Gliomas are solid tumors of the Central Nervous System (CNS) that originated from different glial cells. The World Health Organization (WHO) classified these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as a grade IV. GBM are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.

From professors overwhelmed by anxiety-driven e-mails from students, through faculty and administrative staff wasting valued time on e-mail minutia, misuse of electronic mail in the academy has become ubiquitous. After a brief overview of the unique features of e-mail communication, this study provides insight and guidelines to plan new educational activities on healthy and productive utilization of e-mail in the academy of the digital era. The overall aim is to prioritize scholarly deep work by focusing on teaching and research work, freeing working time wasted on unproductive use of e-mail.

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several of their applications require protein engineering, which in turn would greatly benefit from having a reliable structural model of the nanobody of interest. However, as with antibodies, structural modeling of nanobodies is still a challenge. With the rise of artificial intelligence (AI), several methods have been developed in recent years that attempt to solve the problem of protein modeling. In this study, we have compared the performance in nanobody modeling of several state-of-the-art AI-based programs, either designed for general protein modeling, such as AlphaFold2, OmegaFold, ESMFold and Yang-Server, or specifically designed for antibody modeling, such as IgFold, and Nanonet. While all these programs performed rather well in constructing the nanobody framework and CDRs 1 and 2, modeling of CDR3 sill represents a big challenge. Interestingly, tailoring an AI method for antibody modeling does not necessarily translate into better results for nanobodies.

Biological systems often need to operate in complex environments where conditions can rapidly change. This is possible due to their inherent ability to sense changes and adapt their behavior in response. Here, we detail recent advances in the creation of synthetic genetic parts and circuits whose behaviors can be dynamically tuned through a variety of intra- and extra-cellular signals. We show how this capability lays the foundation for implementing control engineering schemes in living cells and allows for the creation of biological systems that are able to self-adapt, ensuring their functionality is maintained in the face of varying environmental and physiological conditions. We end by discussing some of the broader implications of this technology for the safe deployment of synthetic biology.

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

The Active Distribution Networks (ADNs) are Multi-Input Multi-Output (MIMO) systems with coupled dynamics which cause interactions among the control loops of the Distributed Energy Resources (DERs). This undesired effect lead to performance degradation in the voltage control. To mitigate the effects of these unavoidable coupling, the present paper proposes a systematic design procedure based on the analysis of the interaction's sources. In details, each DER is equipped with a double loop PI to control the active and reactive powers output by the Voltage Source Converter (VSC) which connects the DER to the network's node. Furthermore, to guarantee Ancillary Services (ASs), the two loops are coupled by a simple mechanism of cooperation of the active power to voltage regulation realized by a filtered droop law. To achieve voltage regulation with reduced loop interactions, the PI parameters and the filter's pulse are designed according to a two sequential steps procedure based on the (Internal Model Control) IMC technique. Simulation studies are finally presented to demonstrate that the proposed design method achieves both reduction of the loop interaction and robust voltage control in presence of model parameter uncertainty in the MIMO model.

Premenstrual syndrome is characterized by pain and symptoms affecting the women´s quality of life. We aimed to evaluate the safety and effectiveness of an oral fixed dose combination containing naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg tablet (Analgen Fem®) during the routine clinical practice. A prospective, open-label, multicenter, observational post-marketing study was conducted from December 2017 to December 2019 including 270 women older than 18 years. Primary endpoint was the proportion of adverse events, meanwhile the pain intensity, premenstrual syndrome symptoms, and patient proportion with a pain score reduction by at least 50% were secondary endpoints. The mean age of population was 28.9 ± 8.8 years. Among the 270 women, 8 (3%) experienced 10 adverse events. These were headache (5/8), gastritis (2/8) dyspepsia (1/8), diarrhea (1/8) and nausea (1/8). The investigator discontinued the study medication in 3/8 patients because of adverse events. The median of differences between the pain intensity at baseline and at last observation (-4.5, 95%CI; -5, -4) demonstrated that naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg fixed dose combination reduced pain intensity (p<0.001). In addition, the proportion of patients with pain reduction by at least 50% at the end of the treatment was 70.7%. The study demonstrated that this drug represents a safe and tolerated treatment, reducing pain intensity and premenstrual symptoms.

Purpose: The purpose of this study is to further explore how e-loyalty and E-marketing influences E-trust and satisfy the demand by offering fresh perspectives based on research as well as emphasis on the factors influencing the E-trust such as culture as a mediator. This study not only contributed theoretically but also presented practical implementations. Design/methodology/approach: Online survey was used to obtain data by focusing the Hospitality sector (Hotel Industry) and verifying the conceptual framework. Data was collected in multiple time lags. Findings: Findings showed that the E-trust influenced by E-loyalty and E-Marketing. E-trust comes from the previous experiences, e-loyalty and e-marketing. Further, some trends such as culture influenced the e-trust. Research limitation/implications: The present study is quite suitable for those Researchers interested in learning more about the effects of E-loyalty and E-marketing on user E-trust and how to mitigate cultural influences can benefit from the current study. This research also has implications for those who wish to improve market allure and survival in digital world. This study focused on the hospitality sector (Hotel Industry) in China; however, the sector and geography could be altered to suit the needs of the study's participants. Practical implications: The present study delivers the practical guidelines which are quiet suitable for understanding the formation of E-loyalty, E-marketing, and E-trust through which specific E-marketing strategy can be designed to deal with the consumer’s E-loyalty and their expectations as per their Cultural perspective. At some particular regions/countries, cultural trends are more important than practical market. This research study practically showed that how culture changed the consumer set of mind. Originality/value: The relationship between E-loyalty, E-marketing, E-trust, specifically with the cultural influence in digital market has been the subject of few research.

A dendrochronological investigation was undertaken on subfossil Scots pine (Pinus sylvestris L.) stumps following their discovered during conservation management activities at Wem Moss, a small (28ha) former raised mire in Shropshire, UK. Two ring-width chronologies were constructed from 14 of the 17 trees investigated spanning 198 and 208 years respectively. Whilst absolute dating was not possible, radiocarbon assays provided an estimated age for this mire-rooting woodland of between 3015 – 2505 years Cal BC, coinciding with the age traditionally associated with the widespread mortality of pine trees throughout much of the UK and Ireland, The Pine Decline (circa 4 ka radiocarbon years BP). Placed in a wider geographical context, the Wem Moss pines are located within the wider lowland area of the Meres and Mosses Region, where previous studies on subfossil pine have demonstrated protracted declines in mire-rooting trees. These have included tree mortality significantly post-dating The Pine Decline, notably at larger peatland sites exceeding 5.5 km2. This macrofossil evidence for the presence of Scots pine into the late Holocene is supported by continuous Pinus pollen representation at peatland sites in the Welsh Marches (English-Welsh border) suggesting the possible survival of native Scots pine trees in this area up to the present-day. This research highlights the incomplete and patchy nature of palaeo-vegetational records and also the potential for genetic research on living Scots pine in possible refugial areas in the UK and Ireland.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

Households and businesses are generating unprecedented levels of electrical and electronic wastes (e-waste), fueled by modernisation and rapid obsolescence. While the challenges imposed by e-waste are similar everywhere in the world, disparities in progress to deal with it exists; with developing nations such as South Africa lagging. The increase in e-waste generation increases the need to formulate strategies to manage it. This paper presents an overview of e-waste management on a global and South African scenarios with a specific case for Cathode Ray Tube (CRT) waste management practices in South Africa. CRTs present the biggest problem for recyclers and policy makers because they contain hazardous elements such as lead and antimony. Common disposal practices have been either landfilling or incineration. The research into the South African practices with regards to CRT waste management showed that there is still more to be done to effectively manage this waste stream. This is despite clear waste regulatory frameworks in the country. However, recent developments have placed e-waste as a priority waste stream, which should lead to intensified efforts in dealing with it. Overall, these efforts should aim to maximise diversion from landfilling and to create value-addition opportunities, leading to social and environmental benefits.

