Amidst the dynamic landscape of education, this paper embarks on a transformative journey that explores the integration of Artificial Intelligence (AI) in literature and language education. Through a qualitative exploratory approach, purposeful and maximum variation sampling method, the researcher delves into the experiences of educators and learners, unraveling the multifaceted dimensions of AI-driven pedagogy in SMC. Drawing upon a theoretical framework encompassing Constructivism, Connectivism, and Socio-Cultural Theory, the study examines AI's role in reshaping pedagogical landscapes, fostering critical thinking, and expanding access to education. The results resonate with participants' narratives, unveiling AI's potential in fostering personalized learning pathways, enhancing collaborative engagement, and bridging digital divides. Ethical considerations in AI education are explored, leading to the proposition of responsible guidelines. These findings underline the transformative power of AI in education, aligned with the institution's commitment to quality education and innovation. Overall, the study calls for ongoing exploration, emphasizing the qualitative research method's depth and richness, as well as the theoretical framework's guidance in realizing the study's objectives. As AI continues to shape education's frontiers, this research underscores the significance of adaptability, ethical awareness, and holistic engagement for school administrators, educators, learners, and researchers alike.

Tremor is a prevalent neurological disorder characterized by involuntary shaking or trembling of body parts. This condition impairs fine motor skills and hand coordination to varying degrees and can even affect overall body mobility. As a result, tremors severely disrupt the daily lives and work of those affected, significantly limiting their physical activity space. This study developed an innovative Spatial Augmented Reality (SAR) system aimed at assisting individuals with tremor disorders to overcome their physical limitations and expand their range of activities. The system integrates eye-tracking and Internet of Things (IoT) technologies, enabling users to smoothly control objects in the real world through eye movements. It employs a virtual stabilization algorithm for stable interaction with objects in the real environment. The study comprehensively evaluated the system's performance through three experiments: 1) assessing the effectiveness of the virtual stabilization algorithm in enhancing the system's ability to assist individuals with tremors in stable and efficient interaction with remote objects; 2) evaluating the system's fluidity and stability in performing complex interactive tasks; 3) investigating the precision and efficiency of the system in remote interactions within complex physical environments. The results demonstrate that the system significantly improves the stability and efficiency of interactions between individuals with tremor and remote objects, reduces operational errors, and enhances the accuracy and communication efficiency of interactions.

Halide perovskite materials gain enormous attention for their semiconducting properties, higher power conversion efficiency and potential applications in a wide range field of studies along with their two key limitations: stability and toxicity. In spite of great progress made on the halide perovskites and many promising research developments, overcoming these limitations is not realized yet. Therefore, coordination engineering of new framework for obtaining alternative new halide perovskite materials and fundamental understanding of the coordination chemistry and electronic interactions forming the structure of these newly engineered halide perovskite materials might be one way in order to overcome the issues related to both stability and toxicity. In this review, the current development of halide perovskite families, both lead halide perovskites and lead free halide perovskites followed by coordination engineering of the new frameworks to engineer new halide perovskite materials will be reviewed comprehensively. Moreover, all the concerns of the fundamental ideas of coordination chemistry and electronic interactions that are keys in forming the halide perovskite structures are discussed in detail and form the main aim of this review. Interestingly, we also discuss recent potential energy applications beyond photovoltaic and this review has completed with an essential and open question: ‘what could happen in the future of halide perovskites?’ in order to excite commercial enterprises and research institutions again as well as to get motivating new predictions on the future continuity of this field.

Background: Complementary and alternative medicines (CAM) are widely used, with pharmacies accounting for a significant share of the distribution market. Despite their popularity, many CAMs lack scientific evidence for effectiveness, and some can cause adverse health effects. Limited research exists on CAM-related adverse events and the effectiveness of CAM labels in conveying crucial information. Methods: This cross-sectional study aimed to investigate CAM utilization, consumer perspectives, and the influence of labels on CAM usage in Melbourne, Australia. Data were collected through an online questionnaire and analysed using descriptive statistics, Pearson's correlation, MANOVA, and regression analyses. Results: The study enrolled 125 current CAM users, primarily recruited from pharmacy and supermarket customers (age: predominantly 31-50; gender: 20.8% male, 79.2% female). Participants' perceptions of effectiveness and safety were positively correlated. Label warnings prompted information-seeking, but consultation with healthcare professionals (HCPs), particularly pharmacists, was infrequent (24%). Adverse reactions were reported by 18.5% of participants, with 8.3% experiencing severe reactions. The analysis revealed relationships between CAM usage and demographics. Ordinal logistic regression showed a significant association between calcium consumption and higher age groups (coefficient = 1.658, p = 0.006), while binary logistic regression identified higher iron consumption among females (coefficient = 2.177, p = 0.007). Conclusions: Label warnings significantly prompted consumers to seek more information about CAMs. However, a limited engagement of HCPs, especially pharmacists, suggests an opportunity for improved consumer education and pharmacist involvement in CAMs-related discussions. The findings highlight demographic influences on CAM usage being essential for developing targeted health interventions and policies. Addressing these aspects may lead to safer CAM practices and informed consumer decision-making.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Geothermal energy is a weather-independent, permanently available renewable energy source. In addition to producing heat and electricity, geothermal energy can be used to extract critical raw materials dissolved in the heat-carrying fluid. Researchers working on the frontiers of geothermal energy utilisation may be able to transform ultra-deep metallic mineral formations into “orebody-Enhanced Geothermal Systems”. In the planned technology, the metal-containing geological formation would be manipulated in such a way that cogeneration of energy and metals is possible and can be optimised in the future according to market needs. The potential of geothermal energy for sustainable mineral extraction and energy production aligns with Sustainable Development Goal (SDG) 7, which aims to ensure access to affordable, reliable, sustainable, and modern energy for all. This new technology could substantially decrease Europe’s dependency on importing critical metallic minerals (such as lithium and tungsten) and energy; over and above, it has a small environmental footprint, including very low carbon emissions

Course-based Undergraduate Research Experiences (CUREs) provide active and authentic scientific involvement to tens of thousands of students each year. Through this process, CUREs offer the benefits of increased learning outcomes, improved equity, and increased retention in STEM. During the COVID-19 pandemic, however, research and teaching labs have limited capacity. Some universities are closed for in-person learning altogether, and others are likely to face emergency shut-downs throughout the year. In this setting, the inability to conduct experiments limits a core aspect of CUREs. Without experimentation as a basis for student engagement, interest, and broader relevance, true course-based research this year becomes a major challenge. We suggest that this limitation provides a moment to enhance CUREs with research-enriching learning activities that are obtainable while away from the bench. In this essay we outline a variety of these student-centered activities and review their benefits in terms of student interest, learning, and equity. While useful during emergency teaching transitions during COVID-19, we make the case that these new evidence-based practices for CUREs will also be helpful for the enrichment of research-based learning beyond the current crisis.

Man has always been interested in animal electricity, which seems to be measured in every living cell. He has been fascinated by trying to elucidate the mechanisms by which this potential is created and maintained. Biology is the science that seeks to explain this mystery. Biology is based on basic sciences such as physics or chemistry. The latter, in turn, make systematic use of mathematics to measure, evaluate and predict certain phenomena and to develop "laws" and models that are as general as possible while respecting, as closely as possible, observations and facts. The Nernst equation was one of the pillars of electrochemistry. Biology also uses this same equation as one of the indispensable bases for the computation of membrane potential. Man has established a cellular model that highlights this equation in several forms. However, we are going to show by various means that this model is inadequate or even inapplicable.

Latin America and the Caribbean offer the most favorable natural and social conditions for the emergence of cattle ranching that regenerate and maintains the ecosystem services on which life on Earth depends, that is energy efficient and that contributes to meeting fundamental human food needs. Unlike other major global producers, cattle farming in Latin America and the Caribbean is fundamentally based on pasture. Therein lies both its strength (due to the regenerative potential of well-managed pastures) and its vulnerability (due to the pervasive link between deforestation and pasture formation, especially in the Amazon, where 40% of the Brazilian herd is concentrated). The diversification of pastures (today marked by impressive monotony, with brachiaria accounting for 85% of the species in Brazil), the introduction of legumes and tree plantations within them, and the proper management of herds, open the way to the possibility of drastically reducing the area currently occupied by the activity (especially in the Amazon) while maintaining the supply of its products. Agricultural research has disseminated forms of moderate intensification of cattle ranching, which represent a low opportunity cost of animal feed and, at the same time, regeneration of ecosystem services that have so far been destroyed by the prevailing methods of farming.

