In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

In the early decades of the 19th century, the deaf population in the eastern US and Canada was distributed across a vast area. After the 1817 founding of the American School for the Deaf (ASD) in Hartford, CT and the subsequent establishment of schools for the deaf in New York City (NYSD), Philadelphia, and many other US states, hundreds of deaf students called these schools home for several years. After leaving school, the early American Deaf community faced a challenge: How would the community maintain its social and linguistic ties across a vast geographical area once community members had dispersed to their hometowns? In this paper we analyze the attendance registries of two large gatherings of deaf individuals in Hartford in the years 1850 and 1854. These were among the largest and earliest known gatherings of deaf adults. The demographic data included in these registries open a window onto the evolving American Deaf community of the mid-19th century. Our analyses of the attendees’ school affiliations, ages, and marital status show that the signing community that had taken root among students at schools in Hartford and New York persisted among the adult graduates of those schools in towns across the northeastern US. We compare the places of residence of ASD and NYSD alumni in 1850 and 1854 to their hometowns when they first enrolled at school. Our comparisons suggest the mid-19th-century signing community had become more urban; it was centered to a greater extent in populous cities such as New York, Boston, and Hartford than had been true when the attendees had enrolled in school. We consider how the geography of deafness in the 19th century might inform our understanding of the sources of regional variation in ASL. We also consider how early cross-regional interactions may have inhibited such regional variation.

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structures and functions, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides’ structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragment and water were analyzed. Different quantum mechanical methods were compared for their accuracy in captuing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab-initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These caculations provide the benchmark for different QM methods while providing valuable understanding of the roles of various interamolecular forces in hydrogen bonding and aromatic stacking.

Herein is introduced a simple scalar field model derived from classical based kinetic energy, gravitational potential energy, and Special Relativity’s rest mass energy. By applying a classical orbit over the scalar field, relativistic effects are predicted. The scalar field is then applied to a classical model of the Hydrogen atom resulting in a relativistic effect equal to the binding energy of the Hydrogen atom. In addition, the model derives the fine structure constant due to the gravitational effect. The relativistic effects are then discretized in increments equal to the model’s gravitational induced constant. The discretization produces the Hydrogen atom spectral emissions and an angular moment equal to Planck’s reduced constant. The model is not presented as a replacement for current theory, rather it is for inspection and illustration of how a simplistic model may offer a fundamental bridge between the more complex, time proven theories of General Relativity and Quantum Mechanics.

Wide bandgap (WBG) power semiconductor devices are increasingly replacing silicon IGBTs in high-power and high-voltage power electronics applications. However, there is a significant gap in the literature regarding efficient testing methodologies for high-power and high-voltage converters under constrained laboratory resources. This paper addresses this gap by presenting comprehensive, hardware-focused testing methodologies for high-power and high-voltage WBG power semiconductor based converters, preceding the control evaluation phase. The proposed methods enable thorough evaluation and evaluation of converter hardware, including device switching characteristics, driving circuit functionality, thermal management performance, insulation integrity, and sustained operation at full power. We utilize the double pulse test (DPT) to characterize switching performance in a two-level phase leg configuration, extract circuit parasitics, and validate magnetic components. The DPT is further applied to optimize gate driving circuits, validate overcurrent protection mechanisms, and measure device on-resistance. Additionally, a multicycle test is introduced to rapidly assess steady-state converter performance and estimate efficiency. Recognizing the critical role of thermal management in high-power converters, our methodologies extend to the experimental extraction of key thermal parameters—such as junction-to-ambient thermal resistance and thermal capacitance—via a heat loss injection method. A correlation method between temperature sensor measurements and junction temperature is presented to enhance the accuracy of device temperature monitoring during tests. To ensure reliability and safety, dielectric withstand tests and partial discharge measurements are conducted at both component and converter levels under conventional 60 Hz sinusoidal and high-frequency PWM waveforms. Finally, we highlight the importance of testing converters under full voltage, current, and thermal conditions through power circulating tests with minimal power consumption, applicable to both non-isolated and isolated high-power converters. Practical examples are provided to demonstrate the effectiveness and applicability of these hardware testing methodologies.

Cutaneous Squamous Cell Carcinoma (cSCC) is an increasingly common malignancy of the skin and the leading cause of death from skin cancer in adults over the age of 85. Fibroblast Growth Factor Receptor 2 (FGFR2) has been identified as an important effector of signaling pathways that lead to the growth and development of cSCC. In recent years, there have been numerous studies evaluating the role FGFR2 plays in multiple cancers, its contribution to resistance to anti-cancer therapy, and new drugs that may be used to inhibit FGFR2. This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: 1) to highlight our current knowledge on the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; 2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; 3) to describe how FGFR2 contributes to more invasive disease, 4) to describe its immunosuppressive effects in skin, and 5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.

Sexual Issues played a significant role in Judaism’s engagement with its Greco-Roman world. This paper will examine that engagement in the Hellenistic Greco-Roman era to the end of the first century CE. In part sexual issues were a key element of demarcation between Jews and the wider community, alongside such matters as circumcision, food laws, sabbath keeping and idolatry. Jewish writers, such as Philo of Alexandria, make much of the alleged sexual profligacy of their Gentile contemporaries, not least in association with wild drunken parties, same-sex relations and pederasty. Jews, including the emerging Christian movement, claimed the moral high ground. In part, however, matters of sexuality were also areas where intercultural influence is evident, such as in the shift in Jewish tradition from polygyny to monogyny, but also in the way Jewish and Christian writers adapted the suspicion and sometimes rejection of passions characteristic of some popular philosophies of their day, seeing them as allies in their moral crusade.

n this article a first attempt at formalizing a new approach to the grand unified theory is introduced. This theory named NUVO is based primarily on considering two aspects of inertia. The first aspect is how a mass couples to space, introducing definitions to distinguish massive particles from massless particles. The second aspect is space’s availability to couple to massive particles. In essence these are the two contributions of inertia; mass and space. Postulates, clarifications, and a mathematical structure are introduced. Part 1 covers the physics of the very large (cos- mic), laying ground work for part two which applies the structure to the very small (quantum). The cosmic application of the theory will show a strong correlation to empirical data and correspondence to General Rela- tivity, including; time dilation, length contraction, and orbital advances. Departing from the canonical findings of General Relativity by predicting a quantization of physical units under the effect of acceleration and or gravity.

Apoptosis, the programmed and intentional death of senescent, damaged, or otherwise superfluous cells, is the natural end-point for most cells within multicellular organisms. Apoptotic cells are not inherently damaging, but if left unattended they can lyse through secondary necrosis. The resulting release of intracellular contents drives inflammation in the surrounding tissue and can lead to autoimmunity. These negative consequences of secondary necrosis are avoided by efferocytosis—the phagocytic clearance of apoptotic cells. Efferocytosis is a product of both apoptotic cell and efferocyte mechanisms, which cooperate to ensure the rapid and complete removal of apoptotic cells. Herein, the processes used by apoptotic cells to ensure their timely removal, and the receptors, signaling, and cellular processes used by efferocytes to identify, remove, and process the apoptotic cells, are reviewed.

According to the Water Framework Directive, the Ecological Flow (Eflow) is assumed to be the minimum water discharge required to achieve and maintain the environmental objectives of “good quality status” in a natural water body. It is highly recognized that, the hydrological regime of natural flow plays a primary and crucial role influencing the physical conditions of habitats, which in turn determines the biotic composition and sustainability of aquatic ecosystems. Furthermore, the simple assumption to supply a minimum instream during dry periods is not enough any longer in order to protect the river environment. The recent hydro-ecological understanding states that all flow components might be considered as operational targets for water management, starting from base flows (including low flows) to high and flood regimes in terms of magnitude, frequency, duration, timing and rate of change. Several codes have been developed and applied on different case studies in order to define common tools to be implemented for the Eflow assessment. The study proposes the application of the Indicators of Hydrologic Alteration methodology (IHA by TNC) coupled to the valuation of the Index of Hydrological Regime Alteration (IARI by ISPRA) as an operative tool to define the ecological flow in each monitoring cross section to support the sustainable water resources management and planning. The case study of Agri River, in Basilicata (Southern Italy) is presented. The analyses have been carried out on monthly discharge data derived applying the HEC-Hydrological Modelling System at the basin scale using the daily rain data measurements obtained by the regional rainfall gauge stations and calibrated through the observed inlet water discharge registered at the Lago del Pertusillo reservoir station.

