Ideal Characteristics Research Articles

Accurate image segmentation based on adaptive distance regularization level set method

Level set method has been widely applied in the field of image segmentation. However, the level set formulation is inevitably affected by the regularization function, in-homogeneity and weak edge in the process of evolution, which often leads to the instability and inaccuracy of image segmentation results. To solve these problems, a new distance regularization term defined by a double-well potential function is proposed to satisfy more ideal characteristics of signed distance property. In addition, a novel edge indicator function is introduced to segment images with uneven intensity or weak edge. Finally, the adaptive adjustment formulas of distance regularization and area parameters are derived to alleviate the difficulty of parameter adjustment. Experimental results show that the proposed model provides better accuracy and versatility, quantitative experiment on Weizmann segmentation evaluation database achieves mean Dice score (96.87%), IoU (94.38%), Hausdorff distance (3.20[Formula: see text]mm), Recall (97.68%) and Precision (96.32%), respectively.

Advancement in exosome-based cancer therapeutics: A new era in cancer treatment

In the modern era of rapid development and advancement in cancer therapeutics and management, there is a growing awareness in the application of exosomes as a potential tool to target cancer cells. Exosomes are cell-derived nano-vesicles that modulate intercellular communications and transport. Due to their ideal native structure and characteristics, exosomes have emerged as a promising nanocarrier for clinical use. Nevertheless, their medical application is coupled with some intrinsic restrictions which hinder their widespread use. In order to make exosomes more effective, they are engineered at the cellular level to develop designer exosomes. The focus of this review is to summarize the various exosome bio-engineering approaches aimed at the development of designer exosomes and their application in cancer treatment.

Pacritinib for the treatment of patients with myelofibrosis and thrombocytopenia

Introduction : Myelofibrosis (MF) is a rare myeloproliferative neoplasm characterized by a complex symptom profile, cytopenias, splenomegaly, and potential for leukemic progression. Severe thrombocytopenia is common in patients with MF and correlates with poor prognosis; however, until recently, treatment options for these patients were limited. Pacritinib, a potent Janus kinase (JAK) 2/interleukin-1 receptor-associated kinase 1 (IRAK1) inhibitor, has demonstrated significant reduction in splenomegaly, improved symptom control, and a manageable safety profile in patients with MF regardless of the severity of thrombocytopenia. Areas covered : This review will outline the pacritinib drug profile and summarize key efficacy and safety data, focusing on the 200 mg twice daily dose from phase 2 and 3 studies that formed the basis for the recent US Food and Drug Administration approval of pacritinib in patients with MF and severe thrombocytopenia (platelet counts <50 x 109/L). Expert opinion Pacritinib, with its unique mechanism of action targeting both JAK2 and IRAK1, offers patients with MF and severe thrombocytopenia a new treatment option, providing consistent disease and symptom control. Adverse events are easily manageable. Further analyses to identify ideal patient characteristics for pacritinib and other JAK inhibitors along with studies of pacritinib combinations are warranted, including in related myeloid malignancies.

Steep Switching Si Nanowire p-FETs With Dopant Segregated Silicide Source/Drain at Cryogenic Temperature

Fully silicided source/drain Si gate-all-around (GAA) nanowire (NW) p-FETs with NW diameter of 5 nm are fabricated and characterized from room temperature (RT) down to 5.5 K. Thanks to the improved electrostatics by the scaled NW and 3D GAA structure, close to ideal transfer characteristics are obtained at both RT and 5.5 K with a sharp switching. Benefiting from less defects in Si created by the implantation into silicide (IIS) process, the band tail effects and neutral defects scattering are suppressed. Therefore, the fabricated Si GAA NW p-FETs provide very low subthreshold swing SS of 3.4 mV/dec in the weak inversion region and an average SS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> of 14 mV/dec measured from the off-state to the threshold voltage, as well as an improved transconductance G <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> at 5.5 K.

