Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

There are four commercial pathways to make grill charcoal from wood. These have been modelled to calculate a carbon intensity (CI) for each. Results are presented along with discussion of the sensitivities: biogenic carbon; quality of the charcoal; classification of products, wastes and residues; and division of burden. Grill charcoal’s CI ranges greatly, depending on the pathway by which it is produced. Wood distillation, a commercial process that once was common but now is rare, has a CI 50+% lower than that of the next-lowest commercial process, Kilns. Earth mounds/pits and external-fuelled Retorts have CIs considerably higher still. The carbon efficiency (CE) of Wood distillation is more than twice that of the next-best, again Kilns. CE is defined as normalised, total carbon emitted. This is not the same as CI, it is not usually considered in studies such as this, yet it is important for climate impact. CE could be a useful measure in assessments (such as this) where biogenic carbon is significant.

With the advancement of the economy and society, policymakers acknowledge the significance of improving rural households' well-being as a crucial factor in promoting sustainable economic and social development. Based on the matching data of China Household Finance Survey and Digital Rural County Index, this study empirically examines the effect and mechanisms of digital village construction on subjective well-being of rural households. The results revealed that digital village construction has a significant improvement in their subjective well-being. The impact of digital village construction is particularly significant in rural areas located in the western regions of China, as well as among households possessing higher levels of human capital. The process through which digital village construction enhances the subjective well-being of rural households involves the augmentation of household income, the promotion of non-farm employment opportunities, and the enhancement of rural governance. This study provides robust micro-empirical evidence highlighting the positive welfare effects of digital rural construction. This study provides insights into the digital village construction within the happiness economy framework, offering a new perspective. The imperative to strengthen rural digital infrastructure and improve farmers' proficiency in modern information skills is a strategic policy aimed at enhancing well-being of rural households.

Inorganic chemistry has contributed to the progress of human civilization in several different ways. Its activities at the interface with other scientific disciplines has led to emergence of several new fields like organometallic chemistry, bio-inorganic chemistry, solid-state chemistry, environmental chemistry, etc. In the past few decades, it has made inroads in yet another dimension of immense relevance, i.e. nano-science and –technology. In this assay an attempt has been made to present an overview of utility of inorganic and organometallic compounds as precursors for the synthesis of nano-materials with reference to catalysis and materials science. Applications of metal nanoparticles (NPs) and metal chalcogenide NPs, generated through molecular precursor route, in catalysis have been discussed. Synthesis of ternary and quaternary metal chalcogenide nano-materials by molecular precursor route has been reviewed.

Pursuing "intelligent justice" necessitates an impartial, productive, and technologically driven methodology for judicial determinations. This scholarly composition proposes a framework that harnesses Artificial Intelligence (AI) innovations such as Natural Language Processing (NLP), ChatGPT, ontological alignment, and the semantic web, in conjunction with blockchain and privacy techniques, to examine, deduce, and proffer recommendations for the administration of justice. Specifically, through the integration of blockchain technology, the system affords a secure and transparent infrastructure for the management of legal documentation and transactions while preserving data confidentiality. Privacy approaches, including differential privacy and homomorphic encryption techniques, are further employed to safeguard sensitive data and uphold discretion. The advantages of the suggested framework encompass heightened efficiency and expediency, diminished error propensity, a more uniform approach to judicial determinations, and augmented security and privacy. Additionally, by utilizing explainable AI methodologies, the ethical and legal ramifications of deploying intelligent algorithms and blockchain technologies within the legal domain are scrupulously contemplated, ensuring a secure, efficient, and transparent justice system that concurrently protects sensitive information upholds privacy.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

Player’s performance in an intense sport such as basketball is known to be related to attributes like speed, agility, and power. This study presents a comparative analysis of associations between anthropometric assessment and physical performance in different age-group elite youth basketball players, while simultaneously identifying the predictors for speed and agility in these players. U14 (n=44), U15 (n=45) and U16 (n=51) players were tested for anthropometry, lower body power, speed, and agility. U16 players were found to be taller, heavier, more muscular than U14 and U15 players. Also, the U16 group showed better performance in all performance tests. Age had a significant positive correlation with countermovement (CMJ) and drop jump (DJ) performance in U14 players, and a significant negative correlation with 10m and 20m sprint times in U15 group. CMJ and DJ emerged as the most significant predictors for sprint and agility variables, respectively. Body fat percentage was found to be a significant predictor for the speed and agility tests in all age groups, but a negative lower-body power predictor. Therefore, besides all sport-specific and fitness tests, it is essential to place emphasis on the percentage of body fat when designing players’ individualized training programs, and during team selection.

The idea of an extension of life for CubeSats is proposed to reduce space debris in a low-earth orbit. In this work, a gripper is designed for geometry-based grasping in berthing tasks. The grasping operation is outlined for square- and rectangle-profiled CubeSats. Equilibrium conditions are used to choose fingertips shape and parameters for grasping the CubeSat body. A design scheme is proposed to provide the required accuracy. A design concept is developed into a lab prototype by using low-cost 3D printing technique, and a mock-up grasping task that is representative of the berthing operation is evaluated with the lab prototype. Center-mass hanging setup for the prototype and grasped body is used to evaluate the impact of grasping, partially replicating the conditions in space by reducing the effect of gravity on the system.

The versatility of metal complexes of corroles raised the interest in the use of these molecules as element of chemical sensors. The tuning of the macrocycle properties by synthetic modification of the different components of the corrole ring, such as functional groups, molecular skeleton, and coordinated metal, allows the creation of a vast library of corrole-based sensors. However, the scarce conductivity of most of aggregates of corroles limits the development of simple conductometric sensors and requires the use of optical or mass transducers that are rather more cumbersome and less prone to be integrated in microelectronics systems. To compensate the scarce conductivity, corroles are often used to functionalize the surface of conductive materials such as graphene oxide, carbon nanotubes, or conductive polymers. Alternatively, they can be incorporated in heterojunction devices where they are interfaced with a conductive material such as a phthalocyanine. Herewith, we introduce two heterojunction sensors made of junctions of lutetium bisphthalocyanine (LuPc2) with either 5,10,15-tris(pentafluorophenyl) corrolato Cu (1) or 5,10,15-tris(4-methoxyphenyl)corrolato Cu (2). Optical spectra show that after forming the heterojunction, corroles maintain their original structure. The conductivity of the devices reveals an energy barrier for interfacial charge transport, which is larger in the 1/LuPc2 device. The different interfacial barriers is also manifested by the opposite response respect to ammonia: with a 1/LuPc2 behaving as a n-type conductor and 2/LuPC2 as a p-type conductor. Furthermore, the sensors show a high sensitivity respect to relative humidity with a reversible and fast response in the range 30-60%.

Many studies of hypervelocity impact craters have described the characteristics of quartz grains shock-metamorphosed at high pressures of >10 GPa, but in contrast, few studies have investigated shock metamorphism at lower shock pressures. In this study, we test the hypothesis that low-pressure shock metamorphism occurs in near-surface nuclear airbursts and that this process shares important characteristics with impact-cratering events. To investigate low-grade shock microstructures, we compared quartz grains from Meteor Crater, a 1.2-km-wide impact crater, to those from near-surface nuclear airbursts at the Alamogordo Bombing Range, New Mexico in 1945 and Kazakhstan in 1949/1953. This investigation utilized a comprehensive analytical suite of high-resolution techniques, including transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). Meteor Crater and the nuclear test sites all exhibit metamorphosed quartz grains with closely-spaced, sub-micron-wide fractures that appear to have formed at low shock pressures. Importantly, these micro-fractures are closely associated with Dauphiné twins and are filled with amorphous silica (glass), widely considered to be a classic indicator of shock metamorphism. Thus, this study confirms that glass-filled shock fractures in quartz form during near-surface nuclear airbursts, as well as crater-forming impact events, and by extension, it suggests they also may form in near-surface cosmic airbursts.

The possibility of abrupt transitions threatens to poise ecosystems into irreversibly degraded states. Recently, it has been proposed the use of engineered microbiomes in endangered ecosystems to prevent them to cross tipping points and avoid collapse. Potential targets for such interventions include some of the most prominent life-support systems in the biosphere: drylands and coral reefs. Since engineering can require the introduction of microorganisms not present in resident communities, how can we weight the potential outcomes? One way is to use general models of species interactions where the "synthetic" strain is incorporated into a standard multispecies model. Here we follow this approach by modelling a resource-consumer community where one of the species is a modified one that acts by preserving some key resource. We show how the indirect effect of damping the decay of shared resources results in biodiversity increase, and last but not less, the successful incorporation of the synthetic within the ecological network. Further extensions and implications for future restoration and terraformation strategies are discussed.

Bats are of significant interest as reservoirs for various zoonotic viruses with high diversity. During the past two decades, many herpesviruses have been identified in various bats worldwide by genetic approaches, whereas there have been few reports on the isolation of infectious herpesviruses. Herein, we report the prevalence of herpesvirus infection of bats captured in Zambia and genetic characterization of novel gammaherpesviruses isolated from Macronycteris vittatus bats. By our PCR screening, herpesvirus genomes were detected in 29.2% (7/24) of Rousettus aegyptiacus, 78.1% (82/105) of Macronycteris vittatus, and 100% (1/1) of Hipposideros caffer bats in Zambia. Phylogenetic analyses of the detected herpesvirus genomes revealed that the Zambian bat herpesviruses were divided into seven betaherpesvirus groups and five gammaherpesvirus groups. Two infectious strains of a novel gammaherpesvirus, tentatively named Macronycteris gammaherpesvirus 1 (MaGHV1), were successfully isolated from Macronycteris vittatus bats, and their complete genomes were sequenced. The genome of MaGHV1 encoded 79 open reading frames, and phylogenic analyses of the DNA polymerase and glycoprotein B demonstrated that MaGHV1 formed an independent lineage sharing a common origin with other bat-derived gammaherpesviruses. Our findings provide new information regarding the genetic diversity of herpesviruses maintained in African bats.