This article delves into the intersection of generative AI and digital twins within drug discovery, exploring their synergistic potential to revolutionize pharmaceutical research and development. Through various instances and examples, we illuminate how generative AI algorithms, capable of simulating vast chemical spaces and predicting molecular properties, are increasingly integrated with digital twins of biological systems to expedite drug discovery. By harnessing the power of computational models and machine learning, researchers can design novel compounds tailored to specific targets, optimize drug candidates, and simulate their behavior within virtual biological environments. This paradigm shift offers unprecedented opportunities for accelerating drug development, reducing costs, and, ultimately, improving patient outcomes. As we navigate this rapidly evolving landscape, collaboration between interdisciplinary teams and continued innovation will be paramount in realizing the promise of generative AI and digital twins in advancing drug discovery.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Glioblastoma multiforme (GBM) is one of the deadliest human cancers with very lim-ited treatment options available. The malignant behavior of GBM is manifest in a tu-mor which is highly invasive, resistant to standard cytotoxic chemotherapy and is strongly immunosuppressive. Immune checkpoint inhibitors have recently been in-troduced in the clinic and have yielded promising results in certain cancers. GBM however is largely refractory to these treatments. The immune checkpoint CD47 has recently gained attention as potential target for intervention as it conveys a “don’t eat me” signal to tumor associated macrophages via the inhibitory SIRP alpha protein. In preclinical models, administration of anti-CD47 monoclonal antibodies have shown impressive results with GBM and other tumor models. Several well characterized on-cogenic pathways have recently been shown to regulate CD47 expression in GBM cells and Glioma Stem cells (GSCs) include EGFR, beta catenin and LRIG2. Other macro-phage pathways involved in regulating phagocytosis including TREM2 and glycan binding proteins are discussed as well. Finally, Chimeric Antigen Receptor Macro-phages (CAR)-M could be leveraged for greatly enhancing phagocytosis of GBM and repolarization of the microenvironment in general. Here we comprehensively review the mechanisms that regulate about macrophage phagocytosis of GBM cells.

In this perspective article, we ponder topographical enhancements of artificial neural networks. In our recent paper in JMLR, we proved a quasi-equivalence between the network width and depth and also discussed the power of intra-links, which can be viewed as network height. In 1982, Hopfield published a network to model human associative memory, which contains many loops for dynamic evolution toward fixed points. Based on noising-denoising loops, diffusion models are recently developed to enable Bayesian modeling and inference with big data. Furthermore, we envision development of multi-AI-agent systems through “netware” engineering as a quantum leap of software engineering for emergent behaviors and autonomous AI at individual and population levels. We believe that the novel use of links and loops in space and time via multi-scale coupling would catalyze the next-generation neural networks.

The General equilibrium theory tries to show how and why all free markets tend toward equilibrium in the long run. However, what is meant by equilibrium in this paper is more from a thermodynamical point of view. In order to understand the actual situation, it is necessary to study open systems which are complex. In physics, such a behavior in a complex system can be explain by using Non Equilibrium Thermodynamics. A system is able to self-organize and sustain itself away from equilibrium. Economic systems may fluctuate around a particular point. To sustain it far from the equilibrium state, it needs to degrade more energy and materials. In this study, the energy consumption patterns of Sri Lanka and USA are discussed. The pattern concerning Sri Lanka is close to the model proposed here, whereas the energy consumption pattern of USA is more complicated due to external factors.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.

There are various approaches to managing polyethylene terephthalate waste, including methods for recycling PET. However, at present, only the cleanest wastes that can already be efficiently recycled using known methods are considered in the scientific literature. The study aims to look at other forms of polyethylene terephthalate waste that pose a challenge: low quality PET flakes, polyester tire cord, PET dust and prepolymer waste. The waste was characterized by FTIR spectroscopy, viscosimetry, differential scanning calorimetry, laser diffraction and sieve analysis. The findings describe the composition and properties of various forms of polyethylene terephthalate waste. Low quality PET flake waste and polyethylene terephthalate dust have been shown to be suitable for all chemical recycling methods. When recycling waste polyester tire cord, it is difficult to completely separate the rubber, so its presence in the final product must be taken into account. The most promising way to process a prepolymer is its depolymerization by hydrolysis, alcoholysis or glycolysis to produce monomers for the synthesis of PET, similar in properties to the primary one.

Micro-combs [1-4] - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts [5,6], but in an integrated footprint. The discovery of temporal soliton states (DKS – dissipative Kerr solitons) [4,7-11] as a means of mode-locking micro-combs has enabled breakthroughs in many fields including spectroscopy [12,13], microwave photonics [14], frequency synthesis [15], optical ranging [16,17], quantum sources [18,19], metrology [20,21] and more. One of their most promising applications has been optical fibre communications where they have enabled massively parallel ultrahigh capacity multiplexed data transmission [22,23]. Here, by using a new and powerful class of micro-comb called “soliton crystals” [11], we achieve unprecedented data transmission over standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits per second (Tb/s) using the telecommunications C-band at 1550nm with a spectral efficiency – a critically important performance metric - of 10.4 bits/s/Hz. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with a low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format of 64 QAM (quadrature amplitude modulated). We demonstrate error free transmission over 75 km of standard optical fibre in the laboratory as well as in a field trial over an installed metropolitan optical fibre network. These experiments were greatly aided by the ability of the soliton crystals to operate without stabilization or feedback control. This work demonstrates the capability of optical soliton crystal micro-combs to perform in demanding and practical optical communications networks.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

In this paper, different concepts of reconfigurable RF-MEMS attenuators for beamforming applications are proposed and critically assessed. Capitalizing on the previous part of this work, the 1-bit attenuation modules featuring series and shunt resistors and low-voltage membranes (7-9 V) are employed to develop a 3-bit attenuator for fine-tuning attenuations (&lt; -10 dB) in the 24.25-27.5 GHz range. More substantial attenuation levels are investigated by means of fabricated samples of coplanar waveguide (CPW) sections equipped with Pi-shaped resistors aiming at attenuations of -15, -30, and -45 dB. The remarkable electrical features of such configurations, showing flat attenuation curves and limited return losses, and the investigation of a switched-line attenuator design based on them led to the final proposed concept of a low-voltage 24-state attenuator. Such simulated device combines the Pi-shaped resistors for substantial attenuations with the 3-bit design for fine-tuning operations, showing a maximum attenuation level of nearly -50 dB while maintaining steadily flat attenuation levels and limited return losses (< -11 dB) along the frequency band of interest.

This paper describes different variants of broadband and simple attenuator modules for beamforming applications, based on Radio Frequency Micro Electro-Mechanical Systems (RF-MEMS), framed within Coplanar Waveguide (CPW) structures. The modules proposed in the first part of this work differ in their actuation voltage, topology, and desired attenuation level. Fabricated samples of basic 1-bit attenuation modules, characterized by a moderate footprint of 690 x 1960 µm2 and aiming at attenuation levels of -2, -3 and -5 dB in the 24.25-27.5 GHz range, are presented in their variants featuring both low actuation voltages (5-7 V) as well as higher values (~ 45V), the latter ones ensuring larger mechanical restoring force (and robustness against stiction). Beyond the fabrication non-idealities that affected the described samples, the substantial agreement between simulations and measurement outcomes proved that the proposed designs could provide precise attenuation levels up to 40 GHz, ranging up to nearly -3 dB and -5 dB for the series and shunt variants, respectively. Moreover, they could be effective building blocks for future wideband and reconfigurable RF-MEMS attenuators. In fact, in the second part of this work, combinations of the discussed cells and other configurations meant for larger attenuation levels will be investigated.

This research explores the intricate relationship between gravitational and cosmic redshift phenomena, unveiling a profound understanding of how light behaves as it traverses the cosmos. The study begins with an examination of gravitational redshift, a well-established concept occurring when photons move away from massive gravitational sources, such as stars within galaxies. Gravitational redshift, expressed as λ/λ₀, manifests within the gravitational influence and extends to the boundary of the observed "zero-gravity sphere" enveloping galaxies. Within this remarkable zero-gravity sphere, gravitational effects persist, while the antigravity influence of dark energy remains negligible. As a result, gravitational redshift dominates, and cosmic redshift is notably absent within the sphere. Photons within this sphere maintain their constant speed 'c' and undergo gravitational redshift exclusively. However, as photons exit the zero-gravity sphere at a distance 'r' equivalent to the source star's radius, they encounter the onset of cosmic redshift, quantified as {(λ_obs - λ_emit)/ λ_emit}. Cosmic redshift blends with gravitational redshift, forming the effective redshift of the photon. Critically, the effective cosmic redshift surpasses gravitational redshift, illuminating a profound revelation: photons traverse a greater "light-traveled distance" than their proper distance from the source. In essence, cosmic redshift signifies that photons move across their intended distances at their intrinsic speed c, while the expanding universe introduces a relative distance expansion, influenced by antigravity. This research delves into the intricate dance between gravitational and cosmic redshift, shedding light on their remarkable implications for our comprehension of the expanding universe.

In previous studies, the authors utilized a single-dimensional operationalization of species density that implies induction of hierarchy and time with certain topologies. For further clarification of induced fractals including the relation to renormalization in physics, here a theoretical development is proposed based on a newly identified fact, namely that scaling parameters for magnetization exactly correspond to imaginary parts of Riemann zeta nontrivial zeros. An analogy to magnetization and accompanying Fake Monster Algebra is invoked to lend support to this theory, along with empirical species density data for a wild Dictyostelia community. A master torus and a Lagrangian/Hamiltonian are derived expressing fractal structures as a solution for diminishing divergent terms in renormalization.

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

This article provides a comprehensive review of the intersection of 5G technology and Beyond, and Smart Grids, focusing on the potential of Vehicle-to-Fog as an industrial alternative for addressing energy efficiency challenges in data processing. This study aims to investigate relevant articles and patents to understand the collaborative potential between 5G and Smart Grids. It explores how to establish new regulatory standards within the architectural framework of 5G to facilitate decentralized data processing and remodel energy consumption patterns. The hypothesis suggests that decentralized 5G architecture and Smart Grids can be most effectively applied through vehicular fogging powered by solar energy. A combined quantitative and qualitative methodology guides the exploration of articles and patents. The study concludes by advocating for new standards that embrace decentralized 5G data processing, emphasizing the potential of Vehicle-to-Fog and the future deployment of 6G technology in Smart Grids. These advancements can significantly enhance energy efficiency in the context of 5G and pave the way for future innovations.