Foundational and state-of-the-art anomaly detection methods through power system state estimation are reviewed. The traditional components for bad data detection such as chi-square testing, residual-based methods, and hypothesis testing are discussed to explain the motivations for recent anomaly detection methods given the increasing complexity of power grids, energy management systems, and cyber-threats. In particular, state estimation anomaly detection based on data-driven quickest change detection and artificial intelligence are discussed and directions for research are suggested with particular emphasis on considerations of the future smart grid.

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an “open chromatin” state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell development in vivo.

A novel electrophoretic technique to improve the sensing capabilities of charged particles in solution is presented. The proposed technique may improve the ability of metasurfaces to sense charged particles in solution by forcing them to preferentially sediment within metasurface regions of greatest sensitivity. Such a technique may be useful in various sensing applications, such as in biological, polymer, or environmental sciences, where low concentration particles in solution are of interest. The electrophoretic technique was simulated and experimentally tested using latex nanoparticles in solution. The results suggest that, using this technique, one may theoretically increase the particle density within the metasurface regions of greatest sensitivity by nearly 1900% in comparison to random sedimentation due to evaporation. Such an increase in particle density within the regions of greatest sensitivity may facilitate more precise material property measurements and enhance identification and detection capabilities of metasurfaces to low concentration particles in solution. It was experimentally verified that the electrophoretic technique enabled the preferential gathering of latex nanoparticles within the most sensitive metasurface regions, resulting in 900% - 1700% enhancements in metasurface sensing capabilities.

The ocean’s mixed layer depth (MLD) plays an important role in understanding climate dynamics, especially during extreme weather occurrences like hurricanes. This study investigates the effects of Hurricane Katrina (2005) on the MLD in the Gulf of Mexico, using the Delft3D modeling system. By integrating hydrodynamics and wave dynamics modules, we simulate the ocean’s response to extreme weather, focusing on temperature, salinity and MLD variations. Our analysis reveals significant cooling and mixing induced by Katrina, resulting in spatial and temporal fluctuations in temperature (~± 4°C) and salinity (~± 2.5 ppt). The MLD is estimated using a simple threshold method, revealing a substantial deepening to ~120 m on August 29th-30th during Hurricane Katrina in the middle of northern Gulf of Mexico, compared to an average MLD of ~20-40 m during pre-storm conditions. It took about 18-days to recover to ~84% of the pre-storm level after Katrina. Compared to the stand-alone FLOW model, the coupled FLOW+WAVE model yields a deeper MLD of ~5%. The MLD recovery and wave effect on the MLD provide insights from various scientific, environmental and operational perspectives, offering a valuable basis for ocean management, planning and applications, particularly during extreme weather events.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC shares similarities with regards to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCA) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n= 48 FM and n= 46 LC) and volumetric absorptive micro sampling tips (VAMS, n= 39 FM and n= 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra was acquired using SERS with gold nanoparticles (AuNPs). Soft Independent Modelling of Class Analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNPs SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

In this paper the application of the solid-state cooling based on barocaloric effect in the cold food supply chain is investigated. Barocaloric solid-state technology is applied to the final chain links of the cold food supply chain, regarding the steps of retail and domestic conservation. In this context a barocaloric cooler with regard to food needing to be kept at 5°C (273 K), in order to operate with a promising cooling technology that result energy efficient and environmentally friendly. The categories of food interested in the investigation are meets and fresh food products like soft cheese, yogurt, milk. The energy performances of the barocaloric system have been carried out and compared with a commercial vapor compression refrigerator of a similar size, both operating with R600a under the same working conditions. Basing on the following consideration one can conclude that barocaloric cooling is a favourable technology to be employed in the last link chains of the cold food supply chain if the system operates in ABR cycle at frequencies between 1.25 and 1.50 Hz with a regenerator made of acetoxy silicone rubber as solid-state refrigerant and 50%EG-50%water mixture as heat transfer fluid flowing at the optimal velocity of 0.15 m s-1 that guarantees an appropriate trade-off between the temperature span, the cooling power and the coefficient of performances. Under these conditions the barocaloric system overperforms the domestic vapor compression cooler operating with R600a.

Previous reviews by the authors [1, 2] indicate the continuing development and improvement of thermal protective systems through the introduction of polymer nanocomposites into polymer matrix composites. These materials perform as thermal protective systems for a variety of aerospace applications, such as thermal protection systems (TPS), solid rocket motors (SRM) nozzles, internal insulation of SRM, leading edges of hypersonic vehicles, and missile launch structures. A summary of the most recent, global technical research is presented. Polymeric resin systems continue to emphasize phenolic resins and other materials. New high-temperature organic resins based on phthalonitrile (PN), and polysiloxane are described and extend the increased temperature range of resin matrix systems.

Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lip-idomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community.

A comprehensive design framework is proposed for optimizing sparse MIMO (multiple-input, multiple-output) arrays to enhance multi-target detection. The framework emphasizes efficient utilization of antenna resources, including strategies for minimizing inter-element mutual coupling and exploring alternative grid-based sparse array (GSA) configurations by efficiently separating interacting elements. Alternative strategies are explored to enhance angular beamforming metrics, including beamwidth (BW), peak-to-sidelobe ratio (PSLR), and grating lobe limited field of view. Additionally, a set of performance metrics is introduced to evaluate virtual aperture effectiveness and beamwidth loss factors. The study employs the desirability function and explores optimization strategies for the partial sharing of antenna elements in multi-mode radar applications. A novel machine learning initialization approach is introduced for rapid convergence. Observations include the potential for peak-to-sidelobe ratio (PSLR) reduction in dense arrays and insights into GSA feasibility and performance compared to uniform arrays. The study validates the efficacy of the proposed framework through simulated and measured results. The study underscores the importance of effective sparse array processing in multi-target scenarios and highlights the advantages of the proposed design framework, offering clarity on sparse array efficiency and applicability in processing hardware providing clarity on its advantages over uniform and nonuniform arrays.

A novel technique using a W-band metasurface for the purpose of transmissive fine powder layer sensing is presented. The proposed technique may allow for the detection, identification, and characterization of inhomogeneous ultrafine powder layers which are effectively hundreds of times thinner than the incident wavelengths used to sense them. Such a technique may be useful during personnel screening processes (i.e., at an airport) and in industrial manufacturing environments where early detection and quantization of harmful airborne particulates can be a matter of security or safety. To our knowledge, the requisite science involved in such a novel W-band metasurface sensing technique has not been fully explored.

In this study, we explored the application of deep learning techniques for credit card fraud detection, aiming to improve the performance and reliability of anomaly detection methods in financial transactions. We first utilized the Isolation Forest algorithm, achieving a detection accuracy of 26% for the top 1000 transactions. Subsequently, we experimented with the Autoencoder algorithm, an unsupervised deep neural network model, which enhanced the detection accuracy to 33.6% in the best case despite some fluctuations. The results demonstrate deep learning models' strong feature extraction capability and adaptability, highlighting their potential to surpass traditional methods. However, the high imbalance in the dataset, with only 0.17% of transactions being fraudulent, poses a significant challenge. This study underscores the necessity for further experimentation and optimization of network structures and hyperparameters to achieve more stable and efficient fraud detection. The findings provide valuable insights and reference points for future research in financial fraud detection using deep learning methodologies.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

Emerging data support associations between depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function to treat C. difficile infections, but application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. This review 1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, 2) summarizes prior use of FMT in marmosets, 3) outlines a protocol for studying FMT in aging marmosets, and 4) describes knowledge gaps and future research needs in this field.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

We propose a new statistical analysis of the Acoustic Emissions (AE) produced in a series of triaxial deformation experiments leading to fractures and failure of two different rocks, namely, Darley Dale Sandstone (DDS) and AG Granite (AG). By means of q-statistical formalism, we are able to characterize the pre-failure processes in both types of rocks. In particular, we study AE inter-event time and AE inter-event distance distributions. Both of them can be reproduced with q-exponential curves, showing universal features which are observed here for the first time and could be important in order to understand more in detail rock fractures dynamics.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity, cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review we summarize basic research and translational results applicable to the use of tadalafil in the treatment of different clinical conditions.