The development of biofuels and biodiesel industry specifically, has resulted in the generation of large amounts of glycerol as a surplus. The conversion of glycerol, into chemicals with indus-trial interest, through anaerobic fermentation using E. coli as a biocatalyst is an attractive alter-native to improve economic performance in the biodiesel industry, for example through the bi-otransformation of residual glycerol into ethanol. For 2019, the size of the global ethanol market was valued at $ 89.1 billion US dollar. Biodiesel can be produced from several materials like rapeseed, palm, soya, corn, palm kernel, frying oil or olive-pomace oil (OPO). The last, can be extracted from alperujo, byproduct of olive oil process. However, olive-pomace oil converting into biodiesel is not enough established to achieve a global olive-oil/biodiesel derived process with minimized waste generation. Traditionally biodiesel production process produces an equivalent of 10% by mass of glycerol as a waste or by-product. This work explores the conver-sion of residual glycerol into chemicals like ethanol and hydrogen with a focus on projecting raw material potential availability from OPO, contributing to the promotion of the use of biofu-els and biodegradable compounds.

Purpose is to o review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma (OAG) after Pars Plana Vitrectomy (PPV). Most existing scientific literature on the issue agree on the role of ascorbate as an oxygen scavenger within the vitreous chamber. Oxygen tension in the vitreous and anterior chamber is maximum inn proximity of the retinal surface and endothelium, respectively and steeply decreases toward the lens; on both sides, and trabeculate. Vitreous removal and, to a lesser extent, liquefaction, greatly reduces oxygen tension gradient in vitreous chamber while cataract extraction has similar effects on anterior chamber oxygen gradients. Oxygen derivatives originated from the cornea and retina are actively reduced by the vitreous gel and/or the crystalline lens. Vitreous removal and cataract extraction reduce drastically this function. Most reported clinical series confirm this hypothesis although protocol difference and follow-up length greatly impact the reliability of results.

Ascorbate; Pars Plana Vitrectomy; Open Angle Glaucoma; Oxidative Stress; Vitreous Me-tabolism 0. How to Use This Template

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

As participating molecules in nucleic acids, nucleotides also have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells, the most common example being cyclic AMP (cAMP). In bacteria, a great interest has arisen in studying nucleotide signaling. It has been determined that cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, virulence, and other. Moreover, these cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells for infection. On the other hand, the nucleotide molecules pppGpp, and ppGpp are alarmones involved in regulating bacterial nutritional stress; they are also considered second messengers. These second messengers can be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, different topics on the role of c-di-nucleotides as second messengers in different bacterial processes are addressed.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one tar-get-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy- 2,3-dihydro-1H-inden-1-one (1a), which in the E diastereomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs 1b-h with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound the thermal stable E diastereoisomer, along with the E/Z mixture as produced by UV-B light irradia-tion in the photostationary state (PSS, 75% Z), was investigated for the inhibition of human ChEs and MAOs. The pure E-diastereoisomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC50s 39 and 355 nM, re-spectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z diastereoselectivity of 1h toward the two target enzymes.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

As an established and widely available infrastructure, wireless local area networks (WLANs) have emerged as a viable option for indoor localization of both mobile and stationary users. In planning a mobile communications network and radio system design, the critical role of coverage prediction becomes evident, empowering network operators to optimize cellular networks and elevate the overall customer experience. Moreover, WLANs present several challenges that must be fulfilled when it comes to localization based on Wi-Fi signals to get a proper coverage prediction map. This paper presents a study based on application of the extra trees regression (ETR) for indoor localization by using coverage prediction maps. The aim of the proposed method is to accurately estimate a user’s position within a radio environment map (REM) area using collected received signal strength indicator (RSSI) values. The proposed scheme investigates several machine learning (ML) regression algorithms for localization, where the training dataset is obtained from the REM by using the nearest neighbors method. Parameter tuning is conducted to optimize the performance of the ETR scheme by using 10-fold cross-validation. In the numerical results, we first demonstrate the effectiveness of utilizing ML regression techniques for generating coverage maps, which enables accurate estimation of the Wi-Fi signal strength in indoor environments. Then, we showcase the superior performance of the proposed ETR-based method compared to several other ML schemes for indoor localization using the REM. ML algorithms, including decision tree regression and the ETR, are compared to evaluate the system model. Based on error metrics, the proposed ETR-based approach exhibits the best performance among the evaluated techniques. The combination of coverage map generation and localization using regression techniques offers a powerful approach for analyzing the radio frequency (RF) environment in indoor spaces.

The purpose of this research has been to analyze the organizational structures of the different federations and entities representing the modalities of trail-running, skyrunning and mountain running and how they have settled in the current sports landscape. The main task of these entities is to act as hosts of the legally established modalities, both internationally and nationally, applying their respective regulations and statutes unilaterally. Through an in-depth review of the different regulations, statutes and current articles of all the organizations that represent the different disciplines, we can observe how a sport modality that seems to be the same is nevertheless distant in its execution (regulations, championships, classifications, systems of points, ...) and that has led to the international level being established in different sport modalities (trail-running and skyrunning) and at the level of the Spanish territory, it has led to an administrative dispute to know who has the powers to approve the sports competitions.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

One of the most important problems in the presence of epidemics and pandemics is an accurate prediction and preparedness. Scholars and experts argue that future pandemics and/or epidemics are almost inevitable events and is not whether next pandemics will happen, but when a new heath emergency will emerge. Epidemiologic models for prediction of Coronavirus Disease 2019 (COVID-19) have shown many limitations because of unpredictable dynamics of the new viral agent SARS-CoV-2 in environment and society. The main goals of this study are twofold: first, the analysis of anthropogenic activities and factors that may trigger pandemic threats; second, the planning of new directions for strategies to reduce risks that a pandemic threat emerges and/or in the initial phase to reduce vast diffusion and negative impact of new viral agents that can generate hazards and problems in public health, environment and socioeconomic systems. In particular, the investigation and understanding of sources and driving factors concerning the emergence and diffusion of new pandemics have critical aspects for strategic actions of forecast, prevention and preparation of effective policy responses to cope with next pandemic crises and health emergencies. Insights here endeavor, whenever possible, to clarify these problems to increase the knowledge of the sources and factor determining the emergence of new viral agents in order to design optimal response policies to face next pandemic diseases similar to COVID-19. .