Dengue virus an arbovirus is endemic in an area that comprise almost half of the world's population, contrary to past beliefs that dengue virus differentiate from other neuroinvasive arbovirus due to its lack of neurological invasion and disease related neurological complications excluding hemorrhagic and thromboembolic , the body of evidence have grown to demonstrate a series of neurological manifestations linked to dengue virus with possible mechanisms involving direct virus invasion of the nervous system or immune mediated complications. In this review we provide a wide approach to this neglect but not so rare manifestations of a very common disease.

The leading cause and foremost reason for mortality and morbidity in the world is a group known as Noncommunicable Diseases. The best approach to treat them is to evaluate and control the risk factors. There are shared by all these diseases leading to the existence of some meeting points behind all of them. There should be some key to acquire conditions that modify the cells homeostasis and impaired the cell physiology developing different diseases. Physics try to explain the nature of the phenomena that surround us, at first, at the level of our macroscopic perception. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy; measurement affects the system and change it. Subatomic particles have a wave-particle duality that could be in a coherence statement, also can pass through high-energy barriers. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, especially when classical physics fails to give an accurate description. Quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production, cancer mutations, and microbiome induced pathology. I want to propose that medicine also can be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

We are encouraged to look beyond ɅCDM as there are no satisfactory explanations for either dark energy or dark matter. A data centred phenomenological approach supports an explanation where dark energy is Holographic Dark Information Energy, HDIE. HDIE explains many effects attributed separately to Ʌ and CDM. HDIE mimics Ʌ with sufficient energy and an equation of state parameter, w= -1.03±0.05 at redshifts z<1.35 to account for accelerating expansion. HDIE is clumped around galaxies at densities that distort space-time, explaining many CDM attributed effects. The present ratio of HDIE/baryons ~2.15, required for the observed expansion history, is equivalent to a dark matter fraction ~68%, consistent with many galaxies. The HDIE/baryon model is based largely on proven physics, provides a common explanation for dark energy and dark matter, and solves the cosmological coincidence problem. At earlier times, z > ~1.35, HDIE was phantom, w = -1.82±0.08, enabling the model to be falsified. HDIE fits Planck dark energy wo-wa plots at least as well as Ʌ, and is consistent with other results that suggest dark energy was phantom at earlier times. A new w-parameterisation is proposed, as the usual CPL parameterisation is biased and unsuitable for distinguishing between HDIE/baryon and ɅCDM models.

Background/Objectives: Infectious Endocarditis often requires surgical intervention, with postoperative acute kidney injury (AKI) posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with endocarditis scheduled for valve surgery. Methods: This single center study enrolled 130 consecutive endocarditis patients from 2013 to 2021 undergoing valve surgery. Creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence, the relevance of creatinine levels for AKI detection, and the association of AKI with 30-, 60- and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the 2nd postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dl on the 2nd day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the 2nd day were robust predictors for short-term mortality at 30, 60 and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 hours postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical endocarditis patients. A specific threshold (1.35 mg/dl) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.

This review presents an updated overview of research concerning Leishmania protein structures, primarily sourced from the Protein Data Bank (PDB), that play a role in the metabolic pathways of the Leishmania parasite. Furthermore, we assess the current progress in the identification and development of bioactive chemical agents aimed at addressing this substantially overlooked tropical disease. We have analyzed experimental data obtained from in vitro, in vivo and in silico sources. This data has been categorized into four main areas: a) vector taxonomy and geographic distribution; b) parasite taxonomy and geographic distribution; c) enzymatic functions of proteins engaged in parasite/host interactions throughout various developmental stages (such as oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, and cytokines); and d) established and experimental treatments employing bioactive chemical compounds. Our objective is to establish a foundational point of reference for research efforts concentrating on the elucidation of interaction mechanisms and the processes of ligand-protein activation/inactivation, specifically linked to Leishmania infections. Consequently, we emphasize enzymes recognized for their involvement in the biochemical pathways incited during Leishmania infection episodes. This review encapsulates the current understanding, offering insights to inform and direct future explorations aimed at targeting proteins and pathways to enhance the management of Leishmania-related diseases.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

The selectivity in selective autophagy pathways is achieved via the selective autophagy receptors (SARs) – proteins that bind a ligand on the substrate to be degraded and the Atg8-family protein on the growing autophagic membrane, phagophore, effectively bridging them. In mammals, the most common ligand of SARs is ubiquitin, a small protein modifier that tags substrates for their preferential degradation by autophagy. Consequently, the most common SARs are the ubiquitin-binding SARs, such as SQSTM1/p62 (sequestosome 1). Surprisingly, there is only one SAR of this type in yeast – Cue5, which acts as a receptor for aggrephagy and proteaphagy – pathways that remove the ubiquitinated protein aggregates and proteasomes, respectively. However, recent studies described the ubiquitin-dependent autophagic pathways that do not require Cue5, e.g. stationary phase lipophagy for intracellular lipid droplets and nitrogen starvation-induced mitophagy for mitochondria. What is the role of ubiquitin in these pathways? Here, we propose that the ubiquitinated lipid droplets and mitochondria are recognized by the alternative ubiquitin-binding SARs. Our analysis identifies the proteins that could potentially fulfill this role in yeast. We think that matching of the ubiquitin-dependent (but Cue5-independent) autophagic pathways with the ubiquitin-and-Atg8-binding proteins enlisted here might uncover the novel ubiquitin-binding SARs in yeast.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

The evolution of integrable classical systems leads to conserved quantities and vanishing Poisson brackets. In contrast, such invariants do not exist in the dynamics of non-integrable systems, which include (but are not limited to) deterministic models with long-term chaotic behavior. The object of this review is to briefly survey the mathematical background of nonintegrability and its role in the physics unfolding well-above the Standard Model (SM) scale.

Interactome analyses have traditionally been applied to yeast, human and other model organisms due to the availability of protein-protein interactions data for these species. Recently these techniques have been applied to more diverse species using computational interaction prediction from genome sequence and other data types. This review describes the various types of computational interactome networks that can be created and how they have been used in diverse eukaryotic species, highlighting some of the key interactome studies in non-model organisms.

Deep behavioral covariates (DBCs) introduced in this perspective form a new class of covariates that have the potential to enhance the performance of predictive models and improve analytics in clinical decision support applications. DBCs can measure how engaged a patient tends to be and how he or she tends to respond to events, and they may be highly predictive of the patient’s outcomes for a planned treatment. DBCs may potentially serve as a standard to measure patient engagement and activation and may form highly efficient mechanisms for improving patient outcomes.

The field dynamics of neutral and charged matter (treated as gauge fields) beyond the event horizon of black holes are investigated. As an extension of the work done in Ganesan (2023) [1], the analysis was done using the combined dynamics of the two-dimensional Yang-Mills and Liouville gravity fields beyond the event horizon. The quantum interactions and symmetry breaking mechanisms of the combined two-dimensional fields are discussed. The second part of this paper explores the quantum dynamics occurring at the event horizon. By considering the structure of the event horizon as a Möbius strip (embedded in three-dimensional space), a formulation for the lower bound of the first energy eigenvalue of a quantum particle (electron) at the event horizon is obtained.

We use Big Bang Nucleosynthesis (BBN) to probe Beyond Standard Model physics in the neutrino sector. Recently the abundances of primordially produced light elements D and He-4 were determined from observations with better accuracy. The good agreement between the theoretically predicted abundances of primordially produced and derived from observations light elements allows to update the BBN constraints on Beyond Standard Models (BSM) physics. We provide numerical analysis of several BSM models of BBN and obtain precise cosmological constraints and indications for new neutrino physics. Namely, we derive more stringent BBN constraints on electron neutrino-sterile neutrino oscillations corresponding to 1% uncertainty of the observational determination of the primordial He-4. The cosmological constraints are obtained both for the case of zero and non-zero initial population of the sterle neutrino state. Then in a degenerate BBN model with neutrino νe↔νs oscillations we analyze the change of the cosmological constraints in case lepton asymmetry L is big enough to suppress oscillations. We obtain constraints on the lepton asymmetry L . We discuss a possible solution to the dark radiation problem in degenerate BBN models with νe↔νs oscillations in case L is large enough to suppress neutrino oscillations during BBN epoch. Interestingly, the required value of L for solving DR problem is close to L indicated by EMPRESS experiment and close to the value of lepton asymmetry necessary to relax Hubble tension.

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain on eye movements. Typical ON is associated with Multiple Sclerosis and is generally mild and steroid-responsive, whereas atypical forms are characterized by unusual features, such as optic disc edema, poor treatment response and bilateral involvement, and are often associated with autoantibodies against aquaporin-4 (AQP4) and Myelin Oligodendrocyte Glycoprotein (MOG). However, in rare cases AQP4 and MOG antibodies will come back negative, plunging the clinician in a diagnostic conundrum. Seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis is greatly different. The scope of this review is to describe possible, rarer etiologies of ON when AQP4 and MOG antibodies are negative and discuss their diagnosis and treatment.

In the last four years, the evolution and adoption of blockchain and, more generally, distributed ledger systems have shown the affirmation of many concepts and models with significant differences in system governance and suitable applications. This work aims to update the critical analysis of blockchain technologies carried out by our previous contribution to this journal, extending the focus to distributed ledger components and systems. Starting from the topical concept of decentralization, we introduce concepts and building blocks currently adopted in the available systems centering on their functional aspects and impact on possible applications. We present some conceptual framing tools helpful in the application context, and we will propose the concept of process authenticity, which we will discuss through two use cases: blockchain document dematerialization and e-voting.

Athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer spectrum to avoid overtraining and optimize the effects of training.

Molecular methods have revolutionised virtually every area of biology, and metazoan phylogenetics is no exception: molecular phylogenies, molecular clocks, comparative phylogenomics, and developmental genetics have collectively transformed our understanding of the evolutionary history of animals. Moreover, the diversity of methods and models within molecular phylogenetics has resulted in significant disagreement among molecular phylogenies as well as between these and traditional phylogenies. Here, I argue that tackling this multifaceted problem lies in integrating evidence to infer the best evolutionary scenario. I begin with an overview of recent developments in early metazoan phylogenetics, followed by a discussion of key conceptual issues in phylogenetics revolving around phylogenetic evidence and theory. I then argue that integration of different kinds of evidence is necessary for arriving at the best evolutionary scenario rather than the best-fitting cladogram. Finally, I discuss the prospects of this view in stimulating interdisciplinary cross-talk in early metazoan research and beyond.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, predictability of upright-supine spirometry in terms of diaphragm involvement, and impact of nutrition on muscle strength. This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. Forty-four patients were included in the study. The mean patient age was 10.8±2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and nonambulatory patients (p&lt;0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with malnutrition than in those without (p&lt;0.05). To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for malnutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

Duckweed (Lemnaceae) rises as a crucial model system due to its unique characteristics and wide-ranging utility. The significance in physiological research and phytoremediation highlights the intricate potential of Duckweed in the current era of plant biology. Special attention to Duckweed has been brought due to its distinctive features of nutrient uptake, ion transport dynamics, detoxification, intricate signaling, and stress tolerance. In addition, Duckweed can alleviate environmental pollutants and enhance sustainability by participating in bioremediation processes and wastewater treatment. Furthermore, insights into the genomic complexity of Lemnaceae species and the flourishing field of transgenic development highlight the opportunities for genetic manipulation and biotechnological innovations. The novel methods for germplasm conservation of Duckweed can be adopted to preserve genetic diversity for future research endeavors and breeding programs. This review centers on prospects in Duckweed research promoting interdisciplinary collaborations and technological advancements to drive its full potential as a model organism.

In the context of autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) plays a key role as biomarker of disease progression and response to therapy and has been recently recognized as enrichment biomarker and possible surrogate endpoint. Several imaging modalities and methods are available to calculate TKV, and the choice depends on the purpose of use. Technological advancements have made it possible to accurately assess cyst burden, that can be crucial to assess the disease state and help identifying rapid progressors. Moreover, the development of automated algorithms has increased the efficiency of total kidney and cyst volume measurements. Beyond total kidney and cyst volume, the quantification and characterization of non-cystic kidney tissue show potential to early stratify ADPKD patients, monitor disease progression, and possibly predict renal function loss. A broad spectrum of kid-ney MRI techniques are available to characterize kidney tissue, showing promise to non-invasively pick up early signs of ADPKD progression. Radiomics has been used to extract tex-tural features from ADPKD images, providing valuable information about the heterogeneity of the cystic and non-cystic components. This review provides an overview of ADPKD imaging bi-omarkers, focusing on quantification methods, potential, and necessary steps towards successful translation to clinical practice.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative to surgery for acute cholecystitis (AC) in poor operative candidates. However, the role of EUS-GBD in non-cholecystitis (NC) indications has not been well studied. We compared clinical outcomes of EUS-GBD for AC and NC indications. Consecutive patients undergoing EUS-GBD for all indications at a single center were retrospectively analyzed. Fifty-one patients underwent EUS-GBD during the study period. Thirty-nine (76%) patients had AC while 12 (24%) had NC indications. NC indications included malignant biliary obstruction (n = 8), symptomatic cholelithiasis (n = 1), gallstone pancreatitis (n = 1), choledocholithiasis (n = 1), and Mirizzi’s syndrome (n = 1). Technical success was noted in 92% (36/39) for AC and 92% (11/12) for NC (p &gt; 0.99). Clinical success rate was 94% and 100%, respectively (p &gt; 0.99). There were 4 adverse events in the AC group and 3 in the NC group (p = 0.62). Procedure duration (median 43 vs 45 minutes, p = 0.37), post-procedure length of stay (median 3 vs 3 days, p = 0.97), and total gallbladder related procedures (median 2 vs 2, p = 0.59) were similar. EUS-GBD for NC indications is similarly safe and effective as EUS-GBD in AC.

Natural selection is commonly seen not just as an explanation for adaptive evolution, but as the inevitable consequence of “heritable variation in fitness among individuals”. Although it remains embedded in biological concepts, such a formalisation makes it tempting to explore whether this precondition may be met not only in life as we know it, but also in other physical systems. This would imply that these systems are subject to natural selection and may perhaps be investigated in a biological framework, where properties are typically examined in light of their putative functions. Here we relate the major questions that were debated during a three-day workshop[1] devoted to discussing whether natural selection may take place in non-living physical systems. We start this report with a brief overview of research fields dealing with “life-like” or “proto-biotic” systems, where mimicking evolution by natural selection in test tubes stands as a major objective. We contend the challenge may be as much conceptual as technical. Taking the problem from a physical angle, we then discuss the framework of dissipative structures. Although life is viewed in this context as a particular case within a larger ensemble of physical phenomena, this approach does not provide general principles from which natural selection could be derived. Turning back to evolutionary biology, we ask to what extent the most general formulations of the necessary conditions or signatures of natural selection may be applicable beyond biology. In our view, such a cross-disciplinary jump is in large part impeded by reliance on individuality as a central yet implicit and loosely defined concept. Overall, these discussions thus lead us to conjecture that understanding, in physico-chemical terms, how individuality emerges and how it can be recognised, will be essential in the search for instances of evolution by natural selection outside of living systems. [1] Natural Selection Beyond Life? Observing the physico-chemical world through Darwinian glasses; 12-15 November 2019 - Institut d'Etudes Scientifiques, Cargèse, France

Growing evidence about the negative socio-environmental consequences of plastic pollution led to various initiatives for better plastic scrap governance and its trade. At the same time, an examination of recent data shows that plastic scrap represents only a fraction of recyclable materials which are traded internationally and are also subject to similar problems of cross-border environmental governance. A limited analysis comparing plastics, textiles, paper and ferrous metals suggests that ongoing momentum for improvement of plastic scrap governance and circularity should also be framed to consider other types of secondary materiais.

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

The industry is increasingly relying on fish for toxicity assessment. However, current guidelines for toxicity assessment focus on teratogenicity and mortality. From an ecotoxicological point of view, however, these endpoints may not reflect the “full picture” of possible deleterious effects that can nonetheless result in decreased fitness and/or inability to adapt to a changing environment, affecting whole populations. Therefore, assessing sublethal effects add relevant data covering different aspects of toxicity at different levels of analysis. Impacts of toxicants on neurobehavioral function have the potential to affect many different life-history traits, and are easier to assess in the laboratory than in the wild. We propose that carefully-controlled laboratory experiments on different behavioral domains – including anxiety, aggression, and exploration – can increase our understanding of the ecotoxicological impacts of contaminants, since these domains are related to traits such as defense, sociality, and reproduction, directly impacting life-history traits. The effects of selected contaminants on these tests are reviewed, focusing on larval and adult zebrafish, showing that these behavioral domains are highly sensitive to small concentrations of these substances. These strategies suggest a way forward on ecotoxicological research using fish.

Numerous scientific fields employ entropy, the Shannonian measure of disorder and inaccessible information. Current paper examines educational uses of entropy. The major objectives of this survey are to create a coherent perspective of the applicability of classical entropies and to provide a concise detailed explanation that blends technical pertinence with conceptual extraction from the most recent literature. What's more intriguing are the closing thoughts mixed with a few unsolved issues and the creation of a future work schedule in these areas.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

In this work the author utilizes the quantum geometrization of spacetime for describing the gravitational interaction within the framework of quantum theory. This approach allows for the development of an equation of gravity that is mathematically connected to the fermion and boson fields. This achievement is accomplished by incorporating two fundamental principles: covariance of the quantum field equations and the principle of least action. By considering these principles, a theory is established that enables the calculation of gravitational corrections to Quantum Electrodynamics, and potentially, to the standard model of particle physics as well. The theory also provides an explanation for two phenomena: the existence of a cosmological pressure density similar to quintessence, that is compatible with the small value of the observed cosmological constant, and the breaking of matter-antimatter symmetry at high energies offering insights into why there is an imbalance between the two in the early universe. In the cosmological modeling of the theory, there exists a proposal to account for the formation of supermassive black holes that are accompanied by their own surrounding galaxies, without relying on the process of mass accretion. The model, in accordance with recent observations conducted by the James Webb Space Telescope, supports the notion that galactic configurations were established relatively early in the history of the universe, shortly after the occurrence of the Big Bang.