Recent studies have shown that the mechanical properties of bioinspired periodic composite materials can be strongly influenced by finite deformation effects, leading to highly nonlinear static and dynamic behaviors at multiple length scales. For instance, in porous periodic nacre-like microstructures, microscopic and macroscopic instabilities may occur for a given uniaxial loading process and, as a consequence, wave attenuation properties may evolve as a function of the microstructural evolution, giving it the designation of metamaterials. The numerical outcomes provide new opportunities to design bioinspired soft composite metamaterials characterized by high deformability and enhanced elastic wave attenuation capabilities given by the insertion of voids and lead cores.

The vast majority of autonomous driving systems are limited to applications on roads with clear lane markings and are implemented using commercial grade sensing systems coupled with specialized graphic accelerator hardware. This research reviews an alternative approach for autonomously steering vehicles that eliminates the dependency on road markings and specialized hardware. A combination of machine vision, machine learning and artificial intelligence based on popular pre-trained Convolutional Neural Networks (CNN) and Recurrent Neural Networks (RNN) was used to drive a vehicle along roads lacking lane markings (unmarked roads). The team developed and tested this approach on the ACTor (Autonomous Camus TranspORt) vehicle - an autonomous vehicle development and research platform coupled with a low-cost webcam based sensing system and minimal computational resources. The proposed solution was evaluated on real-world roads and varying environmental conditions. It was found that this solution may be used to successfully navigate unmarked roads autonomously with acceptable road following behavior.

Entropy generation, formulated by combining the first and second laws of thermodynamics with an appropriate thermodynamic potential, emerges as the difference between a phenomenological entropy function and a reversible entropy function. The phenomenological entropy function is evaluated over an irreversible path through thermodynamic state space via real time measurements of thermodynamic states. The reversible entropy function is calculated along an ideal reversible path through the same state space. Entropy generation models for various classes of systems—thermal, externally loaded, internally reactive, open and closed––are developed via selection of suitable thermodynamic potentials. Here we simplify thermodynamic principles to specify convenient and consistently accurate system governing equations and characterization models. The formulations introduce a new and universal Phenomenological Entropy Generation (PEG) theorem. The systems and methods presented––and demonstrated on grease degradation, battery charging and discharging, metal fatigue and pump flow––can be used for design, analysis, and support of diagnostic monitoring and optimization.

With the digital transformation of the logistics industry, smart logistics algorithms have become a core technology to improve efficiency and reduce costs. This paper reviews the development history of traditional logistics technology and discusses the key role of technologies such as the Internet of Things, big data analysis, artificial intelligence, and automation in logistics technology innovation. It focuses on the application of intelligent logistics algorithms in path optimization, intelligent scheduling, data mining and prediction, and intelligent warehousing. To solve the problem of inconsistency between training and testing objectives, this paper proposes DRL4Route, a deep reinforcement learning-based path optimization framework, and designs the DRL4Route-GAE model. Validated through extensive offline experiments and online deployments, the model significantly outperforms existing optimal benchmark methods on real datasets, improving the location deviation squared metrics and the top-three location prediction accuracy metrics. These research results provide important support to further promote the intelligent development of the logistics industry.

Accurate fire severity mapping is essential for understanding the impacts of wildfires on vegetation dynamics in arid savannas. The frequent wildfires in these biomes often cause topkill, where vegetation experiences above-ground combustion, but the below-ground root structures survive, allowing for subsequent regrowth post-burn. Investigating post-fire regrowth is crucial for maintaining ecological balance, elucidating fire regimes, and enhancing the knowledge base of land managers regarding vegetation response. This study examined the relationship between bush fire severity and post-burn coppicing/regeneration events of woody vegetation in the Kalahari Desert of Botswana. Utilizing UAV-derived RGB imagery combined with a Random Forest (RF) classification algorithm, we aimed to enhance the precision of burn severity mapping at a fine spatial resolution. Our research focused on a 1 km2 plot within the Modisa Wildlife Reserve, extensively burnt by the Kgalagadi Transfrontier Fire of 2021. The UAV imagery, captured at various intervals post-burn, provided detailed orthomosaics and canopy height models, facilitating precise land cover classification and burn severity assessment. The RF model achieved an overall accuracy of 79.5% and effectively identified key burn severity indicators, including green vegetation, charred grass, and ash deposits. Our analysis revealed a >50% probability of woody vegetation regrowth in high severity burn areas six months post-burn, highlighting the resilience of these ecosystems. This study demonstrates the efficacy of low-cost UAV photogrammetry for fine scale burn severity assessment and provides valuable insights into post-fire vegetation recovery, thereby aiding land management and conservation efforts in savannas.

Button batteries pose a significant threat to young children and are found in many household items and children’s toys. Along with product manufacturers and retailers, parents and caregivers have a role in button battery ingestion prevention through vigilance regarding items containing button batteries in the home, and knowledge of button battery ingestion symptoms. There is limited information available about parent and caregiver perspectives towards button battery safety. Identifying the areas where increased education is required is important for informing safety campaigns and delivering targeted education. This study aimed to examine parent and caregiver elemental perspectives on button battery safety. One hundred and seventy-four parents and caregivers of children aged 0 to 5 completed a cross-sectional online survey. Distribution occurred via social media. The survey contained multiple-choice questions pertaining to button battery perspectives, and one open-ended question. Respondents recognized the dangers of button battery ingestion, yet only 37% reported being familiar with button battery ingestion symptoms. While 68% knew of household items containing button batteries, only 21% were aware of product recall information sources. Approximately 64% understood immediate post-ingestion steps and 17% found current safety labels unsatisfactory. In an open-ended question, parents and caregivers provided comments about button battery safety that revealed five broad themes; supervision and education; safe storage of button batteries in the home; ensuring children cannot access button batteries; disposing of button batteries safely; and avoiding purchasing items containing button batteries. This study provides a foundation for ongoing investigation of parent and caregiver perspectives on button battery home safety.

Increasingly, conservation genetics pinpoint the use of biological matrices collected without stressing wildlife. Cervid’s antlers seem to fit with this need. We verified the amplification success rate from DNA obtained from red deer antlers collected in the State Nature Reserve of Bosco della Mesola, Northern Italy and its use for conservation purposes. Here occurs the only native red deer population of peninsular Italy, recently recognized as a distinct subspecies (Cervus elaphus italicus). Four antlers stored at room temperature for four years and four samples highly degraded by environmental conditions were analyzed using a multimarker approach. We utilized a simple, inexpensive method to extract DNA from drilled antlers powder. This study confirms that weathered antlers can be a suitable source of DNA also in Mediterranean climate characterized by strong seasonal fluctuations, and not only in dry climates. Our results pointed out that only burr drilling yielded good quality amplifiable DNA. Antlers can be used in particular for molecular genetic studies on rare or threatened species of cervids as providing an efficient and cost-effective non-invasive sampling.

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) to the liver. Although there are established criteria for LT in HCC, the evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.

