Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n=67) were sequenced for clarithromycin and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples that amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C the most common mutation, 90%. While prevalence of metronidazole resistance-associated mutations was higher, 93.9%, mutations were more variable, with D95N the most common, followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider the resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The KRAS mutation is present in 30-50% of CRC patients. This mutation confers resistance to treatment with anti-EGFR therapy. This article aims at proving that Computer Tomography (CT)-based Radiomics can predict the KRAS mutation in CRC patients. The piece is a retrospective study with 56 CRC patients from the Hospital of Santiago de Compostela, Spain. All patients had a confirmatory pathological analysis of the KRAS status. Radiomics features were obtained from the abdominal contrast enhancement CT (CECT), before applying any treatments. We used several classifiers, including adaboost, neural network, decision tree, support vector machine and random forest, to predict the presence or absence of KRAS mutation. The most reliable prediction was achieved using the adaboost ensemble on clinical patient data, with a kappa and accuracy of 53.7% and 76.8%, respectively. The sensitivity and specific were of 73.3% and 80.8%. Using texture descriptors, the best accuracy and kappa were 73.2% and 46%, respectively, with sensitivity and specificity of 76.7% and 69.2%, showing also a correlation between texture patterns on CT images and KRAS mutation. Radiomics could help manage CRC patients, and in the future, it could have a crucial role in diagnosing CRC patients ahead of invasive methods.

Background: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations and sensitivities may differ among these methods. Methods: As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. Results: Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. Conclusions: If a negative result was obtained from methods with lower sensitivity (e.g. Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, with the aim of identifying T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI.

AIM: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with Congenital Hereditary Endothelial Dystrophy (CHED). METHODS: This is a family cohort study that investigated the genetic profile of a selected family in Northern Luzon, Philippines, whose members were diagnosed with Congenital Hereditary Endothelial Dystrophy (CHED). A patient who was diagnosed with CHED prior to this study, served as the proband for this family. A detailed family history and a complete ophthalmologic examination were done to each of the family members. A total of six affected members and three unaffected members were included in this study. DNA was isolated from peripheral blood samples of family members, and polymerase chain reaction (PCR) was used to amplify the gene’s entire coding region, (19 exons and 2 putative promoter regions), and finally, the amplified regions were analyzed using DNA sequencing. RESULTS: Consanguinity was not present in the family. Corneal haze was reported to be present since birth or shortly thereafter in all affected patients. Slit-lamp examination showed edematous corneas. Molecular studies of the SLC4A11 gene revealed four novel homozygous point mutations variably present in six affected members as well as three unaffected members. One unaffected family member (I-1) had a novel sense mutation absent in other family members. All affected siblings showed little phenotypic variability. CONCLUSION: This is the first report that gives us a genetic profile of a Northern Luzon family with members affected by CHED. This study supports earlier findings that the mutations in the SLC4A11 gene are not consistently the same among different ethnic groups worldwide, probably due to the disease’s genetic heterogeneity. Our study documented five novel mutations adding to the growing list of mutations probably responsible for acquiring the CHED phenotype. It is possible that there are more novel mutations waiting to be discovered in this hereditary disease. Screening for these specific mutations in other families may prove useful for genetic counseling, prenatal diagnosis and the future development of gene therapy.

The demand for an efficient utilization of abundant biomasses is growing for the production of biogas and valuable bioproducts. Lignocellulose biomass is a cheap and most abundant carbon source for the production of biofuels such as bioethanol, biobutanediol, and other bio-based chemicals. Due to its complex heterogeneity, its hydrolysis gives rise to a mixture of sugars, mainly glucose; a hexose and xylose; a pentose. Glucose is the most abundant carbohydrate monomer. Most microorganisms have evolved the ability to utilize it preferably due to carbon catabolite repression regulatory mechanism at the detriment of the pentoses. Some microbes even lack the ability to utilize them. This has led to the sequential use of these sugars and accompanying reduced productivity due to inadequate utilization of the pentoses. Also, this sequential utilization of the sugars takes time and makes the overall processes economically costly. Since lignocellulose hydrolysates comprise both hexoses and pentoses, the catabolism of these sugar mixtures to biofuels will require an efficient microbial strain capable of simultaneous utilization. The use of CCR negative mutants can achieve this. CCR negative mutants simultaneously utilize pentoses and hexoses, ensuring an improved fermentation efficacy and greater productivity, thus, making the overall bioprocess economically feasible. This article reviewed several approaches employed in creating these mutant microorganisms. A brief insight on carbon catabolite repression and phosphostransferase system were made. It also highlighted the biogas production processes, factors affecting anaerobic digestion, lignocellulosic biomass structure, challenges with their use and solutions to overcoming the challenges.

Although Darwin‘s evolutionary mutation theory has been widely accepted, many endeavors have been tried to challenge it. With more and more observation of successful hybridization and hybrids, the sexual isolation between species has become vague. The mechanism of evolution has been expanded from the classical model of evolution to multiple routes of speciation. Furthermore, a fundamental crossbreeding theory has been raised and proved by two lines of evidences: paleopolyploidy and fan-shaped spectrum of species. Ancient genome duplications are widespread throughout eukaryotic lineages, particularly in plants. The genome polyploidization, especially in the somatic cell hybridization, can break through the sexual incompatibility between diploid counterparts to hybridize and produce new species. By comparing characteristics, all species in every taxon, both in the extinct fossil and extant organisms, can be arranged into fan-shaped spectrum according to their similarity: left primitive type-middle advanced type-right primitive type. The species are primitive at the two ends and advanced at the middle. The primitive two species always resemble two types of more primitive species that can be confirmed as their ancestors respectively, and the middle species is half similar to the two ancestors respectively. These suggest that the species in the spectrum come from two different ancestors by crossbreeding and gene combination. As a sum, advanced species originated from crossbreeding of two primitive ancestors, by major method of polyploidization, and proved by results of fan-shaped spectrum of species. Then, sex is the cause, force and opportunity for evolution.

2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020-21 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organisation stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and spread to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8 and its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With the knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins can allow better preparedness against H5N8 and other influenza A viruses.

The Sars-CoV-2 is the causative agent of the current coronavirus disease pandemic. To effectively fight this pathogen, it is important to understand its evolution and the mechanism of adaptation to the host. A software workflow has been utilized to scan 26,016 Sars-CoV-2 genomes available in GISAID databank to analyse the distribution and frequency of mutations in the corresponding proteomes. A filtering procedure has been applied to remove data inconsistencies and redundancies. The number of observed mutations appears proportional to protein sequence length except for ORF3a, Nucleocapsid and Nsp2 that seem to accept more mutations than expected. The most pervasive mutations of the three proteins have been reported and the most variable and conservative regions mapped onto the respective sequences. The results suggest that these proteins may have a role in the adaptation of virus to new hosts and influence its pathogenicity and replication. These considerations prompt the experimental study and characterization of the three proteins.

Till date there are three full length COVID 19 virus genome sequences available from India. The earlier two were reported from Kerala, Southern India and the more recent one has been reported from Gujarat, western part of India. In this paper we report two novel mutations in the Spike protein sequence of Gujarat’s isolate. These mutations are based on comparison with the original Wuhan sequence. The two mutations have been found to be located just upstream and downstream of the receptor binding domain (RBD). Out of these two one has also been found to affect the secondary structure of the S1 domain. Since both of these mutations lie near the receptor binding domain, they might influence the spike receptor interactions by changing the conformation of the spike protein S1 domain. These mutations are uniquely placed and might be important in the context of vaccine engineering and therapeutic interventions.

Diffusion magnetic resonance imaging (dMRI) is an imaging technique that provides information on the microstructural organization of biological tissue. dMRI allows for non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, at 7T wavelength effects cause lower transmit magnetic field efficiency in the human brain, mainly in the posterior fossa region, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. Here we demonstrate the feasibility and effectiveness of using this RF enhancer for in-vivo dMRI at 7T. The use of the RF enhancer can effectively recover signal dropouts in the regions with intrinsically lower SNR such as cerebellum, leading to a better depiction of principal fiber orientations and enhanced visualization of extended tracts to the brainstem and pons enabling more comprehensive delineation of the full white matter architecture.

Blueberries are rich in a variety of functional substances and have high nutritional and health values, but they are not resistant to decline during fresh storage. Here, the effects of six Bacillus species on storage quality of, and antioxidant levels in, the southern highbush blueberry ‘O'Neal’ fruit were investigated. Bacillus treatments reduced the fruit decay rate, slowed fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. Bacillus altitudinis Y-14 had the best effect overall. Further, the effects of 1-methylcyclopropene (1-MCP), B. altitudinis Y-14, and 1-MCP+B. altitudinis Y-14 treatments on the storage quality and antioxidant of rabbiteye blueberry ‘Brightwell’ fruit were investigated, and each treatment effectively reduced the decay rate and weight loss of fruit. When stored for 25 days, the decay rate of the 1-MCP+B. altitudinis Y-14 group was only 8.33%, significantly lower than that of the control. The three treatments delayed the fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. The 1-MCP+B. altitudinis Y-14 treatment had the best effect. Thus, the combined 1-MCP and B. altitudinis Y-14 treatment may be an effective way to improve the storage quality and extend the storage period of blueberries.

