Purpose: The study is aimed to quantify the effects of social noise (personal music players (PMP), high-intensity noise exposure events) and road traffic noise exposures in the sample of Slovak university students living and studying in Bratislava. Methods: There were 1,003 university students (306 males and 697 females, average age 23.13±2) enrolled in the study; 347 lived in the student housing facility exposed to road traffic noise (LAeq =67.6 dB) and 656 in the control one (LAeq =53.4 dB). Respondents completed a validated ICBEN 5-grade scale “Noise annoyance questionnaire”. The exposure to PMP was objectified by the conversion of the subjective evaluation of the volume setting and duration. With the cooperation of the ENT specialist, we arranged audiometric examinations on the pilot sample of 41 volunteers. Results: From the total sample of 1,003 students, 794 (79.16 %) of them reported the use of PMP in the course of the last week; average time of 285 minutes. There was a significant difference in PMP use between the exposed (85.59 %) and the control group (75.76 %) (p=0.01). Among PMP users 30.7 % exceeded the LAV (lower action value for industry LAeq,8h = 80 dB). On a pilot sample of volunteers (n=41) audiometry testing was performed indicating a hearing threshold shift at higher frequencies in 22% of subjects. Conclusions: The results of the study on a sample of young healthy individuals showed the importance of exposure to environmental noise from different sources (transportation, neighborhood, construction, entertainment facilities, etc.) as well as social noise and the need for prevention and intervention.

Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

In our recently proposed theory of quantum gravity, a black hole arises from the spontaneous localisation of an entangled state of a large number of atoms of space-time-matter [STM]. Prior to localisation, the non-commutative curvature of an STM atom is described by the spectral action of non-commutative geometry. By using the techniques of statistical thermodynamics from trace dynamics, we show that the gravitational entropy of a Schwarzschild black hole results from the microstates of the entangled STM atoms and is given (subject to certain assumptions) by the classical Euclidean gravitational action. This action, in turn, equals the Bekenstein-Hawking entropy (Area/$4{L_P}^2$) of the black hole. We argue that spontaneous localisation is related to black-hole evaporation through the fluctuation-dissipation theorem.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Although most biological processes are characterized by a strong temporal asymmetry, several popular mathematical models neglect this issue. Maximum entropy methods provide a principled way of addressing time irreversibility, which leverages powerful results and ideas from the3literature of non-equilibrium statistical mechanics. This article provides a comprehensive overview of these issues, with a focus in the case of spike train statistics. We provide a detailed account of the5mathematical foundations and work out examples to illustrate the key concepts and results from non-equilibrium statistical mechanics

We evaluate the complexity of Colombian climate from extreme behavior of gauge temperature and precipitation, using the the novel Tsallis' non-extensive entropy principle based on physical information through the q-index. We find the spatial structure of non additive universal categories (q-index) and compare with some complex systems with the potential to have some degree of dynamical affinity. Our results evidence the great dynamical variability of regional climate expressed in the large range of values of $q$-index, and the high degree of non-extensitivity for both temperature and precipitation.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

Within the fields of English for Academic Purposes (EAP) and English for Research Publication Purposes (ERPP), there is an unquestioned orthodoxy that scholars with English as an Additional Language (EAL) are particularly disadvantaged by the pressure to publish in English (though see Kuteeva 2015 and debate between Hyland 2016a, 2016b and Politzer-Ahlesa et al. 2016). In this paper, I challenge this orthodoxy, raising questions about the evidence upon which it is based. Within a framework of ‘verbal hygiene’ (Cameron 1995, 2012), I will argue that the attention accorded to ‘non-nativeness’ may be disproportionate to its significance for publication success. I conclude by proposing some reorientations for researchers and practitioners in the field that centre on broadening the scope to encompass non-linguistic structures of inequity.

This paper considers a non-mixture cure model for right censored data. It utilizes the maximum likelihood method to estimate model parameters in the non-mixture cure model. The simulation study is based on Fréchet susceptible distribution to evaluate the performance of the method. Comparing with Weibull and exponentiated exponential distributions, the non-mixture Fréchet distribution is shown to be the best in modeling a real data on allogeneic marrow HLA-matched donors and ECOG phase III clinical trial e1684 data.

Field and numerical investigations at Happisburgh, East coast of England, UK, sought to characterize beach thickness and determine geologic framework controls on coastal change. After a major failure of coastal protection infrastructure, removal of about 1 km of coastal defense along the otherwise protected cliffed coastline of Happisburgh triggered a period of rapid erosion over 20 years of ca. 140 m. Previous sensitivity studies suggested that that beach thickness plays a major role in coastal recession. These studies were limited, however, by a lack of beach volume data. In this study, we have integrated the insights gained from our understanding of the Quaternary geology of the area, a novel non-intrusive passive seismic survey method, and a 3D novel representation of the subsurface source and transportable material into a coastal modelling environment to explore the role of beach thickness on the back wearing and down wearing of the cliffs and consolidated platform, respectively. Results show that beach thickness is non-homogeneous along the study site: we estimate that the contribution to nearshore sediment budget via platform down wearing is of a similar order of magnitude as sediment lost from the beach and therefore non-negligible. We have provided a range of evidence to support the idea that the Happisburgh beach is a relatively thin layer perched on a sediment rich platform of sand and gravel. This conceptualization differs from previous publications, which assumes that the platform was mostly till and fine material. This has direct implication on the regional sediment management of along this coastline. The present study contributes to our understanding of a poorly known aspect of coastal sediment budgeting and outlines a quantitative approach that allows for simple integration of geological understanding for coastline evolution assessments worldwide.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

RNAi is considered a major antiviral defense mechanism in insects but its relative importance compared to other antiviral pathways has not been evaluated comprehensively. Here, it is attempted to give an overview of the antiviral defense mechanisms in Drosophila that involve both RNAi and non-RNAi to acquire a sense of their relative importance. While RNAi is considered important in most viral infections, many other pathways can exist that confer antiviral resistance. It is noted that very few direct recognition mechanisms of virus infections have been identified in Drosophila and that the activation of immune pathways may be accomplished indirectly through cell damage incurred by viral replication. In several cases, protection against viral infection can be obtained in RNAi mutants by non-RNAi mechanisms, confirming the variability of the RNAi defense mechanism according to the type of infection and the physiological status of the host. This analysis invites to investigate more systematically the relative contribution of RNAi in the antiviral response and more specifically to ask whether RNAi efficiency is affected when other defense mechanisms predominate. While Drosophila can function as a useful model, this issue may be more critical for economically important insects that are either controlled (agricultural pests and vectors of diseases) or protected from parasite infection (beneficial insects as bees) by RNAi products.