We prove that the Legendre coefficients associated with a function f(x) can be represented as the Fourier coefficients of a suitable Abel-type transform of the function itself. Thus, the computation of N Legendre coefficients can be performed efficiently in O(NlogN) operations by means of a single Fast Fourier Transform of the Abel-type transform of f(x). We also show how the symmetries associated with the Abel-type transform can be exploited to further reduce the computational complexity. The dual problem of calculating the sum of Legendre expansions is also considered. We prove that a Legendre series can be written as the Abel transform of a suitable Fourier series. This fact allows us to state an efficient algorithm for the evaluation of Legendre expansions. Finally, numerical tests are presented to exemplify and confirm the theoretical results.

Canine hemangiosarcoma (HSA) is a relatively common neoplasia, occurring mainly in the skin, spleen, liver and right atrium. Despite the numerous studies investigating the treatment of canine HSA, no significant improvement in survival has been achieved in the last 20 years. Advancements in genetic and molecular profiling presented molecular similarities of canine HSA with human angiosarcoma. It could therefore serve as a valuable model for investigating new and more effective treatments in people and dogs. The most common genetic abnormalities in canine HSA have been found in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and neuroblastoma RAS viral oncogene homolog (NRAS) pathways. Mutations are also found in tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A). Known abnormal protein expression could be exploited to trial new target treatments that could be beneficial for both canine and human patients. Despite the high expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), no correlation with overall survival time has ever been found. In this review, we explore the most recent developments in molecular profiling in canine HSA and discuss their possible applications in the prognosis and treatment of this fatal disease.

Crisis environments, which are becoming systemic, pose significant challenges to smart government strategies. The paper aims to contribute to academic debate by proposing an analytical framework for examining the institutional capacities of smart government systems in addressing local crises. The paper focuses on the recent approach of robust governance and highlights a set of variables that promote effective smart government: contingency planning capacity, analytical capacity, organizational management capacity, and collaborative capacity. The study presents an analytical model for evaluating the robustness and effectiveness of local smart government systems in crises. One of the significant findings of this study has been the identification of critical indicators that inform institutional capacities of smart government systems. By analyzing these indicators, the proposed analytical framework provides a comprehensive approach to assess the preparedness of smart government systems in dealing with crises. Moreover, it can be used to benchmark the performance of local smart government systems in similar contexts and identify best practices for improving crisis management.

The study is focused on identifying areas of individualization in those mature organizations in which employees are free to make changes. In addition, factors affecting work-life balance and overlap between the jobs employees do and would like to do are determined. A critical review of the literature and a diagnostic survey, including interviews, questionnaires and observations, were used in the research process, together with the analysis of data concerning working conditions. Employees' opinions (n=300) on individualization areas, job crafting and overlap between performed and preferred jobs were analyzed. Calculations were done using IBM SPSS. According to the results, the maintenance of work-life balance (WLB) and the implementation of job crafting positively affect employee efficiency, counteracting professional burnout and a decrease in motivation. It turns out that employees of mature organizations are familiar with the areas of individualization and in some cases have freedom to implement job crafting. They like the work they do, which translates into well-maintained work-life balance. However, a big challenge for mature organizations is the constantly changing economic environment, the long-term nature of work-life balance programmes and their deferred effects. The results of the research can be an important starting point for extended studies.

The Paeonia suffruticosa, called as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely paeobenzofuranone A‒E (1‒5), have been characterized. Their structures were determined by spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines with IC50 values ranging from 6.7 to 25.1 μM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time.

The inositol triphosphate associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins, which regulate intracellular Ca2+. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, that is associated with the intracellular Ca2+ channel IP3R-I and the PKGIβ and inhibits IP3R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homologue of IRAG1 and was recently also determined as a PKGI substrate protein. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile and recently elucidated in a variety of human and murine tissues, e.g. of IRAG1 in various smooth muscles, heart, platelets and other blood cells, of IRAG2 in pancreas, heart, platelets and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g. smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these both regulatory proteins to envision its molecular and (patho-)physiological tasks and to unravel its functional interplay as possible (patho-)physiological counterparts.

Abstract: Introduction: A retrospective case-controlled study was performed to evaluate the out-comes of shoulder arthroplasty performed as a day case in carefully selected patients, compared to the traditional inpatient approach. Materials & Methods: Patients who had total or hemiarthro-plasty of the shoulder performed as a day case or inpatient procedure were recruited. The primary outcome compared rates of uneventful recovery, defined by the absence of any complications or readmission to hospital within six months of surgery, between Inpatient and Outpatient groups. Secondary outcomes included examiner-determined functional scores and patient-determined pain scores at one, six, twelve, and twenty-four weeks post-surgery. A further assessment of pa-tient determined pain scores was carried out at a minimum of two years post-surgery (5.8 ± 3.2). Results: 73 patients (36 Inpatients and 37 Outpatients) were included in the study. Within this time frame 25/36 inpatients (69%) had uneventful recoveries compared to 24/37 outpatients (65%) (p = 0.17). Outpatients showed significant improvement over pre-operative baseline levels in more of the secondary outcomes (strength and passive range-of-motion) by six months post-operation. Outpatients also performed significantly better than Inpatients in external rotation (p<0.05) and internal rotation (p=0.05) at six-weeks post-surgery. Both groups showed significant improvement compared to pre-operative baselines in all patient-determined secondary outcomes except level of activity at work and sport. Inpatients, however, less severe pain at rest at six weeks (p=0.03), sig-nificantly less frequent pain at night (p=0.03) and extreme pain (p=0.04) at 24 weeks; and less se-vere pain at night at 24 weeks (p<0.01). By minimum two years postoperation, inpatients were more comfortable repeating their treatment setting for future arthroplasty (16/18) compared to outpatients (7/22) (p = 0.0002). Conclusions: At a minimum of two years follow up, there were no significant differences in rates of complications, hospitalisations, or revision surgeries between pa-tients that underwent shoulder arthroplasty as an inpatient versus as an outpatient. Outpatients demonstrated superior functional outcomes but reported more pain at six months post-surgery. Patients in both groups expressed a preference for inpatient shoulder arthroplasty in future. What is Known About This Subject: Shoulder arthroplasty is a complex procedure, and has tradition-ally been performed on an inpatient basis, with patients admitted for six to seven days post-surgery. One of the primary reasons for this is the high level of postoperative pain, usually treated with hospital-based opioid therapy. Two studies demonstrated outpatient TSA to have a similar rate of complications as inpatient TSA, however these studies only examined patients within a shorter term 90 day postoperative period, and did not evaluate functional outcomes between the two groups or in the longer term. What This Study Adds to Existing Knowledge: This study provides evidence supporting the longer-term results of shoulder arthroplasty done as a day case in carefully selected patients, which are comparable to outcomes in patients that are admitted to hospital post-surgery.

Infrared dim and small target detection is a key technology of various detection tasks. However, due to the lack of shape, texture, and other information, it is a challenging task to detect dim and small targets. Recently, since many traditional algorithms ingore global information of infrared images, they generate some false alarms in complicated environments. To address this problem, in this paper, a coarse-to-fine deep learning-based method is proposed to detect dim and small targets. Firstly, a coarse-to-fine detection framework integrating deep learning and background prediction is applied for detecting targets. The framework contains of coarse detection module and fine detection module. In coarse detection stage, Region Proposal Network (RPN) is employed to generate masks in target candidate regions. Then, for further optimize the result, inpainting is utilized to predict the background by the global semnantic of images. In this paper, inpainting algorithm with a mask aware dynamic filtering module is incorporated into the fine detection stage to estimate background in candidate target areas. Finally, compared with existing algorithms, the experimental results indicate that the proposed framework have effective detection capability and robustness for complex surroundings.

E-commerce is a rapidly evolving global trend that is having a significant impact on consumer behavior and business strategies. Despite its growing impact, e-commerce adoption by Moroccan firms remains low and research on this topic in this context is scarce. This study aims to fill this gap by investigating the main determinants influencing e-commerce adoption by Moroccan firms. We use logit, probit, and conditional mixed process-probit models to identify the critical factors driving e-commerce adoption. Our results reveal five key findings. First, newer firms that are more open to innovation and change are more likely to adopt e-commerce. Second, firms with a higher proportion of highly educated employees are more likely to adopt e-commerce. Third, the digital skills of new employees do not directly influence the likelihood of e-commerce adoption. Fourth, being listed on digital platforms increases the likelihood of e-commerce adoption. Finally, there is a positive relationship between firms engaged in innovation activities and e-commerce adoption. These findings highlight the need for additional investment in promoting modern organizational practices, reskilling workers, and implementing advanced technologies to facilitate effective e-commerce integration among Moroccan SMEs. By addressing these challenges, Moroccan firms can harness the full potential of e-commerce and contribute to the country’s economic growth and digital transformation.