New strategies for enhancing drug delivery to the blood–brain barrier (BBB) represents a major challenge in treating cerebral diseases. Nano-emulsion based nanocarriers represent an ideal candidate to improve drug delivery thanks to their versatility in functionalization and cargo protection. In this work, a paclitaxel loaded nano-emulsion has been firstly functionalized and stabilized with two layers constituted of chitosan and hyaluronic acid, and, secondly, the latter has been conjugated to the CRT peptide. CRT is a bioactive peptide that selectively recognizes bEnd.3 cells, model of the BBB, thanks to its interactions with transferrin (Tf) and its receptor (TfR). Cytotoxic results showed a higher uptake of CRT functionalized nano-emulsion 41.5 % more than the negative control, demonstrating the ability of this novel tool to be accumulated on the brain endothelium tissue. Thanks to these results, our approach can be fully generalizable to the design of multifunctional nanocarriers for delivery of therapeutic agents to the central nervous systems.

Objective To explore the endoscopic anatomical structures of lumbar surgery. Methods A total of 290 patients who underwent lumbar endoscopic surgery due to lumbar intervertebral disc (IVD) herniation from September 2020 to September 2022 were retrospectively reviewed in our hospital,179 patients had complete surgical video recordings, including 108 males and 71 females, aged from 19 to 65 years, with an average age of 41±16 years. The endoscopic structures through the intervertebral foramen and interlaminar space were independently identified by 3 doctors with more than 3 years of related surgery experience. When there were differences of opinions, the three doctors would discuss and come to a consensus. The probability, location, and neighboring structures of each specific structures were statistically analyzed. Results The anatomical structures observed through the lumbar foramen under endoscopy include muscles and ligaments attached to the superior articular process (SAP), main blood vessels inside the intervertebral foramen, blood vessels on the surface of IVD, and blood vessels on the surface of the dural sac and nerve root. The major anatomical structures observed through interlaminar space are multifidus, the conjugated ligament of ligament flavum and capsule ligament (capsule part of flavum ligaments), edges of the lamina, specific vessel bundle to facet with exit nerve root. Conclusion The anatomical structures under spinal endoscopy have certain characteristics, which are grossly different from those under open surgery. Familiarity with these anatomical structures has important clinical significance.

Background: The safety and effectiveness of factor-Xa (FXa) inhibitors for nonvalvular atrial fibrillation (NVAF) remains inconclusive. We investigated the current dosing of rivaroxaban, apixaban and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity. Methods and Results: This multicenter clinical study monitored the drug PC levels and two coagulation biomarkers (fibrinogen: FIB, and fibrin monomer complex: FMC) at peak and trough timing in 268 outpatients receiving rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted according to the dose adjustment criteria of each drug. Based on our previous study, each peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (three on rivaroxaban, two on apixaban and three on edoxaban) in whom bleeding events occurred; among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels remained within the normal range (< 6.1 µg/ml) regardless of PC variation. These finding suggested that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and frequency of dosing. Regarding the change in peak drug PC levels over time, rivaroxaban tended to accumulate more than edoxaban (p

The growing deforestation of tropical forests requires the implementation of restoration actions capable of assisting the recovery of biodiversity and functioning of these ecosystems. This research aimed to identify the environmental factors that influence woody plant recruitment abundance and diversity in an Andean forest restoration project in Medellin (Colombia). Data from all individuals taller than 80 cm was collected in 22 plots of 200 m2. The environmental factors selected were edaphic variables, plantation structure, slope, elevation, prior land use and landscape forest cover. A generalized linear model was adjusted for recruitment density, and linear mixed models were built for recruited species richness, diversity and dominance. Woody plant recruitment attributes in our study area were similar to a typical secondary succession in an Andean forest, but planted trees contributed little to these attributes. While recruitment density was affected by slope, canopy closure and landscape forest cover, recruitment diversity was influenced by physical (bulk density) and chemical (pH, aluminum, CEC) edaphic factors, planted trees diversity (species richness and composition), canopy closure and mortality rate of planted trees. We conclude that a good development of planted trees enhances both recruitment attributes, indicating a synergy between active restoration and passive regeneration processes.

Plastics, once regarded as a revolutionary material shaping modern society, now poses an unprecedented threat to our environment. Household solid waste sorting stations produce several fractions, one of which contains a high concentration of Low-Density Polyethylene (LDPE) film waste (packaging, sunscreen film, etc.). This fraction is difficult to recycle because it contains quite a lot of impurities. Usually, it is sent to the cement factories that burn it together with other fuels. However, with some processing techniques such catalytic pyrolysis this fraction could be valorized. In this paper the experiments which were carried out at a laboratory scale installation, in batches with a processing capacity of 1-3 kg of waste. The pyrolysis reactor is connected to a distillation column giving the possibility to separate the fractions. The gaseous and liquid fractions were characterized by GC-FID-TCD (gases) and GC-MS (liquids) analysis. Natural catalysts such as bentonite or clinoptilolite were studied and used in the melting of plastic mass to simplify the process as much as possible. To test the activity of the catalysts, the pyrolysis of LDPE granules was initially studied. It was found that natural zeolites are much more active than bentonite and that a minimum concentration of 5-10% is needed to have a positive effect on the composition of the fractions (increasing the weight of the light fractions C1-C6, C6-C10 and C11-C13) in relation to the heavy fractions C13-C20 and C20+. Catalytic pyrolysis gives a completely different distribution of light hydrocarbons. The best catalyst selected from LDPE lab experiments, was then tested upon the pyrolysis of plastic film waste obtained by a waste treatment plant. The research objective reported in this paper was to obtain a fraction of combustible gases in the largest possible proportion, which can be much easier exploited by burning in an engine that drives an electric generator.

Academic procrastination, more than merely postponing tasks, represents a significant failure in the self-regulation process of learning. Research on study skills highlights academic time management as one of the crucial elements of learning strategies and sustainable education. These abilities will help achieve the Sustainable Development Goals fourth goal. Therefore, this study aimed to understand how students plan time management in school activities and its influence on study procrastination, analyzing differences between genders and the hours students spend studying. The Time Management Planning Inventory, the Study Procrastination Questionnaire, and a personal and school data sheet were used. A sample of 506 students from elementary schools in northern Portugal was utilized. The results revealed that gender and study hours significantly influence how students plan time management for school tasks in the short and long term. This variable also showed a significant impact on the procrastination of study activities. The practical implications of this study are substantial, as they provide educators and researchers insights into the factors influencing academic procrastination and the role of time management planning and study hours. These insights can be applied to develop effective strategies to reduce academic procrastination and promote sustainable education.

This study investigates anomaly detection of IoT device traffic using Convolutional Neural Networks (CNN) and Variational Autoencoders (VAE) to enhance the detection capability of security threats in IoT environments. A series of hardware configurations, software environments, and hyperparameters were utilized to optimize the training and testing processes of the models. The CNN model demonstrates robust classification performance, achieving an accuracy rate of 95.85% on the test dataset, effectively distinguishing between different types of IoT device traffic. Meanwhile, the VAE model exhibits proficient anomaly detection capabilities by effectively capturing abnormal patterns in the data using reconstruction loss and KL divergence. The combined use of CNN and VAE models offers a comprehensive solution to cybersecurity challenges in IoT environments. Future research directions include exploring diverse IoT traffic data, practical deployment for validation, and further optimization of model structures and parameters to improve performance and applicability.

Introduction: Transportation logistics play a pivotal role in facilitating both individual mobility and supply chain operations on a global scale. However, conventional transportation systems have contributed significantly to urban congestion and environmental degradation. In response to these challenges, there is a growing momentum towards the adoption of intelligent transportation systems (ITS) and sustainable transportation solutions. This research aims to explore the potential of renewable energy sources to power electric vehicles (EVs) and flying automobiles, thereby accelerating the transition towards a low-carbon future. Objectives: The primary objectives of this research are as follows: - Investigate the role of renewable fuels in powering both EVs and flying cars to reduce reliance on fossil fuels and mitigate carbon emissions. - Analyze the dynamic growth and sustainability implications of advancements in battery technology and alternative renewable energy sources, such as Hydrogen Fuel Cells. - Evaluate the challenges and opportunities associated with the integration of flying vehicles into existing transportation infrastructure, focusing on safety, airspace control, and infrastructure development. - Review insights and guidance to stakeholders on promoting sustainable transportation solutions for EVs and flying cars through the utilization of renewable energy sources and the reduction of carbon emissions from the literature. Methodology: This research employs a mixed-method approach, combining literature review, and causal loop diagram analysis. The literature review provides a comprehensive understanding of current trends, challenges, and opportunities in sustainable transportation and renewable energy technologies. A causal loop diagram is utilized to visualize the dynamic interactions between various factors influencing the adoption of EVs and flying cars, including technological advancements, policy interventions, and market dynamics. Results and Discussion: The findings of this research highlight the significant potential of renewable energy sources, such as solar, wind, and hydrogen, in powering both EVs and flying cars. Advances in battery technology and hydrogen fuel cells are identified as key drivers in accelerating the transition towards sustainable transportation systems. However, challenges remain in terms of infrastructure development, safety regulations, and airspace management for flying vehicles. Nevertheless, there is a noticeable advancement in reducing carbon emissions and reliance on fossil fuels with the widespread adoption of EVs. By harnessing renewable energy and implementing effective policy measures, stakeholders might able to promote the widespread adoption of sustainable transportation solutions, thereby contributing to environmental protection and societal well-being. Conclusion: Literally, this research underscores the importance of sustainable transportation solutions in addressing urban congestion, environmental pollution, and energy security concerns. By leveraging renewable energy sources and embracing technological advancements, such as EVs and flying cars, stakeholders pave the way for a more sustainable and resilient transportation system. However, concerted efforts are needed to overcome existing challenges and ensure the successful integration of these technologies into existing infrastructure. Through collaborative partnerships and innovative initiatives, a low-carbon future for transportation logistics can be achieved, benefiting both the environment and society as a whole.