Fourier transform infrared (FTIR) absorption spectroscopy of cold molecules and clusters in supersonic slit jet expansions complements and extends more sensitive action spectroscopy techniques and provides important reference data for the latter. We describe how its major drawback, large substance and carrier gas consumption, can be alleviated by one to two orders of magnitude via direct and continuous recycling of the gas mixture. This is achieved by a combination of dry rotary lobe and screw pump compression. The signal-to-noise ratio is boosted by the established buffered giant gas pulse technique with full interferogram synchronization. The buildup of water impurities typically limits the recycling gain, but is turned into a feature for the study of hydrate complexes of volatile molecules. Continuous operation with a single gas filling over several days becomes practical and useful. Decadic absorbances in the low ppm range are detectable and the mid infrared range can be recorded simultaneously with the near infrared. The less straightforward hydration number assignment of spectral features in direct absorption spectroscopy is supported by a gradual water buildup at a rate of less than 0.5 mg/h. A recent reassignment proposal for the water dimer OH stretching spectrum is refuted and vibrational spectra of vacuum-isolated 18O-water clusters are presented for the first time. Methanol docking on asymmetric ketones is used to illustrate the advantages and limitations of the recycling concept. Previous assignments of the hydrate complex of 1-phenylethanol are confirmed. Additional features of the setup await testing and refinement, but the recycling technique already substantially widens the applicability of direct absorption spectroscopy of neutral molecular clusters. It may be attractive for other high-throughput jet spectrometers.

Land degradation monitoring and assessment in the Sahel zone has relied substantially on temporal trends of remote sensing-based vegetation indices, which are proxies for the bioproductivity of the land. However, prior studies have shown that negative or positive trends in bioproductivity are not necessarily associated with degradation or improvement of land condition. In this short communication, while acknowledging the contributions of remote sensing-based indices and global-scale datasets to dismantling an outdated desertification narrative, we argue that local land users have much to contribute to our understanding of land degradation, and particularly to ensuring that scientific assessments of degradation capture variables relevant to them. We used the participatory photo elicitation method in three sites in the Senegalese Ferlo in order to elicit local pastoralists’ perspectives on land degradation and identify the indicators that they use to characterize pasture quality, while empowering them to lead the discussion. The discussion revealed indicators far beyond bioproductivity, including livestock performance as well as composition and quality of the herbaceous and woody vegetative cover, invasive species, soil quality and water availability. We found that the pastoralists’ knowledge and interest in the issue could potentially be harnessed more systematically, and at larger scales, in order to build a spatially explicit field-based knowledge base of land degradation complementary to remote sensing-based maps of trends in bioproductivity. Such a dataset could serve as a standalone product or as a reference dataset for development and validation of remote sensing-based indicators.

We present the case of a 35-year-old male with first degree family history of gastric cancer (father diagnosed at the age of 45), that was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Purpose: This study aimed to elucidate the various new classifications and the use of LDLT in this context for HCC beyond milan criteria. Methods: The clinical data of patients with HCC outside milan criteria who underwent LT at Jena University between Januar 2007 and August 2023 were retrospectively analyzed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall- and disease-free survival rates were compared between the two groups (LT vs. LDLT) and in context for bridging therapy. Results: Among the 245 patients analyzed, 120 patients were outside milan criteria and 125 patients were inside milan. There was no significant difference for patients outside milan in overall survival for LT versus LDLT (OS 44,3 months vs. 28,3 months; 5y survival, 56,4% vs. 40%; p = 0.84). G3 tumor differentiation, presence of angioinvasion and lack of bridging were statistically significant risk factors predicting tumor recurrence in univariate and multivariate analysis (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provides a significant survival advantage regardless of the transplant procedure (OS: p = 0.008 ; DFS: p < 0.001). Conclusions: Patients with HCC outside milan criteria who underwent LT or LDLT had comparable outcome to patients inside milan criteria. Nevertheless, these patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients depending on tumor differentiation, size and tumor marker dynamics.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder affecting 1 in 500 people in the general population. Although characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray and cardiac fibrosis, HCM is in fact a highly complex disease with heterogenous clinical presentation, onset and complications. While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. Furthermore, large scale genome sequencing studies revealed that many genes previously reported as causative of HCM in fact have little or no evidence of disease association. These findings thus call for a re-evaluation of the sarcomere-centered view of HCM pathogenesis. Here, we summarize our current understanding of sarcomere-independent mechanisms of cardiomyocyte hypertrophy, highlight the role of extracellular signals in cardiac fibrosis, and propose an alternative but integrated model of HCM pathogenesis.

Neovascular age-related macular degeneration (nAMD) accounts for one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardised frequent administration of anti-VEGF injections only improves the vision in approximately 30%-40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term anti-angiogenic effects. Recent research on nAMD has discovered novel therapeutic targets and angiogenic signalling mechanisms involved in its pathogenesis. For example, tissue factor, human intravenous immune globulin, interferon-β signalling, cyclooxygenase-2 (COX-2) and cytochrome P450 monooxygenase lipid metabolites have been identified as key players in the development of angiogenesis in AMD disease models. Furthermore, novel therapies such as NLRP3 inflammasome inhibition, targeted intraceptor nanoparticle therapy, inhibitors of integrins and tissue factor are currently being tested at the level of clinical trials to treat nAMD. The aim of this review is to discuss the scope for alternative therapies proposed to anti-VEGFs for the treatment of nAMD.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Advancements in genomics and molecular biology have propelled our understanding of genetic information far beyond the iconic double helix structure of DNA. This comprehensive review delves into the intricate world of DNA and RNA networks, exploring the complexities that extend beyond the classical model. We investigate the dynamic interactions, regulatory mechanisms, and functional implications of the broader genetic landscape, encompassing both coding and non-coding elements. From chromatin architecture to the diverse array of non-coding RNAs, this exploration seeks to provide a holistic perspective on the multifaceted roles played by DNA and RNA in cellular processes. The three-dimensional organization of genetic material within the cell has emerged as a crucial determinant of cellular function. Chromatin architecture, comprising DNA, histones, and other associated proteins, plays a dynamic role in regulating gene expression. We delve into the intricate choreography of chromatin remodeling, deciphering the interplay between transcription factors, epigenetic modifications, and higher-order structures that modulate gene activity. The exploration of chromatin dynamics unveils a nuanced understanding of how the genome responds to environmental cues, cellular signals, and developmental processes. Moreover, the once-dismissed non-coding portion of the genome has emerged as a key regulator of cellular function. Various classes of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in diverse cellular processes, ranging from fine-tuning gene expression to modulating chromatin structure. The review critically examines the functional roles of these non-coding RNAs, shedding light on their involvement in cellular homeostasis, development, and disease. As I traverse this landscape beyond the double helix, our review synthesizes current knowledge on the intricacies of DNA and RNA networks. By exploring the regulatory mechanisms, functional implications, and emerging paradigms, we aim to inspire a deeper appreciation for the molecular choreography that underlies the cellular symphony of life. Furthermore, we discuss the implications of these findings in the context of disease, highlighting potential diagnostic and therapeutic avenues that arise from a comprehensive understanding of DNA and RNA networks. In doing so, this exploration not only broadens our theoretical understanding but also opens new frontiers for translational research in genetics and molecular medicine.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolu-tionize cancer management. Among various types of FAP ligands, peptides and antibodies, have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides, on tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

Purpose Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20-50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods Patients (N=36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results Median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and 9 (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and 15(42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax, and 9 (25%) to the abdomen or pelvis. Total dose ranged from 18 to 42.5 Gy in 6-17 fractions/ 2.67-5 Gy per fraction. Median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86), and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. Two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort, and 100, 87 (95%CI: 56.4-96.5%) and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI:59.9-90.5%), and 100, 66.1 (95% CI: 36.4-84.4%) and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusion HFRT in HM provides excellent local control without any increase in toxicity.

Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Recently, more research has been conducted on investigating novel subcellular localizations of MMPs and their intracellular roles at the respective locations. In this review article, we focus on the subcellular localization and novel intracellular roles of two MMPs closely related: membrane-type-1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2). Although MT1-MMP is commonly known to localize on the cell surface, the protease also localizes to the cytoplasm, caveolae, Golgi, cytoskeleton, centrosome, and nucleus. At these subcellular locations, MT1-MMP functions in cell migration, macrophage metabolism, invadopodia development, spindle formation and genes expression, respectively. Similar to MT1-MMP, MMP-2 localizes to the caveolae, mitochondria, cytoskeleton, nucleus and nucleolus, and functions in calcium regulation, contractile dysfunction, genes expression and ribosomal RNA transcription. Our particular interest lies in the role MMP-2 and MT1-MMP serve within the nucleus, as it may provide critical insights into cancer epigenetics and tumor migration and invasion. We suggest that targeting nuclear MT1-MMP or MMP-2 to reduce or halt cell proliferation and migration may lead to the development of new therapies in cancer and other diseases.

Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical system. Space agencies can no longer buy down the majority of human system risk through the crew member selection process and emergency re-supply or evacuation. No mature medical solutions exist to close the risk gap. With recent advances in biotechnology, there is promise in augmenting a space pharmacy with a biologically-based space foundry for on-demand manufacturing of high-value medical products. Here we review the challenges and opportunities of molecular pharming, the production of pharmaceuticals in plants, as the basis of a space medical foundry to close the risk gap in current space medical systems. Plants have long been considered an important life support object in space and can now also be viewed as programmable factories in space. Advances in molecular pharming-based space foundries will have widespread application in promoting simple and accessible pharmaceutical manufacturing on Earth.

EuAP2 genes are famous for their role in flower development. A legacy of the founding member of this subfamily of transcription factor, whose mutants lacked petals in Arabidopsis. However, studies of other euAP2 genes in several species have accumulated evidence highlighting the diverse roles of euAP2 genes in other aspects of plant development. Here, we emphasize other developmental roles of euAP2 genes in various species and suggest a shift from regarding euAP2 genes as just flowering genes to consider the global role they may be playing in plant development. We hypothesize that their almost universal expression profile and pleiotropic effects of their mutation suggest their involvement in fundamental plant development processes.