At a basic level, entrepreneurship refers to an individual or a small group of partners that intend to create a new business. Entrepreneurship is at forefront of any competitive economy due to the creation of new products and services that comes from new ideas. In other words, entrepreneurship is associated with economic wealth, growth and innovation. The usage of resources in the creation of new businesses needs to be rational because investors normally are risk averse, and nowadays, the purpose of a new business needs to be for a long-term period, and the usage of resources has to take into mind the possible damage to the planet. In other words, entrepreneurs and the sustainability of the planet are interconnected. Beyond this, entrepreneurs need to take care of the corporate social responsibility of each new business, considering the interests of itself, its stakeholders, and the public. Nevertheless, existing research has not shown in full all the research streams, how they interact with each other and their potential knowledge development. Thus, a literature review on social entrepreneurship and corporate social responsibility in the last decade are opportune. This paper aims to identify research trends in the field through a Systematic Bibliometric Literature Review of social entrepreneurship and corporate social responsibility research. The review includes 69 articles published in the Scopus® database, presenting up-to-date knowledge on the topic.

This work presents a new scheme for autonomous control and obstacle detection of a catamaran unmanned surface vessel. Based on the Newtonian mechanics, hydrodynamics, and maneuvering modelling group modelling principles in the attached coordinate system, a three-degree-of-freedom motion model of the catamaran unmanned surface vessel is constructed. The fuzzy inference method is used to overcome the drawback that the traditional PID control cannot tune the PID parameters online, and the trajectory controller is designed. Meanwhile, 3D LIDAR is used to achieve obstacle detection. The results of the trajectory tracking simulations and experiments verify the accuracy of the model design and the effectiveness of the autonomous control design.

Structured extraction of emergency event information can effectively enhance the ability to re-spond to emergency events. This article focuses on the extraction of Chinese document-level emergency events, which mainly faces two key issues in this field: first, related datasets; Secondly, existing DEE (document-level event extraction) studies mostly use sequence annotation to extract candidate entities in the subtask of candidate entity extraction without considering the problem of role overlapping between candidate entities. On the one hand, this article constructs a Chinese document-level emergency extraction dataset, CDEEE, which first annotates the issues of argu-ment scattering, multiple events, and role overlapping. On the other hand, this article proposes a model RODEE for the problem of role overlapping in DEE tasks. This model first uses two in-dependent modules to represent the head and tail positions of candidate entities, then uses a multiplication attention mechanism to interact with the two to obtain a scoring matrix. Finally, role-overlapping candidate entities are predicted to assist in completing DEE tasks. Experiments were conducted on our manually annotated dataset, CDEEE, and the results showed that RODEE can effectively solve the problem of role overlapping in candidate entities and improve the performance of the DEE model.

Low-temperature plays a vital role in the growth and development of woody plants. In this research, based on the way of artificial low temperature to break dormancy, the Utah model was used to determine the chilling requirements of four early-flowering Prunus mume cultivars, which were widely planted in Henan area of China. At the same time, changes in the carbohydrates, antioxidant enzyme activities, and endogenous hormone contents of the flower buds (FBs) of the above P.mume cultivars were measured during the low-temperature storage process, and the physiological changes of the four cultivars during the low-temperature induction period were explored. The main research conclusions are as follows: (1) The chilling requirements of ‘Gulihong’, ‘Nanjing gongfen’, ‘Zaoyudie’ and ‘Zaohualve’ were 408CU, 396CU, 372CU and 348CU respectively. All the P.mume cultivars belonged to low chilling demand cultivars. The P.mume also bloomed 4 months earlier (2) During the process of releasing dormancy at low temperature, the contents of soluble sugar (SS) in the osmoregulation system of the four Prunus mume cultivars showed an upward trend, while the contents of starch (ST) basically showed an opposite trend with the increase of chilling. The superoxide dismutase (SOD) activity in the FBs of each cultivar gradually decreased with the accumulation of cold and maintained at a low level, the peroxidase (POD) activity showed the opposite trend, and the dynamic changes of the catalase (CAT) activity generally showed a trend of first increasing and then decreasing. The content of abscisic acid (ABA) showed a trend of increasing first and then decreasing as a whole. The changing trend of gibberellin (GA3) content was similar to that of ABA. In addition, it was found that before dormancy was released, the SS and Pro contents of cultivars with lower chilling requirements and early FB germination were significantly higher than those of other cultivars with higher chilling requirements, and the contents of ST and SP were lower. The cultivars with higher chilling requirement and late flower bud germination had higher ABA content, lower GA3 contents, and their enzyme activities were significantly higher than those of the cultivars with lower chilling requirement. Therefore, the changes in the content of various substances in FBs are related to the amount of cooling required by the cultivar and the sooner or later the FBs germinate, and the changes in their contents can be used as one of the indicators for judging the dormancy process of FBs.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/ kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.

Article contents the analytical model of the drift of a separate ice field under action of wind and current, which velocities and directions can vary during time. Model takes into account the mass of ice, added mass of sea water and the effects of the wind and current on the ice field in form the friction on its upper and underwater surfaces and frontal resistance on its end (forward and backward) surfaces. Results of performed the steady wind drift of the ice fields modelling show the drift velocity exceeds considerable known velocity of a compact ice cover wind drift. Drifting ice field has the certain kinetic energy that should be released when collision with unmovable obstacle and spent on brittle breakdown of part of the ice field. Volume of formed small ice pieces (fragments of ice field) was estimated by comparison of the specific energy of the sea ice brittle destruction and the kinetic energy of drifting ice field. Article presents the results of estimation of possible volume of the ice pieces and the scales of formed piles as result of collision with an obstacle depending on initial dimensions of ice field and wind speed. Developed models and the results of computer modelling can be used to estimate the ice pile sizes near the stationary platforms and terminals on the Arctic seas.

We propose a promising model of discrete spacetime based on nonassociative geometry and complex networks. Our approach treats space as a simplicial 3-complex (or complex network), built from "atoms" of spacetime and entangled states forming n-dimensional simplices (n=1,2,3). At large scales, a highly connected network is a coarse, discrete representation of a smooth spacetime. We show that for high temperatures, the network describes disconnected discrete space. At the Planck temperature, the system experiences the phase transition, and for low temperatures, the space becomes a triangulated discrete space. We show that the cosmological constant depends on the universe’s topology. The "foamy" structure, analogous to Wheeler’s "spacetime foam," significantly contributes to the effective cosmological constant, which is determined by the Euler characteristic of the universe.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of random variables has with respect to a target variable into three types of components: redundant, synergistic, and unique. Classical information theory alone does not provide a unique way to decompose information in this manner and additional assumptions have to be made. Inspired by Kolchinsky's recent proposal for measures of intersection information, we introduce three new measures based on well-known partial orders between communication channels and study some of their properties.

Humans have extremely variable skin pigmentation and melanin production influenced by genetics, UV exposure, and some medications. A significant number of skin illnesses that result in pigmentary abnormalities have an impact on patients’ physical appearance as well as their psychological and social well-being. Skin pigmentation can be divided into two basic categories: hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosine, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, four marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Differences are introduced as outputs of linear systems called differencers, being considered two classes: shift and scale-invariant. Several types are presented, namely: nabla and delta, bilateral, tempered, bilinear, stretching, and shrinking. Both continuous and discrete-time are described. ARMA type systems based on differencers are introduced and exemplified. In passing, the incorrectness of the usual delta difference is shown.

Strengthening the analysis and risk assessment of the pig epidemic will help to better prevent and mitigate epidemic risks and promote high-quality development of the pig industry. Based on the systematic grasp of the situation of live pig epidemics, a risk assessment index system was constructed, and the spatial and temporal variation characteristics of the risk of pig epidemics in China were explored by the entropy method. In recent years, the overall trend in pig epidemics in time first increased and then decreased, and in space, the trend in the acceleration of the spread across the country continued to weaken. China still faces challenges, such as many types and a wide range of diseases, large total livestock breeding and weak epidemic prevention and control capacity, and a large risk of introduction of foreign animal epidemics. The spatial and temporal variation in the pig epidemic risk was obvious; there was one high-risk area, two higher-risk areas and 10 medium-risk areas in recent years, and the epidemic risk was highest in Beijing, Hainan, Liaoning, Tibet and Zhejiang. However, there were significant differences in the regional distribution of the risk of pig epidemics in different years. To further build a secure “defense system” for the high-quality development of the pig industry, it is recommended to improve the monitoring and early warning system of pig epidemic risk, perfect the pig epidemic prevention and control system, and strengthen the regional collaboration mechanism of epidemic prevention and control.

A growing number of health conscious consumers are looking for animal protein alternatives with similar texture, appearance, and flavor. There has been a lot of interest in meat analogs as potential meat substitutes. However, research and development still needs to find any alternative non-meat materials. The objective of the current research was to develop fungi minced meat alternative (FMMA) from edible mushrooms. Pleurotus Sajor-caju (SC) was used as the starting material. SC mushroom was selected for starting materials based on high protein content (41.99%.) and sensory attributes. Chickpea flour was used to improve the textural properties by mixing with SC mushroom at a ratio of 0:50, 12.5:37.5, 25:25, 37.5:12.5, and 50:0 (w/w). Textural and sensory attributes suggest that SC mushroom to chickpea at a ratio of 37.5:12.5, shows higher acceptability of FMMA with the protein content up to 47%. Beetroot extract 0.2% (w/w), and 5% (w/w) canola oil showed the most acceptable color parameters and consumer acceptability. This research suggested that SC mushroom with 12.5% chickpea flour, 0.2% beetroot extract and 5% canola oil could be suitable ingredients for the mushroom-based FMMA.