Artificial intelligence and Quantum science supports path-breaking technologies for main technological change. The investigation goal of this study is to examine their scientific and technological development to explain drivers of these disruptive technologies. Analyses of data, based on publications and patents in quantum science and artificial intelligence, with a technometric model show that that quantum science and technology has a growth rate of 1.07, artificial Intelligence ha a rate of growth of 1.37, whereas the interaction of quantum science and artificial intelligence generates a convergent technological trajectory that has an accelerated rate of growth of 1.58, higher than trends of these technologies taken individually. These findings here clarify one of the fundamental determinants of the evolution of path-breaking technologies that can support decision making of policymakers, technology analysts and R&amp;D managers to direct R&amp;D investments towards fruitful inter-relationships between radical technologies that foster scientific and technological change in knowledge economies.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p&lt;0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p &lt; 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p&lt;0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

Acrylamide (AA), a molecule which potentially increases the risk of developing cancer, is easily formed in food rich in carbohydrates, such as biscuits, wafers and breakfast cereals, at temperatures above 120 °C. Thus, it is eminent the need to detect and quantify the AA content in processed foodstuffs, in order to delineate the limits and mitigation strategies. This work reports the development and validation of a high-resolution mass spectrometry-based methodology for identification and quantification of AA in specific food matrices of biscuits, by using LC-MSⁿ with electrospray ionization and Orbitrap as mass analyser. The developed analytical method showed good repeatability (RSD_r 11.1%) and 3.55 μg kg^-1 and 11.8 μg kg^-1 as limit of detection (LOD) and limit of quantification (LOQ), respectively. The choice of multiplexed targeted-SIM mode (t-SIM) for AA and AA-d3 isolated ions provided enhanced detection sensitivity, as demonstrated in this work. Results for AA concentration obtained vary between 323.7 and 2056.1 μg kg^-1. During baking an increase in AA concentration was observed, as well as between samples taken from different areas of the baking oven. Statistical processing of data was performed in order to compare the AA levels with several production parameters, such as time/cooking temperature, placement on the cooking conveyor belt, color and moisture for different biscuits. The composition of the raw materials was statistically the most correlated factor with the AA content when all samples are considered. The statistical treatment presented herein enables an important prediction of factors influencing AA formation in biscuits contributing for putting in place effective mitigation strategies.

Origin, mechanics and properties of the Solar System are analysed in the framework of the Complete Relativity theory (by the same author). According to Complete Relativity, everything is relative. Any apparent absolutism (notably invariance to scale of dimensional constants, absolute elementariness, invariance to time) is an illusion stemming from limits imposed by [or on] polarized observers that will inevitably lead to misinterpretation of phenomena (another illusion) occurring on non-directly observable scales or even on observable but distant scales in space or time. If everything is relative, reference frames will exist where particles are planets and where planets are living beings. Earth is, therefore, analysed here in more detail, both as a particle and, as a living evolving being (of, hypothesized, extremely introverted intelligence). The analysis confirms the postulates and hypotheses of the theory (ie. existence of discrete vertical energy levels) with a significant degree of confidence. During the analysis, some new hypotheses have emerged. These are discussed and confirmed with various degrees of confidence. To increase confidence or refute some hypotheses, experimental verification is necessary. Main conclusions that stem from my research and are further confirmed in this paper are: universes are, indeed, completely relative; Solar System is a scaled (inflated, in some interpretations) Carbon isotope with a nucleus in a condensed (bosonic) state and components in various vertically excited states; life is common everywhere, albeit extroverted complex forms are present on planetary surfaces only during planetary neurogenesis; anthropogenic climate change is only a part (trigger from one perspective) of bigger global changes; major extinction events on a surface of a planet are relative extinctions, a regular part of transformation and transfer of life in the process of planetary neurogenesis.

Lithium titanates are used in various applications, such as anode materials for lithium intercalation (Li4Ti5O12) or breeding materials in fusion reactors (Li2TiO3). Here, we report the formation of nano-crystalline lithium titanates by a mechanochemical approach and present a deeper insight into their structural characteristics by PXRD and solid-state NMR spectroscopy. The compounds were synthesized in a high energy planetary ball mill with varying milling parameters and different grinding tools. NaCl type Li2TiO3 (α-Li2TiO3) was formed by dry milling of lithium hydroxide with titania (rutile or anatase) and by a milling induced structure transformation of monoclinic β Li2TiO3 or spinel type Li4Ti5O12. Heating of mechanochemical prepared α Li2TiO3 induces a phase transformation to the monoclinic phase similar to hydrothermal reaction products, but a higher thermal stability was observed for the mechanochemical formed product. Microstructure and crystallographic structure were characterized by PXRD via Rietveld analysis. Detailed phase analysis shows the formation of the cubic phase from the various educts. A set of two lattice parameters for α Li2TiO3 was refined, depending on the presence of OH- during the milling process. An average crystallite size of less than 15 nm was observed for the mechanochemical generated products. The local Li environment detected by 6Li SPE MAS NMR revealed Li defects in the form of tetrahedral instead of octahedral site occupation. Subsequent adjustment of the structural model for Rietveld refinement leads to better fits, supporting this interpretation.

Almost fifty years after the first installations, I identify the main lessons learned from fighting drought and poverty in Africa with direct solar-powered pumps thanks to Father Bernard Verspieren and Mali Aqua Viva. Six main findings and three main recommendations emerge from the present analysis. They are of direct relevance to all Africa’s countries whose population has gone from 438 million in 1977 to 1,308 million in 2019, with about 600 million still having no access to electricity. In place of “awareness campaigns” and extraordinary courses held by international organizations, I recommend to establish national solar energy institutes whose task will include the education of solar energy professionals giving practice-oriented workshops on solar-powered drip irrigation and rainwater harvesting throughout each Africa’s country. Said education will critically include the economic and social aspects of distributed “generation” of energy and water from sunlight and rainfall.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.

This review deals with the functionalization of double bonds carried out in the presence of a chiral catalyst exploiting the intramolecular attack to haliranium ions by nucleophilic nitrogen of amides or carbamates prepared from achiral aminoalkenes, and the C-N bonds formation leads to highly enantioenriched non-aromatic heterocycles. A range of protocols are reported, emphasizing the synthesis of many natural and biologically active products of pharmacological interest prepared according to this methodology.

Fostering fruitful collaboration between chemistry and physics scholars, the analysis of the differences in the practical approach to single atoms in chemistry and in physics affords a number of conceptual outcomes pointing to a more balanced relationship between chemistry and physics.

Since the global request for freight transportation is continuously increasing to face the requirements of the modern economy, 5G infrastructures and companion technologies are becoming essential to support the digital transformation in logistics and transportation, in particular for their capability to allow data collection through a multitude of different sources across the supply chain, improving the connectivity and making more effective the secure and reliable data sharing. The objective of this work is to assess the penetration and implementation levels of innovative technologies to optimize port operations, by interviewing a set of actors and stakeholders directly involved in the logistics chain of ports.

In 2020, students of Pakistan had to adapt to the online environment for the very first time. This study aims to analyze the perceptions of medical, dental, and allied health students about online education in Pakistan. A descriptive, cross-sectional study was done to assess the level of acceptance of undergraduate students. A pre-validated questionnaire regarding demographics, past-experience of e-learning, advantages disadvantages of e-learning, and general perception of students towards e-learning was distributed. Descriptive statistics were computed for demographics, Mann-Witney-U test was used to compare the differences of perceptions between pre-clinical year and clinical years students. Kruskal-Wallis test was applied to compare the results of three specialties of students. Chi-square was used to compare overall category-wise positive and negative responses of students. 1200 students participated in the study. The major advantage identified by all students was the ‘comfortable environment’ in which they studied online. The major disadvantage selected by preclinical year students was ‘anxiety due to social isolation’ and that chosen by clinical year students was ‘lack of patient interaction’. Overall, 72% of students had a negative perception of e-learning. Student-teacher training, student counselling sessions, and innovative techniques need to be introduced to enhance student engagement and reduce pandemic stress.