State of the intensity of the light power of the light-curing lamps of the faculty of dentistry clinic of the University of Cuenca, school year 2021-2022

Objective: The purpose of this study was to determine the intensity of the light power and the integrity of the active part of the curing lights of the Faculty of Dentistry Clinic of the University of Cuenca in the March-August 2022 term. Lack of knowledge of light-curing units, leads dentists to purchase low-quality equipment, thinking that they all work with the same efficiency, compromising the long-term success of restorations. Therefore, it is important to know the ideal characteristics of a light-curing lamp. Materials and methods: This is a descriptive and observational study whose sample is made up of 72 light-curing lamps assigned by the clinic and the lamps of each student who is attending the clinic. For the development of the project, a radiometer was used. Results: Of the 72 lamps analyzed, 54 (75%) are LED devices and they correspond to the students. Of which, 47 (87.03%) are effective because they have a power greater than 800 𝑚𝑊/𝑐𝑚2. On the other hand, the 18 (25%) are part of the cabin group, in this case there are 15 halogen devices (83.33%) and 3 LED devices (16.67%). Of which, 3 (20%) halogen lamps are effective, while 1 (33.33%) LED device is effective with a power greater than 800 at 𝑚𝑊/𝑐𝑚2. Conclusion: An adequate polymerization is crucial to obtain good mechanical and physical properties and excellent clinical results of the material.

Developing Protection-Use-Strategies Based On Sustainability in Protected Areas: Suuçtu Nature Park Case

This study aims to evaluate the current conservation and use status in a nature park and to develop planning strategies that will provide sustainable use of protected areas for the future. Suuçtu Nature Park in Bursa Province Mustafakemalpaşa district was chosen as the study area. The method of the study consisted of three stages. In the first stage, the current situation was revealed by conducting fieldwork, observations, and interviews. In the second stage, SWOT analysis was carried out to determine the recreational opportunities offered by the area and to evaluate the potential of the study area. It has been determined by SWOT analysis that Suuçtu Nature Park is a strong character due to its unspoiled natural and cultural values, ideal climate characteristics, geological structure and high visual landscape value. In the third stage, conservation and tourism strategies for the future were developed with the TOWS matrix. As a result of the study, by considering the protection and usage conditions of the area, land use strategies have been developed in line with ecological-based tourism and recreation uses in the protected areas.

Managing the external financing constraints of social enterprises: A systematic review of a diversified research landscape

AbstractSocial enterprises, located between non‐profit organisations and for‐profit firms, often struggle to acquire external funding. An increasing amount of research on the external financing of social enterprises stems from a fragmented body of the literature anchored in a variety of subject areas (e.g. entrepreneurship, public sector management, general management and strategy). We systematically review 204 academic articles published between 1998 and 2021 to bridge the knowledge gaps in these subject areas by: (1) mapping the field of the external financing of social enterprises at the individual, organisational and institutional levels; (2) synthesising the findings to develop an overarching framework; and (3) discussing theoretically sound future research avenues. We find that research at the individual level focuses primarily on investors’ perspective of the ideal characteristics of a social entrepreneur. Research at the organisational level often addresses the dual logics of social enterprises and their impact on the successful financing of these businesses and the role of investor–investee collaboration. Research at the institutional level can be clustered into cultural, economic, political and legal factors. Overall, we stress the need for research that adopts an overarching view by considering all three levels of analysis simultaneously and using organisational and economic theories.

Modelling and Design of Asymmetric Vibrations to Induce Bidirectional Force Sensation for Portable Rehabilitation Devices.

Assistive rehabilitation devices have been developed to help post-stroke patients to recover and live independently for a number of years. As a way to communicate with the physical world, force sensation is extremely helpful to rebuild neuroplasticity [1] during the rehabilitation process. This paper presents a model and design of asymmetric vibrations to provide bidirectional force sensation, which can be beneficial to design a portable rehabilitation haptic device. Users will feel a directional cue generated by asymmetric vibrations by holding the device. This directional cue can navigate users around in a rehabilitation training along with visual guidance and provide physical force sensations. The system consists of a current-drive single solenoid rigidly attached to a base. The system's model is verified through experiment at three different frequencies. Our analysis shows that by varying the signal's duty ratio, the direction of peak accelerations change from positive to negative. In addition, two other waveforms (saw-tooth and step-ramp) at several frequencies and different spring's stiffness are also discussed to determine the ideal characteristics of the input signal for rehabilitation applications.