Developing efficient Artificial Intelligence (AI)-enabled system to substitute human role in non-destructive testing is an emerging topic of considerable interest. In this study, we propose a novel impact-echo analysis system using online machine learning, which aims at achieving near-human performance for assessment of concrete structures. Current computerized impact-echo systems commonly employ lab-scale data to validate the models. In practice, however, the echo patterns can be far more complicated due to varying geometric shapes and materials of structures. To deal with a large variety of unseen data, we propose a sequential treatment for echo characterization. More specifically, the proposed system can adaptively update itself to approaching human performance in impact-echo data interpretation. To this end, a two-stage framework has been introduced, including echo feature extraction and the model updating scheme. Various state-of-the-art online learning algorithms have been reviewed and evaluated for the task. To conduct experimental validation, we collected 10,940 echo instances from multiple inspection sites with each sample had been annotated by human experts with healthy/defective condition labels. The results demonstrated that the proposed scheme achieved favorable echo pattern classification accuracy with high efficiency and low computation load.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

The present essay illustrates the methodological and theoretical premises of an emerging research area carrying out both ethological and (bio)ethical implications: the ethology of the freed animal (EFA). Unlike existing ethological fields, EFA focuses neither on non human (NH) animals in natural conditions of freedom in their own environment, nor on NH animals kept in conditions of “captivity”. Rather, EFA consists of a comparative study of NH animals that are released from a condition of more or less abusive captivity and instead relocated in an environment more appropriate to their species-specific and individual characteristics and inclinations. Ideal places for this study are contexts like “Animal sanctuaries” and parks/reserves provided with a camp or station for researchers, where a previously-captive NH animal can be reintroduced in his/her natural habitat. Even though EFA exists already, as a de facto practice of the specialized and/or volunteer personnel running sanctuaries and parks, the field still lacks a recognizable scholarly paradigm, and it is yet to be acknowledged at institutional/academic level. By consequence, one important aim for creating a field like this lies in the establishment of an active interaction between the two parties involved (researchers and sanctuaries/parks operators).

Most of the pore-scale imaging and simulations of non-Newtonian fluid are based on the simplifying geometry of network modeling and overlook the fluid rheology and heat transfer. In the present paper, we developed a non-isothermal and non-Newtonian numerical model of the flow properties at pore-scale by direct simulation of the 3D micro-CT images using a Finite Volume Method (FVM). The numerical model is based on the resolution of the momentum and energy conservation equations. Owing to an adaptive meshing technique and appropriate boundary conditions, rock permeability and mobility are accurately computed. A temperature and concentration-dependent power-law viscosity model in line with the experimental measurement of the fluid rheology is adopted. The model is first applied at isothermal condition to 2 benchmark samples, namely Fontainebleau sandstone and Grosmont carbonate, and is found to be in good agreement with the Lattice Boltzmann method (LBM). Finally, at non-isothermal conditions, an effective mobility is introduced that enables to perform a numerical sensitivity study to fluid rheology, heat transfer, and operating conditions. While the mobility seems to evolve linearly with polymer concentration, the effect of the temperature seems negligible by comparison. However, a sharp contrast is found between carbonate and sandstone under the effect of a constant temperature gradient. Besides concerning the flow index and consistency factor, a good master curve is derived when normalizing the mobility for both the carbonate and the sandstone.

This work updates the characterization of winter fish communities in salt marsh areas of Guadiana estuary (SE-Portugal) and discusses the potential risks of habitat dominance by a non-indigenous species (NIS). To this effect, six field campaigns were carried out during winter season targeting the collection of fish species. Individuals from seven different families (marine and estuarine) were collected although the community was dominated by two estuarine species – the native Pomatoschistus sp. (goby) and the NIS Fundulus heteroclitus (mummichog). Goby controlled the majority of salt marsh habitats, except one specific, marsh pool, where extreme environmental conditions were registered, namely high temperature and salinity. Such conditions may have boosted the intrusion of mummichog in this area. This species is well adapted to a wide range of abiotic factors enabling them to colonize habitats where no predators inhabit. Impacts of mummichog intrusion in the Guadiana salt marsh area are still unpredictable since this is the first recorded in such high density. Nevertheless, in scenarios of increased anthropogenic pressure and, consequently, habitat degradation, there is a potential risk of mummichog spread to other habitats and therefore compete for space and food resources with native species.

Remote sensing image registration plays an important role in military and civilian fields, such as natural disaster damage assessment, military damage assessment and ground targets identification, etc. However, due to the ground relief variations and imaging viewpoint changes, non-rigid geometric distortion occurs between remote sensing images with different viewpoint, which further increases the difficulty of remote sensing image registration. To address the problem, we propose a multi-viewpoint remote sensing image registration method which contains the following contributions. (i) A multiple features based finite mixture model is constructed for dealing with different types of image features. (ii) Three features are combined and substituted into the mixture model to form a feature complementation, i.e., the Euclidean distance and shape context are used to measure the similarity of geometric structure, and the SIFT (scale-invariant feature transform) distance which is endowed with the intensity information is used to measure the scale space extrema. (iii) To prevent the ill-posed problem, a geometric constraint term is introduced into the L2E-based energy function for better behaving the non-rigid transformation. We evaluated the performances of the proposed method by three series of remote sensing images obtained from the unmanned aerial vehicle (UAV) and Google Earth, and compared with five state-of-the-art methods where our method shows the best alignments in most cases.