(1) Background: The lateral arm flap has been the very useful choice in the reconstruction of small- to medium-sized defects like hand, extremity, oral head and neck area reconstructions. Its versatile characteristics and surgical feasibility allow this flap to be widely applied, but the reconstructive potential in facial subunit after tumor ablative procedures has never been reported. In this study, we aimed to utilize the advantages of the flap to treat facial temple subunit defect reconstruction. (2) Methods: Between 2020 and 2023, 12 patients underwent temple reconstruction with lateral arm free flaps after malignant tumor wide excision. There were 7 women and 5 men, and the mean patient age was 60.6 years old. Among the patients with cancer, 6 had squamous cell carcinoma, 5 had basal cell carcinoma and 1 had myxofibrosarcoma. All the flaps were elevated under general anesthesia. Aloprostadil(PGE1, Eglandin®) were administered postoperatively. (3) Results: All the flap types were fasciocutaneous type with varied sizes from 3 × 4 to 5 × 7 cm (Average size of flap 22.7cm2) were utilized. The average pedicle length was 6.1cm. The versatility of the lateral arm flap enabled successful coverage of all cases with no specific complications. Good functional outcome and range of motion in the recipient arm were obtained after surgery. (4) Conclusion: The authors successfully verified the advantages of lateral arm flaps in the treatment of medium sized facial subunt temple defect reconstruction.

Background: Self-harm (SH) refers to self-injury or intentional self-poisoning with varying degrees of suicidal intent and is a major public health issue for children and adolescents (C&A) worldwide. Given significant gaps exist in our understanding of the associated psychopathology in C&A, this paper outlines the protocol for a prospective clinical study examining risk factors of SH and additional candidate parameters (not routinely assessed) during an acute SH episode. Methods: The EXPAAND (EXploring Psychiatric and Attentional risk-factors in Adolescents Needing intervention for Deliberate self-harm) is a randomised control trial to assess additional novel candidate risk factors for SH in C&A and to evaluate the effectiveness of SH-targeted brief psychological intervention (Therapeutic Assessment (TA)), within a real-world acute clinical setting, as we include neurodiversity and gender diversity in this study. EXPAAND is conducted in 4 phases: (i) recruitment & randomisation; (ii) extended assessment; (iii) randomised intervention; and (iv) follow-up observational period to ascertain clinical outcomes for comparison. Expected Results: We envisage that by diagnosing and treating attentional disorders when detected will mitigate potential confounding effects of these conditions. We also expect that SH-focused TA will be effective in reducing subsequent SH and in improving engagement in follow-up and subsequent treatments.

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

This research follows the publication of recent scoping and systematic reviews of existing literature on vaccine literacy (VL), its relationship to vaccine hesitancy (VH), and associated variables, such as vaccination beliefs, attitudes, and behaviors towards immunization. In this review, 17 articles were selected, published between December 2022 and November 2023, in which VL tools were used, most of which support the notion of a negative association between VL and VH, although not confirmed by others. Moreover, the definitions of the variables under consideration were not homogeneous between studies, some aimed to evaluate the association of VL with vaccine confidence, while others were more focused on outcomes such as willingness to be vaccinated or vaccine uptake. The complexity of the factors underlying VL, and the heterogeneity of the methods applied in the studies, in particular the limitations of cross-sectional surveys, still make it difficult to have a comprehensive understanding of the role of VL. Therefore, it is important to develop future assessment tools that consider not just the measurement of psychological factors connected to the motivational aspect of VL, but also those related to knowledge and competencies. For this purpose, a theoretical framework is proposed, where the positioning of VL at the intersection between antecedents and beliefs/attitudes leading to behaviors explains why and how VL serves as a tool and a critical, direct, or mediating driver of vaccination choices, overcoming VH and increasing vaccination rates, operating at personal, as well as at organizational and community level.

The Yellow-legged Hornet (Vespa velutina nigrithorax) (YLH) is an invasive insect that arrived in Europe in 2004 and is now spread across nine countries. It is a threat to the native entomofauna and harmful to beekeeping and agriculture, as it is a ravenous predator of the European Honey Bee (Apis mellifera) and other pollinating species. Its expansion has been unstoppable and all resources are needed to fight against it, including native vertebrate predators. Among these, the European Bee-eater (Merops apiaster) (EBE) is a potential one, but little is known about its predation on YLH. In a study carried out in Portugal, remains of YHL were detected in EBE nesting sites, which to the best of our knowledge is the first such report. This means that this bird could be one more agent in the biological control of this pest (although research on predation intensity is still needed), in conjunction with other natural predators and other strategies. In the Iberian Peninsula both species are allopatric in vast regions, so the role of EBE may be more limited. However, in the rest of Europe, at a country or continent scale, the scenario may be different and sympatry may occur to a greater extent.

This study uses the social impact theory to analyse consumer behaviour amidst Covid-19. Fear of scarcity has changed consumer buying behaviour in crisis times such as the now abating global health crisis – i.e., Covid-19. The study asserts that the existing five-stage model of consumer purchasing decisions does not fit neatly in turbulent times. It proposes a shortened four-stage process of need recognition, purchase, ownership and satisfaction as a better and more adaptable fit. Cutting out information search and evaluation of alternatives in the old model, and replacing these with ownership, is where the main contribution of the study lies. The study has implications for managing the marketing mix as we know it. It asserts that not all the 4Ps of the marketing mix are important in crisis times.

Reproductively lethal mutations (RLMs) are mutations that, upon expression of the encoded lethal phenotypes, cause individuals carrying them to die or to be sterile. An underappreciated fact is that loss-of-function RLMs in protein-coding genes can be phenotypically shielded by favorable environments rendering these genes conditionally non-essential, or by their sister alleles in diploid organisms. Absent of rigorous mitigation, such phenotype-shielding causes the number of genes incurring RLMs to increase over time, and simultaneously allows each RLM to reach high allele frequencies in a conspecific population. Over-accumulation of RLMs then sets the population up for eventual concurrent expression of large numbers of RLMs, and massive deaths in rapid succession, possibly even population-level extinction. This hypothetical scenario in turn predicts that organismal lineages that evolved means to minimize the allele frequencies of phenotypically shielded RLMs are favored by natural selection. We argue that bottlenecking the genome copies destined for reproduction is a universal strategy adopted by all living beings to compel phenotype-based RLM purging. We further postulate that primitive RNA replicons must first evolve bottlenecked reproduction before evolving the capacity to encode diffusible products. In more complex, multicellular organisms, RLM management through bottlenecked reproduction gains additional reinforcement through sexual reproduction. In short, the evidence chronicled in this essay strongly suggest that the Bottleneck, Isolate, Amplify, Select (BIAS) principle, originally proposed to explain intracellular evolutionary dynamics of viruses, may be universally applicable to all living beings.

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases. Methods: Cross-sectional descriptive study with 501 individuals aged 35 to 75 years recruited from five health centers by random sampling stratified by age and sex (55.90±14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor® device and carotid intima-media thickness using Sonosite Micromax® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X® accelerometer. Results: The mean VAI value was 61.23±12.86; (Men 63.47±13.75 and women 59.04±11.54; p

The increasing adoption of student-centred learning environs by the institutions of higher education in business, has led to new mechanisms and methodologies such as the Simulation-Based Learning (SBL), Problem-Based Learning (PBL) and Challenge-Based Learning (CBL). Literature has shown evidence of raising interest in these methodologies towards a more experiential paradigm with regard to upcoming events from the surrounding real-world context. This paper presents a Systematic Bibliographic Literature Review (SBLR) with respect to the integration and application of these innovative and collaborative methodologies in higher education. It aimed to identify its relevant advantages, challenges, and consequences for the future of business education. Bibliographic databases were searched for documents published up to May 2024 to categorize key topics discussed in the literature on SBL, PBL and CBL. The review process identified 89 empirical and non-empirical papers on SBL, PBL and CBL, business related paperwork, which resulted from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) method. PRISMA is a framework with evidence-based data designed to help authors perform a systematic literature review. Data analysis revealed diverse subthemes for those methodologies uses in business higher education institutions. The research questions “What are the advantages, challenges and implications of SBL, PBL and CBL altogether, in the training of business students?” guided the study. The central output of the research is the discovery of the varying uses of SBL, PBL and CBL overall, to cope with diverse demands arising within environmental context. Future research directions are suggested.

Introduction: The escalating morbidity, mortality, and healthcare costs associated with invasive candidiasis pose significant challenges in pediatric intensive care units (PICUs). Conventional diagnostic methods fall short in effectiveness, while various risk factors exacerbate the prevalence of these infections. This study introduces a novel model that amalgamates the Candida Score with key predictors to enhance the specificity and applicability of mortality risk assessments for pediatric patients with fungemia. Methods: This retrospective cohort study aimed to develop an integrated model for estimating mortality risk in children with fungemia in PICUs. We constructed and evaluated multiple predictive models using the Candida Score and other relevant clinical and laboratory variables. The discriminative abilities of the models were assessed using the area under the receiver operating characteristic curve (AUC). Results: The study cohort comprised 85 pediatric patients admitted between 2016 and 2020, with a median age of 6 months and a male predominance of 62.4%. The mortality rate was 45.9%. Candida albicans was the most prevalent causative agent, accounting for 37.55% of fungemia cases. Multivariable Logistic regression revealed the duration of mechanical ventilation, and the Candida Score were significant predictors of mortality. Each additional day of ventilation increased mortality odds by 11.5% (OR = 1.115, 95% CI: 1.025-1.212, p = 0.011), while a higher Candida Score more than doubled the odds (OR = 2.205, 95% CI: 1.359-3.578, p = 0.001).The Random Forest predictive model demonstrated superior discriminative performance, with an AUC of 0.838 (95% CI: 0.738-0.917), outperforming Gradient Boosting and Logistic Regression models, which had AUCs of 0.7759 (95% CI: 0.667-0.877) and 0.7085 (95% CI: 0.589-0.813), respectively. Although the internal validation yielded satisfactory results, external validation is warranted. Conclusion: This study presents an innovative approach for accurately assessing the risk of mortality due to fungemia in PICU patients by integrating the Candida Score with critical predictors. The Random Forest model emerged as the most effective predictive tool due to its exceptional discriminative ability.