Technical Considerations for the Conformation of Specific Competences in Mechatronic Engineers in the Context of Industry 4.0 and 5.0

The incursion of disruptive technologies, such as the Internet of Things, information technologies, cloud computing, digitalization and artificial intelligence, into current production processes has led to a new global industrial revolution called Industry 4.0 or Manufacturing 4.0. This new revolution proposes digitization from one end of the value chain to the other by integrating physical assets into systems and networks linked to a series of technologies to create value. Industry 4.0 has far-reaching implications for production systems and engineering education, especially in the training of mechatronic engineers. In order to face the new challenges of the transition from manufacturing 3.0 to Industry 4.0 and 5.0, it is necessary to implement innovative educational models that allow the systematic training of engineers. The competency-based education model has ideal characteristics to help mechatronic engineers, especially in the development of specific competencies. This article proposes 15 technical considerations related to generic industrial needs and disruptive technologies that serve to determine those specific competencies required by mechatronic engineers to meet the challenges of Industry 4.0 and 5.0.

Fattening Management Of Skinny Bali Catle Variety (Bos Sondaicus) By Utilization Of Agricultural Waste And Local Plant In Sumbawa

Sumbawa is one area that has the potential to be developed as a center for beef cattle production which is quite competitive in Indonesia. The proportion of cattle in Sumbawa itself is around 21% which is generally dominated by the Bali cattle variety (Bos sondaicus). Therefore, a business that has great potential to support this goal is cattle fattening. Unfortunately, one of the main problems encountered in fattening cattle is the cost of feed. Thus, the management of Bali cattle fattening that utilizes agricultural waste for the manufacture of feed is urgently needed. In addition, the management of fattening cattle must also be complemented by other components, such as the manufacture of medicines to treat diseases of underweight Bali cattle using local plants, the process of bathing, drying, and monitoring the cattle to be fattened. From the research and observations conducted, it is known that the time needed to get the cow display condition with ideal characteristics and optimal weight in the fattening process is 3 months. During this time, the selling price of lean fattened cows increased by about 2-2.3 times. It can be concluded, that the fattening management of lean Bali cattle carried out in Pungka Village, Unter Iwes District, Sumbawa Regency is quite profitable. In addition, this can also be used as part of community waste management that is integrated with community livestock business.

Preparation and properties analysis of ethanol/furan-derivative/diesel alternative microemulsion fuel

Nowadays, the energy revolution is imperative and in the transition from fossil fuel energy structure to new energy, the alternative fuel with mature technology and reasonable cost is urgently needed. Biomass such as ethanol is a completely renewable organic liquid, but its application is restricted due to the incompatibility of ethanol and diesel. In this paper, the ethanol-diesel stabilized fuel was proposed with furan-derivative as co-solvent, furthermore, furan-derivative is also a kind of renewable biomass. By using a nanoparticle size analyzer and a conductivity analyzer, it was found that the blends of ethanol/furan-derivative/diesel were in the state of microemulsion and had good phase stability. As the ratio of ethanol increases, the microemulsion structure changes from water-in-oil (W/O) to double-continuous-phase until oil-in-water (O/W). Tetrahydrofuran had relatively weak corrosive effect on polymers. For a ratio with ideal characteristics at 20 °C (diesel accounts for 64%, ethanol 27% and tetrahydrofuran 9%), the low calorific value of the fuel is 33 MJ/L, and the cost of this fuel to provide 1 MJ of heat is 0.19 yuan, which is comparable to that of diesel. Therefore, the designed fuel can be used directly in the existing engines without modified.