Feline infectious peritonitis (FIP), caused by the feline coronavirus (FCoV), is a devastating dis-ease in cats. Based on its antigenicity, FCoV can be divided into two serotypes: FCoV-I and FCoV-II. Furthermore, according to its pathogenicity, FCoV can be divided into feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). There are numerous factors that affect the pathogenesis of FIP, among which host immunity and viral genetics can play an es-sential role in the development of FIP. Owing to the lack of specific symptoms, existing individual diagnostic methods can only support the suspicion of FIP, and multiple diagnostic methods and test data need to be combined to make a diagnosis. Although there are still no effective FIPV vaccines or commercial drugs available in the market, various studies have shown that some compounds can be used for treatment. Therefore, FIP is no longer incurable in cats

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Lead-free copper halide perovskite nanocrystals (NCs) are emerging materials with excellent photoelectric properties. Herein, we present a colloidal synthesis route of orthorhombic Cs2CuCl4 NCs with well-defined cubic shape and an average diameter of 24 ± 2.1 nm. The Cs2CuCl4 NCs exhibit bright deep blue photoluminescence, which is attributed to the Cu(II) defects. In addition, passivating the Cs2CuCl4 NCs by Ag+ can effectively improve the photoluminescence quantum yield (PLQY) and environmental stability.

The present study examined music-induced dopamine release, as measured by a proxy measure of spontaneous eye blinks. Specifically, we explored the effects of uplifting and sombre tones in different sections of Vivaldi's Four Seasons to investigate the affective content of musical pieces within one composition. Seventeen participants listened to four concertos (Major modes: Spring, Autumn, Minor modes: Summer and Winter) and a silence condition while completing the 3-Stimulus Odd-ball attention task. Electrooculograms were recorded from electrodes placed above and under the left eye. Self-reported arousal and music preference measures were also gathered during the testing session. In addition, the P3a Event-Related Potential (ERP) component was analysed as another potential index of dopamine function. Results revealed significant differences in the blink rates during music listening and silence, with the largest effect observed for the sad, melancholic Winter concerto. However, no significant correlation was found between blink rate and music preference or arousal. Furthermore, no reliable association was found between blink rate and the P3a ERP component, suggesting that these measures tap into different aspects of dopamine function. These findings contribute to understanding the link between dopamine and blink rate, particularly in response to classical music. Crucially, the study's discovery that the Winter concerto, with its sorrowful tone, significantly increased the blink rate highlights the significance of sad music and perhaps the programmatic qualities of this concerto to induce a strong emotional response.

The prospective applications of chitosan-based hydrogels (CBHs), a category of biocompatible and biodegradable materials, in biomedical disciplines such as tissue engineering, wound healing, drug delivery, and biosensing have garnered great interest. The synthesis and characterization processes used to create CBHs play a significant role in determining their characteristics and effectiveness. The processing procedure could be tailored to obtain specific features like porosity, swelling, mechanical strength, degradation rate, and bioactivity, affecting the properties of CBHs to a great extent. Additionally, characterization methods aid in gaining access to the microstructures and properties of CBHs. Especially, this review provides a comprehensive assessment of the state-of-the-art with a focus on the affiliation between particular properties and application domains. The main obstacles and prospects for the future of CBH development for biomedical applications are also covered in the review.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

Microbial communities inhabiting the human body play a crucial role in protecting the host against pathogens and inflammation. Disruptions to the microbial composition can lead to various health issues. Microbial transfer therapy (MTT) has emerged as a potential treatment option to address such issues. Fecal microbiota transplantation (FMT) is the most widely used form of MTT and has been successful in treating several diseases. Another form of MTT is vaginal microbiota transplantation (VMT), which involves transferring vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity with the goal of restoring normal vaginal microbial composition. However, VMT has not been extensively studied due to safety concerns and a lack of research. This paper explores the therapeutic mechanisms of VMT and discusses future perspectives. Further research is necessary to advance the clinical applications and techniques of VMT.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

With the increased liberation of trade and fierce competition in the automotive industry, Proton needs to embark on a strategic reform to survive and remain relevant in the challenging market. This case study aims to explain the effectiveness of the Post Geely acquisition's ten years master plan to enhance Proton's self-reliance and global competitiveness. This case suggests that while the company's ten-year Master Plan is holistic and shows positive results in the early years, there is a need for a new business strategy, given the challenges imposed by climate change's impact on the automotive industry moving forward. The potentials of the Electric Vehicles (EVs) market and the Internet of Things (IoT) to develop the necessary long-term competitive advantage. A market strategy integrating the 4Ps and 4Cs framework suggests a two-dimensional convergence of the market mix, incorporating the organization's market strategy with a more consumer expectations-centric and user experience. Strategic integration of Geely's technological assets in developing Proton's technical know-how can address Proton's challenges and opportunities ahead.

In the context of Shared Autonomous Vehicles, the need to monitor the environment inside the car will be crucial. This article focuses on the application of deep learning algorithms to detect objects, namely lost/forgotten items to inform the passengers, and aggressive items to monitoring if violent actions may arise between passengers. For object detection algorithms was used public datasets (COCO and TAO) to train state-of-the-art algorithms, such as YOLOv5. For violent action detection was used the MoLa InCar dataset to train on state-of-the-art algorithms such as I3D, R(2+1)D, SlowFast, TSN and TSM. At the end an embedded automotive solution was used to demonstrate both methods running in real-time.

Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), some defects prevent its clinical application, such as severe side effects and loss of anticancer activity due to lack of selectivity to cancer cells and hydrolysis of ring E, respectively. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity as irinotecan against human cervical cancer HeLa cells, albeit inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert the potent anticancer activity through the synergism of SN38 and valproic acid, indicating that the design concept is an effective strategy for structural modification of SN38.

pump as turbine (PAT); computational fluid dynamics; variable rotational nominal speed; OpenFoam.

When an aircraft malfunctions, quickly and accurately identifying the faulty unit is essential for ensuring normal operation. Unfortunately, maintenance engineers often struggle to acquire the necessary fault-related knowledge due to poor management and utilization of aircraft fault documents. To address this issue, we introduce knowledge graph technology into the field of aircraft fault diagnosis, exploring its construction and application for effective knowledge management. Our work starts by analyzing the critical knowledge elements required for aircraft fault diagnosis and designing a schema layer for fault knowledge graphs. We then we then combine deep learning and heuristic rules to extract fault knowledge from both structured and unstructured data, enabling the construction of aircraft fault knowledge graphs. Finally, we develop a fault question-answering system based on fault knowledge graphs that can accurately give solutions to questions posed by maintenance engineers. Our practice demonstrates that knowledge graphs provide an effective means of managing aircraft fault knowledge, assisting engineers in locating fault reasons accurately and quickly.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

This study assesses the biomethane (CH4) generation and greenhouse gas (GHG) emissions resulting from municipal solid waste landfilling in Phnom Penh, Cambodia, with a focus on the impact of fugitive CH4 emissions and operation processes in four landfilling scenarios: simple dumping (S1), improved management with leachate treatment (S2), engineered landfill with flaring (S3), and engineered landfill with energy recovery (S4). The study also considered the environmental benefits of carbon sequestration and landfill gas utilization. The LandGEM and IPCC FOD models were used to calculate CH4 generation over the period of 2009-2022, and it was found that approximately 18 and 21 M kg/year of CH4 are released, respectively. The energy potential from CH4 recovery was 51–61 GWh/year. Overall GHG emissions in S2 were the highest, amounting to 409–509 M kg CO2-eq/year, while S1 had lower emissions at 397–496 M kg CO2-eq/year. Flaring captured CH4 in S3 could reduce GHG emissions by at least 55%, and using captured CH4 for electricity production in S4 could mitigate at least 83% of GHG emissions. Electricity recovery (S4) could avoid significant amounts of GHG emissions (˗104.5 kg CO2-eq/tMSW). The study suggests that landfill gas-to-energy could significantly reduce GHG emissions.

This paper presents ROSGPT, an innovative concept that harnesses the capabilities of large language models (LLMs) to significantly advance human-robot interaction. We develop ROSGPT as a ROS2 package that seamlessly integrates ChatGPT with ROS2-based robotic systems. The core idea is to leverage prompt engineering with LLMs, specifically ChatGPT, utilizing its unique properties such as ability eliciting, chain-of-thought, and instruction tuning. The concept employs ontology development to convert unstructured natural language commands into structured robotic instructions specific to the application context through prompt engineering. We capitalize on LLMs' zero-shots and few-shots learning capabilities by eliciting \textit{structured} robotic commands from \textit{unstructured} human language inputs. To demonstrate the feasibility of this concept, we implemented a proof-of-concept that integrates ChatGPT with ROS2, showcasing the transformation of human language instructions into spatial navigation commands for a ROS2-enabled robot. This versatile concept can be easily adapted to various other robotic missions. ROSGPT serves as a new stride towards Artificial General Intelligence (AGI) and paves the way for the robotics and natural language processing communities to collaborate in creating novel, intuitive human-robot interactions. The open-source implementation of ROSGPT on ROS 2 is available on GitHub.

Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.

in this work formulations of "environmentally compatible" silicone-based antifouling synthesized in the laboratory and based on copper and silver on silica/titania oxides have been characterized, capable of replacing the non-ecological antifouling paints currently on the market. The texture properties and the morphological analysis of these powders with an antifouling action indicate that their activity is linked to the nanometric size of the particles and to the homogeneous dispersion of the metal on the substrate. The presence of two metal species on the same support limits the for-mation of nanometric species and therefore the formation of homogeneous compounds. The presence of the antifouling filler (specifically the one based on TiO2 and Ag) facilitates the achievement of a higher degree of cross-linking of the pure resin, and therefore a better compactness and completeness of the coating. This leads to a consequent better degree of adhesion to the tie-coat and therefore to the steel support used for the construction of the boats.

Since the worldwide spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), treating taste and saliva secretory disorders associated with coronavirus disease 2019 (COVID-19) has become one of the most critical issues in the COVID-19 era. The aim of the present study was to update information on treatments being applicable to such oral symptoms and discuss their pathogenic mechanisms. Promising treatments include different types of methods using tetracycline, corticosteroid, zinc, stellate ganglion block, phytochemical curcumin, traditional herbal medicine, nutraceutical vitamin D, photobiomodulation, antiviral drug, malic acid sialagogue, chewing gum, acupuncture, and/or moxibustion. At present, however, fully validated treatments are still lacking for COVID-19-associated ageusia/dysgeusia/hypogeusia and xerostomia/dry mouth/hyposalivation. An appropriately selected treatment and oral healthcare should be provided to COVID-19 patients and survivors suffering from taste and saliva secretory disorders. Understanding of currently available treatment options is required for dental profes-sionals because they not only experience patients who were infected with SARS-CoV-2 or recov-ered from COVID-19 but first become aware of their abnormal taste and salivary secretion. By doing so, dentists and dental hygienists can play a crucial role in managing COVID-19-associated oral symptoms and contribute to improving the oral health-related quality of life of the relevant dental patients.

Abstract: Agarose is known to form a homogeneous thermoreversible gel in aqueous medium over a critical polymer concentration. The solid-liquid phase transitions are thermoreversible but depend on the molecular structure of the agarose sample tested. Then, in a first step, the structure was characterised by 1H and 13C NMR in D2O and in DMSO which is a solvent of agarose whatever the temperature. A low yield in methyl substituent on the D-galactose unit was determined. Then, evolution of the 1H NMR spectrum was followed as a function of temperature in increasing and decreasing temperature process from 25 to 80°C. A large thermal hysteresis is obtained and discussed. It helps to interpret rheological behaviour. In fact, NMR signals are related to proton relaxation and especially to proton involved in H-bonds between water and -OH agarose for tightly bound water and agarose/agarose in chain packing. In a second step, water was exchanged against ethanol which is a non solvent of agarose. A stable gel was demonstrated and characterised by rheology to be compared with aqueous behaviour. Bound water playing the role of plasticizer is probably removed and the gel is much stronger (and brittle) in ethanol with a larger thermal stability. It is the first time that such gel is characterised without phase transition when passing from a good-solvent to a non-solvent. This extends the domains of application of agarose.

Background: Irish dance is growing in popularity, evolving to a more athletic and demanding dance style. Aims: To conduct a systematic review, previously registered with PROSPERO, to identify prevalence, incidence, and injury pattern among Irish dancers and analyse associated risk factors. Methods: Six online databases, plus two dance-specific science publications were searched systematically. Studies were included if the pattern of injuries among Irish dancers were evaluated or the factors associated with injury were analysed, published in English or Portuguese, in peer-reviewed scientific journals. Four reviewers assessed the quality and level of evidence using the Downs and Black criteria and a modified Oxford Centre of Evidence-Based Medicine 2009 model, respectively. Results: Eleven articles were included, 8 level 3c (cross-sectional) and 3 level 3b (prospective). Mean DB percentage score was 63% ± 7,2%. Prevalence ranged from 72,2% to 92,6%, affecting mostly the foot/ankle complex. Only 2 articles reported incidence, which ranged from 3,4–10,6 injuries/1000 hours danced depending on injury definition. Psychological factors, elite level, and insufficient/poor sleep were associated with musculoskeletal injury. Conclusions: Injury prevalence and incidence is high in Irish dancers, with the foot and ankle more affected. Due to heterogeneity in injury definitions, methods, and populations, along with the need for improvement in studies quality, recommendations were made for future research.

Reptilians or reptoids are staple characters of Hollywood cinema, science fiction literature, ufology and conspiracy theories. Despite its popularity, the reptoid has been dismissed by the scientific community as a figment of the imagination; born out of a speculation, paranoia and wanton anthropocentricism. In this paper, however, the Life Sequence Conjecture is advanced as a supportive framework for the notion of reptilian extraterrestrials. This paper is not an argument in support of the existence of extraterrestrials. Rather, it proposes that if extraterrestrials do exist, then a reptilian morphology is not untenable.

Lassa fever, commonly known as Lassa hemorrhagic fever (LHF), is one of the progressive illnesses invading a large population of two to three million individuals in West Africa. The infection transmitted through the rodents severely impacts the local population and the medical professionals in surrounding areas, which were also the primary target of LHF. In epidemic areas, Lassa fever causes a public health threat since it poses a significant morbidity and fatality Case rate (CFR) ≥ 50%). The disease is widespread in West Africa and has developed into one of the most common and life-threatening viral hemorrhagic fevers. Monitoring and preventing persistent disease outbreaks has been challenging in affected regions due to insufficient healthcare facilities, diagnostics labs, care centers, and low socioeconomic conditions. An absence of public awareness and the emergence of an ecological niche is advantageous for the survival and multiplication of the mouse (Mastomys natalensis) inhabiting the Lassa virus serving as the disease's natural host and reservoir. The current review focuses on early diagnosis and appropriate treatment, highlighting the immediate requirement of clinically approved vaccines for LHF, causing preventative and control actions more difficult in the present era.

This article aims to provide a comprehensive understanding of vaping from various perspectives that contributes to the origin, development, achievement, and consequences of the greed of e-cigarette manufacturers. In our analysis, multiple elements of the social landscape, including economic, cultural, moral, psychological, and philosophical dimensions, contributed to the origin and development of the vaping greed and shaped people’s behaviors. Further discussion was made on how the specific characteristics of e-cigarette products and the marketing strategies of the companies, especially social media marketing, fostered the growth of such greed. Through interviews, we have also discussed the unfolding of this greed within the community of teenage vapers. The growth of the vaping greed was manifested in the large market share taken by the companies, but these all significantly harm people’s health and the communities. Nicotine and other chemicals in e-liquids promote each other’s negative effects in the mechanism leading to pulmonary symptoms and addiction, which are not limited to the physical level. We described that addiction could be transgenerational and can induce trauma both at an individual level and a community level. Overall, the greed of the vaping industry is a very complex system. The treatment of the greed shall be complicated as well: Besides the public health measures taken to treat the symptoms of the greed, we should educate individuals to be aware of their unfulfilled needs to regain authenticity and establish an infallible authority to enforce universal morality, which eradicates the complications of addiction and the root of the capitalists’ greed, respectively.

We still do not have satisfactory answers about the inflationary and accelerating expansions of the universe, the missing mass problem, and the origins of the four fundamental forces and the quantum phenomena. Here, we introduce a new model of matter and space and a postulate on a constant of motion, and then show that an equation of motion derived from the constant of motion could provide new understandings of the above problems. For example, we show that there is a natural inflation scenario and that the co-moving distance to the closest accelerating supernova is clearly given as $c/(\sqrt{3} H)$ ($\sim$8.1 billion ly). In addition, we show that, in a system including a proton and an electron, the equation of motion has eight acceleration terms, some of which are suspected to be responsible for the four fundamental forces and the galaxy rotation anomaly. From further discussion, we conjecture that in order to understand the gravitational and strong interactions and the quantum phenomena, it is necessary to consider the expansion of the universe. The lensing mass distribution is explained, based on another postulate on a method of representing superposition.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

Social media has revolutionized the way we communicate and interact with each other. While it has brought many benefits, it has also presented many ethical challenges. Social media platforms have access to an enormous amount of personal data, and there are concerns about how this data is being stored, collected, and used. Users often need to fully understand the risks of sharing sensitive information. Social media platforms have made it easy for fake news to spread rapidly, which can be dangerous and have serious consequences. Misinformation and propaganda can influence people's decisions and beliefs. In this paper, we will analyze the issues and challenges that may arise, and it will be necessary for individuals and society to address these challenges ethically and responsibly.

Recently, a paper was written to reformulate and strengthen the theory of semi-structured complex numbers H (a new number set invented to enable division by zero). Whilst the paper had profound results, the application of this number set in many areas of engineering and science has not been fully explored. Consequently, the aim of this paper was to establish the number set H as a useful mathematical tool by providing an amalgam of results arising from its application in several areas of engineering and science. In the process, this paper makes four major contributions: these are (1) determining the product of the gradients of a horizontal and vertical line; (2) developing new Euler formulas relating exponential, trigonometric and hyperbolic functions in the 3D semi-structured complex number Euclidean space; (3) establishing semi-structured complex numbers as a better extension of the complex number set than quaternions; (4) resolving singularities that may arise in engineering and science equations (because of division by zero) to develop reasonable conclusions in the absence of experimental data. These results and their applications provide a firm foundation to advance the number set H as a useful mathematical tool.