Habenaria, a member of Orchidaceae family is the cosmopolitan distributions, which has significant medicinal and ornamental values. Regardless of morphology and molecular data that have been studied in recent times, the phylogenetic relationship is still under debate. Here, we sequenced, assembled, and annotated the whole chloroplast (cp) genome of two species (Habenaria aitchisonii Rchb.f. and Habenaria tibetica Schltr.ex Limpricht) of Habenaria grown on the Qinghai-Tibetan Plateau (QTP), and combined with seven already published cp genomes which may assist to uncover their genomic profiling. The two genomes ranged from 155259-155269 bp in length and both encoded 132 genes, including 86 protein, 38 tRNA and 8 rRNA. In the cp genomes, the tandem repeats (797), SSRs (2195) and diverse loci (3214) were identified. Comparative analyses of codon usage, amino frequency, microsatellite, oligo repeats and transition and transversion substitutions showed similarities among the species. Moreover, we identified 16 highly polymorphic regions with nucleotide diversity above 0.02, which may be suitable for robust authentic barcoding and inferring in the phylogeny of Habenaria species. Among the polymorphic regions, positive selection was significantly exerted on the several genes such as cemA, petA, and ycf1. This may suggest that the important adaptation stratagem for two Habenaria species on the QTP. The phylogenetic relationship displayed that H.aitchisonii and H. tibetica have closer relationship than others and the rest seven species clustered in the other three groups. Our findings also supported the idea that Habenaria could be divided into different sections. This study enriched the genomics resources of Habenaria, which may be helpful for the conservation efforts of these endangered species.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has changed considerably, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could lead not only to stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumor that finally permits liver transplantation. There are increasing reports of patients that have performed liver transplantation after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs to stimulate the immune response against tumors, they could also cause graft rejection. This review aims to evaluate the readiness and outcomes of liver transplantation in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to liver transplantation. While early evidence supports the feasibility of LT following ICI therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

Surface water plays a crucial role in climate change, human production, and life, making accurate monitoring and observation of surface water particularly important. However, due to the significant diversity and complexity of water distribution in surface space, accurate mapping of surface water faces considerable challenges. When extracting water bodies from medium-resolution satellite remote sensing images, CNN methods may suffer from limitations in receptive fields and insufficient context modeling capabilities, leading to the loss of water body boundary details and poor fusion of multiscale features. Currently, there is relatively little research on this issue; therefore, it is necessary to explore new combinations of deep learning networks to address these challenges. The purpose of this study is to address the above issues. We propose a new combination of deep learning networks that fully utilize multiscale information to enhance water features. Specifically, we first combine deformable convolutions with the Swin Transformer to increase effective receptive fields while better integrating global semantic information. This combination can capture features of water bodies at different scales, improve the accuracy and integrity of water extraction, and provide reliable technical support for detailed water body extraction. We tested the newly constructed model using Sentinel-2 satellite images. Our model achieved results of over 90%, with an average accuracy of 97.89%, average precision of 94.98%, average recall of 90.05%, and an average F1 score of 92.33%. In addition, our model achieved an accuracy of 98.03% in mountainous areas. Our experiments and results validate the potential of combining the Swin Transformer and deformable convolutions in detailed water body extraction.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

The deaf-mute and individuals with hearing disabilities who communicate through sign language should not be overlooked or excluded. It is a social responsibility to strive for an inclusive world without inequality. Advances in technology offer various solutions to address the communication gap, one of which is the use of computer-based sign language recognition systems. This project proposes a Malaysian Sign Language recognition model utilizing MobileNetV1, a convolutional neural network-based algorithm, to interpret sign language in real-time settings through a website application using Streamlit. The outcome of the model test shows that it has achieved a recognition rate of 96 percent. Although the proposed model has demonstrated the ability to recognize sign language, it is suggested that further improvement can be achieved by enhancing the quality and diversity of the dataset. The implementation of a more comprehensive dataset would lead to improved performance and increased accuracy of the model. This project underscores the importance of considering and accommodating the needs of the deaf-mute and individuals with hearing disabilities and highlights the potential of technology to bridge communication barriers and achieve a more inclusive society.

Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

The institutionalization of people with intellectual disabilities has been a common international response across cultures and generations that persists to this day. This chapter recounts its inheritance and manifestation in modern service provision. An institutional mind-set persists among clinicians and managers despite policies that emphasise the rights of persons with intellectual disability and anti-discriminatory practice. Alternative provision is rooted in person-centred practice; with a growing body of evidence for the improved quality of life that results from it. A reflective activity encourages readers to examine a recent case when they were associated with an institutional placement and what alternatives might have been sought. Yet alliances with other professionals, self-advocates and family carers will be needed to effect real and lasting changes in our service cultures and even then, the long shadows of institutional care may still persist.

Objective To investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. Design A single- center pilot trial Setting Faculty of Health, Tsukuba University of Technology, Japan Participants hypertensive community-dwelling elderly people Intervention Microcirculation was observed before and 1 min after arm-curl exercise by means microscopy of capillary with non-exercised limb. Additionally, we examined other health-related indicators. Outcome measures: Acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters.　 Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3±6.7 to 2.7±0.2 log µm/s (P

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

As the fast growth of information technology (IT), the safety of image transmission and the storing of images are increasingly concerned. Traditional image encryption algorithms have certain limitations in transmission and security, so there is an urgent need for a secure and reliable image encryption algorithm. A universal compression sensing (CS) image encryption (IE) algorithm based on DNA-triploid mutation (DTM) is presented in this paper. Firstly, by using CS algorithm an image is compressed while obtaining a range of chaotic sequences by iteration of chaotic map. Then DNA sequences are generated by encoding the image, and based on the DTM, new mutant DNA sequences are generated according to specific rules. Next, the chaotic sequences are operated at the DNA level to do confusion and diffusion operations on the image to ensure the security of the data. At last, DNA decoding is carried out to obtain the compressed-encrypted image. Both simulation experiments and performance tests fully show that a high level of security and reliability of the proposed algorithm in protecting image privacy is achieved.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

During the progression of cancer cells, the degree of genome instability increases leading to genome chaos in populations of malignant cells. While normally chaos is associated with er-godicity, i.e., the state when the time averages of relevant parameters is equal to their phase space averages, the situation with cancer propagation is more complex. Chromothripsis, a catastrophic massive genomic rearrangement, is observed in many types of cancer leading to increased mu-tation rates. We present an entropic model of genome chaos and ergodicity and experimental evidence that increasing the degree of chaos beyond the non-ergodic threshold may lead to the self-destruction of the tumor cells. We study time and population averages of chromothripsis frequency in cloned rhabdomyosarcoma from rat stem cells. Clones with frequency above 10% result in cell apoptosis possibly due to mutations in the BCL2 gene. Potentially this can be used for suppressing cancer cells by shifting them into a non-ergodic proliferation regime.

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

Evaluating mutation testing behavior can help decide whether refactoring successfully maintains the expected initial test results. Moreover, manually performing this analytical work is both time-consuming and prone to errors. This paper extends an approach to assess test code behavior and proposes a tool called MeteoR. This tool comprises an IDE plugin to detect issues that may arise during test code refactoring, reducing the effort required to perform evaluations. A preliminary assessment was conducted to validate the tool and ensure the proposed test code refactoring approach is adequate. By analyzing not only the mutation score but also the generated mutants in the pre- and post-refactoring process, results show that the approach is capable of checking whether the behavior of the mutants remains unchanged throughout the refactoring process. This proposal represents one more step toward the practice of test code refactoring. It can improve overall software quality, allowing developers and testers to safely refactor the test code in a scalable and automated way.

Data-Flow and Higher-Order Mutation are white-box testing techniques. To our knowledge, no work has been proposed to compare data flow and higher-order mutation. This paper compares all def-uses data-flow and second-order mutation criteria. This compassion investigates the subsumption relation between these two criteria and evaluates the effectiveness of test data developed for each. To compare the two criteria, a set of test data satisfying each criterion is generated, which is used to explore whether one criterion subsumes the other criterion and assess the effectiveness of the test set that was developed for one methodology in terms of the other. The results showed that the mean mutation coverage ratio of the all du-pairs adequate test cover is 80.9%, and the mean data flow coverage ratio of the 2nd-order mutant adequate test cover is 98.7%. Consequently, 2nd-order mutation “ProbSubsumes” the all du-pairs data flow. The failure detection efficiency of the mutation (98%) is significantly better than the failure detection efficiency of data flow (86%). Consequently, 2nd-order mutation testing is “ProbBetter” than all du-pairs data flow testing. In contrast, the size of the test suite of 2nd-order mutation is more significant than the size of the test suite of all du-pairs.

Abstract: Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2 which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (S) used for viral entry. These mutations, especially in the S, enable the virus to evade the immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase their immunogenicity.