(Invited) Investigating Defects in the High-k/Ingaas System at Cryogenic Temperature

III-V RF devices operating at cryogenic temperature are highly desirable for application areas such as space communication or quantum computing. In the case of quantum computation, integration of the readout and control electronics close to the quantum bit (Qubit) stage is needed to allow scaling of the number of Qubits needed for practical applications. Many characteristics of high frequency operation at cryogenic temperature in novel III-V devices are not fully understood. In this study, we will focus on the behaviour of defects at or near the interface between the high dielectric constant (high-k) oxide and InGaAs semiconductor at cryogenic temperature and how it may affect the full device operation at low temperature.The thermal budget constraints associated with the processing III-V semiconductor devices prohibit the use of high temperature thermal treatments to reduce oxide defect densities in the high-k. This leads to defective oxides presenting higher instability, variability, and degradation issues than in the Si/SiO2 system. The methods developed to investigate defects in the Si/SiO2 metal oxide semiconductor (MOS) system generally attribute the divergence in capacitance voltage (CV) and conductance voltage (GV) from the ideal CV and GV characteristics mostly to interface state defects (ITs) [1], which is not the case of the III-V MOS system. As a consequence, attempts to fit the multi-frequency CV and GV response of III-V MOS structures in the weak inversion regime, using interface states alone, cannot recreate the experimental data.In this study, we present an advanced MOS defects characterisation method capable of discerning between the contributions of oxide defects (sometimes labelled ‘border traps’) and ITs. The method relies on the fully physics based simulation of MOS systems, including inelastic tunnelling from the semiconductor to localized defects in the oxide [2] to reproduce the experimental multi-frequency CV and GV characteristics. The simulations include physical models accurately describing the carrier capture/emission processes by oxide traps, and which incorporate tunneling into the dielectric in conjunction with lattice relaxation at the interface/border trap sites [3, 4]. The results will show that the simulations are able to reproduce the room temperature experimental data (both CV and GV) of InGaAs/Al2O3 MOS structures in all bias regions. This new method enables the precise extraction of the density, energy and spatial distribution away from the interface of electrically active oxide defects from different experimental results.Results will also be presented showing how the multi-frequency CV and GV response of n-InGaAs/Al2O3 and p-InGaAs/Al2O3 MOS structures change with reducing temperature. Measurements at 223K show a marked reduction in the CV and GV dispersion with frequency in the accumulation and depletion regions, consistent with a phonon assisted tunnelling interaction of electrons and holes with defects in the Al2O3. Reduction in the measurement temperature to 10K still demonstrates a residual dispersion of the capacitance and conductance with frequency, which is more marked in the case of the p-InGaAs/Al2O3 MOS structure. The models and trap distributions extracted from room temperature will be applied to the reduced temperature measurements (233 K and 10 K) to investigate the validity of the models and to gain further understanding of defect behaviour and associated device implications at cryogenic temperatures.[1] E. H. Nicollian and J. R. Brews, “MOS Physics and Technology,” John Wiley & Sons, New York, 1982.[2] A. Palma, et al. Phys. Rev. B Condens. Matter Mater. Phys., 56 (15), pp. 9565-9574 (1997).[3] E. Caruso, et al. IEEE Trans. Electron Devices, 67 (10), pp. 4372-4378 (2020)[4] G. Sereni, et al. “IEEE Trans. Electron Devices, vol. 62, no. 3, pp. 705–712, (2015).

Versatile aza‐BODIPY‐based low‐bandgap conjugated small molecule for light harvesting and near‐infrared photodetection

AbstractThe versatile nature of organic conjugated materials renders their flawless integration into a diverse family of optoelectronic devices with light‐harvesting, photodetection, or light‐emitting capabilities. Classes of materials that offer the possibilities of two or more distinct optoelectronic functions are particularly attractive as they enable smart applications while providing the benefits of the ease of fabrication using low‐cost processes. Here, we develop a novel, multi‐purpose conjugated small molecule by combining boron‐azadipyrromethene (aza‐BODIPY) as electron acceptor with triphenylamine (TPA) as end‐capping donor units. The implemented donor–acceptor–donor (D–A–D) configuration, in the form of TPA‐azaBODIPY‐TPA, preserves ideal charge transfer characteristics with appropriate excitation energy levels, with the additional ability to be used as either a charge transporting interlayer or light‐sensing semiconducting layer in optoelectronic devices. To demonstrate its versatility, we first show that TPA‐azaBODIPY‐TPA can act as an excellent hole transport layer in methylammonium lead triiodide (MAPbI3)‐based perovskite solar cells with measured power conversion efficiencies exceeding 17%, outperforming control solar cells with PEDOT:PSS by nearly 60%. Furthermore, the optical bandgap of 1.49 eV is shown to provide significant photodetection in the wavelength range of up to 800 nm where TPA‐azaBODIPY‐TPA functions as donor in near‐infrared organic photodetectors (OPDs) composed of fullerene derivatives. Overall, the established versatility of TPA‐azaBODIPY‐TPA, combined with its robust thermal stability as well as excellent solubility and processability, provides a new guide for developing highly efficient multi‐purpose electronic materials for the next‐generation of smart optoelectronic devices.image