Evaluation of road safety is a critical issue having to be conducted for successful safety management in road transport systems, whereas safety management is considered in road transportation systems as a challenging task according to the dynamic of this issue and the presence of a large number of effective parameters on road safety. Therefore, evaluation and analysis of important contributing factors affecting the number of crashes play a key role in increasing the efficiency of road safety. For this purpose, in this research work, two machine learning algorithms including the group method of data handling (GMDH)-type neural network and a combination of support vector machine (SVM) and the grasshopper optimization algorithm (GOA) are employed for evaluating the number of vehicles involved in the accident based on the seven factors affecting transport safety including the Daylight (DL), Weekday (W), Type of accident (TA), Location (L), Speed limit (SL), Average speed (AS) and Annual average daily traffic (AADT) of rural roads of Cosenza in southern Italy. In this study, 564 data sets of rural areas were investigated and relevant effective parameters were measured. In the next stage, several models were developed to investigate the parameters affecting the safety management of road transportation for rural areas. The results obtained demonstrated that "Average speed" has the highest level and "Weekday" has the lowest level of importance in the investigated rural area. Finally, although the results of both algorithms were the same, the GOA-SVM model showed a better degree of accuracy and robustness than the GMDH model.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, at least in part, of exclusion. AOSD is generally mild, however a small percentage of patients can develop a fearsome as well potentially fatal complication, the macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with a cytokine storm production and monocyte/macrophage overactivation, and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. The Histiocyte Society, which is a nonprofit organization committed to improving the lives of patients with histiocytic disorders, currently suggests etoposide in combination with dexamethasone for the treatment of HLH/MAS, although a multidisciplinary collaboration using the resources and expertise of several specialists (e.g. rheumatologist, infectiologist, critical care medicine specialist) is always recommended. Hereby we propose the detailed description of the clinical case of a previously healthy young woman in which MAS was the dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge.

The rapid growth of the global wearable technologies market is projected to reach $61.30 billion by 2030 which reflects a shift towards personalised health monitoring embedded in everyday activities. This paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. Experimental results demonstrate the sensor’s capability to detect water droplets and glucose concentrations, showcasing promising applications for health monitoring. The embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

With a relatively small population, Russia accesses huge oil, natural gas, coal and uranium resources, and hosts advanced nuclear energy, oil and natural gas industries. However, the combined effect of today’s low cost electricity generation via photovoltaic modules, water and wind turbines and similarly low cost storage in Li-ion battery and solar hydrogen obtained via water electrolysis will have a profound impact on Russia’s energy and automotive industries.

A quantum time-dependent spectrum analysis, or simply, quantum spectral analysis (QSA) is presented in this work, and it’s based on Schrödinger’s equation. In the classical world, it is named frequency in time (FIT), which is used here as a complement of the traditional frequency-dependent spectral analysis based on Fourier theory. Besides, FIT is a metric which assesses the impact of the flanks of a signal on its frequency spectrum - not taken into account by Fourier theory and let alone in real time. Even more, and unlike all derived tools from Fourier Theory (i.e., continuous, discrete, fast, short-time, fractional and quantum Fourier Transform, as well as, Gabor) FIT has the following advantages, among others: a) compact support with excellent energy output treatment, b) low computational cost, O(N) for signals and O(N2) for images, c) it does not have phase uncertainties (i.e., indeterminate phase for a magnitude = 0) as in the case of Discrete and Fast Fourier Transform (DFT, FFT, respectively). Finally, we can apply QSA to a quantum signal, that is, to a qubit stream in order to analyze it spectrally.

This study investigates the suitability of the timestamp approach algorithm for predicting blood pressure (BP) using wearable and comfortable devices, showcasing its accuracy even with low-frequency sampled signals. Developed within the SINTEC European project, the algorithm utilizes Electrocardiogram (ECG) and Photoplethysmogram (PPG) sensors, demonstrating promising results in both laboratory and hospital settings. The research emphasizes the algorithm’s potential to transform continuous and non-invasive BP monitoring through wearable technology, offering frequent measurements with minimal discomfort. While the study shows promise, further exploration is needed, focusing on optimizing machine learning coefficients for long-term monitoring applications and addressing potential changes over time. Technological improvements, including the implementation of edge computing algorithms, hold the key to enhancing BP accuracy, denoising techniques, and integrating alarm systems for future wearable solutions. This study emphasizes the adaptability of the algorithm for diverse healthcare environments, paving the way for broader applications in convenient and reliable BP monitoring.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Knowledge on the function of Connexin-43 on macrophages is gradually increasing and recent studies show how macrophages utilise Connexin-43. Migration, antigen-presentation and some forms of intercellular communication in macrophages are Connexin-43-dependant. Delicate processes, such as electrochemical support in conduction of the heartbeat in the AV-node, immunomodulatory regulation in the lungs and macrophage-differentiation are performed using Connexin-43 in macrophages. The relevance on pathophysiology becomes evident in inflammatory bowel disease, tumour networks and HIV in which aberrant function of Connexin-43 has been observed. Although many physiological, as well as pathophysiological functions were found to be Connexin-43-dependant, some still remain debated: the involvement of Connexin-43 in phagocytosis and polarisation, as well as its involvement in the mortality in murine sepsis are still unclear. These functions as well as further involvement in increasingly complex functions of the macrophage pose possible fields of research.

The Bay of Espirito Santo is located in the Espírito Santo State, in the eastern part of Brazil. It is surrounded by the city of Vitoria on one side and by the Atlantic Ocean on the other. Superficial sediments of Espirito Santo Bay were analyzed at 12 (western shallow silt sediments) + 8 (eastern sandy sediments and relatively deep sampling stations) = 20 uniformly distributed sampling points where geochemical analysis was performed. Nineteen elements were analyzed: Mo, Cu, Pb, Zn, Ag, Ni, Mn, Fe, As, U, Th, Sr, Cd, Sb, Bi, V, Cr, Ba, and Al. This selection was made based on the most representative heavy metals present in this area and according to the results obtained from the geochemical analysis. Their concentrations were compared with metal contamination benchmarks like Screening Quick Reference Tables (SQuiRTs), Effects Range-Low (ERLs) and Effects Range-Median (ERMs), TELs (Threshold Effects Levels), PELs (Probable Effects Levels), ERM (Effects range median), and AETs (Apparent Effects Thresholds). Results indicate that there is no particular pollution condition able to alter the condition of any part of this water body. The Authors conclude that the Espirito Santo Bay is only moderately polluted and some elements are virtually absent.

The Bay of Espirito Santo is located in the Espírito Santo State, in the eastern part of Brazil. It is surrounded by the city of Vitoria on one side and by the Atlantic Ocean on the other. Superficial sediments of Espirito Santo Bay were analyzed at 12 (western shallow silt sediments) + 8 (eastern sandy sediments and relatively deep sampling stations) = 20 uniformly distributed sampling points where geochemical analysis was performed. Nineteen elements were analyzed: Mo, Cu, Pb, Zn, Ag, Ni, Mn, Fe, As, U, Th, Sr, Cd, Sb, Bi, V, Cr, Ba, and Al. This selection was made based on the most representative heavy metals present in this area and according to the results obtained from the geochemical analysis. Their concentrations were compared with metal contamination benchmarks like Screening Quick Reference Tables (SQuiRTs), Effects Range-Low (ERLs) and Effects Range-Median (ERMs), TELs (Threshold Effects Levels), PELs (Probable Effects Levels), ERM (Effects range median), and AETs (Apparent Effects Thresholds). Results indicate that there is no particular pollution condition able to alter the condition of any part of this water body. The Authors conclude that the Espirito Santo Bay is only moderately polluted and some elements are virtually absent.

Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self antigens, respectively. A deep understanding of the biology and functions of type I, II and NKT-like cells as well as their interplay with cell types acting in innate (Neuthrophils, Innate Lymphoid cells, Machrophages and Dendritic cells) and adaptive immunity (CD4+,CD8+ and Double Negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

CAMx-LPiG (Comprehensive Air Quality Model with Extensions – Linear Plume in Grid) is an online hybrid model, based on the Chemistry and Transport Model (CTM) CAMx, that includes a sub-grid scale module to simulate the dispersion of linear road traffic emissions, called LPiG. LPiG is a plume in grid module specifically developed by extending the capabilities of the Lagrangian puff sub-grid model available in CAMx. The online integration of the local scale model within the Eulerian CTM allows for a multiscale simulation of air quality from the regional scale to the urban scale, preserving a coherent description of the chemical state of the atmosphere at all spatial scales and avoiding any double counting of the emissions simulated by the sub-grid module. In this work the model is presented and evaluated against measured NO2 concentrations for the city of Milan for the month of January 2017. The model is able to introduce road traffic induced gradient in NO2 concentration at sub-grid resolution. Moreover, CAMx-LPiG is shown to reduce the bias compared to CAMx stand-alone simulations.

This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.

The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration the cells undergo differentiation changes where a pool of unique stem/precursor cells at the limbus yields the mature cells that reach the corneal center. Differentiation is heralded by the expression of the corneal-specific Krt12. Processing data acquired by scRNA-Seq we found that the increase of Krt12 expression occurs in four distinct steps within the limbus plus a single continuous increase in the cornea. Differential gene analysis demonstrated that these domains reflect discreet stages of CE differentiation and yielded extensive information of the genes undergoing down or up regulation in the sequential transition from less to more differentiate conditions. The approach allowed the identification of multiple gene cohorts, including a) the genes that have maximal expression in the most primitive, Krt12-negative cell cohort, which is likely to include the stem/precursor cells; b) the sets of genes that undergo continuous increase or decrease along the whole differentiation path, and c) and the genes showing maximal positive or negative correlation with the changes in Krt12.

This study aims to investigate a friction stir welded joint between steel and aluminum alloy. Friction stir welding is nowadays one of the most interesting joining technique due to the possibility to connect materials and thicknesses that are difficult or impossible to weld with traditional techniques. The main advantage is that Materials are not affected by thermal cycle problems during solidification and cooling and the absence of fumes and pollution during the process favors the quality of the welded joint. The life of metal joints could be greatly reduced in a corrosive environment, since the less noble material will tend to increase its corrosion rate while the nobler one will reduce its electrochemical dissolution. Accelerated ageing tests (i.e. salt fog test) are used to estimate the lifetime of metal joints in highly aggressive environments. The aim of the present work is to evaluate the durability at long ageing time in salt spray test (according to ASTM B117) of carbon steel/aluminum alloy joints, obtained by FSW. In this first part, mechanical tests results are reported. A deep metallographic and chemical investigation are going to be reported in the part 2.

Friction Stir Welding is a suitable solid-state joining technology to connect dissimilar materials. To produce an effective joint, it requires a phase of optimization which leads to the definition of process parameters such as pin geometry, tool rotational speed, rotation direction, welding speed, thickness of the sheets or tool tilt angle. The aim of this review is to present a complete and detailed frame of the main process parameters and their effect on the final performance of a friction stir welded joint in terms of mechanical properties and microstructure. Particularly, the attention was focused on the connection between different aluminum alloys. Moreover, the experimental results were correlated to the development and the applications of tools, which can effectively use in the design of the manufacturing process, such as finite element analyses, artificial neural networks, statistical studies. The review wants to be also a point of reference to identify the best combinations of process parameters based on the dissimilar aluminum to be joined.

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482

This article provides a systematic review of the crosslinking strategies used to produce microgel particles in microfluidic chips. Various ionic crosslinking methods for gelation of charged pol-ymers are discussed, including external gelation via crosslinkers dissolved or dispersed in the oil phase, internal gelation methods using crosslinkers added to the dispersed phase in their non-active forms, such as chelating agents, photo-acid generators, sparingly soluble or slowly hydrolyzing compounds, and methods involving competitive ligand exchange, rapid mixing of polymer and crosslinking streams, and merging polymer and crosslinker droplets. Covalent crosslinking methods using enzymatic oxidation of modified biopolymers, photo-polymerization of crosslinkable monomers or polymers, and thiol-ene “click” reactions are also discussed, as well as the methods based on sol-gel transitions of stimuli responsive polymers triggered by pH or temperature change. In addition to homogeneous microgel particles, the production of structurally heterogeneous particles such as composite hydrogel particles entrapping droplet interface bi-layers, core-shell particles, organoids, and Janus particles are also discussed. Microfluidics offers the ability to precisely tune chemical composition, size, shape, surface morphology, and internal structure of microgels by bringing in contact multiple fluid streams in a highly controlled fashion using versatile channel geometries and flow configurations and allowing controlled crosslinking.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. A variety of risk factors, such as BMI and age, have been associated with increased risks of gestational diabetes. However, in many cases gestational diabetes occurs in healthy nulliparous women with no obvious risk factors. Emerging data suggest that the tendency to develop gestational diabetes has genetic and environmental components. Here we develop a polygenic risk score for gestational diabetes. We further investigate relationships between the genetic architecture of GDM and genetically constructed risk factors and biomarkers. Our results show that genetics can be used as an early screening tool that identifies at-risk at higher risk of GDM before its onset to propose comprehensive monitoring and preventative programs to mitigate the risks.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Large-scale integration of solar energy technologies in Rome’s built environment epitomizes the needed general adoption of distributed generation via functionalization of buildings of all size and end use across the world, to become active energy generators and no longer energy users only. This paper identifies selected technology solutions and critical policy and educational initiatives to effectively achieve within the next decade (2018-2027) the widespread uptake of decentralized solar energy systems in the built environment on a global scale.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

As customer demand for green products increases in the digital economic era, this study analyses the green innovation of the e-tailer and supplier in drop shipping models. Moreover, drop shipping e-tailers and suppliers with a drop shipping option need to make choices regarding whether to provide green or normal products to the market. When a supplier with a drop shipping option produces green products, more fees may be invested on the production of green products than on normal products. The drop shipping e-tailers and suppliers with a drop shipping option can also choose to sell normal products at a low cost, as before. This study designs four models of drop shipping e-teilers and suppliers with a drop shipping option under different choices, analyzes their operational process in drop shipping models, and investigates five theorems. The optimal pricings decisions and green degree of drop shipping e-tailers and suppliers with a drop shipping option were evaluated in this study. The impacts of the green innovation factor, green elasticity coefficient, manufacturing and distribution costs on the drop shipping e-tailers and suppliers with a drop shipping option, and the effect of other environmental parameters on the green degree of green products are also analyzed through computer simulation. The findings of the simulation analysis provide valuable guidance for e-tailers and suppliers with green innovation in drop shipping models and offer important academic and practical implications for e-commerce and the digital economy.

Whistler mode waves play a major role in regulating the lifetime of trapped electrons in the Earth's radiation belts. Specifically, whistler mode hiss waves are one of the mechanisms that maintains the slot region between the inner and outer radiation belts. The generation mechanism of hiss is a topic still under debate with at least three prominent theories present in the literature. Lightning generated whistlers in their ducted or non-ducted modes, are considered to be one of the possible sources of hiss. We present a study of new observations from the Radio Receiver Instrument (RRI) on the Enhanced Polar Outflow Probe (ePOP: currently known as SWARM-E). RRI consists of two orthogonal dipole antennas, which enables polarization measurements, when the satellite boresight is parallel to the geomagnetic field. Here we present 75 passes of ePOP - RRI from 2014 - 2018, in which lightning whistlers and hiss waves were observed. In more than 50% of those passes hiss is found to co-exist with the lightning whistlers. Moreover, the whistler observations are correlated with observations of wave power at the lower-hybrid resonance. The observations and a whistler mode ray-tracing study suggest that multiple-hop lightning induced whistlers can be a source of hiss and plasma instabilities in the magnetosphere.