The performance of modified electrode of nanocomposite film consisting of polypyrrole-chitosan-titanium dioxide (Ppy-CS-TiO2) has been explored as non-enzymatic glucose biosensors. The synergy effect of TiO2 nanoparticles and conducting polymer on the current response of electrode resulted in higher sensitivity for nanocomposite modified electrode. The incorporation of TiO2 nanoparticles in the nanocomposite films were confirmed by XPS spectra. The FESEM and HR-TEM provided more evidences for the presence of TiO2 in Ppy-CS structure. Glucose biosensing properties were determined by amperommetry and cyclic voltammetry (CV) methods. The interfacial properties of nanocomposite electrodes were studied by electrochemical impedance spectroscopy (EIS). The developed biosensors showed a good sensitivity over the liner range of 1-14 mM with a detection limit of 614 μM for glucose. It also exhibited good selectivity and long term stability with no interference effect. The Ppy-CS-TiO2 nanocomposites film presented high electron transfer kinetics.

MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.

Non-suicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

In the present paper, the effect of the non-linear thermal radiation on the neutral gas mixture in the unsteady state is investigated for the first time. The unsteady BGK technique of the Boltzmann kinetic equations for a neutral non-homogenous gas is solved. The solution of the unsteady case makes the problem more general significance than the stationary one. For this purpose, the moments' method, together with the traveling wave method, is applied. The temperature and concentration are calculated for each gas component and mixture for the first time.Furthermore, the study is held for aboard range of temperatures ratio parameter and a wide range of the molar fraction. The distribution functions are calculated for each gas component and the gas mixture. The significant non-equilibrium irreversible thermodynamic characteristics the entire system is acquired analytically. That technic allows us to investigate the consistency of Boltzmann's H-theorem, Le Chatelier principle, and thermodynamics laws. Moreover, the ratios among the different participation of the internal energy alteration are evaluated via the Gibbs formula of total energy. The final results are utilized to the argon-helium non-homogenous gas at different magnitudes of radiation force strength and molar fraction parameters. 3D-graphics are presented to predict the behavior of the calculated variables, and the obtained results are theoretically discussed.

This study investigates the impact of fintech, particularly blockchain technology and non-fungible tokens (NFTs), on the art market. As fintech has been widely accepted, the art market has undergone transformations, including increased transaction transparency, enhanced liquidity, improved risk management capabilities, reduced entry barriers to the market, and more developed copyright protection. Using a Vector Autoregression (VAR) model, this paper clarifies the significant effects of fintech, especially the NFTs, on the size and profitability of the art market. The findings not only emphasize the importance of NFTs in developing the art market and increasing investment returns but also provide insights and constructive suggestions for the future growth and sustainable development of the art market. By fostering transparency, efficiency, and accessibility, fintech contributes to a more resilient and sustainable art market, ensuring its long-term prosperity and cultural enrichment.

Splenic rupture and hematoma are significant complications that can arise in patients with non-Hodgkin lymphoma (NHL). Understanding these associations is essential for optimal patient management and patients' enhancing outcomes. Histopathological and immunohistochemistry analyses are crucial in diagnosing NHL and assessing splenic involvement. A judicial autopsy was requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from the gurney, reporting a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. Abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy, but the patient showed signs of hemodynamic shock and subsequently died. The evidence emerging from the autopsy allowed us to diagnose a Mantle Cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess splenic rupture's diagnosis and time estimation. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering underlying hematological malignancies when investigating delayed splenic rupture. Immunohistochemical study of spleen samples allowed the assessment of the timing of splenic hematoma and rupture, leading to establishing a causal relationship with trauma.

Forest resources are renewable,rational exploitation and utilization of forest resources are not only conducive to sustainable development of population, but also can obtain higher economic benefits. Based on actual timber harvesting problems,a combined harvesting model of timber and non-timber with nonlinear harvesting term was established.Firstly, using the qualitative theory of ordinary differential equations, the dynamic behavior of the model is studied, and the existence and stability of the equilibrium point of the model are proved .Secondly, the optimal control solution is obtained by using the optimal control theory.Finally, the optimal harvesting strategy of timber and non-timber products is given based on the numerical simulation results, which provides a certain theoretical basis for the sustainable development of forestry ecological economy.

Mexico is a well-known seismically active country, which is primarily affected by several tectonic plate interactions along the southern Pacific coastline and by active structures in the Gulf of Baja California. In this paper we investigate this seismicity in the context of a non-extensive statistical approach based on Tsallis entropy. The analysis is performed using data from the corrected Mexican seismic catalogue provided by the National Seismic Service, spanning a period from January 2000 to October 2023. The Gutenberg-Richter law fitting to the earthquake sub-catalogues for all six regions studied indicates magnitudes of completeness between 3.30 and 3.76. All six regions display values of the entropic index in the range 1.52≲q≲1.61, which are lower than the previously estimated range 1.54≲q≲1.70 using catalogue data from 1988 to 2010. The cause of this discrepancy is certainly due to the use of modern recording devices, which are sensitive enough to detect a larger number of low-magnitude events compared to older instrumentation.

(1) Background: The aim of the research was to present and emphasize the importance of magnetic resonance imaging (MRI) in diagnosing Achilles tendon (AT) ruptures by presenting case reports. (2) Materials and Methods: The sample of respondents included 7 patients (4 males and 3 females, 2 athletes and 5 non-athletes), aged 25 to 58 years, with AT injuries, who were examined and treated at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. Ankle examinations with MRI were conducted using the Esaote O-scan 0.3 T machine. The examinations were performed without the application of a paramagnetic contrast agent and without the use of anesthesia. Results: The MRI method's sensitivity and overall diagnostic accuracy were excellent, with 100% true positives. In our study, the method accurately detected the presence, location, and severity of AT injuries in all cases. MRI is an important and reliable method for detecting AT injuries, classifying them, monitoring the course of recovery, and assessing the effects of therapy. Conclusions: An unrecognized or delayed diagnosis of an AT injury can lead to chronic changes. Timely diagnosis (clinical examination, ultrasonography, magnetic resonance imaging) and appropriate treatment (conservative or operative) enable patients to return to normal activities, including sports. Unfortunately, the use of MRI is limited by restricted access and the cost of the examination.