Rojolele is an Indonesian traditional rice variety from Klaten (Central Java) that classified as tropical japonica and low land rice which become a premium rice variety and have higher price in the market due to a delicious taste and a fragrance aroma. The agronomic characteristics of Rojolele are having high plant stature with sturdy stems and upright plant shape, thick and rough leaves, strong and deeper root systems, long panicle length, and long duration of life. Rojolele rice cultivation is facing important challenges from drought, diseases, long duration, and lodging. Thus, breeding Rojolele cultivars with resistance to drought, diseases, lodging, and short duration is the major focus for Rojolele rice improvement. Indonesian farmer have learned to successfully cultivate Rojolele by applying practical skills, leading to increase the rice productivity. Molecular breeding program, including quantitative trait loci (QTL), genome-wide association study (GWAS), genomic selection, and genome editing can be applied to improve Rojolele characteristics. In this review, important agronomic and quality traits, intensification system for irrigation and pest control, mutation breeding, transgenic lines, and also future perspectives for Rojolele research were presented. Rojolele is useful for rice breeding program in order to guarantee the food security to overcome increasing population and climate change.

The development of new cultivars is important for the profitability of the floriculture industry. There are a limited number of cultivars of Zantedeschia aethiopica, an iconic ornamental cut flower, garden plant, and potted plant, due to the incompatibility of interspecific crossings within the genus. Most present-day varieties are the result of spontaneous mutations or classical breeding within the species, followed by a long selection process. Breeders are very interested in the development of a time- and cost-effective method for producing new Z. aethiopica cultivars with novel characteristics. Here, Z. aethiopica mutants were generated by treating seeds with 100 Gy of X-ray radiation. The resulting putative mutants were selected based on particular flowering parameters and compared to non-irradiated, control plants. Over two growing seasons, characteristics such as early flowering, flower size and shape, yield and response to soft-rot disease were monitored and considerable variation was observed among the mutated lines. Out of 319 mutants, 20 lines were selected based on their phenotypes and then propagated and further analyzed. Within this group, only two phenotypes displayed at least five improved flowering properties under natural, Mediterranean conditions. The rest displayed two to four desired combinations of flowering traits, some with great commercial potential.

Alzheimer’s disease (AD) is a genetically complex senile neurodegeneration with unknown etiology. The first gene discovered to be mutated in early-onset AD, the amyloid precursor protein (APP), has been widely assumed as a causal factor in the disease cascade due to its generation of Aβ species. APP has an evolutionarily conserved biological role and activates a signaling program with notable similarities to integrin—a cell adhesion receptor with a wide array of functions. Intriguingly, several AD genome-wide association study (GWAS) candidate genes, including the SHARPIN locus recently reported by us and others, influence signaling of the integrin pathway. Integrins are focal adhesion regulators and serve in nervous system development, synaptic plasticity, and Tau phosphorylation. These observations suggest that the function of APP probably goes beyond Aβ generation in AD. Aging—the strongest risk factor for AD—is associated with various clock-like events in cells. For instance, neurons are continuously impacted by stochastic ‘hits’ to their genomes in aging, in the forms of DNA damage, insertion-deletions, copy-number variations (CNVs) and other types of somatic mutations. DNA damage and somatic mutations can result in neoplastic changes and cancer in mitotically active cells. However, their consequences in post-mitotic cells such as aging neurons are less defined. The current hypothesis holds that the stochastic loss of DNA sequence data at random loci in aging affects longer genes by chance more frequently. As a result, the biological processes coordinated by long genes may be more vulnerable to such random aging effects. Curiously, as shown by us and others, long genes are strongly enriched for synapse- and cell adhesion-related ontologies, more than any other biological process or cellular compartment. In addition, among various cell types, neurons possess the highest levels of long gene expression and are therefore more vulnerable to such harmful effects. The long gene vulnerability hypothesis provides a simple link between aging and the genetic landscape of AD and warrants new strategies for disease modification.

There are many theories of carcinogenesis arguing against the orthodox mutation theory, debating on such as “epigenetic alteration” that is inheritable and yet, theoretically, reversible. Our integrated theory describes that any extracellular, intracellular, or intranuclear stressors, mutagenic or not, can initiate a lengthy tumorigenesis to engender a benign or malignant tumor, but the aberrations directly establishing cellular immortality and autonomy may be epigenetic or genetic alterations in the genomic DNA. A neoplasm is considered a semi-new organism with autonomy; it therefore should have genetic mutations to be “new”. We may be able to direct cancer cells towards differentiation as a remedy, because the extracellular milieu may control the phenotype of a cell and the tissue or organ made of the cell’s progenies, and the cytoplasm of a cell may override the nucleus in the phenotypic control. However, the nucleus retains the capacity to manifest itself if allowed by the microenvironment, which then allows the already reversed cells to revert back to tumor cells again. Neoplasms are malignant if they bear epigenetic or genetic anomalies in mutator genes defined as those whose alterations allow or accelerate alterations to occur in other genes, whereas neoplasms are benign if they bear epigenetic or genetic aberrations only in non-mutator genes. It is imperative to identify the immediate tumor-causing cellular alterations defined as those directly responsible for immortality and autonomy, and for treatment purposes to identify the extracellular and intracellular factors that control the phenotype of cancer cells.

Ploidy is a significant type of genetic variation, describing the number of chromosome sets per cell. Ploidy evolves in natural populations, clinical populations, and lab experiments, particularly in fungi. Despite a long history of theoretical work on this topic, predicting how ploidy will evolve has proven difficult, as it is often unclear why one ploidy state outperforms another. Here, we review what is known about contemporary ploidy evolution in diverse fungal species through the lens of population genetics. As with typical genetic variants, ploidy evolution depends on the rate that new ploidy states arise by mutation, natural selection on alternative ploidy states, and random genetic drift. However, ploidy variation also has unique impacts on evolution, with the potential to alter chromosomal stability, the rate and patterns of point mutation, and the nature of selection on all loci in the genome. We discuss how ploidy evolution depends on these general and unique factors and highlight areas where additional experimental evidence is required to comprehensively explain the ploidy transitions observed in the field and the lab.

Novel SARS-CoV-2, a bat based virus originated in Wuhan, China that caused a global pandemic in December, 2019 belongs to the Betacorona virus family and contains single stranded genome of ~29Kbp. The host cell invasion of SARS-CoV-2 is facilitated by interaction of C-Terminal Domain (CTD) of Spike (S) protein of virus and host ACE2 receptor in the presence of TMPRSS seine protease secreted by the host cell. In this study the mutation hotspots of S-protein will be identified and the impact of such mutation in the binding affinity will be studied. Additionally, the lead molecule which can bind to the mutated protein also will be identified. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D614G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated proteins were modelled based on wild type homolog and docked to ACE2 receptor. When the mutated S protein is docked, the ∆G (binding free energy) value is very minimal in mutated protein showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these drugs Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with higher docking score (lesser than -8.5 Kcal/mol) to both wild type and mutants.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

Limited research has been conducted on the metabolites present in the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (PR, syn. Lamiophlomis rotata (Benth.) Kudô), and their potential pharmacological activities, such as antioxidant properties, are often overlooked. We conducted a metabolomics-based screening to identify the characteristic metabolites (CMs) in the EOs extracted from PR. Meanwhile, we evaluated their in vitro antioxidant activities (AOAs). The EOs obtained through hydro-distillation are characterized by a light yellow color and a fresh, elegant fragrance. Cryoprecipitation was used to separate the crystals (Crs) from the EOs, resulting in the crystal-free EOs (CFs). A total of 121 components are identified and quantified in the EOs, Crs, and CFs. Among them, 84 were reported for the first time from such EOs. The major compounds include long-chain fatty acids (LCFAs) and their esters, such as palmitic acid (PA), myristic acid (MA), linoleic acid (LA), oleic acid (OA), stearic acid, and methyl palmitate (MP). Furthermore, 11 kinds of apocarotenoids (also called norisoprenoids) were first systematically investigated. Among them, eight C13-norisoprenoids, with trans-β-damascenone (DN) being particularly notable for its flavor, were identified. A sum of 11 CMs are screened , including PA, MA, LA, OA, MP, hexahydrofarnesyl acetone, phytol (PT), DN, stearic acid, linalool, and hexanal. These CMs are biosynthesized through FAs and 2-C-Methyl-D-erythritol 4-phosphate/1-Deoxy-D-xylulose 5-phosphate pathways. The in vitro AOAs of EOs, Crs, CFs, and seven selected CMs (PA, MA, LA, OA, MP, PT, and DN) were evaluated. Generally, PA and MA exhibited pro-oxidant activities (POAs) or weak AOAs. LA and OA demonstrated POAs or weak AOAs at lower concentrations, but at higher concentrations, they displayed medium to strong AOAs. Importantly, the CFs typically exhibited stronger AOAs compared to the corresponding EOs and Crs, potentially due to variations in their PA content. Overall, this study provides valuable insights into the potential utilization of EOs from PR.