The assessment of seismic risk in urban areas with high seismicity is certainly one of the most important problems that territorial managers have to face. A reliable evaluation of this risk is the basis for the design of both specific seismic improvement interventions and emergency management plans. Unappropriate seismic risk assessments may provide misleading results and induce bad decisions with relevant economic and social impact.The seismic risk in urban areas is mainly linked to three factors, namely, “hazard”, “exposure” and “vulnerability”. Hazard measures the potential of an earthquake to produce harm; exposure evaluates the amount of population exposed to harm; vulnerability represents the proneness of considered buildings to suffer damages in case of an earthquake. Estimates of such factors may not always coincide with the perceived risk of the resident population. The propensity to implement structural seismic improvement interventions aimed at reducing the vulnerability of buildings depends significantly on the perceived risk.This paper investigates on the difference between objective and perceived risk and highlights some critical issues. The aim of this study is to calibrate opportune policies, which allow addressing the most appropriate seismic risk mitigation options with reference to current levels of perceived risk. We propose the introduction of a Seismic Policy Prevention index (SPPi). This methodology is applied to a case-study focused on a densely populated district of the city of Catania (Italy).

Knowledge regarding egg morphology can aid the selection of postharvest fumigants for insect control. Accordingly, scanning electron microscopy (SEM) was used to examine eggs of spotted lanternfly (SLF), Lycorma delicatula (White) (Hemiptera: Pentatomidae), a pest recently invasive to the mid-Atlantic region of the United States. As the overwintering life stage of SLF, eggs are deposited on a variety of refugia, including many forestry products that can be distributed geographically via travel, commerce, and/or trade. For fumigation to control SLF, and potentially translate into a viable strategy for limiting the spread of SLF by subject pathways, the fumigant must permeate the chorion to react with biomolecules and/or disrupt cellular processes. SLF chorion was characterized by a porous network of aeropyles localized around the operculum, in cranial and caudal relation to the developing nymph, as well as an interstice between the operculum edge and the opercular rim. The confirmation of chorionic ultrastructure that allows for ready gas exchange warrants further investigation of fumigation efficacy, even for those “non-reactive” fumigants, such as phosphine and hydrogen cyanide, which must overcome the suppression of cellular processes coincident with overwintering.

The objective of this study is to preliminarily evaluate a new CT-biopsy guidance device, an origami needle guide. The device is created by laser cutting the structure from a sheet of cardboard, 3D printing two radiocontrast agent grids on to the surface and folding the structure into a rectangular prism with a viewing window. An abdominal imaging phantom was used to evaluate the device through CT imaging and the targeting of lesions for needle insertion. The lesion targeting trials resulted in a mean targeting error of 1.88 mm with a standard deviation of 0.73 mm. The device attaches to the patient and is rigid enough to adequately support standard biopsy needles, reducing the effect of gravity and the risk of laceration by the needles, making it potentially advantageous for biopsy of superficial lesions and lesions approached from a horizontal orientation. The device supports insertion of multiple needles at once, making it particularly suitable for composite ablation using multiple needles. Another advantage of the device is that it can guide off-axial needle insertion. The low-cost and disposability of the device make it well-suited for the minimally invasive image guided therapy environment.

Heavy rains result in significant threats to human health and life. Floods and other natural disasters, which have a global impact annually, can be attributed to extended periods of intense precipitation. Accurate rainfall prediction is crucial in nations such as Bangladesh, where agriculture is the predominant field of occupation. The efficiency of machine learning methods is enhanced by the nonlinearity of rainfall, surpassing the effectiveness of other approaches. This study proposes the novel combination of rainfall occurrence prediction, rainfall amount prediction, and daily average temperature prediction. This research implements machine learning techniques and an ensemble-based classifier to predict rainfall occurrence, as well as machine learning regressor models and an ensemble-based regressor to predict the rainfall amount and daily average temperature, using the Bangladesh Weather Dataset. The ensemble classifier demonstrated an accuracy of 83.41% and a recall of 78.17%, exhibiting the best performance in predicting when it will rain, but its precision was the lowest, at 51.16%. The ensemble regression model outperformed the base models, including linear regression, random forest, and support vector regression in rainfall amount prediction, with the lowest mean absolute error of 0.36 and root mean squared error of 0.90. Additionally, this model provided the most precise daily average temperature prediction results with the lowest mean absolute error of 0.42 and root mean squared error of 0.54, highlighting its superiority over the other regression models in forecasting temperature. Ensemble approaches consistently exhibit superior task performance metrics.

Seismic vulnerability assessment in urban areas would in principle require the detailed modeling of each single building and the implementation of complex numerical calculations. This procedure is clearly difficult to apply at urban scale where many buildings have to be considered and therefore it is essential to have simplified, but at the same time reliable, approaches to vulnerability assessment. Among the proposed strategies, one of the most interesting concerns the application of machine learning algorithms, able to classify buildings according to their vulnerability on the basis of training procedures applied to existing datasets. In this paper machine learning algorithms will be applied to a dataset which collects and catalogs the structural characteristics of a large number of buildings and reports the damage observed in L’Aquila territory during the intense seismic activity occurred in 2009. A combination of a trained neural network and a random forest algorithm allows to identify an opportune “a-posteriori” vulnerability score, deduced from the observed damage, which is compared to an “a-priori” vulnerability one, evaluated taking into account characteristic indexes for building’s typologies. By means of this comparison an inverse approach to seismic vulnerability assessment, which can be extended to different urban centers, is proposed.

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.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Over the last few years, Earth Observation (EO) data has shifted towards increased use to produce official statistics, particularly in the agriculture sector. National statistics offices worldwide, including in Asia and the Pacific, are expanding their use of EO data to produce agricultural statistics such as crop classification, yield estimation, irrigation mapping, and crop loss estimation. The advances in image classification, such as pixel-based and phenology-based classifications, and machine learning create new opportunities for researchers to analyze EO data applied to agriculture statistics. However, it requires the ground truth (GT) data because classification result mainly depends on the quality of GT. Therefore, in this study, we introduced a random sampling approach to design and collect GT data using EO imagery and ancillary data. As a result of data collection, GT data improve the algorithms and validates classification results. Nevertheless, despite the importance of GT data, they are rarely disseminated as a data product in themselves. Thus, this results in an untapped opportunity to share GT data as a global public good, and improved use of survey and census data as a source of GT data.

Background: Underreporting of Visceral Leishmaniasis (VL) in India remains a problem to public health controls. Effective and reliable surveillance systems are critical for monitoring disease outbreaks and public health control programs. However, in India, government surveillance systems are affected by levels of scarcity in resources and therefore, uncertainty surrounds the true incidence of asymptomatic and clinical cases, affecting morbidity and mortality rates. The State of Bihar alone contributes up to the 40\% of the worldwide VL cases. The inefficiency of surveillance systems occurs because of multiple reasons including delay in seeking health care, accessing non-authentic health care clinics, and existence of significant asymptomatic self healing infectious cases. This results in a failure of the system to adequately report true transmission rates and number of symptomatic cases that have sought medical advice (thus, high underreporting of cases). Objectives and Methods: There are several methods to estimate the extent of underreporting in the surveillance system. In this research, we use a mathematical dynamic model and two different types of data sets, namely, monthly incidence for 2003-2005 and yearly incidence from 2006-2012 from the Bihar's 21 most VL affected districts out of its 38 districts. The goals of the study are to estimate critical metrics to measure level of transmission and to evaluate the estimation process between the two data sets and 21 districts. In particularly, our focus is on (i) estimating infection transmission potential, underreporting level in incidence and proportion of self-healing cases, (ii) quantifying reproduction number of the$R_0$, and (iii) comparing underreporting incidence levels and proportion of self-healing cases between the two periods 2003-2005 and 2006-2012 and between 21 districts. Results: Our research suggests that the number of asymptomatic individuals in the population who eventually self-heal may have a significant effect on the dynamics of VL spread. The estimated mean self-healing proportion (out of all infected) is found to be $\sim 0.6$ with only 7 out of 21 affected districts having self-healing proportion less than $0.5$ for both data sets. The estimated mean underreporting level is at least $64$\% for the state of Bihar. The estimates of the basic reproduction numbers obtained are similar in magnitude for most of the districts, being in the range of (0.88, 2.79) and (0.98, 1.01) for 2003-2005 and 2006-2012, respectively. Conclusions: The estimates for the two types (monthly and yearly) of temporal data suggest that monthly data are better for estimation if less number of data points are available, however, in general, using such data set results in larger variances in parameters as compared to estimates obtained through aggregated yearly data. Estimated values of transmission related metrics are lower than those obtained from earlier analyses in the literature, and the implications of this for VL control are discussed. The spatial heterogeneity in these control metrics increases the risk of epidemics and makes the control strategies more complex.