The identification of fetal cells in the blood and tissues of healthy mothers raised questions about the potential alloreactive origins of various diseases, such as autoimmunity, diabetes, arteriosclerosis, and cancer. However, the extent to which alloreactivity contributes to these diseases remains unverified. This study presents a basic mathematical disease model based on the genes’ origin and immunological interactions. This model, grounded in set theory, classifies these immunological interactions based on their intrinsic, extrinsic, and allogeneic nature. Therefore, this model offers an unexpected common theoretical foundation for understanding alloreactivity, genetic diseases, and infections. Furthermore, this model provides a valuable framework for scrutinizing the role of alloreactivity in health and disease.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

We present the full case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and associated complication of a very rare case of occult unicornuate right uterus with rudimentary non-communicating functioning left horn and its natural evolution following an initially incomplete surgical treatment.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in broader range of patients. Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g. documented history of HF, left ventricular ejection fraction ≤40%, or BNP levels ≥100 pg/mL). Participants, aged 61±10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. Results: Lower baseline BNP correlated with reduced AFEQT scores. Post-CA, all groups showed significant AFEQT score improvements. Lower BNP group displayed notable enhancements (18.2±1.2, 15.0±1.1, 12.6±1.2, 13.6±1.2, p<0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/ml) exhibited significant QOL improvements. Comparing PAF and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. Conclusion: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvement.

Multiple sources influence air quality and regional climate in complicated atmospheric emission situations like urban agglomerations. To resolve pollution plumes and source influences in polluted areas, a comprehensive chemical fingerprinting of sources utilizing non-methane hydrocarbons (NMHCs) and the identification of acceptable tracer molecules and emission ratios is required, in contrast to pristine locations, where reliance on a single or a few chemical tracers is frequently sufficient. We have characterized the prevalence of NMHCs fingerprints in the urban areas and quantified the correlation of windspeed with the concentration of these pollutants. eNose sensors and Air quality management stations provide the data to identify the emission sources of such pollutants. Based on our analysis, the average NMHC concentration in 2021 has been recorded 0.424 ppm at point 1 AQMS whereas at point 2 AQMS it was 0.256 ppm. Such outcomes could be attributed to the proximity of emissions sources, the direction and speed of the wind, or both. Moreover, traffic can be a major contributor to pollution levels in any urban area. More research based on a larger dataset is required before definitive conclusions can be drawn, and viable solutions can be proposed.

Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

The continuous casting tundish is non-isothermal due to heat losses and temperature variation from the inlet stream generating relevant convection forces. This condition is commonly avoided through qualitative fluid dynamic analysis only. This work searches to establish the conditions for which non-isothermal simulations are mandatory or for which isothermal simulations are enough to accurately describe the fluid dynamics inside the tundish by quantifying the buoyant and inertial forces. The mathematical model, simulated by CFD software, considers the Navier-Stokes equations, the realizable k- model for solving the turbulence, and the Lagrangian discrete face to track the inclusion trajectories. The results show that temperature does not significantly impact the volume fraction percentages or the mean residence time results, nevertheless, bigger velocity magnitudes under non-isothermal conditions than in isothermal conditions and noticeable changes in the fluid dynamics between isothermal and non-isothermal cases in all the zones where buoyancy force dominates over inertial forces were observed. Because of the results, it is concluded that isothermal simulations can accurately describe the flow behavior in tundishes when the flow control devices control the fluid dynamic, but the simulation without control devices or with a weak fluid dynamic dependence on the control devices requires non-isothermal simulations.

Exosomes, a subset of extracellular vesicles, have emerged as pivotal mediators of intercellular communication, revolutionizing our comprehension of cellular interactions. Their diverse cargo, comprising proteins, nucleic acids, and bioactive molecules, plays a crucial role in various physiological and pathological processes. In the intricate landscape of adult neurogenesis, exosomes wield significant influence, actively participating in the generation of new neurons within the adult mammalian brain. Originating predominantly from non-niche cells, these vesicles contribute substantially to the regulation of neuroinflammation, thereby impacting neurogenesis and offering therapeutic promise for neurological disorders. In the specific context of Parkinson's disease (PD), exosomes assume a multifaceted role, prominently implicated in the propagation of α-synuclein oligomers and the orchestration of neuroinflammation. Stem cell-derived exosomes present themselves as promising therapeutic agents, capable of reshaping the microenvironment, repairing neuronal damage, and mitigating apoptosis. The ongoing exploration of exosomes continues to unravel intricate biological processes, paving the way for innovative medical interventions and treatments, particularly within the challenging landscape of neurodegenerative diseases such as PD. The comprehensive understanding of exosomal functions holds the potential to advance our therapeutic approaches, offering new avenues for intervention and treatment strategies in the realm of neurodegenerative disorders.

Background and Objectives: Previous studies revealed anti-angiogenic, antiproliferative and anti-inflammatory effects of Vitamin D on cancer cells. Although this body of evidence supported the correlation of high Vitamin D levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). Aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on Vitamin D serum status, dietary intake, and Vitamin D receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. Inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating Vitamin D serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between Vitamin D serum levels and NMSC is highlighted. However, dietary/supplementation of Vitamin D doesn’t exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review showed that high Vitamin D levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

The software design of autonomous vehicles (AVs) incorporates artificial intelligence (AI) characteristics to enhance their safety and overall driving performance. Central to vehicle’s operation is the ability to reason effectively in complex and uncertain environments. However, traditional logical systems, such as monotonic logic, often struggle to handle the inherent uncertainties and exceptions encountered in real-world scenarios. This paper proposes the utilization of non-monotonic logic in order to enhance the reasoning capabilities of autonomous vehicles. By incorporating non-monotonic reasoning, vehicles can navigate intricate traffic scenarios, make plausible inferences, and adapt their decisions when faced with conflicting information. This research aims to provide a comprehensive review of non-monotonic logic's application in autonomous vehicles, highlighting its advantages over traditional logical systems and its potential impact on safety and performance. Additionally, through this research, we seek to contribute to the advancement of autonomous driving technology by enhancing the reasoning capabilities of vehicles in various scenarios, such as car- following related to critical safety events. The personalized cognitive agent is proposed in driving behavior to consider particularly in their assumptions of homogeneous drivers. The personalized cognitive agent is incorporating heterogeneous driving behaviors, based on individual user preferences, characteristics, and needs. Driving behavior is a complex interplay of various factors, encompassing both human and external elements. Human factors, including age, experience, and gender, contribute significantly to how individuals navigate the roads. These factors influence decisions, reactions, and risk-taking tendencies on the part of drivers. Additionally, external factors such as weather conditions further compound this intricate dynamic, requiring drivers to adapt their behavior to the prevailing environment. The goal of a personalized cognitive agent is to provide tailored and customized experiences to cognitive vehicles, taking into account the unique requirements and individual preferences of occupants inside autonomous vehicles.