The agricultural sector provides employment and income to the majority of Myanmar's population. The sector, however, is extremely susceptible to severe weather, rising temperatures, and changes in precipitation. This paper aims to analyze how vulnerable Myanmar's agricultural sector is to climate change and highlights the key sectors that are most at risk. This report also examines historical climate information, and the anticipated effects of climate change on Myanmar's agricultural sectors. In-depth literature reviews and summaries of Myanmar's climate change adaptation efforts are included in the report, along with recom-mendations for targeted, locally appropriate actions to strengthen the country's agricultural sector's resilience. Additionally, the study reviews Myanmar's in-stitutional framework for climate action and government priorities for adaptation measures, emphasizes the urgent need for climate action in Myanmar's agricul-ture sectors and calls for more research and development efforts on the effects of climate change on rural livelihoods and agriculture.

To further explore the bearing capacity and sustainable construction of vacuum drainage pipe (VDP) piles, field tests were carried out to compare and analyze the ultimate single pile bearing capacity, pile side friction and pile end resistance of ordinary piles and vacuum drainage pipe piles. The effect of the VDP pile on energy conservation and emission reduction in practical projects is discussed. The results shows that the VDP pile basically eliminated the soil squeeze and did not cause excessive relative displacement of pile and soil after vacuum consolidation. The VDP pile enhances pile side friction resistance, resulting in a 17.6% increase in ultimate bearing capacity compared to traditional piles. The VDP pile method can reduce carbon emissions by 31.4% compared to traditional methods. This study provides guidance for the production and design of VDP piles in the future and demonstrates their potential for energy conservation and emission reduction benefits compared to traditional methods.

In the realm of computer vision, semantic segmentation is the task of recognizing objects in images at the pixel level. This is done by performing a classification of each pixel. The task is complex and requires sophisticated skills and knowledge about the context to identify objects’ boundaries. The importance of semantic segmentation in many domains is undisputed. In medical diagnostics, it simplifies the early detection of pathologies, thus mitigating the possible consequences. In this work, we provide a review of the literature on deep ensemble learning models for polyp segmentation and we develop new ensembles based on convolutional neural networks and transformers. The development of an effective ensemble entails ensuring diversity between its components. To this end, we combine different models (HarDNet-MSEG, Polyp-PVT, and HSNet) trained with different data augmentation techniques, optimization methods, and learning rates, which we experimentally demonstrate to be useful to form a better ensemble. Most importantly, we introduce a new method to obtain the segmentation mask which is more suitable for combining transformers in an ensemble. In our extensive experimental evaluation, the proposed ensembles exhibit state-of-the-art performance.

Background Hop creep continues to present an unresolved issue for the brewing industry, specifically stemming from those hops added to beer during fermentation. Hops have been found to contain four dextrin-degrading enzymes: alpha amylase, beta amylase, limit dextrinase, and an amyloglucosidase. One recent hypothesis predicts that these dextrin-degrading enzymes could originate from microbes rather than the hop plant itself. Scope and Approach This review begins by describing how hops are processed and used in the brewing industry. It will then discuss hop creep’s origins with a new beer style, antimicrobial factors from hops and resistance mechanisms that bacteria use to counter them, and finally microbial communities that inhabit hops, focusing on whether they can produce the starch degrading enzymes which drive hop creep. After initial identification, microbes with possible links to hop creep were then run through several databases to search the genomes (if available) and for those specific enzymes. Key Findings and Conclusions Several bacteria and fungi contain alpha amylase as well as unspecified glycosyl hydrolases, but only one contains beta amylase. Finally, this paper closes with a short summary of how abundant these organisms typically are in other flowers.

Clinical and histological similarities between sarcoidosis and tuberculosis have driven repeated investigations looking for a mycobacterial cause of sarcoidosis. Over 50 years ago “anonymous mycobacteria” were suggested to have a role in the etiology of sarcoidosis. Both tuberculosis and sarcoidosis have a predilection for lung involvement though each can be found in any area of the body. A key histopathologic feature of both sarcoidosis and tuberculosis is the granuloma – while the tuberculous caseating granuloma has an area of caseous necrosis with a cheesy consistency; the non-caseating granuloma of sarcoidosis does not have this feature. This article reviews and reiterates the complicity of the infectious agent, Mycobacterium avium ss. paratuberculosis (MAP) as a cause of sarcoidosis. MAP is involved in a parallel story as the putative cause of Crohn’s disease, another disease featuring noncaseating granulomas. MAP is a zoonotic agent infecting ruminant animals and is found in dairy products and in environmental contamination of water and air. Despite increasing evidence tying MAP to several human diseases, there is a continued resistance to embracing its pleiotropic roles. "Who Moved My Cheese" is a simple yet powerful book that explores the ways in which individuals react to change. Extending the metaphor, the “non-cheesy” granuloma of sarcoidosis actually contains the difficult-to-detect “cheese”, MAP; MAP did not move, it was there all along.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

Scholarly publication in international journals depends on qualified, unbiased and available referees: (1) qualified in their ability to assume each role inherent to being a peer reviewer and in willingly and competently accepting the responsibilities that coincide with these roles; (2) unbiased in focusing on the submitted research content irrespective of their own research programs in judging the submission’s merit; and (3) available to devote time to read and understand the paper, check the accuracy and relevance of references, and write a comprehensive review commenting on the strengths and weaknesses of the manuscript, the ability of the research to be replicated, and the contribution of the work to the discipline. This study investigates the range of reviewer’s roles and responsibilities in relation to author’s own assessment as a frequent reviewer for fourteen journals representing five publishing houses—and as an active researcher—in comparison with a 2019 comprehensive study of the views of 224 authors on peer review. Based on this investigation, advice will be provided to potential reviewers regarding what is expected of them in undertaking their work. Recommendations will be offered for peer review to mitigate weaknesses in the process and increase the pool of qualified peer reviewers.

Using geometric considerations, we provide a clear derivation of the integral representation for the error function, known as the Craig formula. We calculate the corresponding power series expansion and prove the convergence. The same geometric means finally help to systematically derive handy formulas that approximate the inverse error function. Our approach can be used for applications in e.g. high-speed Monte Carlo simulations where this function is used extensively.

This article discusses the impact of new financial technologies, such as Non-Fungible Tokens (NFTs) on traditional industries such as art, sports, and game, while focusing on the recently formed "Metaverse" market. As a component of the overall blockchain ecosystem, the history of the establishment of NFT is analyzed. The impact of Web3 and intelligent contracts on Fintech are also investigated. This study examines the general trends in the NFTs market, including their price formation, price-influencing factors, and available patterns. Then the paper provides classifications and examples of NTFs. Besides, the technological application and primary technical path are also described. Later, the paper assesses the market's and marketplaces' accessibility. Finally, this study evaluates the management applications of NFTs and analyzes existing platforms, and demonstrates how they can be implemented effectively in various settings. The concluding portion discusses technological obstacles. The study concludes with a discussion of potential applications for the results and prospects for future research.

Airborne virus, such as COVID-19, caused pandemics all over the world. Virus-containing particles produced by infected individuals are suspended in the air for extended periods of time, actually results in viral aerosols and the spread of infectious diseases. Aerosol collection and detection devices are essential for limiting the spread of airborne virus diseases. This review provides an overview of the primary mechanisms and enhancement techniques for collecting and detecting airborne viruses. Indoor virus detection strategies for scenarios with varying ventilations are also summarized based on the excellent performance of existing advanced comprehensive devices. This review provides guidance for the development of future aerosol detection devices and aids in the control of airborne transmission diseases, such as COVID-19, monkeypox, and other airborne transmission viruses.

We recently formulated Modular Dvoretzky, Type-Cotype, Khinchin-Kahane and Grothendieck Inequality problems in the Appendix of \textit{[arXiv:2302.03718v1]}. For the sake of wide accessibility we give a separate treatment of them.

The presence of the quantum Rayleigh scattering, or spontaneous emission, inside a dielectric medium such as a beam splitter or an interferometric filter, prevents a single-photon from propagating in a straight-line. Modelling a beam splitter by means of a unitary transformation is physically meaningless because of the loss of photons. Additional missing elements from the conventional theory are: 1) the quantum Rayleigh stimulated emission which can form groups of photons of the same frequencies, and 2) the unavoidable parametric amplification of single-photons in the original parametric crystal. An interference filter disturbs, through multiple internal reflections, the original stream of single-photons, thereby confirming the existence of groups of photons being spread out to lengthen the coherence time. The approach of modelling individual, single measurements with statistical ensemble probability amplitudes leads to the counterintuitive explanations of the experimental outcomes and should be replaced with pure states describing instantaneous measurements which are afterwards averaged.

The adoption of harmful postures due to a sedentary lifestyle, which involves long periods at work in offices, is a factor that exacerbates musculoskeletal risks. To examine these risks, there are numerous postures analysis methods, such as Rapid Upper Limb Assessment (RULA) and Rapid Office Strain Assessment (ROSA). RULA is a consolidated method to evaluate the exposure of individual workers to ergonomic risk factors associated with upper extremity musculoskeletal disorders. In turn, ROSA is a more recent method that quantifies exposure to risk factors in an office work environment. This research aims to identify whether there is harmony between these two methods, ROSA and RULA. Through applied research, from a qualitative perspective, the scientific procedures adopted were direct observation and ROSA and RULA postural assessment instruments. The study was conducted in the radiology service and focused on the outpatient reception workstation. Results indicated that further investigation must occur to make working conditions changes as soon as possible and that both methods are harmonic. As contributions of the analysis, we have discussed the working conditions and suggested improvements to reduce the risks of musculoskeletal morbidity symptoms. We recommend future studies aimed at measuring the levels of complementarity between these methods by quantitative approaches.