Fluorinated cytokinins have emerged as promising alternatives to traditional cytokinins in plant tissue culture, offering enhanced stability and bioactivity. However, their metabolic fate and impact on endogenous cytokinin profiles remain largely unexplored. This study investigated the cytokinin metabolism of Phalaenopsis orchids under varying exogenous cytokinin treatments (BA, FmT, FmTR) and culture conditions (open vs. closed containers). The results reveal distinct metabolic profiles associated with each treatment, highlighting the complex interplay between exogenous and endogenous cytokinin levels. Additionally, we proposed an alternative inactivation pathway involving the conversion of FmTR and BA to pT and pTR. These findings provide valuable insights into the intricate relationship between cytokinin metabolism and plant growth under in vitro conditions, with implications for optimizing micropropagation protocols

The increasing focus on sustainability and the adoption of green practices across industries underscore the necessity of equipping future professionals with competencies in implementing sustainable solutions. This study explores the perceptions of former students from two departments within the technological sector towards sustainability practices. A cross-sectional online survey was carried out among alumni from two programs at the University of Thessaly, a university recognized for its commitment to sustainability and green initiatives as a member of the INVEST European University alliance. The survey questionnaire included background inquiries and 16 statements designed to gauge alumni perspectives towards sustainability practices. Specifically, it aims to assess their views through self-assessment and compare differences between the two alumni groups. Responses were collected on a 5-point Likert scale ranging from strongly disagree to strongly agree. A total of 300 graduates from the Computer Science and Telecommunications as well as Electrical Engineering undergraduate programs were encouraged to take part in the survey, achieving a response rate of 69%. Of those who responded, 61% (n = 126) represented the Computer Science and Telecommunications group, while 39% (n = 81) were from the Electrical Engineering program. Our findings indicate a generally positive attitude towards sustainability, with statistically significant differences in perspectives on the implementation of sustainable technologies and stakeholder engagement. These results underscore the necessity of integrating sustainability education deeply within the curricula of technological programs to cultivate a workforce capable of addressing future environmental challenges. This study illuminates the critical role of educational frameworks in shaping the sustainability competencies of technology professionals.

Introduction: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, character-ized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). Purpose: This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p=0.001 and p=0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p3gr/24h with diffuse fusion of podocyte foot processes (p=0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine represent markers of podocyte dysfunction and in our study they were associated both with serum creatinine and histological chronicity indices.

The rise of the Internet has enabled people to express their opinions on various subjects through social media, blogs, and website comments. As a result, there has been a significant increase in research on sentiment analysis. However, most of the research efforts have focused on analyzing sentiment in English-language data, neglecting the wealth of information available in other languages. In this paper, we provide a comprehensive review of the current state-of-the-art in multilingual sentiment analysis. The survey investigates techniques for data preprocessing, representation learning, and feature extraction in multilingual sentiment analysis. It explores cross-lingual transfer learning, domain adaptation, and data augmentation methods that enhance the performance of sentiment analysis models, particularly in low-resource languages and domains. It provides insights into the state-of-the-art approaches, challenges, and opportunities in this evolving field and encourages further advancements in multilingual sentiment analysis research.

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included "central giant cell granuloma," "recurrence," "treatment modalities," and "surgical excision". Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon alpha therapy and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (&gt;3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options.

The clothing industry is a hotbed for exploitative working conditions and environmental damages, of which affluent global North countries remain a substantial driver. The circular economy is a potential solution to these issues, but its social implications remain unclear. Using the UK as a case study, this article analyses the global social impacts of a transition to circular clothing economies in the global North, finding these to be (almost) entirely dependent upon the intentions and design of the associated politics. Some aspects of a transition will be unambiguously good for some people; others will only be beneficial with careful governance. Moreover, entrenched global economic inequalities leave trade-offs borne largely by the global South, highlighting the need for circular economy research – its drive for localisation notwithstanding – to look globally to consider how a fair transition can be achieved.

This research aims to explore the adoption and impact of green supply chain practices (GSCP) on sustainable development in Bangladesh. The study seeks to understand the current state of GSCP adoption across various industries, identify key drivers and barriers, assess the perceived benefits and challenges, and evaluate the overall impact on environmental sustainability, economic performance, and social well-being. The research employs a qualitative approach, utilizing interviews with key stakeholders, document analysis, and literature review to gather data and insights. Interviews were conducted with representatives from government agencies, businesses, civil society organizations, and academia to obtain diverse perspectives on GSCP adoption and its implications for sustainable development in Bangladesh. The findings reveal a mixed scenario of GSCP adoption across different industries in Bangladesh, with sectors such as textiles leading the way. Key drivers of GSCP adoption include regulatory pressures, market forces, corporate social responsibility initiatives, and financial incentives. However, organizations face significant barriers such as high upfront costs, lack of awareness and expertise, regulatory uncertainty, and supply chain complexity. Despite these challenges, GSCP offer various benefits, including environmental sustainability, economic performance, and social well-being. Successful initiatives demonstrate tangible impacts, highlighting the potential of GSCP to contribute to sustainable development. The research is limited by its qualitative nature and focus on selected industries and stakeholders. Future studies could employ quantitative methods and broader sampling to provide a more comprehensive understanding of GSCP adoption and its implications in Bangladesh. The findings provide actionable insights for policymakers, industry leaders, and other stakeholders to promote GSCP adoption and enhance sustainable development in Bangladesh. Strategies for overcoming barriers and maximizing benefits are outlined, emphasizing the importance of collaboration and capacity-building initiatives. GSCP adoption can have positive social implications by promoting ethical labor practices, improving working conditions, and fostering community engagement. By prioritizing sustainability, businesses can contribute to social well-being and inclusive growth. This research contributes to the literature on GSCP adoption and sustainable development in Bangladesh by providing empirical insights and practical recommendations. The study adds to the understanding of the drivers, barriers, benefits, and challenges associated with GSCP adoption, highlighting the importance of integrating environmental, economic, and social considerations in supply chain management.

The Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical composition. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with concentrations of EOs. Repellent rates ranged from 80.50% to 100.00% after treating D. citri for 6 hours with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 hours of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24-hour repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, both ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

The purpose of this research is to examine the benefits and limitations of implementation of novel digital academic advising systems using automated collection and reporting processes for ABET student outcomes data based on principles of authentic OBE for effective developmental advising. We examine digital developmental advising models of undergraduate engineering programs in two universities that employ customized features of the web-based software EvalTools® - Advising Module based on assessment methodology incorporating the Faculty Course Assessment Report, Performance Indicators and hybrid rubrics classified according to the affective, cognitive and psychomotor domains of Bloom’s learning model. A case study approach over a six-year period is adopted for this research. The two case studies present results of samples of developmental advising activity employing sequential explanatory mixed methods models using a combination of quantitative and qualitative analyses of a) detailed students’ outcomes and Performance Indicators information; and b) self-evaluation of their professional development and lifelong learning skills. The findings of this study show that digital advising systems employing the Faculty Course Assessment Report using Performance Indicators and hybrid rubrics can provide comprehensive and realistic outcomes data to help both developmental advisors and students easily identify the specific cause of performance failures, implement practical recommendations for remedial actions and track improvements. Inherent strong skills can also be identified in academically weak students by observing patterns or trends of relatively better performing outcomes to reinforce natural affinity for learning specialized competencies and pursue related and successful career paths.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

This study presents a groundbreaking approach in the field of gaming AI, focusing on the classic game” Pacman” through the lens of DRL integrated with advanced optimization techniques. The core of the research involves adapting DRL models for” Pacman”, utilizing the ESO for hyper- parameter tuning. These novel adaptations significantly enhance the AI agent’s performance, demonstrating a remarkable improvement in adaptability, responsiveness, and efficiency within the game environment. A pivotal aspect of this research is the innovative integration of metaheuristic optimization techniques into the DRL framework, a first in the domain of Atari gaming AI. This integration has proven essential in fine-tuning the DRL models, leading to a more effective and dynamic gaming experience. The study thoroughly evaluates and compares the performance of these algorithms, providing empirical support for their effectiveness and setting a new benchmark in AI-driven game development. The implications of this research extend beyond gaming AI, opening up possibilities for future exploration in several directions. Expanding DRL models to other complex gaming environments, continuous algorithmic enhancements, real-time learning adaptations, and applying these principles to robotics and autonomous vehicles are examples. The research also emphasizes ethical and responsible AI use in gaming to address fairness and addiction issues.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

Verification of inclusivity of molecular detection methods gives indications on the reliability of viral infections diagnosis because of the tendency of viral pathogens to undergo sequence variation. This study was aimed to select inclusive probe based reverse transcription quantitative PCR (RT-qPCR) assays for the diagnosis of the most widespread and detrimental viruses infecting honeybees, namely the acute bee paralysis virus (ABPV), the black queen cell virus (BQCV), the chronic paralysis bee virus (CBPV), the deformed wing virus variants A (DWVA) and B (DWVB), and the sacbrood virus (SBV). Therefore, detection methods previously described were re-evaluated in silico for specificity and inclusivity. Based on this evaluation, selected methods were modified or new ones were designed and tested in duplex RT-qPCR reactions. The limits of detection (LODs), effect of multiplexing on sensitivity and viral RNA quantification potential in bees and hive debris were assessed. This study made available diagnostic assays able to detect an increased number of virus variants compared to previously described tests and two viral pathogens in a single PCR reaction.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Coal bottom ash (CBA) is a byproduct of coal-burning power plants. This material can be used as a fine aggregate replacement in concrete to reduce global natural material depletion. Concrete usage is increasing rapidly; subsequently, the industry’s carbon footprint is increasing. Using CBA in the construction industry will reduce the technical and economic problems associated with power plants by reducing solid waste. This project aimed to determine if adding new sustainable materials, such as CBA, to concrete will reduce natural raw material usage, energy consumption, and greenhouse gas emissions while improving performance. This study included two projects: comparing increased CBA content to the two-control project and determining the optimum content based on the compressive strength. The optimum CBA content is 50%, which reduces fine aggregate usage in a concrete mix by 50% while maintaining equivalent or better concrete strength than a pure Portland concrete mix without CBA. The air content of the concrete mix containing % CBA decreased with increased CBA content and compressive strength, possibly due to the spacing factor of the voids in the mix and CBA’s porous and fineness behavior. The CBA optimum content had a unit weight lower than the controls for both projects, which makes the CBA mix a lightweight concrete. Using this material can significantly reduce natural material usage and environmental harm by reducing CBA waste disposal and improving concrete performance.