Outdoor exercise is beneficial for psychophysical well-being. Limited studies have compared outdoor and virtual reality (VR) indoor physical activities, especially in coastal settings. Therefore, this study aimed to assess the impact of outdoor coastal walking and indoor walking in a VR simulation with a similar environment on physiological and psychological variables in healthy adults. Twenty-six subjects (14M and 12F; age 25.2 ± 2.5 years) voluntarily participated in this crossover randomized controlled and counterbalanced study and were allocated under three conditions: VR indoor walking (INVR), outdoor walking (OUT) and standard indoor walking (IN). IN and INVR conditions were performed on a treadmill (speed 4.5 Km/h) and the OUT was per-formed on a seaside pedestrian road. The same outdoor environment was displayed in the visor during the INVR. Heart rate (HRmean/max), Physical Activity Enjoyment (PACES-It) and State of Mindfulness for Physical Activity (SMS-PA) were assessed at the end of each condition. The OUT condition showed significantly greater PACES-It scores and HRmean than IN and INVR (p<0.001) and greater SMS-PA scores and HRmax than IN (p<0.01 and p<0.05, respectively). No significant dif-ferences were found between OUT and INVR regarding HRmax and SMS-PA scores (p>0.05). Findings suggest that physical activity in an immersive technology may lead to physiological loads comparable to the outdoor environment. OUT is more enjoyable than IN and INVR but exhibits a mindfulness response comparable to INVR. Therefore, INVR could be an alternative to OUT for those who cannot engage in outdoor activities for various reasons.

Dynamic analyses and seismic assessments of multi-storey buildings at urban level require large-scale simulations and computational procedures based on simplified but accurate numerical models. At this aim the present paper propos-es an equivalent non-uniform beam-like model, suitable for the dynamic analysis of buildings with asymmetric plan and non-uniform vertical distribution of mass and stiffness. The equations of motion of this beam-like model, which pre-sents only shear and torsional deformability, are derived through the application of Hamilton’s principle. The linear dy-namic behaviour is evaluated by discretizing the continuous non-uniform model according to a Rayleigh-Ritz approach based on a suitable number of modal shapes of the uniform shear-torsional beam. In spite of its simplicity, the model is able to reproduce the dynamic behaviour of low- and mid-rise buildings with a significant reduction of the computa-tional burden with respect to that required by more general models. The efficacy of the proposed approach has been tested, by means of comparisons with linear FEM simulations, on three multi-storey buildings characterized by different irregularities. The satisfactory agreement, in terms of natural frequencies, modes of vibration and seismic response, proves the capability of the proposed approach to reproduce the dynamic response of complex spatial multi storey frames.

In this paper we present experimental results concerning Acoustic Emission (AE) recorded during cyclic compression tests on two different kinds of brittle building materials, namely concrete and basalt. The AE inter-event times were investigated through a non-extensive statistical mechanics analysis which shows that their decumulative probability distributions follow q-exponential laws. The entropic index q and the relaxation parameter q  1=Tq, obtained by fitting the experimental data, exhibit systematic changes during the various stages of the failure process, namely (q; Tq) linearly align. The Tq = 0 point corresponds to the macroscopic breakdown of the material. The slope, including its sign, of the linear alignment appears to depend on the chemical and mechanical properties of the sample. These results provide an insight on the warning signs of the incipient failure of building materials and could therefore be used in monitoring the health of existing structures such as buildings and bridges.

Lagoons are becoming sporadically utilised albeit they are equipped with high potential for the outsourcing of environmental and industrial benefits. It leads to the endangered pollution of lagoon water aquatic system. The prime reason is the lack of knowledge among stakeholders and researchers regarding the influential parameters in establishing the lagoon water quality. The optimal quality for lagoon water is critical for the longevity of aquatic ecosystem. This study focuses on using bibliographic references to find the most influential factors determining the water quality in lagoons for deriving a comprehensive long-term water quality monitoring plan to ensure the sustainability of the lagoon water ecosystem. The lagoon water quality was classified in this study into biological, physical, and chemical parameters and studied for their importance upon enhancing the water quality. Experiments were conducted on selected parameters using the water samples from the selected Sri Lankan lagoons with available facilities to observe the water quality. The overall findings on physiochemical and biological characteristics using the experiments temperature, turbidity, pH, salinity, DO, BOD, COD, phosphates, nitrates, ammonia content and faecal coliforms in water specimens suggest that the selected Sri Lankan lagoons are heavily polluted due to their distinctive variations from the allowable threshold limits specified in the literature sources. To increase such increased risks associated with lagoon water systems, a long-term monitoring strategy is recommended to be incorporated at lagoon waters in order to assure their sustainability.

The work consisted in identifying possible effects from heavy metals (HMs) pollution due to waste disposal activities in three potentially polluted sites located in Basilicata (Italy), where a release of pollutants with values over the thresholds allowed by the Italian legislation was detected. The potential variations in the physiological efficiency of vegetation have been analyzed through the multitemporal processing of satellite images. In detail, Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images were used to calculate the Normalized Difference Vegetation Index (NDVI) trend over the years. Then, the multitemporal trends were analyzed using the median of Theil-Sen, a non-parametric estimator particularly suitable for the treatment of remote sensing data, being able to minimize the outlier effects due to exogenous factors. Finally, the subsequent application of the Mann-Kendall test on the trends identified by Theil-Sen slope allowed the evaluation of trends significance and, therefore, the areas characterized by the effects of contamination on vegetation. The application of the procedure to the three survey sites led to the exclusion of the presence of significant effects of HMs contamination on the vegetation surrounding the sites during the years of waste disposal activities.

Cryonotothenioidea is the main group of fishes that thrive in the extremely cold Antarctic environment, thanks to the acquisition of peculiar morphological, physiological and molecular adaptations. We have previously disclosed that IgM, the main immunoglobulin isotype in teleosts, display typical cold-adapted features. Recently, we have analyzed the gene encoding the heavy chain constant region (CH) of the IgT isotype from the Antarctic teleost Trematomus bernacchii (family Nototheniidae), characterized by the near-complete deletion of the CH2 domain. Here, we aimed to track the loss of the CH2 domain along notothenioid phylogeny and to identify its ancestral origins. To this end, we obtained the IgT gene sequences from several species belonging to the Antarctic families Nototheniidae, Bathydraconidae and Artedidraconidae. All species display a CH2 remnant of variable size, encoded by a short Cτ2 exon, which retains functional splicing sites and therefore is included in the mature transcript. We also considered representative species from the three non-Antarctic families: Eleginopsioidea (Eleginops maclovinus), Pseudaphritioidea (Pseudaphritis urvillii) and Bovichtidae (Bovichtus diacanthus and Cottoperca gobio). Even though only E. maclovinus, the sister taxa of Cryonotothenioidea, shared the partial loss of Cτ2, the other non-Antarctic notothenioid species displayed early molecular signatures of this event. These results shed light on the evolutionary path that underlies the origins of this remarkable gene structural modification.