The overexploitation of forest resources in the charcoal production basin of the city of Lubum-bashi (DR Congo) is reducing the resilience of miombo woodlands and threatening the survival of the riparian as well as urban human populations that depend on it. We assessed the socio-economic value and availability of plant-based non-timber forest products NTFPs in the rural area of Lubumbashi through ethnobotanical (100 respondents) and socio-economic (90 respondents) interviews, supplemented with floristic inventories, in two village areas selected on the basis of the level of forest degradation. The results show that 60 woody species, including 46 in the degraded forest (Maksem) and 53 in the intact forest (Mwawa), belonging to 22 families are used as sources of NTFPs in both villages. Among these species, 25 are considered priority species. NTFPs are collected for various purposes, including handcrafting, hut building, and traditional medicine. Moreover, the ethnobotanical lists reveal a similarity of almost 75%, indicating that both local communities surveyed use the same species for collecting plant-based NTFPs, despite differences in the level of degradation of the miombo woodlands in the two corresponding study areas. However, the plant-based NTFPs that are collected from miombo woodlands and traded in the urban markets have significant economic value, which ranges from 0.5 to 14.58 USD per kg depending on the species and uses. NTFPs used for handicraft purposes have a higher economic value than those used for other purposes. However, the sustainability of this activity is threatened due to unsustainable harvesting practices that include stem slashing, root digging, and bark peeling of woody species. Consequently, there is a low availability of plant-based NTFPs, particularly in the village area where forest degradation is more advanced. It is imperative that policies for monitoring and regulation of harvesting, and promoting sustainable management of communities’ plant-based NTFPs priority, be undertaken to maintain their resilience.

Amorphous germanium films on non-refractory glass substrates were annealed by ultrashort near-infrared (1030 nm, 1.4 ps) and mid-infrared (1500 nm, 70 fs) laser pulses. Crystallization of germanium irradiated at a laser energy density (fluence) range from 25 to 400 mJ/cm2 under single-shot and multi-shot conditions was investigated using Raman spectroscopy. The dependence of the fraction of the crystalline phase on the fluence was obtained for picosecond and femtosecond laser annealings. The regimes of almost complete crystallization of germanium films over the entire thickness are obtained (from the analysis of Raman spectra with excitation of 785 nm laser). The possibility of scanning laser processing is shown, which can be used to create films of micro and nanocrystalline germanium on flexible substrates.

Preterm infants often experience frequent intermittent hypoxia (IH) episodes which is associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal in-flammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hy-peroxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) dai-ly caffeine citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ke-torolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in room air (RA) with no further treatment. For late treatment, pups received similar treatments from P15-P21 (caffeine and/or ketorolac), or P15-P17 (ibuprofen). RA control were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, mye-lination, and biomarkers of inflammation. IH caused significant inflammation, reduced mye-lination, and apoptosis in preterm rat brains, an effect that was improved predominantly with combined caffeine/NSAID early treatment. Early caffeine/NSAID co-treatment confers syner-gistic neuroprotection against IH-induced damage.

We present a mixing length based algebraic turbulence model calibrated to pipe flow; the main purpose of the model is to capture the increasing turbulence production-to-dissipation ratio observed in connection with the high Reynolds number transition region. The model includes the mixing length description by Gersten and Herwig which takes the observed variation of the von Kármán number with Reynolds number into account. Pipe wall roughness effects are included in the model. Results are presented for area-averaged (integral) quantities which can be used both as a self-contained model and as initial inlet boundary conditions for computational fluid dynamics simulations.

This article is devoted to methods of processing random processes. Of particular relevance is the task of processing broadband non-stationary random processes. The processing of random processes is usually related to the assessment of their probabilistic characteristics. Very often, a non-stationary broadband random process is represented by a single implementation in a priori uncertainty about the type of distribution function. Such random processes occur in information and measuring communication systems in which information is transmitted at a real time pace (for example, radio telemetry systems of spacecraft). The use of methods of traditional mathematical statistics, for example, maximum likelihood methods to determine probability characteristics, in this case is not possible. The article discusses a method of processing non-stationary broadband random processes based on the use of non-parametric methods of decision theory. An algorithm for dividing the observation interval into stationary intervals using non-parametric Kendall statistics is considered, as well as methods for estimating probabilistic characteristics on the stationary interval using ordinal statistics. The article presents the results of statistical modeling using the Mathcad program.

The zero-catch problem is a key issue in CPUE(Catch Per Unit Effort) standardization, and previous studies have treated all zero-catch data uniformly, but this actually loses some correctly-labeled samples. On the other hand, for the main catches with few zero-catch samples, the problem of low performance of fisheries forecasting remains unsolved even though the forecasting model structure is updating constantly, since we cannot know whether the samples are correctly recorded. In this paper, we propose a method based on confident learning theory to detect anomalous samples in the datasets and unify zero-catch and non-zero samples as noise through an overarching framework of learning with noisy labels, which reveals the heterogeneity among zero-catch samples (as well as among non-zero samples) and the homogeneity between zero-catch samples and non-zero samples. Using three species of tuna in the tropical Atlantic Ocean with the spatial resolution of 0.5 ◦ × 0.5 ◦ and time resolution of days from 2016 to 2019 as experimental material, performance on all three classical machine learning models(Random forest, Support Vector Machine and XGBoost) is significantly improved compared to each baseline.This confirms that we propose a self-adaptive, effective method for detecting and repairing anomalous samples in the fishery dataset.