The Sustainable Development Goals (SDGs) purport to report holistically on progress towards sustainability and do so using more than 231 discrete indicators with a primary objective to achieve a balance between the environment, social and economic aspects of development. The research question underpinning the analyses presented in this paper is: are the indicators in the SDGs sufficient and fit-for-purpose to assess the trajectory of natural resources towards sustainability? We extracted the SDG indicators that monitor the state of natural resources, or alternately support policy or governance for their protection, and determined if these are adequate to provide the essential data on natural resources to achieve the aims of the SDGs. The indicators are clustered into four natural resource categories; land, water (both marine and freshwater), air and biodiversity. Indicators for monitoring land resources show that the most comprehensive land resource indicator, for degraded land, is not fully implemented and that missing from land monitoring is an evaluation of vegetation health outside of forests and mountains, the condition of soils, and most importantly the overall health of terrestrial ecosystems. Indicators for monitoring water resources have substantial gaps, unable to properly monitor water quality, water stress, many aspects of marine resources and most significantly, the health of fresh and salt water ecosystems. Indicators for monitoring of air have recently become more comprehensive, but linkage to IPCC results would benefit both programmes. Monitoring of biodiversity is perhaps the greatest weakness of the SDG Agenda, having no comprehensive assessment even though narrow aspects are monitored. Again, deliberate linkages to other global biodiversity programmes (e.g. CBD and the Post 2020 Biodiversity Framework; IPBES; Living Planet, etc.) are recommended on condition that data can be defined at a country level. While the SDG list of indicators in support of natural resource is moderately comprehensive, it lacks holistic monitoring in relation to evaluation of ecosystems and biodiversity to the extent that these missing but vital measures of sustainability threaten the entire SDG Agenda. In addition, an emerging issue is that even where there are appropriate indicators, the amount of country-level data remains inadequate to fully evaluate sustainability. This signals the delicate balance between the extent and complexity of the SDG Agenda and uptake at a country level

Despite the advancements in evidence-based medicine, many hospitals still maintain high rates of patients undergoing prolonged preoperative fasting. The goal of this study is to determine the prevalence of prolonged fasting time among patients undergoing elective surgeries at a Brazilian university hospital and its associations with clinical and sociodemographic variables. This cross-sectional study was conducted between May and November 2019 and included patients of all ages undergoing elective surgeries. Out of the 293 patients analyzed, 64.2% were male, with ages ranging from 1 to 85 years, and 93.9% were classified as ASA I or II. The prevalence of preoperative fasting exceeding 8 hours was 89.4%. An average fasting time exceeding 11 hours was observed across all age groups. Patients who underwent procedures in the afternoon had an average fasting time that was 16% longer than those in the morning period (13.84 vs. 11.92, p<0.001). Surgery time (r=0.134, p<0.03) and anesthesia times (r=0.121, p<0.04) demonstrated a weak correlation with fasting time. Despite the international consensus on preoperative fasting time, our study demonstrated low adherence to current recommendations. Therefore, healthcare professionals should ensure the comprehension of fasting guidelines, and further studies should aim to identify effective solutions to mitigate prolonged fasting.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

Coordinated sets of extremely numerous digital data, on a given social or economic event, are treated by Artificial Intelligence tools to obtain reasonably accurate, valuable predictions. The same approach, applied to biomedical issues, as how to choose the right drug to completely cure a given cancer patient, does not reach satisfactory results. It is the “organized biological complexity”, which requires a different systems approach, to integrate, in an Augmented Intelligence strategy, statistical computations of digital data, network construction of “omics” findings, well-designed mathematical models and new experiments in an iterative pathway to reconstruct the “logic” beneath the “organized complexity”, as shown here for Systems Metabolomics of cancer. On this basis new diagnostic approaches, able to identify precision drug treatments, as well as new discovery strategy for more effective anti-cancer drugs are described.

The persistence of Traditional Ecological Knowledge (TEK) among Indigenous and local communities is often associated with socio-economic constraints, poverty, and lack of choices. Such a perspective argues against underpinning profound environmental consciousness and sustainable practices that underlie TEK. The paper challenges reductionism—viewing TEK solely as a creation of necessity—and tries to argue that it entails a sophisticated understanding of ecological balance and conservation ethics. Through various examples, the paper exemplifies how TEK contributes to environmental sustainability for biodiversity conservation, management and use of natural resources, and the enhancement of resilience to climatic change—the same elements crucial for culture, tradition, and community living.

Acute vertigo and dizziness are frequent presenting symptoms in patients on the emergency department. With a broad differential diagnosis and symptoms/signs often subtle and transient, the diagnostic approach to the dizzy patient remains challenging. Previous work emphasized the value of combining structured history-taking and a targeted examination focusing on subtle oculomotor signs. Here I review different bedside algorithms proposed for the acutely dizzy patient. Comparing area-under-the-curve ROC-characteristics and sensitivity/specificity, highest diagnostic accuracy was observed for algorithms focusing on subtle oculomotor signs. Both the HINTS+ bedside-exam and the STANDING algorithm have demonstrated higher diagnostic accuracy for identifying strokes than early (<24-48h after symptom-onset) MRI-DWI. Importantly, HINTS and STANDING require moderate training to allow reliable application. Thus, for physicians lacking dedicated training, other approaches are needed. Various scores that rely on vascular risk-factors, clinical symptoms and focal neurologic findings have been proposed (e.g., ABCD2-score, PCI-score, TriAGe+-score). While these scores are more readily applicable for frontline providers, they provide intermediate diagnostic accuracy at best and often lack external validation, thus are an insufficient substitute for algorithms assessing subtle oculomotor findings. Providing dedicated training in HINTS+ or STANDING techniques will be key to improve the diagnostic accuracy and to avoid unnecessary brain imaging.

Previous research has either neglected to consider misbehaviour or misconduct in the virtual workplace during the current COVID-19 pandemic or highlighted some challenges encountered with remote working or work from home but in isolation, e.g., misbehaviours or ethical concerns associated with improper use of technology when accessing clients’ confidential information, without understanding their aetiology and context in a holistic manner. This has impacted the ability of existing research in providing recommendations organisations can practically implement to improve the sustainability and productivity of the virtual workplace, especially as they seek to navigate the current pandemic and prepare for the global business environment in the next decade. Instead, this study, for the first time, proposes a novel holistic methodology to identify the aetiologies of ethical and performance challenges with focus to the Information Technology consulting sector, as well as developing a set of recommendations companies can adopt to manage such behavioural and productivity challenges. Thus, this study illustrates the key issues associated with remote working implemented to respond to the current COVID-19 pandemic, which mine not only the individual performance in an organisation but also its overall productivity, as well as suggests the main performance and reward management strategies that can be leveraged to mitigate them. Tailored strategies are described and discussed as referred to this industry to help in navigating a more unstable yet competitive market to manage the virtual employees’ misbehaviours in the workplace and drive growth for individuals and organisations alike.

This article challenges the assumption that journals and peer review are essential for developing, evaluating and disseminating scientific and other academic knowledge. It suggests a more flexible ecosystem, and examines some of the possibilities this might facilitate. The market for academic outputs should be opened up by encouraging the separation of the dissemination service from the evaluation service. Publishing research in subject-specific journals encourages compartmentalising research into rigid categories. The dissemination of knowledge would be better served by an open access, web-based repository system encompassing all disciplines. There would then be a role for organisations to assess the items in this repository to help users find relevant, high-quality work. There could be a variety of such organisations which could enable reviews from peers to be supplemented with evaluation by non-peers from a variety of different perspectives: user reviews, statistical reviews, reviews from the perspective of different disciplines, and so on. This should reduce the inevitably conservative influence of relying on two or three peers, and make the evaluation system more critical, multi-dimensional and responsive to the requirements of different audience groups, changing circumstances, and new ideas. Non-peer review might make it easier to challenge dominant paradigms, and expanding the potential audience beyond a narrow group of peers might encourage the criterion of simplicity to be taken more seriously - which is essential if human knowledge is to continue to progress.

Extensive post reproductive lifespan (PRLS) is observed only in a few species, such as humans or resident killer whales, and its origin is under debate. Hypotheses like mother-care and grandmother-care invoke strategies of investment—provision to one’s descendants to enhance one’s overall reproductive success—to explain PRLS. The contribution of an investment strategy varies with the age of the caregiver, as the number of care-receiving descendant changes with age. Here we simulated an agent based model, which is sensitive to age-specific selection, to examine how the investment strategies in different hypotheses affect survival and reproduction across different stages of life. We found that extensive PRLS emerges if we combine multiple investment strategies, including grandmother-care but not mother-care, which allow an individual to have an increasing contribution as it ages. We also found that, if mother-care is further introduced to the PRLS-enabling strategies, it will let contribution at mid-life to substitute contribution at late life, which consequently terminates extensive PRLS.

The present paper presents findings from the follow-up of 185 of these nurses who had been involved in the front-line care of COVID-19 patients in urban centres in Northern England, during and after the “second wave” of COVID patients in November, 2020. Measures of adjustment, stress (including PTSD), and Maslowian self-actualization were added to earlier measures of personality, adjustment, work-life stress, and career intention. Cluster analysis identified three types in the 2020-2023 cohort: I ‘Actualizing Professionals’; (N=62); II ‘Strong Professionals’ (N=56); III ‘Highly Stressed Nurses’ (N=45). These latter very stressed nurses included all nurses (N=16) identified as having PTSD symptoms.