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

The fresh bulbs of Stenomesson miniatum, a plant belonging to Amaryllidaceae family with a poorly investigated phytochemical profile, were traditionally employed by Andean healers to treat tumors and abscesses. The aims of this study were to characterize the alkaloid extract from the bulbs of S. miniatum and test its cytotoxic and antibacterial potential. The alkaloid extract was characterized by dereplication using various techniques (CPC, NMR, UPLC-HRMS) and referring to in-home or online databases for spectroscopic data matching. Cytotoxic activities were evaluated on A431 human epidermoid carcinoma cells through a metabolic assay, and on Jurkat human acute T-leukemia cells through a cell-impermeant fluorescent nuclear probe. Antibacterial assays were carried out against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes by using a standardized microdilution broth method 96-well plate. Eleven known Amaryllidaceae alkaloids were identified together with another compound determined as being an extraction artefact. The alkaloid extract showed good cytotoxic activity against both the tumor cell lines, reaching an IC50 of 3.3 µg/mL against A431 cells and of 10.9 µg/mL against Jurkat cells. The analysis of the fractions allowed the activity to be attributed to the presence of pretazettine and haemathamine. Conversely, no antibacterial activities were recorded for any of the samples.

Background: The work and life of a junior doctor has changed dramatically over the past 50 years. Descriptions of historic working conditions are usually anecdotal and tinted with nostalgia. But presented with the facts, do heath care professionals feel working conditions things have improved or declined in the last 50 years? Methods: An interview was conducted with a retired surgeon who, in 1970, worked as a house surgeon (Foundation Year 2, FY2 equivalent) at a regional burns service. This was compared with a review of available literature to assess objectively working conditions in that period. The information generated from this produced a poster summarizing the key differences over a 53-year timeframe. This information was presented to the current medical work force and a survey was conducted to determine their preference. Statistical analysis including binary logistic regression was performed. Results: The questionnaire was completed by 76 respondent healthcare workers of mixed grades and backgrounds. The majority of respondents (64%) would choose to work in today’s burns unit. The age of the respondent was the best predictor for preference of working conditions (p = 0.043). Conclusions: Multiple changes in the working conditions were identified. The majority of respondents consider today’s working conditions to be better than that of the past. However, more senior clinicians were more likely to prefer the conditions of 1970 to present day, suggesting a generational shift in opinion.

The detection of subtle changes in the pituitary dimensions has relevant implications since this gland is crucial for the endocrine system. In cats, few studies established the cut-offs values of the pituitary gland’s dimensions, but using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age and weight on pituitary dimensions; to evaluate the inter- and intra-observer agreement for such measurements. Exclusion criteria were: clinical, laboratory or CT alterations of pituitary gland or brain diseases, fractures of the neurocranium, or diabetes mellitus. Pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficient for intra- and inter-observer reliability showed good/excellent and moderate/good reliability, respectively. No differences between sexes were detected, and negligible correlations were found with age and weight. Findings from the current study provided normal reference values for pituitary height (1.88 – 4.01 mm) and P:B ratio (0.25 – 0.49), useful for assessing abnormally enlarged pituitary gland in DSH cats.

This paper presents a comprehensive comparative analysis of four different computational vision algorithms for implementing an unpalleting system in a factory environment, under typical edge computing constraints. The primary objective is to automate the process of detecting and locating specific variable-shaped objects on a pallet, enabling a robotic system to accurately unstack them. The four algorithms evaluated are Pattern Matching, Scale-Invariant Feature Transform, Oriented FAST and Rotated BRIEF, and Haar cascade classifiers. Each technique is described in detail in this paper, and their implementations are outlined. Experimental results are thoroughly analyzed, assessing the algorithms’ performance based on accuracy, robustness to variability, computational speed, detection sensitivity, and resource consumption. The findings reveal the strengths and limitations of each algorithm, providing valuable insights for selecting the most appropriate technique based on the specific requirements of the unpalleting system. This research contributes to the advancement of automated object detection and localization in industrial environments, paving the way for more efficient and reliable unpalleting systems.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

The direct measurements of the magnetic flux density in steel blocks within Compact Muon Solenoid (CMS) magnet yoke are performed with 22 flux loops installed in selected regions of the yoke. The 10,000-ton CMS magnet flux return yoke encloses a 4 T superconducting solenoid with a 6-m-diameter by 12.5-m-length free bore and consists of five dodecagonal three-layered barrel wheels and four end-cap disks at each end. The yoke steel blocks, mostly up to 620 mm thick, serve as the absorber plates of the muon detection system. A TOSCA 3-D model of the CMS magnet has been developed to describe the magnetic field everywhere outside of the tracking volume which was measured with a field-mapping machine. In the present study, for the first time, the reliable reconstruction of the magnetic flux density in the steel blocks of the yoke is performed using the CMS magnet standard discharges from the operational magnet current of 18.164 kA. To provide this reconstruction, the voltages induced in the flux loops (with amplitudes of 20–250 mV) have been measured with six 16-bit DAQ modules and integrated offline over time. The results of the flux loop measurements during three magnet ramp downs are presented and discussed.

While some research supports utilizing plain radiography for measuring biomechanical alignment of the spine for prognosis and treatment, there are contrasting viewpoints regarding both the value and utilization of these procedures in conservative care. Evaluation of both conservative and non-conservative approaches to spinal care revealed vast differences in radiographic utilization and interpretation between orthopedic surgeons, primary care physicians, chiropractic physicians, and physical therapists, which may account for the different viewpoints and rationale in the literature. A research summary is provided regarding the various methods of spinal analysis utilized by these professions to help determine if there is any unique diagnostic or prognostic value associated with radiographic utilization that could assist in advancing conservative spinal assessment and treatment. Understanding any unique value provided through biomechanical assessment utilizing plain radiography of the spine established in the literature may help chiropractic physicians determine the appropriate use of radiographic procedures in clinical practice and how to coordinate efforts with other conservative and non-conservative professions to improve spinal healthcare.

This work is aimed at the development of innovative, easy and cheap methods for the stabilization, inertization and valorisation of the organic fraction of municipal solid waste (OFMSW). For the first time, two original processes for transforming the organic waste into an inert, odorless and sanitized material were here proposed. The first one, called dual step, starts with grinding of the OFMSW, by means of an industrial shredder. After being finely ground, the organic waste was exposed to a sterilization process by means of UV/ozone radiations or thermal treatment (stabilization phase) in order to obtain a complete removal of the OFMSW’s bacterial activity. By means of several microbiological analyses, the best sterilization method was chosen. The incorporation in a thermosetting matrix was, then, carried out through mixing the sterilized and finely ground organic waste into a water soluble urea formaldehyde (UF) based resin, with a formaldehyde content less than 1% wt, followed by a thermal treatment for UF-resin crosslinking (inertization phase). An alternative cheaper and easier process, called one step, was also proposed and investigated, by combining the sterilization with the curing thermal process (at higher temperature) of the thermosetting matrix. The preliminary experimental results reported in this paper suggest that both the proposed methods could be considered suitable for the production of high valorized innovative OFMSW-derived panels or bricks, that could find application in several fields, such as building or constructions materials. Finally a brief description of the prototype machinery is reported properly designed for implementing OFMSW stabilization and valorisation processes developed in this research work.

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p=<0.001) and 28.1% (mean value 8.2 Gy vs 12.8 Gy, p=<0.001) in DIBH plans compared to FB plans. The strongest predictor of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

The availability of new self-sensing cement-based strain sensors allows the development of dense sensor networks for Structural Health Monitoring (SHM) of reinforced concrete structures. These sensors are fabricated by doping cement-matrix materials with conductive fillers, such as Multi Walled Carbon Nanotubes (MWCNTs), and can be embedded into structural elements made of reinforced concrete prior to casting. The strain sensing principle is based on the multifunctional composites outputting a measurable change in their electrical properties when subjected to a deformation. Previous work by the authors was devoted to material fabrication, modeling and applications in SHM. In this paper, we investigate the behavior of several sensors fabricated with and without aggregates and with different MWCNTs content. The strain sensitivity of the sensors, in terms of fractional change in electrical resistivity for unit strain, as well as their linearity are investigated through experimental testing under both static and dynamically varying compressive loadings. Moreover, the responses of the sensors when subjected to destructive compressive tests are evaluated. Overall, the presented results contribute to improving the scientific knowledge on the behavior of smart concrete sensors and to furthering their understanding for SHM applications.