The goal of the study presented in this article is to investigate interconnection issues of the Intelligent Electrical Networks (IENs) with the existing ones, as well as the deployment of the appropriate load forecasting demand techniques. The concept of IENs has recently emerged as a potential solution to the global energy problem, due to the more flexible dispersed production units that are involved. In the same context, additional issues, such as the reduction of production-transfer-distribution costs as well as power losses are analyzed as well, via the penetration of Renewable Energy Sources (RESs). To this end, it is necessary to use appropriate advanced infrastructure, where in combination with modern telecommunication networks will make possible the full exploitation of IENs. Moreover, to make the electricity system more efficient, to avoid voltage and frequency imbalance issues and to implement optimal production and consumption planning, the Electric Load Forecast (ELF) is a vital process and plays a key role in the planning as well as in the management of electricity systems. Therefore, recent state of the art approaches in ELF methods are discussed as well.

Irregular female migration to Europe is a growing phenomenon, as more and more women are fleeing their countries of origin due to gender inequality and violence. During the migration process, women experience physical, psychological and social problems that affect their sex lives. The aim of our study is to describe and understand how irregular migrant wom-en living in humanitarian reception centers experience their sexuality at different stages of the migration process. This qualitative phenomenological study collected data through a sixteen in-depth interviews with irregular migrant women between January and February 2023. Data anal-ysis was carried out using ATLAS-ti 23.0 software, from which three themes were extracted: 1) The sexual reality of sub-Saharan women, 2) In search of a better life: take the risk or surrender, and 3) The migrant sexual revolution. The sexual reality of sub-Saharan women is subject to a complex normative order. The migratory process has severe consequences on migrant women's sex life. The sexual needs of irregular migrant women admitted to humanitarian reception cen-ters undergo a process of change that must be understood by healthcare providers in order to make improvements to care provision.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

Reducing the levels of toxic chemicals that cause adverse health and environmental impacts is a challenge for the international community. There is a need of a global strategy. Indeed, too often the problems associated to the exposure of chemical substances is recognized a posteriori, in the presence of consequences already observed. The prediction of the likely effects of chemical exposure on human health is based on classical tests with animals, which are time and money consuming, may deviate from an accurate prediction towards humans, and arises ethical concerns. Regulations are now considering the adoption of in silico (or computational) methods, which can be used for prioritizing substances according to the probability to be toxic for the biosphere. Several initiatives have prioritized chemicals, typically based according to some criteria, such as chemicals which may be endocrine disruptors, or persistent, bioaccumulative, or toxic (PBT). However, these initiatives focused on a certain range of adverse properties, and covered a certain number of substances only. We applied a set of largely validated and widely used predictive methods to large collections of chemicals: (i) to about 340,000 with a defined function, and (ii) to about 6 millions, which have been synthetized. The aim of this study is to quantify the putative impact of existing and future chemicals on towards human health, ecological and environment properties. The impact on the environment is the cause of major concern. This is the case of pesticides and hazardous, which is quite expected; however, also pharmacologically active candidate compounds of natural origin may have a high level of ecotoxicity. Pesticides and hazardous are also the categories of higher concern for humans, followed by pharmaceuticals. The pesticides and the hazardous are the categories of higher concern also on the environmental point of view. The results of our analysis could be the basis for the identification of new safety rules.

This review article seeks to systematically identify appropriate ways to measure managerial skills. The systematic literature review was conducted according to the criteria in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide, and the eligibility criteria were declared through the PICOS tool (population, interventions, comparators, outcomes and study); a tool based on 6,803 records identified bibliometrically in the Web of Science database. The literature review stages determined a reduced set of articles that presented valid and reliable measurement scales covering some determinant constructs on managerial skills for employability such as fundamental, emotional, managerial, leadership, decision-making, communication and teamwork skills.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family - E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be dif-ferent. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that E. radiata EAq was effective against all three strains, while E. cinerea EAq was only effective against E. coli. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a pro-tein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 75% at a concentration of 250 g/ml, significantly higher than the placebo. Ellagic acid, a pri-mary phytochemical found in the extracts, demonstrated noteworthy toxic and pharmacokinetic characteristics and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in sili-co. The study suggests that the extracts and their primary phytochemicals could enhance the effi-cacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As phar-maceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.

Bangladesh's railway system mostly uses typical manual railway crossing technique or boom gates through its 2,955.53 km rail route all over the country. The accidents are frequently happening in the railway crossings due to not having obstacle detectable and quickly operating gate systems, and also for fewer safety measures in the railway crossing. Currently, there are very few automatic railway crossing systems (without obstacle detectors) available, however, all of them are dependent on the national power grid without a backup plan for any emergency cases. Bangladesh is still running a bit behind in the power generation of its consumption, hence it is not possible to have a continuous power supply at all times all over the countryside. We aim to design and develop a smart railway crossing system with an obstacle detector to prevent common types of accidents in the railway crossing points. We design to use two infrared (IR) sensors to operate the railway crossing systems which will be controlled by the Arduino Uno. This newly designed level crossing system will be run with the help of sustainable renewable energy which is cost-effective, eco-friendly, and apply under the national green energy policy towards achieving sustainable development in Bangladesh as a part of the global sustainable goal to face climate change challenges. We have summarized the simulated results of several renewable energy sources including a hybrid system and optimized the Levelized Cost of Energy (LCOE), and the payback periods.

In addition to CD4+ T lymphocytes, myeloid cells, and, particularly, differentiated macrophages, are targets of the human immunodeficiency virus type-1 (HIV-1) infection via interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication although with substantial differences. In contrast to activated CD4+ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing of curtailing virus replication in macrophages and T cells particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factor determining restriction or reactivation of virus replication in myeloid cells.

AbstractBackground: In digitalization era, health care system was conditioned with the health worker’s ability to adapt media of digital technology. Digital technology media was used to strengthening and fasted the health care for patient and community. Aims: This study aimed to explore the accurate information of health professional utilization digital technology during doing the job at the health facilities in Timor-Leste. Methods: This study was used correctional study with 56 respondents was participated in the study. Was collected the data from 1 to 30 February 2023. Was used questioner of google form based for data collection. Data collection was distributed via online with google form to social media as WhatsApp’s, email and face book and twitter to completed by respondents. The inclusive Criteria are: health professional living in Timor-Leste, to able response the questioner. Was used descriptive analysis in this study. Finding: This study was indicated that majority of health professional was participated in the study as 54,2% man then women have 45,8%. About 100% health professional used hand phone to facilitate their daily activities including related with their work activities. Other side indicated in digital technology tools use are able to use Microsoft word is 78,3%, able to use Microsoft Excel is 76,7% and able to use Power Point is 81,7%. E-mail use about 89,2%, WhatsApp’s use 81,7%, About 74,2% was used zoom/webinars/Google meet application, about 72,5% sad that they were used computer in the work place until now. Around 96.4% need to improve or deepen their knowledge and skills in using ICT in the future to facilitate they are activity. Conclusion: Majority of health professional in Timor-Leste was used the computer, internet, hand phone in daily activities. Majority need to gate the training to improve their knowledge, attitude and psychomotor in the future.

Driven by the rapid uptake of battery electric vehicles, Li-ion power batteries are increasingly reused in stationary energy storage systems, and eventually recycled to recover all the valued components. Offering an updated global perspective, this study provides a circular economy insight on lithium-ion battery reuse and recycling.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Background Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on people and society. The study's goal is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, lipid profiles, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects, divided into control D1: Diabetics without cardiovascular issues. D2: Diabetics with heart disease. D3: Diabetics with stroke. D4: Diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia, defined as elevated levels of total cholesterol, triglycerides, LDL, HDL, and VLDL, as well as uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM, were linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 75.4% of the population, with greater rates among the elderly. Stage 2 hypertension was more prevalent in all age groups. Apolipoprotein E gene polymorphism was discovered, with genotypes 3/3, 4/4, 2/3, and 3/4 being the most prevalent. Genotype 3/4 was more common in diabetics who had IHD/stroke or both problems, whereas genotype 2/3 was linked to DM and stroke. Conclusion: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in diabetic patients by affecting the lipid profile.

Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Raman spectroscopy (RS) turns out to be a promising tool for cancer di- agnosis. In particular, in the last years several studies have demonstrated how the diagnostic performances of Raman Spectroscopy can be significantly improved by employing Machine Learning (ML) algorithms for the interpre- tation of Raman-based data. In line with these findings, in this paper, we demonstrated how RS coupled with ML allowed to accurately distinguish the three grades of Chondrosarcoma and to distinguish Chondrosarcoma and a benign counterpart called Enchondroma. We obtained such results by ana- lyzing a dataset composed of a relatively small number of Raman spectra, collected in a previous study. Such spectra were acquired from micromet- ric tissue sections with a Confocal Raman Microscope. In particular, we tested the classification performances of a Support Vector Machine and a Random Forest Classifier, as representative of Machine Learning, and two versions of the Multi-Layer Perceptron, as representative of Deep Learning (DL). These models showed excellent classification performances, especially those belonging to DL, with accuracy reaching 99.7%. This outcome makes the aforementioned models a promising route for future improvements of di- agnostic devices focused on detecting bone cancerous tissues. In addition, we highlighted how the ML models studied resulted in slightly worse classifi- cation performances in comparison to DL. Alongside the diagnostic purpose, the aforementioned approach allowed to identify characteristic molecules, i. e. amino acids, nucleic acids and bioapatites, relevant for the obtainment of the final diagnostic response, through the analysis of the so-called Per- mutation Feature Importance. Permutation Feature Importance could hence represent a promising parameter for the understanding of the biochemical processes on the basis of the tumor progression. In turn, the spectral bands highlighted by Permutation Feature Importance could represent precious in- dicators in the attempt to restrict the spectral acquisition to specific Raman bands. This last objective could help to reduce the amount of experimental data needed to obtain an accurate final grading outcome, with consequent reduction of the computational cost.

Objectives We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods Retrospective cohort study of 3319 individuals who received Acamprosate® in the East of Scotland in a 10-year period using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. Primary outcome was adherence between one to six months of initiating Acamprosate® medication. Secondary outcome was all cause morbidities and mortality. Results Of the total 3319 individuals identified, good adherence index of >80% was found in 59% of those prescribed Acamprosate® after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (HR1.2), medical morbidities especially neoplasm (HR 4.1|) and poisoning (HR 1.4) and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of Acamprosate® treatment. Discussion and Conclusions Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to Acamprosate® and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.

Variability is the predisposition of the elements in systems to assume different values over time and space. In biology, the variability is basic to explain differences and development in organisms but in the fields of scientific and technological information, the effects of variability on evolutionary dynamics of disciplines and technologies are unknown. In a broad analogy with the principles of biology, the variability within research fields can be a central argument to explain trajectories in scientific development and technological evolution. The purpose of the present study is to see whether statistical evidence supports the general hypothesis that the rate of growth in technologies can be explained by the level of variability in scientific fields and with this principal goal to analyze the relation between scientific variability and rate of growth in technologies. Proposed hypothesis of scientific variability here endeavors to explain basic sources of scientific development and technological evolution to lay the foundations for a general theory. The test here is based on emerging research fields of quantum technologies: Quantum Imaging, Quantum Meteorology, Quantum Sensing and Quantum Optics. A preliminary statistical evidence seems in general to support the hypothesis stated that the rate of growth in technological fields can be explained by the level of scientific variability in research fields, measured with relative entropy index. Nonparametric correlation based on Spearman’s rho shows a positive coefficient of 0.80 of these variables; linear model of the rate of technological growth = f(scientific variability) reveals a coefficient of regression equal to 1.63 (R²=0.60). Findings here suggest a general law that scientific variability positively drives scientific development and technological evolution. In particular, a higher variability within research fields can support scientific development and a high rate of growth in technological evolution (measured with scientific and technological information). Proposed hypothesis of scientific variability is especially relevant in environments of rapid change to explain determinants and dynamics of technological change within a general theoretical framework that supports technological management and forecasting of promising innovations.

A proposed interpretation of the characteristics and causes of the variation in science dynamics for technological evolution is described. The theoretical approach focuses on variability in research topics that guide scientific and technological evolution. Statistical method verifies the proposed approach by applying entropy, measures of dispersion and variance decomposition. The statistical evidence, using data of four main research fields in quantum technologies, suggests the following empirical properties: a) the growth of heterogeneity in research topics is inversely proportional to the age of research fields: recent research fields have a higher variability between topics with uncertainty in evolutionary dynamics, whereas older research fields have a lower variability and more concentration in specific research topics with stable evolution towards clear directions; b) the nature of research fields has a systematic effects in variability guiding the evolution of technologies. The theoretical approach and findings clarify main characteristics and causes of the evolution of science and technologies considering the underlying homogeneity or heterogeneity in research topics, providing main implications to improve the scientific and technological forecasting that may support appropriate R&amp;D investments towards promising research fields and technologies

True randomness is necessary for the security of any cryptographic protocol, including quantum key distribution (QKD). In QKD transceivers, randomness is supplied by one or more local private entropy sources of quantum origin, which can be either passive (e.g. a beam splitter) or active (e.g. an electronic quantum random number generator). In order to understand better the role of randomness in QKD we revisit the well-known "detector blinding" attack on BB84 QKD protocol, which utilizes strong light to achieve an undetectable and complete recovery of the secret key. We present two findings. First, we show that the detector blinding attack is in fact an attack on the receiver’s local entropy source. Second, based on this insight, we propose a modified receiver station and a statistical criterion which together enable robust detection of any bright-light attack and thus restore security.

Preprints are regularly cited in peer reviewed journal articles, books and conference paper. Are preprint citations somehow less important than citations to peer reviewed research papers? This study investigates citation patterns between 2017 and 2020 for preprints published in three preprint servers, one specializing in biology (bioRxiv), one in chemistry (ChemRxiv), and another hosting preprints in all disciplines (Research Square). As evaluation of scholarship continues to largely rely on citation-based metrics, this analysis and its outcomes will be useful to inform new research-based education in today’s scholarly communication.

In most world’s countries, scholarship evaluation for tenure and promotion continues to rely on conventional criteria of publications in journals of high impact factor and grant funding. Continuing to hire and promote scholars for their achievements in research and in securing research funds exposes universities at risk because students, directly and indirectly through government funds, are the main source of revenues for academic institutions, whereas talented young researchers are those who actually carry out most of the published research. Purposeful scholarship evaluation needs to include all three areas of scholarly activity: research, teaching and mentoring, and service to society. Young scholars seeking tenure and promotion benefit from the practice of open science because it provides better and more impactful results with respect to each of the three areas of scholarship.

In the digital era in which over 4 billion people regularly access the internet, the conventional process of publishing scientific articles in academic journals following peer review is undergoing profound changes. Following physics and mathematics scholars who started to publish their work on the freely accessible arXiv server in the early 1990s, researchers of all disciplines increasingly publish scientific articles in the form of freely accessible and fully citeable preprints before or in parallel to conventional submission to academic journals for peer review. The full transition to open science, I argue in this study, requires to expand the education of students and young researchers to include scholarly communication in the digital era.