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

In the present study we examine the relationship among sovereign yields, temperature and precipitation using a large monthly panel data set which consists of 20 eurozone members, over the period 1980M1 – 2023M4. To account for possible asymmetries along the distribution of the climate variables we assume a quadratic modelling specification and apply various mean panel estimation techniques of heterogeneous coefficients. At a next step, to consider possible nonlinearities in the distribution of the dependent variable (sovereign yields), we apply the quantile via moments methodology of Machado and Santos Silva (2019), which accounts for possible cross-sectional dependence and slope heterogeneity. We contribute to the existing literature in two main ways. First, by applying a quantile methodology that provides a more in-depth analysis of the climate effects along the distribution of the sovereign yields, especially in the presence of non-normally distributed data. Second, we find that climate change, as proxied by higher temperatures or lower precipitation (drought), will increase the sovereign risk of all countries, but the magnitude of the impact will be higher for countries that are already characterized by higher sovereign risk levels and/or face extreme weather conditions (hotter countries and/or countries with low levels of precipitation).

As the telecommunications landscape braces for the post-5G era, this paper embarks on delineating the foundational pillars and pioneering visions that define the trajectory towards 6G wireless communication systems. Recognizing the insatiable demand for higher data rates, enhanced connectivity, and broader network coverage, we unravel the evolution from the existing 5G infrastructure to the nascent 6G framework, setting the stage for transformative advancements anticipated in the 2030s. Our discourse navigates through the intricate architecture of 6G, highlighting the paradigm shifts towards super convergence, non-IP-based networking protocols, and information-centric net-works, all underpinned by a robust 360-degree cybersecurity and privacy-by-engineering design. Delving into the core of 6G, we articulate a systematic exploration of the key technologies earmarked to revolutionize wireless communication including terahertz (THz) waves, optical wireless technology, and dynamic spectrum management,while elucidating the intricate tradeoffs necessitated by the integration of such innovations. This paper not only lays out a comprehensive 6G vision accentuated by high security, affordability, and intelligence but also charts the course for addressing the pivotal challenges of spectrum efficiency, energy consumption, and the seamless integration of emerging technologies. In this study, our goal is to enrich the existing discussions and research efforts by providing comprehen-sive insights into the development of 6G technology, ultimately supporting the creation of a thoroughly connected future world that meets evolving demands.

The field of nephrology has recently directed a considerable amount of attention towards the stimulator of interferon genes (STING) molecule since it appears to be a potent driver of chronic kidney disease (CKD). STING and its activator, the cyclic GMP-AMP synthase (cGAS) are among the most relevant inducers that promote the expression of type I interferons (IFN-Is). These cytokines have been long recognized as part of the mechanism used by the innate immune system to battle viral infections; however, their involvement in sterile inflammation remains unclear. Mounting evidence pointing to the involvement of the IFN-I pathway in sterile kidney inflammation provides potential insights into the complex interplay between the innate immune system and damage to the most sensitive segment of the nephron, the glomerulus. The STING pathway is often cited as the cause of renal disease originating from non-infection related caused by the induction of IFN-I expression. However, other receptors have been implicated in this process, mainly by recognizing host-derived nucleic acids. This review explores the main endogenous inducers of IFN-I in glomerular cells, discusses what exposure to the main autocrine and paracrine cytokines has on these cells, and identifies the pathways that are implicated in the development of glomerular damage.

The growing dependence on large language models (LLM)s highlights the urgent need to deepen trust in these technologies. Regular, rigorous validation of their expertise, especially in nuanced and intricate scenarios, is essential to ensure their readiness for clinical applications. Our study pioneers the exploration of LLM utility in the field of cardiology. We stand at the cusp of a transformative era where mature AI and LLMs, notably ChatGPT, GPT-4, and Google Bard, are poised to influence healthcare significantly. Recently, we put three available LLMs, OpenAI's ChatGPT-3.5, GPT-4.0, and Google's Bard, to the test against a significant Polish medical special-ization licensing exam (PES). The exams cover the scope of completed specialist training, focusing on diagnostic and therapeutic procedures, excluding invasive medical procedures and interven-tions. In our analysis, GPT-4 consistently outperformed the others, ranking first, with and Google Bard and ChatGPT- 3.5 following, respectively. The performance metrics underscore GPT-4's no-table potential in medical applications. Given a score improvement of over 23.5 % between two AI models released just four months apart, clinicians must stay informed and up-to-date about these rapidly evolving tools and their potential applications to clinical practice. Our results provide a snapshot of the current capabilities of these models, highlighting the nuanced performance dif-ferences when confronted with identical questions

In order to provide high capacity and universal access of telecommunication networks, this paper reviews and prospects the advanced multiplexing technology, physical layer digital signal processing technology, infrastructure sharing technology, security protection technology, intelligent control management and other key technologies for beyond 100G next generation passive optical network (NG-PON).

The difficulty in obtaining commercial fertilizers by smallholder farmers in sub-Saharan Africa makes it very important to optimize the use of local organic resources. In VilanKulo, Mozambique, a study was carried out on okra (Abelmoschus esculentus) over two growing seasons in a haplic Lixisol, a loamy-sand textured soil, applying both bat guano and biochar prepared by an artisanal process. Bat guano was applied at two rates (5 and 10 t ha−1), one month and just before sowing. Biochar was also used at two rates (5 and 10 t ha−1) applied close to sowing. Mixtures of biochar and guano at two rates (1 and 4 t ha−1, and 2 and 8 t ha−1, respectively) were also used along with a non-fertilized control. Field trials were arranged in a completely randomized design with three replicates. The treatments receiving high rates of guano tended to show significantly higher fruit yields (&gt; 10 t ha−1, being the two-year average) in comparison to the control, which showed the lowest average okra fruit yield (6.21 t ha−1). In guano treatments, the apparent recovery by okra of some important nutrients, such as nitrogen (N), was greater than the amount of nutrient contained in the guano itself. This result, together with many others related to tissue nutrient concentration, soil properties and residual fertilizing value in guano plots, indicates a strong mineralization of guano during the growing season, probably due to its low carbon (C)/N ratio and favourable environmental conditions for the mineralization process, such as high temperature and well-aerated soil. The result also suggests some kind of manuring effect, i.e., a fertilizing effect of guano beyond what can be explained by the nutrient supply. The use of biochar increased total organic C in the soil and cation exchange capacity (CEC) compared to the control, but did not affect variables related to plant performance, such as tissue nutrient concentration or plant growth and yield.

We present a new post-processing method for Quantum Key Distribution (QKD) that raise cubically the secret key rate in the number of double matching detection events. In Shannon’s communication model information is prepared at Alice’s side then it is intended to pass it over a noisy channel. In our approach, secret bits do not rely in Alice’s transmitted quantum bits but in Bob’s basis measurement choices. Therefore measured bits are publicly revealed while bases selections remain secret. Our method implements sifting, reconciliation and amplification in a unique process, it just require a round iteration, no redundancy bits are sent and there is no limit in the correctable error percentage. Moreover, this method can be implemented as a post processing software into QKD technologies already in use.

Chronic diseases are characterised by cell’s autophagy and proteins disarrangement resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia couses worse prognosis independentely of the principal disease. Currently, the cornerstone of therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of hematopoiesis. However, treatment strategies should incorporate the addition of heme, the principal biochemical constituent of haemoglobin. Heme synthesis follows a complex biochemical pathway. The limiting step of heme synthesis is D-ALA availability which, for its synthesis, requires Glycine and Succinil-CoA. Consequently, treatment of anaemia should not be based only on iron availability, but also on the availability of the molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate the standard iron infusion and the supply of essential amino acids and vitamins involved in the heme synthesis. We report preliminary data in selected elderly anaemic patients with congestive heart failure (CHF) and catabolic disarrangement, who, in addition to standard iron therapy, received personalized therapy with essential-AAs and vitamins involved in the maintenance of heme. Notably, such individualized therapy resulted in a significant increase in the serum concentration of haemoglobin after 30 days of treatment compared to standard iron therapy.

The safety of people is an important phenomenon nowadays. This importance arises due to the crowded places including subway station, universities, colleges, airport, shopping mall and square, and city squares. Therefore, the development of an effective system based on physical characteristics of crowd layout is of significant demand. In this paper, we proposed a novel automated and intelligent systems for crowd event analysis based on a set of physical elements. For this purpose, we take into account optical flow and spatial-time gradient, contour features, and Gaussian processes. Our method combine these characteristics into a unique model to deal with the challenging problem of crowd event analysis. For evaluating our proposed method, we consider a benchmark dataset and a number of different performance metrics. These analysis demonstrate the robustness and effectiveness of our proposed method.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Although global life expectancy has increased over the past 20 years due to improvements in managing infectious diseases, one in five people still succumbs to infections. Humanity is tirelessly working towards developing vaccines and antimicrobial agents in response to this ongoing threat. However, pathogens continue to acquire numerous resistance mechanisms and proliferate. Meanwhile, the COVID-19 pandemic has prompted us to recognize that focusing solely on the killing strategies of immunology and microbiology in complex and multisystemic infectious diseases is insufficient for understanding survival. In essence, there is a need for a treatment approach centered on disease tolerance, capable of alleviating pathology and/or promoting physiological functions in conjunction with the existing strategies of host immune response and pathogen destruction. Against this backdrop, this narrative review comprehends and introduces microbiome therapeutics, which recently garnered attention as next-generation treatments regarding two defense strategies against infectious diseases. First, we delineate the application of existing probiotics and then the microbiome in infectious diseases. Subsequently, we expand this concept to encompass host microbiome crosstalk and present related microbiome therapeutics' current status and direction. Ultimately, the review presents a fresh perspective on understanding microbiome therapeutics in infectious diseases based on a cooperative defense system.