The static formation temperature (SFT) is required to determine the thermophysical properties and production parameters in geothermal and oil reservoirs. However, the SFT is not easy to be obtained by both experimental and physical methods. In this paper, a mathematical approach to predicting SFT based on a new model describing the relationship between bottom hole temperature (BHT) and shut-in time was proposed. The unknown coefficients of the model were derived from least squares fit by Particle Swarm Optimization (PSO) algorithm. Besides, the ability to predict SFT based on a few BHT data (such as first 3, 4, or 5 ones of a data set) was evaluated. The accuracy of the proposed method to predict SFT was testified with a deviation percentage less than ±4% and high values of regression coefficient R² (>0.98). The proposed method could be used as a practical tool to predict SFT in both geothermal and oil wells.

Species belonging to the Bauhinia genus, usually known as "pata-de-vaca", are popularly used to treat diabetes. Among them is Bauhinia ungulata var. obtusifolia (Ducke) Vaz, whose leaves are used, as a tea, for medicinal purposes in the Amazon region. The microencapsulation of the aqueous extract of its leaves, containing phenolic compounds, using five different wall materials (maltodextrin: DE11-14, and DE4-7; β-cyclodextrin; pectin, and sodium carboxymethylcellulose) is described in this paper. The microstructure, particle size, thermal behavior, yield, and encapsulation efficiency were investigated and compared using different techniques. Using high-performance liquid chromatography, phenolics, and flavonoids were detected and quantified in the microparticles. Microparticles, obtained with yield and phenolics encapsulation efficiency ranging between 60-83 % and 35-57 %, respectively, showed a particle size distribution between 1.15 and 5.54 µm, spherical morphology, and wrinkled surface. Among them, those prepared with sodium carboxymethylcellulose and pectin proved to be thermally the most stable. They had the highest flavonoid content (23.07 and 21.73 mgRUTE/g Extract) and total antioxidant activity by both the DPPH· (376.55 and 367.86 µmolTrolox/g Extract) and ABTS·+ (1085.72 and 1062.32 µmolTrolox/ g Extract) assays. The chromatographic analyses allowed for quantification, in the microparticles, chlorogenic acid (1.67-1.98 mg/g Extract), p-coumaric acid (0.06-0.08 mg/g Extract), rutin (11.1-12.9 mg/g Extract) and isoquercitrin (0.47-0.53 mg/g Extract), compounds considered responsible for the antidiabetic property attributed to the species.

Since 1970s, a great deal of attention has been paid to the development of semiconductor–based biosensors because of the numerous advantages they offer, including high sensitivity, faster response time, miniaturization, and low–cost manufacturing for quick biospecific analysis with reusable features. Commercial biosensors have become highly desirable in the fields of medicine, food, environmental monitoring as well as military applications (e.g., Hoffmann–La Roche, Abbott Point of Care, Orion High technologies, etc.), whereas increasing concerns on the food safety and health issues have resulted in the introduction of novel legislative standards for these sensors. Numerous devices have been developed for monitoring of biological–processes such as nucleic–acid hybridization, protein–protein interaction, antigen–antibody bonds and substrate–enzyme reactions, just to name a few. Since 1980s scientific interest moved to the development of semiconductor–based devices which also include integrated front–end electronics, such as the extended–gate–field–effect–transistor biosensor which is one of the first miniaturized chemical sensors. This work is intended to be a review of the state of the art focused on the development of biosensors based extended–gate–field–effect–transistor within the field of bioanalytical applications, which will highlight the most recent research works reported in the literature. Moreover, a comparison among the diverse EGFET devices will be presented giving particular attention to the materials and technologies.

BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.

The accurate detection of clouds is an important first-step in the processing of remotely sensed satellite data analyses and subsequent cloud model predictions. While initial cloud retrieval technology began with the exploitation of one or two bands of satellite imagery, it has accelerated rapidly in recent years as sensor and retrieval technology have exploded, creating a new era in space exploration. Additionally, initial emphasis in satellite retrieval technology focused on cloud detection for cloud forecast models, more recently cloud screening in satellite acquired data is playing an increasingly critical role in the investigation of cloud free data for the retrieval of soil moisture, vegetation cover, ocean colour concentration and sea surface temperatures, as well as environmental monitoring of a host of products, e.g. atmospheric aerosol data, to study the Earth’s atmospheric and climatic systems. With about 60% of the Earth covered by clouds, on average, it is necessary to both accurately detect clouds in remote sensing data to screen cloud contaminate data in remote sensing analyses. In this paper, the evolution of cloud detection technology is highlighted with advancement in sensor hardware technology and possible AI algorithmic advances. Additionally, a discussion is presented on methods to obtain the cloud truth data needed to determine the accuracy of these cloud detection approaches.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

In the current study, we assessed the effects of conventional and Ultra High Dose Rate (UHDR) irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus-interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage; conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percent Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percent of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test, suggesting that the reduced percent Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

Results-Based Financing (RBF) in pediatrics, in regions with scarce resources like Northern Uganda, provides an innovative approach to enhancing healthcare delivery. RBF aligns financial incentives with desired health outcomes, boosting service quality, efficiency, and effectiveness by tying compensation to achieving specific, measurable health targets. Lacor and Kalongo hospitals, before the introduction of RBF, faced numerous challenges, including limited resources, staffing shortages, and inconsistent quality of care. RBF adoption requires critical health outcomes to target, such as lowering child mortality rates, enhancing vaccination coverage, and increasing the frequency of timely prenatal care visits. The empirical application of RBF in pediatric services at Lacor and Kalongo Hospital from 2018 to 2024 shows improved healthcare quality and outcomes. Healthcare systems can identify ways to implement RBF models better, ensuring that financial incentives effectively contribute to attaining superior health outcomes.

We here report the de novo transcriptome assembly and functional annotation of Eusirus cf. giganteus clade g3, providing the first database of expressed sequences from this giant Antarctic amphipod. RNA-sequencing, carried out on the whole-body of a single juvenile individual likely undergoing molting, revealed the dominant expression of hemocyanins. The mRNAs encoding these oxygen-binding proteins cumulatively accounted for about 40% of the total transcriptional effort, highlighting the key biological importance of high hemocyanin production in this Antarctic amphipod species. We speculate that this observation may mirror a strategy previously described in Antarctic cephalopods, which compensate the decreased ability to release oxygen to peripheral tissues at sub-zero temperatures by massively increasing total blood hemocyanin content compared with temperate species. These preliminary results will undoubtedly require confirmation through proteomic and biochemical analyses aimed at characterizing the oxygen-binding properties of E. cf. giganteus clade g3 hemocyanins, and at investigating whether other Antarctic arthropod species exploit similar adaptations to cope with the challenges posed by the extreme conditions of the polar environment.

Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Crypto-ransomware has emerged as one of the most significant cybersecurity threats in recent years. Ransomware attacks, particularly those involving the encryption of data and demanding payment in cryptocurrency, have caused severe disruptions across various critical industries, including healthcare, energy, and finance. The proliferation of these attacks is largely attributed to the anonymity provided by cryptocurrency transactions and the increasing sophistication of cybercriminal tactics. The impact of ransomware extends beyond immediate financial losses, often leading to prolonged operational downtime, reputational damage, and even risks to public safety. In this research paper, we explore the growing threat of crypto-ransomware by examining real-life case studies in key industries, analyzing the countermeasures taken, and proposing additional solutions to mitigate the risk. The goal is to raise awareness and provide actionable insights for organizations to better protect themselves against this pervasive threat.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

As artificial intelligence (AI) makes significant headway in various arenas, the field of Speech-Language Pathology is at the precipice of experiencing a transformative shift towards automation. This study introduces QuickPic AAC, an AI-driven application designed to generate topic-specific displays from photographs in a "just-in-time" manner. Using QuickPic AAC, this study aimed to (a) determine which of two AI algorithms (NLG-AAC and GPT-3.5) results in greater specificity of vocabulary (i.e., percentage of vocabulary kept/deleted by clinician relative to vocabulary generated by QuickPic AAC; percentage of vocabulary modified); and to (b) evaluate perceived usability of QuickPic AAC among practicing speech-language pathologists. Results revealed that the GPT-3.5 algorithm consistently resulted in greater specificity of vocabulary and that speech-language pathologists expressed high user satisfaction for the QuickPic AAC application. These results support continued study of the implementation of QuickPic AAC in clinical practice and demonstrate the possibility of utilizing topic-specific displays as just-in-time supports.