Diagnostic Performance of a Noninvasive Breath Test for Colorectal Cancer: COBRA1 Study

Diagnostic Performance of a Noninvasive Breath Test for Colorectal Cancer: COBRA1 Study

Poster 176: International Expert Consensus on Return to Sport Criteria Following Shoulder Stabilization Surgery: A Delphi Study

Objectives:A comprehensive approach to standardize the criteria of return to sport (RTS) following common shoulder procedure in athletes is required to safely return the physically active population to sport postoperatively. There is lack of studies validating the RTS criteria following arthroscopic and/or open shoulder stabilization surgery. We developed a list of widely accepted criteria of RTS following shoulder stabilization surgery using Delphi consensus methods with international experts.Methods:A working group developed a list of approximately 50 criteria. Experts included 27 world renowned shoulder surgeons from various countries who have been recognized as international experts in the field and were invited speakers to international sports medicine meetings rated their agreement to each of the listed criteria. Experts were surveyed on 3 occasions to establish consensus on the inclusion of each RTS criterion in the final list of accepted criteria of RTS after shoulder stabilization surgery. For each round, a 70% agreement was used as a cutoff for consensus. Statements without this level of agreement were excluded in subsequent rounds. Descriptive statistics were used for analysis. Predefined criteria were used to refine item lists after each survey. Final list of criteria of RTS following shoulder stabilization surgery was complied by the working group and included those that received > 75% agreement on all 3 rounds of rating by experts.Results:We initially identified 50 RTS criteria following shoulder stabilization surgery from the literature that the experts were asked to rate their agreement. Twenty-seven international experts completed the rating in all 3 rounds. The RTS criteria were divided consisted of 5 subgroups including current evidence, ideal characteristics of the RTS criteria, general considerations for RTS criteria, specific considerations for RTS criteria, and dissemination of RTS criteria following shoulder stabilization. For Round 1, the response rate was 100% and 10 (20%) of 47 criteria were eliminated leaving 37 statements for evaluation in Round 2. Round 2 had a 100% response rate, and 1 (2.5%) statement was eliminated leaving 36 criteria for the final round. Round 3 had a 96% response rate, and no statements were eliminated. Respondents agreed on a total 36 statements to define the RTS criteria following shoulder stabilization in athletes. Table 1 provides the final list of accepted criteria and the percentage of agreement for each individual criterion.Conclusions:The final list of statements agreed upon by international experts provide insight into a standardized return to sport criteria following shoulder stabilization surgery in physically active patients. This agreed upon criteria can aid those providing care to athletes in their decision making when determining optimal timing for return to sport.Table 1.Statements that reached an expert consensus above 70% in 3 rounds.

Applications and Limitations of 3D Bioprinters in Tissue Culturing: A Review

3D bioprinting is an advanced technology that uses different biomaterial like hydrogels and bio-inks to develop artificial tissue cells and organs. There are three types of bioprinting techniques: Jetting-based bioprinting, extrusion based bioprinting, and integrated bioprinting. Biomaterials used in 3D bioprinter should have some ideal characteristics such as they should be biocompatible, printable, and provide mechanical and structural properties. There are different types of bio-inks, hydrogels, and growth factors used to overcome the crisis of organ shortage. Bioprinting technology is essential for the development of eleven organ systems as there is a need for organ replacement and tissue regeneration. It is possible to make complex tissue culture structures by using 3D bioprinting. The mixture of biomaterial and living cells used for bioprinting is called bio-inks. Hydrogels are one of the ideal components of biomaterials as it has similar characteristics as natural extracellular matrix and provides a hydrated environment for cells to divide. Generation and transportation of many tissues, including skin, heart tissues, cartilaginous constructs, and tracheal tissues is done by 3D bioprinting. It is used for research purposes, drug testing, and drug discovery. But our focus is to highlight the applications of 3D bioprinters in tissue engineering and the development of organ systems. Skin tissues have also been engineered to overcome complex skin treatment procedures and to save time and cost. Keywords: 3D bioprinting; Bio-inks; Biomaterials; Hydrogels; Tissue Culturing