User experience-related challenges play a significant part in user-technology interactions. However, design processes have not always kept up with the evolving needs of users in terms of technology interactions. This paper aims to present the design, structure and evaluation of an integrated mental health intervention platform (AMGR-I), emphasizing the importance of user-centred design and engagement in addressing the evolving needs of users in technology interactions, specifically focusing on individuals with mental health disorders. The AMGR-I pilot platform integrates community, e-learning, and care sub-platforms to provide a holistic approach to mental health intervention. The study utilizes participatory design research with targeted users to gather insights into user preferences and expectations. By involving the targeted audience in the design process, the platform’s user-centered design can be improved effectively. The platform recognizes the changing view of users, who now seek products that deliver pleasure, enjoyment, engagement, and embodiment. This research contributes to the field by highlighting the importance of user-centered design in the development of a comprehensive platform for mental health support.

Construction 4.0 is witnessing exponential growth in Digital Twin (DT) technology developments and applications, revolutionizing the adoption of Building Information Modelling (BIM) and other emerging technologies used throughout the lifecycle of the built environment. BIM provides technologies, procedures, and data schemas representing building components and systems. At the same time, DT enhances this with real-time data for cyber-physical integration, enabling live asset monitoring and better decision-making. Despite being in the early stages of development, DT applications have rapidly progressed in the AEC sector, resulting in a diverse literature landscape due to the various technologies and parameters involved in fully developing the DT technology. The intricate complexities inherent in digital twin advancements have confused professionals and researchers. This confusion arises from the nuanced distinctions between the two technologies, i.e., BIM and DT, causing a convergence that hinders realizing their potential. To address this confusion and lead to a swift development of DT technology, this study presents a holistic review of the existing research focusing on the critical components responsible for developing DT applications in the construction industry. The study identifies five crucial elements: technologies, maturity levels, data layers, enablers, and functionalities. Additionally, it identifies research gaps and proposes future avenues for streamlined DT developments and applications in the AEC sector. Future researchers and practitioners can target data integrity, integration and transmission, bi-directional interoperability, nontechnical factors, and data security to achieve mature digital twin applications for AEC practices. This study highlights the growing significance of DTs in construction and provides a foundation for further advancements in this field to harness its potential to transform built environment practices.

This publication delves into the intricate world of human communication, extending beyond the realm of spoken and written language to explore the profound influence of non-verbal communication. Focusing on body language—comprising gestures, facial expressions, postures, and movements—it reveals the pivotal role it plays in conveying emotions, intentions, and psychological states. The rapidly evolving fields of neuroscience and cognitive science are investigating the neural mechanisms and cognitive processes that underpin the interpretation and utilization of these non-verbal cues. Notably, the amygdala's involvement in processing emotional facial expressions has provided a neurological foundation for our emotional understanding in non-verbal communication. Concurrently, cognitive psychology sheds light on how perception, attention, and memory influence our interpretation of non-verbal cues and communication strategies.In our modern, technologically advancing society characterized by global interconnectivity and cultural diversity, the significance of non-verbal communication, especially in digital and virtual contexts, is paramount. The transformation of non-verbal expression into digital symbols like emoticons and emojis raises questions regarding its ability to maintain authenticity and emotional understanding. This publication endeavors to comprehensively explore the fundamental role of body language and non-verbal communication in contemporary society. By integrating insights from psychology, neuroscience, social sciences, and digital technologies, it aims to elucidate the underlying mechanisms guiding non-verbal communication. Additionally, it delves into the implications of non-verbal communication across diverse domains, including interpersonal communication, the workplace, politics, advertising, and the virtual world.The research presented herein strives to offer a thorough understanding of interpersonal dynamics, relationships, and social behavior, with the goal of promoting the development of more effective, conscious, and ethically guided communication strategies. Ultimately, this analysis aspires to inspire further interdisciplinary research and reflection, addressing emerging challenges and fully leveraging the potential of non-verbal communication in modern society. This, in turn, guides our path towards a communication landscape that is more inclusive, authentic, and empathetic.

The main purpose of study is to identify the impact of COVID-19 pandemic on the green financing of banks and non-bank financial institutions (NBFIs) in an emerging economy such as Bangladesh. Also, this study shows the green banking activities of the banks and NBFIs during the pandemic. To analyze the impact of the pandemic on green financing, secondary data were obtained from the quarterly and annual reports of Bangladesh Bank (BB) on green financing as well as the annual reports and websites of 61 banks and 34 NBFIs in Bangladesh for the period 2021–2019. Subsequently, the study deployed dependent t-test statistics, growth rate (year-on-year), descriptive statistics, relative percentage changes, and varying tables and graphs to analyze the obtained secondary data. The empirical findings revealed that during the COVID-19 pandemic, there was an increase in green finance for all banks and NBFIs compared to before the epidemic, indicating that the pandemic had no negative impact on the total green finance growth of all banks and NBFIs. On the other hand, compared to the pre-pandemic period, bank-wise growth in green financing was higher for state-owned commercial banks (SOCBs), specialized banks (SDBs), and private commercial banks (PCBs) but lower for foreign-owned commercial banks (FCBs) during the COVID-19 epidemic. This suggests that the pandemic does not affect the expansion of green finance by SOCBs, SDBs and PCBs but significantly impacted the growth of green financing by FCBs. Furthermore, the research findings showed that the total outstanding and classified loans within the green finance investment decrease for both banks and NBFIs during the COVID-19 pandemic. The results indicated that the Bangladeshi banks’ level of automation towards green banking were satisfactory during the pandemic. Therefore, major policy implications for the green economic recovery by the government, BB, and managers of the banks and financial institutions in emerging economies like Bangladesh were discussed.

The monitoring of sick newborns is a challenging task that health care providers in Neonatal Intensive Care Units (NICU) must contend with each day. Conventionally, newborns are monitored via probes that are affixed to their skin and attached to processing monitors (Fig.1). However, an alternative exists in contactless imaging to record such physiological signals (Physio-Markers), surface changes and internal structures which can be used independently of, or in conjunction with conventional monitors. Advantages of contactless monitoring methods include: i) quick data generation; ii) lack of contact with skin, which reduces skin breakdown and decreases risk of infection; and iii) minimizing the number of probes and monitors affixed to the skin, which allows greater body surface-area for other care. This paper is an attempt to build a foundation for and to provide a vision of the potential neonatal clinical applications of technologies that use non-contact modalities such as Visible Light Imaging (VLI), Near InfraRed Spectrum (NIRS), and Thermal Imaging (TI) using InfraRed Spectrum (IRS).

Increased proliferation of IT services in all sectors has reinforced the adoption and diffusion across all levels of education and training institutions. However, lack of awareness of and knowledge about the key challenges and opportunities of elearning, seem to allude policymakers, resulting in low adoption or increased failure rate of many e-learning projects. Our study tries to address this problem through a review of relevant literature in e-learning. Our goal was to draw from the existing literature, insights into the opportunities and challenges of e-learning diffusion, and the current state-of-research in the field. To do this, we employed a systematic review of literature on some of the salient opportunities and challenges of e-learning innovation for educational institutions. These results aimed to inform policymakers and suggest some interesting issues to advance the research and adoption and diffusion of e-learning. Moreover, the bibliometric analysis shows that the field is experiencing high research attraction among scholars. However, several research areas in the field witnessed relatively low research paucity. Based on these findings, we discussed topics for possible future research.

There is a need for alternatives or complements to synthetic fertilizers to enhance agricultural sustainability. Applying organic amendments can play a significant role in this. Insect droppings show high potential, though studies evaluating their agronomic value have only recently begun to emerge. This study compared black soldier fly (Hermetia illucens) and mealworm (Tenebrio molitor) larvae frass with another organic amendment (Nutrimais) derived from composting forestry, agro-industrial, and domestic waste. The experiment also included ammonium nitrate at two rates [the same as the organic amendments, 50 kg ha–1 nitrogen (N) (FullR), and half that rate (HalfR)] and an unfertilized control. The study spanned two growth cycles of lettuce (Lactuca sativa L.) grown in pots, followed by unfertilized oats (Avena sativa L.) to assess the residual effects of the fertilizing treatments. Mealworm larvae frass mineralized rapidly, with an apparent N recovery of 37.4% over the two lettuce growth cycles, indicating its high availability to soil heterotrophic microorganisms. The average dry matter yield (DMY) of lettuce was the highest among all treatments (12.8 and 9.8 g plant–1 in the first and second lettuce cycles), even compared to the FullR treatment (12.2 and 7.8 g plant–1), though without significant differences. Although mealworm larvae frass exhibited a high mineralization rate, the DMY cannot be attributed solely to N supply, as plants in the FullR treatment showed better N nutritional status. Mealworm larvae frass provided strong evidence of a plant biostimulant effect, not explained by the variables measured in this study. Black soldier fly larvae frass exhibited typical behavior of a moderately reactive organic amendment, while Nutrimais showed low reactivity, with a near-neutral mineralization/immobilization balance. The results suggest mealworm larvae frass is recommended for early maturing vegetable crops, whereas Nutrimais appears more suitable for perennial crops with low short-term nutrient requirements.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.