To facilitate the promotion and application of the whole process engineering consulting (WPEC) model, the transmission mechanism of influencing factors in WPEC's promotion and application is investigated. It identifies and categorizes the influencing factors within the framework of "external environment-project factors-stakeholders", systematically organizing and summarizing ten primary categories and thirty-eight secondary influencing factors of WPEC's promotion and ap-plication. Utilizing the complex network analysis method, a network of influencing factors in the promotion and application of WPEC is constructed. The network is then converted into three binary networks based on weight, which are subjected to structural analysis and motif analysis. On this basis, the transmission mechanism of influencing factors in WPEC's promotion and applica-tion and its causations are explored.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

HIV incidence remains alarmingly high among female sex workers (FSWs) in low- and middle-income countries, with Uganda being no exception. The elevated risk of HIV transmission among this vulnerable population can be attributed to a complex interplay of factors, including engaging in sexual activities with multiple partners, inconsistent condom usage, substance use, and structural barriers, such as legal criminalization and pervasive stigmatization by healthcare providers. To combat this epidemic, various HIV prevention interventions have been devised, targeting these multi-faceted challenges. This study involved conducting focus groups among FSWs and healthcare providers in Uganda, with the overarching objective of informing the development of a tailored HIV prevention intervention aimed squarely at FSWs. Through these discussions, valuable insights were gained into FSWs’ perceptions of their HIV risk, their attitudes regarding HIV prevention strategies, and their recommendations regarding the content and delivery of future interventions.

Insulin therapy is a cornerstone in the management of diabetes, yet the pursuit of optimizing its pharmacokinetic profile remains a focal point in diabetes research. For instance, insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising once-weekly treatment option for diabetic patients. However, designing insulin analogues with lower receptor affinity than that of insulin icodec could still produce a further extended duration of action than that of insulin icodec through the suppression of receptor-mediated internalization of insulin analogues. In this study, therefore, I present the design of a novel series of insulin analogues engineered towards lower binding affinity to the insulin receptor compared to that of insulin icodec. Through computational structural biophysics-based rational design strategies, this article aims to further extend the duration of action while maintaining therapeutic efficacy of insulin analogues. Utilizing homology molecular modeling and structural biophysics-based binding affinity calculations, this article puts forward a set of insulin analogues with lower binding affinity to insulin receptor than that of insulin icodec from a structural and biophysical point of view. Overall, this article calls for subsequent in vitro and in vivo evaluations of the efficacy and prolonged action of the engineered insulin analogues to pharmacokinetically test whether these analogues acutally surpass that of insulin icodec as hopeful candidates for next-generation insulin analogue therapies with improved duration of action and enhanced control of blood glucose levels for diabetic patients in future.

A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

Background: There is a paucity of evidence on people with thoracic aortic aneurysm and dissection. We aimed to determine the prevalence of genetic variants and associations with phenotypes. Methods: In the current cross-sectional single centre cohort study of consecutive patients who underwent endovascular or open-surgical repair of thoracic aortic aneurysm and dissection, we applied genetic analysis using four-stage Next Generation Sequencing and confirmed findings with Sanger sequencing. We collected personal and family history on comorbidities, clinical examination, anthropometrics, skeletal deformities, joint function ophthalmological measures. Cardiovascular risk- and phenotype scores were calculated. Results: 95 patients were eligible (mean age 54±9 years, 70% males, 56% aortic dissection). One-fifth had a family history of aortic disease, 95% and 54% had a phenotype score of ≤5 and ≤2, respectively. There weren’t significant differences in the distribution of phenotype characteristics according to age, sex, aortic pathology, or performed invasive procedure. Genetic variants were detected in 40% of patients; classic variants comprised 18% of all variants. We observed no significant association with cardiovascular and phenotype score but with higher joint function scores (p=.015). Conclusion: Genetic variants are highly present in clinically-relevant aortic pathologies. Variants appear to play a larger role than previously described. The different variants don’t correlate with specific phenotypes, nor with age, pathology, sex, or family history.

Peripheral arterial diseases (PAD) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors such as smoking, hypercholesterolemia, and hypertension have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. This article aims to provide a comprehensive review of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PAD. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases including PAD. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. The review delves into the relationship between CH and PAD, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further re-search to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.

We aimed to assess the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, as well as in synergic interaction with other standard risk factors. All cases were tested for BRAFV600E mutation by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event (tumor recurrence/distant metastasis) or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meyer analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p=0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age≥55 years-old (p<0.001), male gender (p<0.001), conventional (p=0.005) and tall cell (p=0.014) histology, tumor size&gt;40mm (p=0.001), extrathyroidal extension (p=0.001), multifocality (p=0.001) and lymph node metastasis (p&lt;0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p=0.018) was found for BRAFV600E mutated cases. Our results highlight the prognostic value of BRAFV600E mutation in PTCs. Moreover, the synergic interaction between BRAFV600E mutation and other risk factors seems more valuable in terms of prognosis, compared to BRAFV600E mutation alone.

Genomic surveillance represents an important strategy for understanding evolutionary mechanisms, transmission profile, and infectivity of different SARS-CoV-2 variants. We assessed the epidemiological profile of 366 individuals who tested positive for SARS-CoV-2 from 29 municipalities in Rondônia between December 2021 to March 2022. Samples were collected, RNA was ex-tracted and screened using RT-qPCR for Alpha, Beta, Gamma, Delta and Omicron VOCs and viral quantification was performed. Sequences were analyzed for phylogeny, mutations and lineages. Of the samples analyzed, 93.71% were positive for the Omicron variant and 6.28% were positive for the Delta variant. The symptoms observed were cough, sore throat, and fever, with a mean duration of 5 days; no hospitalizations or deaths were reported. We noted that among the positive individuals, 51% had been immunized with two doses, 22% received three doses, 13% received one dose, and 13% were not immunized. Just 242 samples were amenable to analysis for alignment and phylogenetic characterization; corresponding to variants BA.1 and BA.1.1; a total of 120 mutations were identified, 36% of which were found in the S gene. In conclusion, there was a high frequency of mutations in the SARS-CoV-2 genome, but no record of clinical severity, demonstrating the positive effect of vaccination.

Resistance to Pyrimethamine, an antimalarial medicine has been reported to be due to mutations in Dihydrofolate reductase-thymidylate synthase (DHFR-TS). Phytochemicals, particularly from plants that been used in ethnomedicine, have been reported to have privileged structures that might bind strongly to the mutants of DHFR-TS. The aim of this study is to identify phytochemicals of Acalypha wilkesiana, Cymbopogon citratus, Azadirachta indica, and Morinda lucida with high binding affinities for the Plasmodium falciparum DHFR-TS. The three-dimensional structures of the phytochemicals, wide type and mutant forms of DHTR-TS were obtained from PubChem and Protein Databank (PDB) respectively. They were appropriately prepared and molecular docking simulations was implemented to predict binding affinities of the phytochemicals to the wildtype and mutant forms of DHTR-TS. Druglikeness assessment was implemented to triage the top binding phytochemicals and molecular dynamics simulations was done to establish the stability of the interaction of the top-ranked phytochemical with one of the mutants of DHFR-TS. Nineteen phytochemicals showed higher binding affinities to both the wild type and mutant forms DHFR-TS than Pyrimethamine. Molecular dynamics revealed that the receptor-ligand binding of luteolin, the top-ranked, drug like phytochemicals, to the quadruple mutant was stable.

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 12 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. Today these patients are excluded from treatment with Trikafta. In Italy CF patients carrying F508del/unknown represent about 3% (156 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment.This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.

NPM interaction with tumor suppressor p53 is a part of a complex interaction network and considerably affects cellular stress response. An impact of characteristic AML-associated NPM mutations on interaction with p53 has not been investigated yet, although consequences of NPMmut-induced p53 export to the cytoplasm are important for understanding of leukemogenic potential of these mutations. We investigated p53-NPM interaction in live HEK-293T cells by FLIM-FRET and in cell lysates by immunoprecipitation. Results were confirmed in leukemia cell lines. eGFP lifetime-photoconversion was used to follow redistribution dynamics of NPMmut and p53 in Selinexor-treated cells. We confirmed the p53-NPMwt interaction in intact cells and newly documented that this interaction is not compromised by the NPM mutation causing displacement of p53 to the cytoplasm. Importantly, the interaction was not abolished for non-oligomerizing NPM variants with truncated oligomerization domain, suggesting that oligomerization is not essential for interaction of NPM forms with p53. Inhibition of the nuclear exporter XPO1 by Selinexor caused expected nuclear relocalization of both NPMmut and p53. However, significantly different return rates of these proteins indicate nontrivial mechanism of p53 and NPMmut cellular trafficking. We suggest that the altered p53 regulation in cells expressing NPMmut offers a new target for AML therapy.

Viruses have established symbiotic relationships with almost every other living organism on Earth and at all levels of biological organisation, from other viruses up to entire ecosystems. In most cases, peacefully coexisting with their hosts, but in most relevant cases, parasitising them and inducing diseases. Viruses are playing an essential role in shaping the eco-evolutionary dynamics of their hosts, and have been also involved in some of the major evolutionary innovations either by working as vectors of genetic information or by being themselves coopted by the host into their genomes. Viruses can be studied at different levels of biological organisation, from the molecular mechanisms of genome replication, gene expression and encapsidation, to global pandemics. All these levels are different and yet connected through the presence of threshold conditions allowing for the formation of a capsid, the loss of genetic information or epidemic spreading. These thresholds, as it occurs with temperatures separating phases in a liquid, define sharp qualitative types of behaviour. These {\em phase transitions} are very well known in Physics. They have been studied by means of simple, but powerful models able to capture their essential properties, allowing to understand them. Can the physics of phase transitions be an inspiration for our understanding of viral dynamics at different scales? Here we review well-known examples of transition phenomena in virology and their simplest mathematical modelling approaches. We suggest that the advantages of abstract, simplified pictures used in Physics are also the key to properly understand the origins and evolution of complexity in viruses. By means of several examples, we explore this multilevel landscape and how minimal models provide deep insights into a diverse array of problems. The relevance of these transitions in connecting dynamical patterns across levels and their evolutionary and clinical implications are outlined.