In this study, we resequenced the mitogenomes of P. megacephalus from different regions using a “primer bridging” approach with Sanger sequencing technologies. The mitogenome of this species was found to contain two copies of the ND5 genes and three copies of the control regions. Furthermore, multiple tandem repeats were identified in the control regions. Notably, we observed that there was no correlation between the distribution of species and their genetic distance. However, our research revealed the discovery of the “missing” ATP8 gene in P. megacephalus as well as three other previously published Polypedates, as a result of manual data curation. Using the mitogenome, gene expression analysis was performed via RT-qPCR of liver samples and determined that COIII, ND2, ND4, and ND6 were reduced to 0.64±0.24, 0.55±0.34, 0.44±0.21 and 0.65±0.17 under the low-temperature stress (8℃), respectively, as compared with controls (P<0.05). Remarkably, the transcript of long non-coding RNA (LncRNA) between positions 8029 and 8612 decreased significantly with exposure to low-temperature stress (8℃). Antisense ND6 gene expression showed a downward trend but this was not significant. These results reveal that modulations of protein-coding mitogenomes genes and lncRNAs of P. megacephalus play a crucial part in the molecular response to cold stress.

Many researches have identified that adverse childhood experiences (ACEs) are associated with non-suicidal self-injury (NSSI) and suicidality. However, most studies have been restricted to a few types of ACEs. This study aims to investigate associations of 13 common types of ACEs with NSSI, suicidal ideation (SI) and suicide attempt (SA), as well as the mediation of depressive and anxiety symptoms therein. A total of 1771 students aged 11-16 years who participated in the baseline survey of the Chinese Adolescent Health Growth Cohort study were included for the analysis. ACEs, SI, SA, depressive and anxiety symptoms were recorded by standard questionnaire. Of included participants, 92.0% reported one or more category of ACEs. Smoking, parent-child separation, emotional abuse, physical abuse and being bullied were positively associated with NSSI, with the adjusted odds ratio (aOR) of 2.41(95%CI, 1.01-5.75), 1.80(1.28-2.54), 1.69(1.21-2.37), 2.08(1.44-3.01) and 1.87(1.35-2.59), respectively; smoking (4.03, 1.66-9.81), parent-child separation (1.42, 1.07-1.90), emotional abuse (1.91, 1.41-2.59), physical abuse (1.80, 1.27-2.57), emotional neglect (1.78, 1.28-2.49) and being bullied (2.08, 1.54-2.81) were positively associated with SI; smoking(4.30, 1.67-11.10), emotional abuse (2.42, 1.58-3.72) and being bullied (1.75, 1.17-2.60) were positively associated with SA. The associations of ACEs with NSSI, SI and SA were each partially or completely mediated through depressive and anxiety symptoms. Children and adolescents who had experiences of smoking, physical abuse and being bullied during childhood are consistently and independently associated with NSSI and suicidality, and these associations may be largely mediated through depressive and anxiety symptoms.

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.

In ancient buildings, timber members could need specific on-site interventions, including reinforcement or repair, sometimes inserting of reinforcing material into grooves routed in the original sound wood. Grooves number, positions and dimensions, and strengthening materials may differ, according to the desired increase of bending stiffness and strength. The Modulus-of-Elasticity (MOE) of each beam is of key importance, but the incisions can affect it, net of the reduction of the removed wood. In this study 12 old beams were accurately measured and their static and dynamic MOEs calculated before and after the grooves processing, to simulate the operations of typical reinforcing interventions. One groove was routed along the length of each beam and deepened progressively by three steps. Tests have showed how the MOE is affected by the groove depth, decreasing up to one third. The paper proves how the weakening effect of grooves on-site can be assessed with dynamic MOE and roughly predicted by means of visual survey. Grooves need for strengthening beams, must be carefully evaluated because of the variation of the actual mechanical properties, net to lost wood.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

Microbial fuel cells (MFCs) offer sustainable solutions for various biotechnological applications and are a crucial area of research in biotechnology. MFCs can effectively treat wastewater and biodiesel waste by decomposing organic matter and generating electricity. Certain Pseudomonas species possess extracellular electron transfer (EET) pathways, enabling them to transfer electrons from organic compounds to the MFC's anode. Moreover, Pseudomonas species can grow under low oxygen conditions, which is advantageous considering that the electron transfer process in an MFC typically leads to reduced oxygen levels at the anode. This study focuses on evaluating MFCs inoculated with a new Pseudomonas species, grown with 1 g.L-1 glycerol, a common byproduct of biodiesel production. Pseudomonas sp. BJa5 exhibited a maximum power density of 39 mW.m-2. Also, the observed voltammograms and genome analysis indicate the potential production of novel redox mediators by BJa5. Additionally, we investigated the bacterium's potential as a synthetic biology non model chassis. Through testing various genetic parts, including constitutive promoters, replication origins, and cargos using pSEVA vectors as a scaffold, we assessed the bacterium's suitability. Overall, our findings offer valuable insights into utilizing Pseudomonas spp. BJa5 as a novel chassis for MFCs. Synthetic biology approaches can further enhance the performance of this bacterium in MFCs, providing avenues for improvement.

This paper presents the development of an underwater crack detection system for structural integrity assessment of submerged structures, like offshore oil and gas installations, underwater pipelines, underwater foundations for bridges, dams etc. Focus is on use of machine learning based approaches. First a detailed literature review of state of the current methods for underwater surface crack detection is presented highlighting challenges and opportunities. An overview of image augmentation approach for creation of underwater optical effects is also presented. Experimental results using standard network based machine learning approach, used for surface crack detection in onshore environment, is presented. Series of Test cases are presented where existing networks performance are improved using augmented images for underwater conditions. The experimental results demonstrate the effectiveness and accuracy of the proposed system in detecting cracks in underwater structures. The system has the potential to improve the safety and reliability of underwater structures and prevent catastrophic failures.