DNA is stored in the nucleus of a cell in a folded state; however, only the necessary genetic information is extracted from the required group of genes. The key to extracting genetic information is chromatin ambivalence. Depending on the chromosomal region, chromatin is characterized into low-density "euchromatin" and high-density "heterochromatin", with various factors being involved in its regulation. Here, we focus on chromatin regulation and gene expression by the yeast FACT complex, which functions in both euchromatin and heterochromatin. FACT is known as a histone H2A/H2B chaperone and initially reported as an elongation factor associated with RNA polymerase II. In budding yeast, FACT activates promoter chromatin by interacting with the transcriptional activators SBF/MBF via the regulation of G1/S cell cycle genes. In fission yeast, FACT plays an important role in the formation of higher-order chromatin structures and transcriptional repression by binding to Swi6, an HP1 family protein, at heterochromatin. This FACT property, which refers to the alternate chromatin-regulation depending on the binding partner, is an interesting phenomenon. Further analysis of nucleosome regulation within heterochromatin is expected in future studies.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

The dominant view of cleaning compulsion as a dimension of OCD is that it is motivated by contamination anxiety. However, in daily life, much cleaning is undertaken as part of tidying one’s home. Such cleaning as well as the other tidying chores may equally assume obsessive-compulsive proportions. However, empirical interest in this phenomenon has remained sparse so far. This article aims to increase awareness of this ill-acknowledged symptom cluster among OCD researchers and to invite them to investigate it. After the introduction, clinical evidence for this OCD dimension is dealt with. Next, empirical studies with OCD inventories, which contain items referring to compulsive tidying, are discussed. Two of these made use of an OCD-inventory, devised by the present author. These also provide the data for the main investigation to be discussed in this paper. In that latter study, six OCD-item clusters, among which tidying compulsion, are predicted. These predictions are tested by evaluating and comparing the item-cluster correlations of all six clusters. These also offer a basis to optimize the clusters toward more homogeneous and distinct ones. By comparing predicted with final clusters, the items can be qualified as either hits, false positives, or false negatives. This output provides the details for revising the predictions, but also allows for calculating the values of two global “goodness-of-fit” measures for each predicted cluster. Though the results do not completely endorse the predicted composition of part of the clusters in the second sample, tidying compulsion is doing rather well. To determine the incidence of tidying compulsion based on the cluster scores, decisions had to be made about what constitute a cluster score, how its gravity can be estimated, and what should be the cut-off per cluster to divide the sample into clinical and subclinical cases on each cluster. If these ‒ unavoidably arbitrary ‒ decisions are accepted, both samples show an incidence of tidying compulsion of around 25%. After a brief critical evaluation of all discussed studies, it is concluded that the evidence presented, though modest, is solid enough to warrant further research into tidying compulsion.

Agrivoltaics (Agri-PV, AV) – the joint use of land for the production of agricultural products and energy – has recently been rapidly gaining popularity, as it can significantly increase income per unit of land area. In a broad sense, AV systems can include converters of not only solar, but also energy from any other local renewable source, including bioenergy. Current approach to AV represents an evolutionary development of agroecology and integrated PV power supply to the grid. That results in nearly doubled income per unit area. While AV could provide a basis for revolution in large-scale unmanned precision agriculture and smart farming which is impossible without on-site power supply, chemical fertilisation and pesticides reduction, and yield processing on-site. These approaches could change the logistics and the added value production chain in agriculture dramatically, and so, reduce its carbon footprint. Utilisation of decommissioned solar panels in AV could make the technology twice cheaper and postpone the need for bulk PV recycling. Unlike the mainstream discourse on the topic, this review feature is in focusing on the possibilities for AV to be stronger integrated into agriculture that could also help in relevant legal collisions (considered as neither rather than both components) resolution.

The Lokpaukwu Uru Quarry was examined geologically, geophysically, and core-wise. The location is between 5056.149'N and 5056.193'N and 7028.312'E and 7028.356'E. The study location may include the Asu River Group and the Eze-Aku Formation. This area has five rock units. In the eastern research region, siltstone forms a "CAP" on the shale. Shale underlies half of the study area. The west has calcareous sandstone. The eastern part of the area is dolerite, the main rock that spans siltstone and shale. The region's geological matter contains iron. Two geological sections were analysed and interpreted to identify the five rock units and their outcrops in the study area. electroresistivity in geophysical research Schlumberger found that the western, northwesterly, and central sections of the research region had a thick sedimentary sequence, whereas the eastern half has an igneous body, the project's main component. Sandstone, siltstone, and shale follow the high-resistivity rock in this location. The rock unit in the region was found in eleven core samples from the east half of the study area. Nine rock-unit core samples were found near Obichioke. The Lokpaukwu area's core data shows the rocks' positions, kinds, minerals, and strengths. Geologic mapping shows that a major fault separates the viable Uru end from the unviable Obichioke lot. Recrystallization dominates the fault track (alcitic matter). Thus, prior to quarrying igneous (basic) units, comparable investigations are advised.

There have been several developments in the field of nanopore biosensor development and sequencing applications that address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making these platforms a mainstay in contemporary research labs. Equipped with the ability to provide long and short-read sequencing information with quick turn-around times and simple sample preparation, nanopore sequencers are quickly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We conclude with examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.

NASA/ESA/CSA joint venture James Webb Space Telescope is about to be launched. It is hypothesized to operate in near-infrared range. It is also hypothesized to unveil early star formation, galaxies, and universe due to its orbit, point in orbit and orbital motion. It has been under manufacturing for over 20 years at a staggering cost of 10 billion US dollars (most expensive scientific experiment in history). Beryllium (Be) is chosen to be element for construction of its main mirrors due to its high stiffness, low density, low linear coefficient of thermal expansion (α) in cryogenics and high thermal conductivity. It is followed by gold (Au) layer deposition on its (Be) surface to enhance its sensitivity towards infrared radiation as later is hypothesized to bear superior properties. However, serious mistakes have been made in selecting this material for this application. Owing to its crystal structure (hexagonal close packed (hcp)), slip planes (basal, prismatic and pyramidal) and mechanisms of their activation, Be necessitates easy fracture at cryogenic temperature. It has anisotropic properties and prone to transverse fracture under tensile loading. Furthermore, its ductile to brittle transition temperature is very low making it entirely unsuitable for such an application. It is one of most expensive metals on planet. This study constitutes revisiting these fundamental properties and mechanisms which were entirely ignored during materials selection thus rendering whole project useless.

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease has been shown to be related to insulin resistance and multiplied blood sugar ranges. Further, it has been found that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire will be conducted to determine the prevalence of breast cancer among women using metformin in the Ha’il region. Result: Incidence of breast cancer among women using metformin in the Ha’il region is very low. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study have corroborated the literature for the same by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes

Electrons moving at slow speeds much lower that the speed of light are described by a wave function which is a solution of Pauli’s equation. This is a low velocity limit of the relativistic Dirac equation. Here we compare two approaches, one which is the more conservative Copenhagen’s interpretation denying a trajectory of the electron but allowing a trajectory to the electron expectation value through Ehrenfest theorem. The said expectation value is of course calculated using a solution of Pauli’s equation. A less orthodox approach is championed by Bohm, and attributes a velocity field to the electron also derived from the Pauli wave function. It is thus interesting to compare the trajectory followed by the electron according to Bohm and its expectation value according to Ehrenfest. Both similarities and differences will be considered.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Rural tourism plays an increasing role in maintaining sustainable rural development. In-11 tegrating culture into rural tourism is multifaceted. Local communities have often been regarded as 12 homogeneous, and different voices within them are selectively presented or re-interpreted by pow-13 ers. A better understanding of how and why cultures are integrated into rural tourism is urgently 14 needed. This paper aims to investigate (1) the aims and motives of tourism managers to integrate 15 cultural concepts into rural tourism; (2) who has participated in the cultural integration process; and 16 (3) how cultures have been integrated into rural tourism. Based on a scoping literature review, we 17 found that cultures could add more attractions, such as historical heritage, artwork, cultural land-18 scape, customs, food, and language, to the natural landscape and bring more tourists to rural areas. 19 However, integrating cultures into rural tourism is not always successful. Conflicts of interest 20 among different stakeholders are also often found. Some of the worst cases of cultural integration 21 have even destroyed the original natural landscape and local cultures. While cultural integration is 22 complicated, injustice and perverse effects do not have to be a consequence of integrating cultures 23 into rural tourism. Multi-way communication among tourism providers, managers, and consumers 24 can mitigate disruptive outcomes and unlock positive social outcomes.

In this research, new setting is introduced for new SuperHyperNotions, namely, an 1-failed SuperHyperForcing and Neutrosophic 1-failed SuperHyperForcing. Assume a SuperHyperGraph. Then an ``1-failed SuperHyperForcing'' $\mathcal{Z}(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex; a ``neutrosophic 1-failed SuperHyperForcing'' $\mathcal{Z}_n(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum neutrosophic cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex. Assume a SuperHyperGraph. Then an ``$\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} cardinality such that either of the following expressions hold for the (neutrosophic) cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)| > |S\cap (V\setminus N(s))|+\delta,~|S\cap N(s)| < |S\cap (V\setminus N(s))|+\delta.$ The first Expression, holds if $S$ is an ``$\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is an ``$\delta-$SuperHyperDefensive''; a``neutrosophic $\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} neutrosophic 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} neutrosophic cardinality such that either of the following expressions hold for the neutrosophic cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)|_{neutrosophic} > |S\cap (V\setminus N(s))|_{neutrosophic}+\delta,~ |S\cap N(s)|_{neutrosophic} < |S\cap (V\setminus N(s))|_{neutrosophic}+\delta.$ The first Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperDefensive''. A basic familiarity with SuperHyperGraph theory and neutrosophic SuperHyperGraph theory are proposed.