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&lt;0.001), KPS (&lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Background: SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020.^{2, 3, 4, 5} By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods: We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results: We identified 5 recently emerged mutations in many isolates (up to 40%). Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain in the SARS-CoV-2 genomes deposited in GenBank and GISAID by April 13, 2020. Conclusion: The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants may exist. The findings of current study lay the foundation for further investigation into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the G119S mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8 ± 3.5 % mortality) and propoxur (55.71 ± 2.9 %) but a full susceptibility to the organophosphate fenithrothion. The TaqMan genotyping of the G119S mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1^R and carbamate resistance at allelic [(bendiocarb; OR = 75.9; P<0.0001) and (propoxur; OR= 1514; P<0.0001)] and genotypic [RR vs SS (bendiocarb; OR = 120.8; P<0.0001) and (propoxur; OR= 3277; P<0.0001) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1^R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1^R represents a serious challenge to future implementation of IRS-based interventions using carbamates or organophosphates in Cameroon

Heat shock protein 47kDa (HSP47) serves as a client-specific chaperone, essential for collagen biosynthesis and its folding and structural assembly. To date, there is no comprehensive study on mutational hotspots and protein network for human HSP47. Using five different human mutational databases, we deduced a comprehensive list of human HSP47 mutations and we found 24 67, 50, 43 and 2 deleterious mutations from the 1000 genomes data, gnomAD, COSMICv86, cBioPortal, and CanVar. We identified thirteen top-ranked missense mutations of HSP47 with the stringent cut-off of CADD score (>25) and Grantham score (≥151) as Ser76Trp, Arg103Cys, Arg116Cys, Ser159Phe, Arg167Cys, Arg280Cys, Trp293Cys, Gly323Trp, Arg339Cys, Arg373Cys, Arg377Cys, Ser399Phe, and Arg405Cys with the arginine-cysteine change as the predominant mutation. We also found that HSP47 is up-regulated and down-regulated in 11 and 4 of cancers types. Upon constructing protein interactome map of human HSP47, we found that a set of molecular chaperones is interaction partners of HSP47, which included two copies each of CREB binding proteins, HSP27, HSP40, HSP70, HSP90, ubiquitin proteins and one copy each of cartilage associated protein (CRTAP), HSPH1, HSBP1, FK506-binding protein B (FKBP), kruppel-like factor (KLF13), peptidyl-prolyl isomerase PIPB and Prolyl 4-hydroxylase beta subunit (P4HB). This suggested a cocktail of different chaperones interact with HSP47. These findings will assist in the evaluation of roles of HSP47 in human disease including different types of cancers.

Present experimental study assesses the mechanical properties of glass/carbon/glass hybrid composite laminates after exposure to moisture and elevated temperatures for extended periods. The top and bottom layers of the hybrid laminates are glass fiber reinforced and the middle layer is carbon fiber reinforced with the matrix specified as a polymer material. The hybrid laminates were manufactured using the resin transfer molding method and their compressive and tensile properties were determined using a tensile testing machine. The material parameters such as the storage modulus, the loss modulus, and the damping factors of the laminates were identified using dynamic mechanical analysis as a function of the temperature and the vibration frequency. The experimental results on compressive and tensile properties revealed slight variations when the hybrid laminates were kept at low temperatures for extended periods. This might occur due to the increasing molecular cross-linking of the polymer network. As the temperature increased, compressive, tensile, storage modules, loss modulus, and damping factors decreased. This might occur due to the increasing mobility of the binder material. Particularly, the highest stiffness parameters were obtained on -80°C/GCG (Glass/Carbon/Glass) laminates due to the presence of beta transition on the glassy region. The relationships between the glass transitions and the targeted frequencies were characterized. The values of the glass transition shift towards higher temperatures as the frequency increases. This might occur due to a reduction in the gaps between the crosslinking of the epoxy network when the frequency increases. The accuracy of the storage modulus results was compared with the empirical models. The model based on the Arrhenius law provided the closest correlation. Meanwhile, another model was observed that was not accurate enough to predict when gamma and beta relaxations occur under a glassy state.

With firm commitment to energy labelling, it is not a question of if but only of when the European Union will introduce an energy label for electric cars. To support such policy efforts, we conducted a scoping analysis of energy consumption and efficiency trade-offs for 342 electric car models sold in Europe. The results suggest that certified and real-world energy consumption average 19 ± 4 kWh/100 km and 21 ± 4 kWh/100 km, translating into drive ranges of 440 ± 120 km and 380 ± 110 km, respectively. Energy consumption is correlated with vehicle mass, frontal area, and battery capacity, but less so with rated power and vehicle price. Each 100 kg of vehicle mass and 0.1 m2 of frontal area tend to increase energy consumption by 0.20 ± 0.06 kWh/100 km and 0.72 ± 0.05 kWh/100 km. Raising battery capacity by 10 kWh increases vehicle mass by 145 kg, energy consumption by 0.6 kWh/100 km, and drive range by 45 km. Efficient vehicles are available at any price but drive range has a cost. Our findings point to considerable efficiency trade-offs that could be tapped by a dedicated energy label. We propose several options for categorizing vehicles on an efficiency scale from A to G, with and without additional utility parameters. Our analysis provides rationale for energy labelling of electric cars in Europe and could inspire similar analyses for other vehicle categories such as e-scooters, lightweight three- and four-wheelers, e-busses, e-trucks, and electric non-road machinery.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of hepatocyte growth factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Reducing the carbon footprint of energy production is one of the most pressing challenges facing humanity today. Lignocellulosic biomass residues from fruit production industries show promise as a viable energy source. This paper presents a study of the Italian context concerning the utilization of orchard lignocellulosic residues for energy production as electricity or bioethanol. The potential of various orchard residues was assessed through chemical and physical analysis, and an equivalent electrical energy of about 6441.62 GWh or an amount of 0.48 Mt/y of bioethanol was obtained based on the average annual dry residue mass availability of about 3.04 Mt/y. These data represent the 9.30% of the national electrical energy production from renewable sources, as well as the 6.21% of the Italian demand for gasoline in 2022. Electricity generation from these residues shown its potential as a reliable and sustainable baseload power source, as well as source of renewable transportation fuel. The studied process could be a valuable reference to expand these concepts on global scale to achieve a greener and more sustainable energy future.

It has been empirically observed that the upper tail of the firm size distribution follows either the Pareto distribution or the Zipf distribution, with both patterns being explained by Gibrat’s law (Gabaix, 1999). This article analyzed firm revenue data from China, spanning from 2005 to 2013, to examine the whole range of the firm size distribution. Our empirical analysis revealed that firm revenue data over these years is well fitted by a three-parameter generalized Pareto distribution, with the fitted parameters indicating a dichotomy: The size distribution of large-sized firms, namely the upper tail, is asymptotically characterized by a Pareto distribution or a Zipf distribution, whereas the size distribution of smaller and medium-sized firms is approximated by an exponential distribution. This finding suggests that Gibrat’s law should be extended to account for the emergence of a generalized Pareto distribution.

A hypothesis that the generally accepted value of the LiPON conductivity should be attributed to the absorption and displacement currents is substantiated. The reason is a small contribution of the drift current due to field screening by the electric double layer. The basis for this assumption is the measurement of the LiPON absorption capacitance, according to which its dielectric constant is about 106. An alternative equivalent circuit containing a non-ideal absorption element is proposed and its impedance is calculated. It is shown that the Bode diagrams of the alternative circuit well approximate the experimental curves. Parameters and the magnitude of electric field screening are calculated basing on proposed model of a double electric layer. Considering the screening effect, the drift conductivity of LiPON is obtained, which value is in good agreement with the data on lithium concentration and mobility.

Per- and polyfluoroalkyl substances (PFAS), a large group of developing contaminants, have recently become the subject of increased concern due to their potentially hazardous effects. They are classified as poisonous substances that can be found in a variety of aquatic situations. The widespread usage of PFAS across numerous industries has resulted in a high environmental and biological accumulation of the substance. Identification and elimination of PFAS from the environment is crucial since they are tenacious and have the potential to cause cancer. Traditional methods of PFAS content assessment, while useful in some cases, are often inadequate for continuing environmental control and monitoring. Within academia, there is a noticeable desire for rapid, cost-effective, durable, and readily transportable techniques targeted at detecting PFAS compounds in field settings. As a result, environmental labs and other governmental and non-governmental bodies may start testing more often as mandated by legislation. PFAS-detecting sensors, which offer an innovative solution that can be applied in situ and is affordable and simple to use, have emerged as a promising method for assessment based on the existing research. In addition, it may give administrators and users of water worldwide useful information they can use. This article provides a thorough summary of recent developments, limitations, and performance considerations in PFAS detection sensors. The Surface-enhanced Raman scattering (SERS) method has also been covered because of its excellent sensitivity and specificity for detecting pollutants, making it a potential solution for sensing PFAS. Intelligent sensing systems for PFAS detection should benefit from this research.