Bridge load testing is crucial in evaluating bridge load-carrying capacity and construction quality. However, conventional techniques have many limitations such as the need for direct contact and low acquisition frequency. This study provides a comprehensive examination of the static and dynamic load tests of a multi-span cable-stayed bridge utilizing a ground-based radar inter-ferometer (GB-radar). The case study was conducted at the Fifth Nanjing Yangtze River Bridge (FNYRB), which is recognized as the world's first lightweight steel-concrete composite cable-stayed bridge, with two spans measuring 600 m. To enhance measurement accuracy, a method was proposed to detect and recover radar phase jumps caused by vehicle motion. Furthermore, precise geometry projection was employed to acquire vertical displacements from GB-radar which were taken along the line-of-sight (LOS) direction. Moreover, during the static load test, a continuous deformation was observed with a maximum pace of 0.31 mm/min, indicating a post-construction settlement caused by soft soil consolidation. This case study highlights the high sampling frequency, high measurement accuracy, and exceptional weatherproof ability of GB-radar, thereby demonstrating its potential to be an alternative to the structural health monitoring (SHM) system.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

The splitting method developed in a previous study for linear, multi – component, convection-diffusion mass transfer equations is extended to non-linear, multi-component, convection-diffusion mass transfer equations. The diffusion term is non-linear (the diffusion coefficients depend on chemical species concentrations). Theoretical results about the splitting error are presented, as well as numerical simulations for mixtures with n ≤ 5. The numerical experiments show second-order accuracy and stability for the present splitting algorithm.

Aim: This study aimed to evaluate the sociodemographic, behavioral, and biological profile and its relationship with the emergence of chronic non-communicable diseases in riverside populations in the Xingu region, Pará, Brazil. Methods: Characteristics related to health indicators and which risk factors are considered most important were also analyzed. This is a cross-sectional, exploratory, and descriptive study. The sample consisted of riverside people over 18 years of both sexes. The sample size (n.86) was calculated with a confidence level of 95% and a sample error of 5%. To divide the groups, the K-means clustering algorithm was adopted through an unsupervised method and the values were expressed as median. For continuous and categorical data, the Mann-Whitney and Chi-square tests were used, respectively, and the significance level was set at p<5%. To classify the degree of importance of each variable, the multi-layer perceptron algorithm was applied. Results: Based on this information, the sample was divided into two groups: the group with low or no education, with bad habits and worse health conditions, and the group with opposite characteristics. The risk factors considered for cardiovascular diseases and diabetes in the groups were low education (p < 0.001), sedentary lifestyle (p < 0.01), smoking, alcoholism, body mass index (p < 0.05) and the waist-hip ratio, with values above the expected, in both groups. Conclusions: The factors considered important to have a good health condition or not were the educational and social conditions of these communities and a part of the riverside population was considered healthier than the other.

The assessment of an organization/product's environmental footprint is based on the protocols developed by the Joint Research Centre of the European Union, which take into account 16 impact categories. Among the categories covered are toxicity to freshwater ecosystems and to humans. Standard protocols use only chemical parameters as input data, preventing the true impact of entire complex mixtures, such as emissions discharged into the environment, from being determined. Biological assays allow us to bridge this gap: in the current study, assays were used to determine baseline toxicity towards aquatic organisms (green algae, luminescent bacteria, and crustaceans) as well as specific toxicity (mutagenicity and carcinogenicity). Expected impacts were compared using two approaches (standard and bioassay-centered results obtained are not always in line and, in general, the traditional method underestimates impacts). This demonstrates the importance of these assays and suggests that they be used in LCA (Life Cycle Assessment) protocols as well.

Usually in quantum optics, the theory of large- and small-scale waveguide beam splitters is the same. In this paper it is shown that the theory of the nanoscale waveguide beamsplitter has a significant difference from a similar device, but of a larger scale. It is shown that the previously known theory of the waveguide beam splitter is a particular case of the theory presented here. The wave function at the output ports of the nanoscale beam splitter is analyzed. The results obtained are sensitive to the size of the beam splitter, the coupling parameter of the two waveguides, and the degree of nonmonochromaticity of the photons entering the first and second ports of the beam splitter. The results are important for quantum technologies using a nanosized beam splitter.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

Dormancy is a physiological state that confers winter hardiness to and orchestrates phenological phase progression in temperate perennial plants. Weather fluctuations caused by climate change increasingly disturb dormancy onset and release in many plant species including tree crops leading to aberrant growth, flowering, and fruiting. Currently, research in this field is impeded by the lack of affordable non-invasive methods for on-line monitoring of dormancy. We report on an automatic framework for low-cost, long-term, and scalable dormancy studies in deciduous plants. The proposed method is based on continuous near-field sensing of the photosynthetic activity of shoots via pulse-amplitude modulated chlorophyll fluorescence sensors connected remotely to a data processing system. The resulting high-resolution time series of JIP-test parameters indicative of the responsiveness of the photosynthetic apparatus to environmental stimuli are subjected to frequency-domain analysis. The proposed approach allows to overcome the variance coming from diurnal changes of insolation and to derive estimations on the depth of dormancy. Our approach was validated over three seasons in an experimental apple (Malus × domestica Borkh.) orchard by collating the non-invasive estimations with the results of traditional methods (growing of the cuttings obtained from the tress at different phases of dormancy) and the output of commonly used chilling requirement models. We discuss the advantages of the proposed monitoring framework such as prompt detection of freeze damages along with its potential limitations.