Sharing the same raw material, recycling and composting are in direct conflict with incineration of municipal solid waste in combined heath and power plants. Indeed, waste-to-energy plants in regions with high recycling rates import urban waste from other countries to use otherwise unused capacity, and raise revenues. Using the case of Italy’s second largest and economically most developed region, I discuss the economic viability of municipal solid waste incineration to produce electricity and heath in the context of the increasing role of electricity production from renewable energy sources as well as of the emerging mass-scale uptake of bioplastics. Four lessons and three guidelines aimed to local authorities and policy makers emerge from the present study.

During the last 25 years the scientific community has coexisted with the most fascinating protocol due to Quantum Physics: quantum teleportation (QTele), which would have been impossible if quantum entanglement, so questioned by Einstein, did not exist. In this work, a complete architecture for the teleportation of Computational Basis States (CBS) is presented. Such CBS will represent each of the possible 24 classical bits commonly used to encode every pixel of a 3-color-channel-image (red-green-blue, or cyan-yellow-magenta). For this purpose, a couple of interfaces: classical-to-quantum (Cl2Qu) and quantum-to-classical (Qu2Cl) are presented with two versions of the teleportation protocol: standard and simplified.

During the last century, entanglement was the bone of contention between the two main pillars of Physics: General Relativity (GR) and Quantum Mechanics (QM). This began in 1935 with the Einstein-Podolsky-Rosen paradox (EPR paradox) which concluded that although Quantum Mechanics is not wrong, it is an incomplete theory to represent physical reality. In this paper it is demonstrated that some byproducts resulting from entanglement and which we will call avatars act as a hinge that link both theories making the completeness of QM clear. Moreover, a thorough analysis of the non-locality of this effect will be carried out. Besides, it is demonstrated that entanglement is an instantaneous phenomenon and that it does not require the use of a superluminal signaling for this purpose. Finally, the avatars will also appear in each wormhole resulting from an entanglement process (WREP) demonstrating that they are traversable with an equivalent path of null length which can be crossed in a null time with all that this implies in Quantum Communications.

A simplified version of the quantum teleportation protocol is presented in here. Its experimental confirmation will have deep implications for a better understanding of Quantum Entanglement with a particular projection on Quantum Communications.

On June 8 and June 9, 2017, we gave two invited lectures at the Zelinsky Institute of Organic Chemistry (ZIOC) of the Russian Academy of Sciences, Moscow. The first lecture, “Sol-Gel Catalysts: Making Green Chemistry Possible”, focused on the practical outcomes of 25 years of research on sol-gel entrapped catalysts. The second, “Chemistry for the Bioeconomy: From Discussion to Action”, offered a critical insight to the forthcoming bioeconomy. Both lectures aroused much interest in the audience and ended with a vigorous discussion lasting about one hour. An outlook is provided herein.

Solar green roofs, namely rooftops functionalized with properly selected living vegetation and photovoltaic modules, achieve an ideal symbiotic relationship in which promotion of biodiversity and onsite renewable energy production are both enhanced whereas the roof provides a wide range of environmental, health, aesthetic and economic benefits. This study provides a unified outlook of this eminent sustainable technology at the dawn of its uptake across the world, especially in polluted urban areas.

The Leguminosae (legume family) is divided into three sub-families, the Caesalpiniodeae, Mimosoideae and Papilionoideae. Here, the literature on legume-rhizobia symbioses was reviewed, and genotypically characterised rhizobia related to the taxonomy of the legumes they were isolated from. Only data from field soils were considered. The objective of the work was to assess to what extent legume specificity for rhizobial symbiont is related to legume taxonomy. Bradyrhizobium spp. were the exclusive rhizobial symbionts of species in the Caesalpinioideae but data are limited. Where tested, species within the two Mimosoideae tribes, Ingeae and Mimoseae were nodulated by different rhizobial genera. Generally, Papilionoideae species with indeterminate nodules were promiscuous in relation to rhizobial symbionts but high specificity for rhizobial partners appears to hold at tribe level for the Fabeae (Rhizobium spp.), genus level for Medicago (Ensifer spp.), Cytisus (Bradyrhizobium spp.) and Lupinus (Bradyrhizobium spp.), and species level for Galega spp. (Neorhizobium galegeae), Hedysarum coronarium (Rhizobium sullae), Cicer arietinum (Mesorhizobium spp.) and New Zealand native Sophora spp. (Mesorhizobium spp.). High legume specificity for rhizobial symbionts was linked to specific rhizobial symbiosis genes. For Papilionoideae species with determinate nodules, the Dalbergieae were primarily nodulated by Bradyrhizobium but were promiscuous with respect to Bradyrhizobium spp. while those in the Desmodieae, Phaseoleae, Psoraleae and Loteae were promiscuous across different rhizobial genera. Possible advantages and disadvantages of high specificity or promiscuity are discussed.

There have been beaching events of the marine alga pelagic sargassum in coastal regions of the Caribbean Sea, West African countries, and the north-northeast region of Brazil since 2011. Its presence has caused environmental and socioeconomic impacts while several studies were conducted in order to understand the causes of this phenomenon, as well as alternatives to mitigate its impacts. The objective of this research was to evaluate pelagic sargassum biomass as a raw material for the manufacture of medium-density multilayer particleboards. These are composed of 30% sargassum particles in their inner layer and 70% sugarcane bagasse particles on their outer layers which are bonded with castor oil-based polyurethane resin. A physical and chemical characterization was carried out in order to evaluate sargassum particles while physical and mechanical tests were carried out in order to evaluate the panels. Results were subsequently compared with indications from NBR 14810-2:2018 and ISO 16893:2016 standards. A life cycle assessment based on ISO 14040:2006 and 14044:2006 was carried out as to complement the feasibility study of these panels and to compare their different manufacturing processes. The multilayer panels met the minimum requirements for physical and mechanical properties established by regulations, indicating that the Sargassum spp. biomass can be used as filling. The life cycle assessment study indicates that sargassum panels produced in the Belém-PA-Brazil region present lower environmental impacts in four of seven evaluated categories when compared to conventional panels. As such, they constitute an alternative way to mitigate environmental impacts generated by beaching events.

Hydroxychloroquine, a known antiviral metabolite of chloroquine, is increasingly used along with antibiotic azithromycin for the treatment of COVID-19 infection. In about one month India, the world’s largest manufacturer, delivered hydroxychloroquine for treating COVID-19 to over 50 countries. The therapy is being used across the world both for patients staying at home at the early phase of symptoms, as well as for patients hospitalized. We summarize achievements as of late April 2020, review possible modes of action and suggest avenues for the quick scale-up of production of hydroxychloroquine.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

The natural distribution of stress in the femur is altered when total hip arthroplasty (THA) is performed. In fact, when a stem is inserted inside the femur, there is a variation in stress due to the difference in rigidity between the material with which the stem is made and the femur. This generates the phenomenon of stress-shielding. The aim of this study is to design an optimized prosthesis that guarantees excellent rotational stability and re-duced stress shielding. Methods: through the finite element method (FEM) the mechanical behavior of the stem subjected to the loads described by ISO 7206-4: 2010 is studied. Re-sults: Through topological optimization, there is a reduction in stress shielding in the proximal zone of 31.46%. The addition of ridges on the dorsal side of the stem also im-proves rotational stability by 27.82%. Conclusions: The decrease in stiffness that is rec-orded with the optimized stem, guarantees a greater distribution of stress on the bone. The presence of dorsal ridges also favors the corticalization of the bone as it loads the bone near the dorsal ensuring further stability. The perforated prosthesis presented in this study, shows an increase in primary stability and an improvement in rotational stability. As there is also a bone regrowth inside the prosthesis.