Lithium-ion (Li-ion) batteries are becoming more common in portable electronic devices due to their high energy density, lack of memory effect, and high charge and discharge rate capabilities. Li-ion batteries are a relatively new technology, first marketed in the early 1990s, and research and development work are ongoing to improve safety and increase capacity, charge/discharge rate, and lifetime [1]. In this paper, we review the types and characteristics of Li-ion batteries and summarize charging methods and safety considerations. Following, we design and fabricate Li-ion battery and highlight the steps of fabrication that ensure fast charge/discharge rates that give the battery more reliability and high energy density

Insulin signaling plays a crucial role in cellular uptake of glucose and different metabolic pathways. Impairment in cellular insulin sensitivity due to various molecular pathways leads to Insulin resistance (IR) as well as fatty liver. In this review, mechanisms by which zinc involved in decreasing IR are described, focusing on oxidative stress, inflammation, immune system, gut flora and hepatic lipophagy. This study reviews the cause of IR and highlights the role of zinc in mechanisms diminishing IR and fatty liver.

Patches of Diopatra species from Brazilian sandy beaches were followed for ca. 50 years. Data were accessed from papers, gray literature, images and collections to verify time changes in the South Brazilian Bight (SBB) from 1974-2021. We modeled maximum density over time at 15 beaches, observing very high densities (&gt; 100 ind.m-2) in 1974 followed by a decrease (~ 10 ind.m-2) of three species of Diopatra until 1995 and a strong decline (1996-2002) when populations were almost regionally extinct (0-1 ind. m-2). A slight recovery (3-4 ind.m-2) occurred after 2006 for a single species, D. marinae, associated with warmer northern waters, suggesting a range shift. This pattern was associated with a) heatwaves linked to an El-Niño event (1988) and gradual SST surface warming of ca. 1 oC since 1974. The usage of Diopatra spp. as fishing bait could also be associated with such a reduction. After 2016, D. neapolitana, a likely alien species, was established in the SBB in high densities. Projections based on Species Distribution Modeling (SDM) suggest a potential of invasion in the same range of the known species of D. cuprea complex along the Brazilian coast despite that there are no signs of competition between both species.

Emotional intelligence and educational level are commonly associated with success in life and well-being. While multiple studies have explored these concepts independently, few studies have examined the impact of educational level on emotional intelligence and associated variables, such as well-being. A total of N = 202 participants were recruited online. Participants completed measures of emotional intelligence, well-being (i.e., happiness, self-esteem, personal growth). Overall, participants who previously obtained a bachelor’s degree displayed higher levels of emotional intelligence, happiness, self-esteem, and personal growth compared to those without an undergraduate degree. However, no differences were observed on any variable between individuals currently enrolled in a university and non-students. The results suggest that, while completing a university degree increases emotional intelligence and well-being, the stress of being a student may negatively impact the benefits obtained from attending university. Limitations and possible directions for future research are discussed.

Acacia nubica is well-adapted to harsh conditions and offers valued socio-economic and environmental benefits. This research studied seed germination and seedling growth of A. nubica in vitro in response to the application of different concentrations of sodium hypochlorite, sucrose, and Murashige and Skoog (MS) medium. The synchrony, percentage, and rate of germination of A. nubica seed were studied. Seedling development was assessed by measuring the shoot, root, and number of nodes. Sodium hypochlorite at 10% produced the maximum germination percentage, while 5% induced a faster and more uniform emergence. Sucrose has various effects on seed emergence and germination depending on the concentrations; 30 g/L elicited the highest germination, while 10 g/L improved seed emergence rate with higher uniformity. The highest seed germination was achieved on ¼-MS medium, although 0-MS strength recorded faster and more synchronized germination. The development of A. nubica seedlings was influenced by MS medium strengths and sucrose concentrations. Full MS medium produced the highest shoot length and the highest vigor index with the addition of 20 g/L sucrose and the maximum root length with 50 g/L sucrose. Also, 30 g/L sucrose gave the maximum number of nodes and the maximum root/shoot ratio. However, ½-MS strength yields the highest seedling biomass with 30 g/L sucrose. This is the first successful report on the seed germination and seedling growth of A. nubica in vitro.

A recent paradigm shift in diagnostics of medulloblastoma allows the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow better clinical management for therapies targeting druggable mutations, but also offers a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery, radio- and chemotherapy, but also controversial theories on the cell of origin, animal models and the use of liquid biopsy.

Since its introduction almost 50 years ago, the concept of ‘flow’ has been descriptive of optimal experiences, also in relation to play. However, the explorative nature of play leads to some discrepancies between flow and the optimal experience of play. In this paper the differences between flow and play are explored, leading to proposing the state of ‘wonder’ (directed at exploration) as an alternative to ‘flow’. From this perspective, the study further explores how we may design toys that enable meaningful experiences of play, identifying opportunities in designing for toys as the enablers of immersed experiences of wonder.

As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.

Maternal infectious disease may pose considerable challenges to the fetal health due to the distribution of important elements of the sanguine and lymphatic system from the mother via the umbilical cord. The mother and the fetus have a degree of interdependence that is similar to the one between the eukaryotic cell and the mitochondrion, particularly during the first half term of the pregnancy, which explains the increased appetite of the expecting mother during the first stages of the fetal development. There is a solid bridge between the adaptive immune system and the encephalon that was only discovered a few decades ago. As a result, scientists may still be in the introductory stages of research, and there might be a significant and profound degree of association between the immune system and a healthy neurological development. There is a significant link between the onset of significant maternal infectious disease and the onset of neurodevelopmental disease in the fetus, and virtually all immune cells play major roles in the promotion and inhibition of neurogenesis alike. Likewise, there is a probability that maternal infectious diseases during pregnancy represent a risk factor of fetal neurodevelopmental disease, as a pressurised development of the adaptive immune memory could result in a pressurised or inhibited neurological development, which both can result in a delayed development of certain sub-regions of the brain. For example, the fetus may display poorer social abilities and sharp analytical skills later in life, which is an important sign of neurodevelopmental disease. A pressurised development of the adaptive immune memory could not require the development of a significant form of disease, but rather just a sharp rate of immune preparation against several important pathogenic agents during the introductory stages of life, when the encephalon experiences the sharpest increase rate in development. The problem per se is not the process of immunisation, but a much sharper process of immunisation over the first stages of life in case of an exposure to one dangerous pathogen or more numerous kinds of pathogens and antigens that normally cause moderate disease morbidity. The more dangerous the microbe is, the sharper the development of the adaptive immune memory will be, and the same happens in the case of an increased number of infectious microbes and antigens that infected the cells of the mothers and the fetuses in cause, and this may, in the majority of the situations, still be the case even if the pathogens are already significantly weakened or lifeless, given that the gain of adaptive immune memory alone constitutes an important factor of neurogenesis and an increased rate of neurological development, and that the infant will become almost or fully protected against the pathogens in cause, despite not having had experienced the disease beforehand. In this case, neurodevelopmental delays are possibly not caused by an impaired neurogenesis, but by an excessive one, whilst maternal infection-associated neurodevelopmental delays may be caused by an impaired neurogenesis. Nevertheless, the aetiology of immunity-related neurodevelopmental delays may be more complex in nature and implicate a chronological and spatial sequence of induced excedentary and deficitary rates of neurogenesis, hence reflecting the incredibly complex nature and various forms of neurodevelopmental disease. It is important to mention that a single dose of infant immunisation brings significantly lower risks of adverse neurological events than the onset of a significant maternal infectious disease during pregnancy. The objective of paediatric neuro-immunological studies may be to improve the understanding of the association between a healthy immune developmental rate and a balanced ratio of the developmental rates of important brain regions and sub-regions.

Nano/micron-sized bioactive glass (BG) particles are attractive candidates for both soft and hard tissue engineering. They can chemically bond to the host tissues, enhance new tissue formation, activate cell proliferation, stimulate the genetic expression of proteins, and trigger unique an-ti-bacterial, anti-inflammatory, and anti-cancer functionalities. Recently, composites based on bi-opolymers and BG particles have been developed with various state-of-the-art techniques for tis-sue engineering. Gelatin, a semi-synthetic biopolymer, has attracted the attention of researchers because it is derived from the most abundant protein in the body, viz., collagen. It is a polymer that can be dissolved in water and processed to acquire different configurations, such as hydro-gels, fibers, films, scaffolds, etc. Searching "bioactive glass gelatin" in the tile on Scopus renders 80 highly relevant articles published in the last ~10 years, which signifies the importance of such composites. First, this review addresses the basic concepts of soft and hard tissue engineering, in-cluding the healing mechanisms and limitations ahead. Then, current knowledge on gelatin/BG composites including composition, processing and properties is summarized and discussed both for soft and hard tissue applications. This review explores physical, chemical and mechanical features and ion-release effects of such composites concerning osteogenic and angiogenic respons-es in vivo and in vitro. Additionally, recent developments of BG/gelatin composites using 3D/4D printing for tissue engineering are presented. Finally, the perspectives and current challenges in developing desirable composites for the regeneration of different tissues are outlined.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.