Use of Hyaluronic Acid in Periodontal Disease Treatment: A Systematic Review

The main purpose of the present study was to investigate the potential benefit of local use of hyaluronic acid as an adjunct to periodontal therapy, since commercial products of hyaluronic acid (HA), due to its anti-inflammatory and anti-bacterial actions and its significant role in wound repair, have been proposed as adjuncts to either nonsurgical or surgical periodontal therapy. A total of 19 electronic databases were searched and the appropriate studies were identified with the use of specific eligibility criteria, according to PRISMA guidelines. Two reviewers independently screened and selected the studies and made the data extraction and the assessment of risk of bias, by using the Cochrane risk of bias tool. Out of 3,186 papers, 38 randomized clinical trials (8 related to gingivitis therapy, 20 related to nonsurgical periodontal therapy, and 10 related to surgical periodontal therapy) were finally included in the review. The outcomes were categorized as primary (that answered the focus question) and secondary (regarding additional quality characteristics). The adjunct use of HA combined to all treatment modalities shows improvement of patients' postoperative course, in terms of decreased inflammatory reactions, and changes in periodontal pocket depth and clinical attachment level. No side effects were reported in any of the included studies. Among the secondary outcomes were the variety of HA formulations and chemical forms, the variety in application, follow-up protocol and blinding design, the uneven geographic distribution of the studies, and the low bibliometric characteristics of most studies. Overall and despite the positive effects reported, further research is needed to define the ideal HA compound, formulation, and regimen characteristics for periodontal disease treatment. The adjunct use of HA may lead in the reduction of the prescription of nonsteroid anti-inflammatory drugs and achieve improved clinical parameters, including periodontal probing depth, periodontal inflammation, and clinical attachment level.

Facilitators and barriers to point-of-care testing for sexually transmitted infections in low- and middle-income countries: a scoping review

BackgroundSexually transmitted infections (STIs) in low- and middle-income countries (LMICs) are predominantly managed by syndromic management. However, most STIs are asymptomatic. These untreated STIs cause individual morbidity, and lead to high STI prevalences.There is increasing interest in the use of point-of-care tests (POCTs) for STIs in LMICs, which could facilitate same day testing and treatment. To best utilise these tests, we must understand the facilitators and barriers to their implementation. The aim of this review is to explore how point-of-care testing for STIs has been implemented into healthcare systems in LMIC and the facilitators and barriers to doing so.MethodsA scoping review was conducted by searching MEDLINE, Embase, Emcare, CINAHL, Scopus, LILACS, the Cochrane Library, and ProQuest Dissertations and Theses for studies published between 1st January 1998 and 5th June 2020. s and full articles were screened independently by two reviewers. Studies were considered for inclusion if they assessed the acceptability, feasibility, facilitators, or barriers to implementation of point-of-care testing for chlamydia, gonorrhoea, trichomoniasis or syphilis in LMICs. Thematic analysis was used to analyse and present the facilitators and barriers to point-of-care STI testing.ResultsThe literature search revealed 82 articles suitable for inclusion; 44 (53.7%) from sub-Saharan Africa; 21 (25.6%) from Latin American and the Caribbean; 10 (12.2%) from East Asia and the Pacific; 6 (7.3%) from South Asia; and one (1.2%) multi-regional study. Thematic analysis revealed seven overarching themes related to the implementation of POCTs in LMICs, namely (i) Ideal test characteristics, (ii) Client factors, (iii) Healthcare provision factors, (iv) Policy, infrastructure and health system factors, (v) Training, audit, and feedback, (vi) Reaching new testing environments, and (vii) Dual testing.ConclusionImplementation of POCTs in LMICs is complex, with many of the barriers due to wider health system weakness. In addition to pressing for broader structural change to facilitate basic healthcare delivery, these themes may also be used as a basis on which to develop future interventions. The literature was heavily skewed towards syphilis testing, and so more research needs to be conducted assessing chlamydia, gonorrhoea, and trichomoniasis testing, as well as home or self-testing.

