in such a heterogeneous network is the maintenance of device location and unique identity to ensure the smooth functioning of location-aware applications. Hence, this paper presents a stateless spatiotemporal IPv6 addressing scheme called four-dimensional IP addressing (FDIPA). It is founded on the idea that two objects can not be in the same place at the same time. It uses the time and location information of the device to generate the target IPv6 address and assigns it to the device after verifying its uniqueness with the duplicate address detection (DAD) protocol. It not only maintains spatial and temporal information but also guarantees a unique identity for a large-sized network. Analytically, it is proved that FDIPA will always generate a unique identity if there is no technological limitation. However, the performance of FDIPA is evaluated based on metrics such as Assignment Success Rate (ASR), communication overhead, and total energy consumption in the assignment of a unique IPv6 address. The experimental results show that FDIPA achieves good ASR while keeping low energy consumption and less overhead in the network. [ABSTRACT FROM AUTHOR]

The device equipped with a multi-homing feature optimally exploits multiple network interfaces in modern communications networks such as the Internet of Things (IoT) and machine-to-machine communication using the concurrent multipath transfer (CMT). This enhances system performance by concurrently scheduling data chunks on multiple network paths. For a while, several scheduling criteria have been developed to optimize performance. However, it has been identified that CMT still suffers from many serious problems, such as spurious retransmission, receiver buffer blocking, improper congestion window (CWND) growth, re-ordering and long round trip time, resulting in poor performance. These problems occur due to the asymmetric nature of path characteristics. Thus, this paper introduces a path rank-based CMT (R-CMT) that schedules data chunks according to the rank of the path. The proposed scheduling method calculates the rank of each network path based on the ratio of successfully received and transmitted chunks. The simulation results indicate that the proposed R-CMT scheduling achieves higher performance in terms of network latency, throughput and CWND growth. [ABSTRACT FROM AUTHOR]