Coccidioides spp are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with a symptomatic pneumonic disease as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haemato-chemical parameters as a POAF onset biomarker in subjected to cardiac surgery. Materials and Methods: We enrolled 90 patients (mean age= 66.9±2.8 years; 40 men and 20 females) with diverse heart pathologies and subjected to cardiothoracic surgery. Their blood samples were collected and used to determine haemato-chemical parameters. The tree test approach was used to detect the best data-driven ferritin cuff-off value (=141 ng/ml) to predict POAF risk. Results: The data obtained demonstrated significant higher concentrations, absolute values, and percentages, of ferritin, RDW, PLTs, in POAF patients. However, the ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥ 141 ng/ml identifies the subjects at the highest POAF risk. Conclusions: Ferritin values≥ 141 ng/ml might be used as predictive POAF biomarker.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new HA+Carnosine formulation (FidHycarn) on the inflammatory response and on the cartilage degradation in in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25µl normal saline having 1mg of monosodium iodoacetate solution (MIA) in the knee joint. MIA injection caused histological alterations and degradation of cartilage as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and weight distribution of hind paw as well as decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. However, interestingly, in more cases, the effects of FidHycarn were not statistically different to Naproxen used as positive control. Thus, the new formulation containing Carnosine and HA could represent an interesting therapeutic strategy to combat osteoarthritis.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

IntroductionParamedicine is a domain of practice and health profession that specialises in the provision of health and social care across a range of settings including, but not limited to, emergency and primary care. Paramedics work in a variety of clinical settings such as paramedics services, hospitals, and clinics, in the community as well as non-clinical roles, such as education, leadership, policy work, public health and research. A previous competency framework for paramedics in Canada had become increasingly poorly aligned with contemporary practice. We sought to develop a competency framework that represents contemporary paramedic practice in Canada. MethodsThis project was guided by a conceptual framework informed by systems thinking and used a six-step model for developing competency frameworks. We engaged paramedics from across Canada in working groups to explore various contexts of paramedic practice. We gathered data using multiple methods and coded this data into activity statements. We grouped these statements and developed or expanded corresponding professional activities through five drafts of the framework from 2022 to 2024. A technical committee reviewed and edited the draft framework throughout the process, culminating in a public review period from January to March 2024, and a subsequent final version of the National Competency Framework for Paramedics (NCFP). ResultsThe National Competency Framework for Paramedics reflects contemporary paramedic practice in Canada. It describes the professional activities of paramedics organised under five domains - Person-Centred Care; Collaborative Care; Safe Care; Self-Care; and Professional Care. Paramedics perform these activities across multiple contexts of practice by enacting a variety of roles depending on the event. Discussion and conclusion By exploring the variety of practice contexts and the expectations of paramedics across Canada, the NCFP provides a holistic, contemporary description of paramedic practice in Canada, providing a foundation for professional practice in a variety of settings. The five domains provide a comprehensive representation of paramedic practice helping to ensure care is ultimately and sufficiently aligned with the needs of the community and settings in which paramedics can practice. The NCFP can be used to inform education programs to better prepare paramedics for complex, interprofessional health and social care practice now and as practice continues to evolve.

Septic arthritis (SA) represents an orthopedics urgency and mainly affects the knee joint. Due to its devastating effects on cartilage, immediate management is crucial. SA is characterized by an an-nual incidence of 2 to 10 cases per 100,000 individuals, with mortality rates fluctuating between 0.5% and 15%, with a substantially higher mortality rate observed in older people (15%) in con-trast to younger cohorts (4%). The etiology of septic arthritis is multifactorial: a spectrum of Gram-positive and Gram-negative bacteria can contribute to the development of this condition, especially Staphylococcus aureus. The treatment involves urgent (arthroscopic or arthrotomic) debridement associated with adequate antibiotic therapy. Intra-articular antibiotic carriers can also be used to increase their local concentration and effectiveness. The case of a 67-years-old woman affected by knee SA from methicillin-susceptible S. aureus is presented. She was treated with an arthroscopic debridement enhanced by intra-articular antibiotic-loaded calcium sulphate beads, together with antibiotic therapy. At 2-year follow-up, the infection has been eradicated and the patient fully recovered. This is the first description, to our knowledge, in English Literature of the use of antibiotic-loaded calcium sulphate beads as an adjuvant in the surgical treatment of SA of a native knee joint.

Head and neck squamous cell carcinoma (HNSCC) arise from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here we focus on SMN in cancer context. We conducted a pilot study in a total of 20 patients with LSCC where SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumours. This study candidates SMN as novel therapeutic target in LSSC, and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of SMN in human cancer.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic/subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. Indeed, we observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to our knowledge, this is the first study that provides the evidence of a co-localization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection could reprogram mitochondrial activity in highly specialized maternal/fetal interface.

Background: There has been a lack of tools to identify listening difficulties in school settings for both hearing and hearing-impaired Italian students. Thus, the present study aimed to realize cross-cultural adaptation and validation of the Listening Inventory for Education-Revised for Italian students (LIFE-R-ITA). Methods: Following the validation of two forward-backward translations by a multidisciplinary committee, the content validation for the LIFE-R-ITA was performed by pre-testing six implanted children (8-18 years old). After minor cross-cultural adaptations, normative data were collected from a sample of 223 hearing students enrolled in different school settings and educational degrees. Results: For the LIFE-R-ITA, hearing students showed an average score of 72.26% (SD=11.93), reflecting some listening difficulties. The subscales (LIFE total, LIFE class, and LIFE social) indicated good internal consistency. All items were shown to be relevant. Most challenging situations happened when listening in large rooms, especially when other students made noise. LIFE social scores were significantly worse than those of LIFE class (p &lt; 0.001). Conclusions: The LIFE-R-ITA may support teachers and clinicians in assessing students’ self-perception of listening at school. Such understanding may help students overcome their listening difficulties, by planning and selecting the most effective strategies among classroom interventions.

Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.

Introduction: Drug interactions (DDIs) represent an important clinical problem particularly in elderly patients due to polytherapy, comorbidity and physiological change in pharmacodynamic and pharmacokinetic pathways. In this study we investigated the association between drugs prescribed during hospital or clinical room discharge and the development of DDIs with drugs daily used from each patient. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug interactions (DDIs) were measured using the drug interactions probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 1,622 medical records. We recorded the development of DDIs in 10.3% of patients, of those 11.6% induced the hospitalization. Logistic regression showed an association between DDIs and sex and number of drugs used (P = 0.023). Conclusion: this real-life study shows that DDIs are common in elderly patients and physicians must take more attention after hospital discharge revaluating the treatment in order to reduce the risk of DDIs and hospitalization.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. In this narrative review, we develop an analytical framework to examine mask usage, considering and synthesizing the relevant literature to inform multiple areas: population impact; transmission characteristics; source control; PPE; sociological considerations; and implementation considerations. A primary route of transmission of COVID-19 is via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. Given the current shortages of medical masks we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory droplets become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask-wearing by infectious people ("source control") with benefits at the population-level, rather than mask-wearing by susceptible people, such as health-care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.