Bonferroni Weighted Logarithmic Averaging Distance Operator Applied to Investment Selection Decision Making

Distance measures in ordered weighted averaging (OWA) operators allow the modelling of complex decision making problems where a set of ideal values or characteristics are required to be met. The objective of this paper is to introduce extended distance measures and logarithmic OWA-based decision making operators especially designed for the analysis of financial investment options. Based on the immediate weights, Bonferroni means and logarithmic averaging operators, in this paper we introduce the immediate weights logarithmic distance (IWLD), the immediate weights ordered weighted logarithmic averaging distance (IWOWLAD), the hybrid weighted logarithmic distance (HWLD), the Bonferroni ordered weighted logarithmic averaging distance (B-OWLAD) operator, the Bonferroni immediate weights ordered weighted logarithmic averaging distance (B-IWOWLAD) operator and the Bonferroni hybrid weighted logarithmic distance (HWLD). A financial decision making illustrative example is proposed, and the main benefits of the characteristic design of the introduced operators is shown, which include the analysis of the interrelation between the modelled arguments required from the decision makers and the stakeholders, and the comparison to an ideal set of characteristics that the possible companies in the example must portray. Moreover, some families, particular cases and brief examples of the proposed operators, are studied and presented. Finally, among the main advantages are the modeling of diverse perspectives, attitudinal characteristics and complex scenarios, through the interrelation and comparison between the elements with an ideal set of characteristics given by the decision makers and a set of options.

Efficacious Preclinical Repurposing of the Nucleoside Analogue Didanosine against COVID-19 Polymerase and Exonuclease.

Analogues and derivatives of natural nucleosides/nucleotides are considered among the most successful bioactive species of drug-like compounds in modern medicinal chemistry, as they are well recognized for their diverse and efficient pharmacological activities in humans, especially as antivirals and antitumors. Coronavirus disease 2019 (COVID-19) is still almost incurable, with its infectious viral microbe, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak devastation around the world. This global crisis pushed all involved scientists, including drug discoverers and clinical researchers, to try to find an effective and broad-spectrum anti-COVID-19 drug. Didanosine (2′,3′-dideoxyinosine, DDI) is a synthetic inosine/adenosine/guanosine analogue and highly active antiretroviral therapeutic agent used for the treatment of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). This potent reverse-transcriptase inhibitor is characterized by proven strong pharmacological effects against the viral genome, which may successfully take part in the effective treatment of SARS-CoV-2/COVID-19. Additionally, targeting the pivotal SARS-CoV-2 replication enzyme, RNA-dependent RNA polymerase (RdRp), is a very successful tactic to combat COVID-19 irrespective of the SARS-CoV-2 variant type because RdRps are broadly conserved among all SARS-CoV-2 strains. Herein, the current study proved for the first time, using the in vitro antiviral evaluation, that DDI is capable of potently inhibiting the replication of the novel virulent progenies of SARS-CoV-2 with quite tiny in vitro anti-SARS-CoV-2 and anti-RdRp EC50 values of around 3.1 and 0.19 μM, respectively, surpassing remdesivir together with its active metabolite (GS-441524). Thereafter, the in silico computational interpretation of the biological results supported that DDI strongly targets the key pocket of the SARS-CoV-2 RdRp main catalytic active site. The ideal pharmacophoric characteristics of the ligand DDI make it a typical inhibiting agent of SARS-CoV-2 multiplication processes (including high-fidelity proofreading), with its elastic structure open for many kinds of derivatization. In brief, the present results further uphold and propose the repurposing potentials of DDI against the different types of COVID-19 and convincingly motivate us to quickly launch its extensive preclinical/clinical pharmacological evaluations, hoping to combine it in the COVID-19 therapeutic protocols soon.