So that the levels of water stress are not harmful to the development of the crop and affect its productivity, its detection and monitoring are necessary, and it can occur in different ways. One of them is through the Crop Water Stress Index (CWSI). This index quantifies water stress through the normalization of leaf temperature between the maximum and minimum plant temperatures as a function of evaporation conditions. The responses of a low-cost infrared (IR) sensor were crossed with image processing through segmentation by the Excess Green model to develop a water stress detection system using CWSI. A soil/plant temperature map was generated through a point-to-point scan of the IR sensor. And when it overlaid with a segmented image of the experimental area, only points identified as plants had their temperature values maintained. The Non-Water-Stressed Baseline (NWSB) equation was parameterized for the same conditions of the experiment and external environmental. The experimental area was divided into three different treatments, maintained under stable water conditions throughout the experiment and the system was able to identify stably different stress values between treatments. Although the relationship between crop and environment affected the results, this work showed that using an irrigation system based on CWSI is possible.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

The Chebyshev collocation method (ChC) implemented as Chebfun is used in order to solve a class of second order one-dimensional singular and genuinely nonlinear boundary value problems. Efforts to solve these problems with conventional ChC have generally failed, and the outcomes obtained by finite differences or finite elements are seldom satisfactory. We try to fix this situation using the new Chebfun programming environment. However, for toughest problems we have to loosen the default Chebfun tolerance in Newton's solver as the ChC runs into trouble with ill-conditioning of the spectral differentiation matrices. Although in such cases the convergence is not quadratic the Newton updates decrease monotonically. This fact, along with the decreasing behaviour of Chebyshev coefficients of solutions, suggests that the outcomes are trustworthy, i.e., the collocation method has exponential (geometric) rate of convergence or at least an algebraic rate. We consider first a set of problems that have exact solutions or prime integrals and then another set of benchmark problems that do not possess these properties. Actually, for each test problem carried out we have determined how Chebfun solution converges, its length, the accuracy of the Newton method and especially how well the numerical results overlap with the analytical ones (existence and uniqueness).

Acute myeloid leukemia (AML) is a hematological malignancy that is the culmination of genetic and epigenetic alterations in the hematopoietic progenitor cells, leading to uncontrolled proliferation at the expense of normal hematopoiesis and bone marrow exhaustion. Although the outcomes for pediatric AML have improved in recent decades, at least one third of children still have relapses. Recent studies have notably highlighted the important role of dysregulated epi-genetic mechanisms in myeloid leukemogenesis. Epigenetic modifications are frequently reversible compared to genetic alterations, thus providing opportunities for targeted epigenetic therapy. In this review, we summarize the landscape of epigenetic alterations and the progress to date in epigenetic targeted therapy, and focus on the future role of epigenetic abnormalities in predicting relapse and the precision therapy in pediatric AML.

In this work, we analytically describe a superconducting transition in a non-equilibrium state taking into account many-body interactions; the obtained transition temperatures indicate the presence of superconductivity at room temperatures.First, we consider many-body interactions and discuss the case of locally thermal equilibrium with many-body interactions; in this section, we derive statistical equations that describe many-body interactions at locally thermal equilibrium state. Then, the same theory is used to derive a many-body statistical equation that is expanded to include the case of non-equilibrium states; in this case a transition temperature is derived. Moreover, a wave function of an Einstein–Podolsky–Rosen pair (EPR pair) is calculated according to the Lorentz conservation, and a specific condensation is observed and the Meissner effect is found to be present.Furthermore, considering the Lorentz conservations, relativistic energy, and Boltzmann statistics, algorithms are presented to calculate charge density, current density, and internal local energy. We note that these calculations do not require a specific code but instead utilize the software Microsoft Excel.We present plots showing the charge density and current density vs. the applied electric potential, which demonstrate the practical applicability of the theory. Moreover, internal local energy was found to be close to zero for sufficiently large electric potentials at room temperature.In the discussion section, the universally induced superconducting current is derived, which can be employed as the renewable energy.This paper describes non-equilibrium and EPR-pair type superconductivity, with the complete consideration of many-body interactions.

Regression models are mostly used in all fields of sciences for modelling the relationship between a dependent variable and independent variable(s). The least square method is often used to estimate the parameters in a linear model because it is the best linear unbiased estimator. These estimates can only be reliable if the assumption of normality is satisfied. In some cases the dependent variable might be bimodal and shows a non-linear relationship with the independent variable(s). In this case, a non-linear model should be used. In non-linear model, the standard errors are often obtained by linearizing the nonlinear function around the parameter, assuming central limit theorem. After the linearization, the least square parameter estimates are obtained. It should be noted that the error of the non-linear model is different from that of the transformed linear model. Thus, there is a need to transform back to the original non-linear model. In this note, a novel non-linear function was developed into a non-linear regression model, called Normal-Power model. The least square method was used to estimate the parameter of the transformed model. Its usefulness in regression model was demonstrated using real data of Nigeria Economy-Tourism model.

Contact toxicity against Periplaneta americana has never been tested with S. collinsiae root extract. Hexane, dichloromethane, ethanol and water extracts were tested in final-instar nymphs and adult P. americana by topical application method. The dichloromethane extract showed the high-est potency of contact toxicity against the final-instar nymphs (41-100% corrected mortality at 48 hours), lowest LC50 (1.5±0.2 %w/v at 48 hours), and lowest LT50 (36.1±0.8 hours at 10%w/v) while the water crude extract lacked the contact toxicity (0-0% corrected mortality at 48 hours). Signs of toxicity, such as excited movement, trembling body, motionlessness, and swollen abdomen segment including irregularly extended foregut were found at the both stages of P. americana dropping with solutions of dichloromethane extract. Detection of didehydrostemofoline distri-bution using IMS revealed that didehydrostemofoline distributed in the tissue of the dead fi-nal-instar nymph and adult P. americana contacting with dichloromethane extract, but it was not found in tissue of euthanized P. americana which exposed to the water extract. Didehydrostemo-foline in the extract was a cause of toxicity signs and death of P. americana via a contact route. Thus, dichloromethane extract and didehydrostemofoline could be used as an active ingredient and chemical marker in aerosol and spray formulations for cockroach control.

Alternating current field measurement (ACFM) testing is one of promising techniques in the field of non-destructive testing with advantages of the non-contact capability and the reduction of lift-off effects. In this paper, a novel crack detection approach is proposed to reduce the effect of the angled crack (cack orientation) by using rotated ACFM techniques. The sensor probe is composed of an excitation coil and two receiving coils. Two receiving coils are orthogonally placed in the centre of the excitation coil where the magnetic field is measured. It is found that the change of the x component and the peak value of the z component of the magnetic field when the sensor probe rotates around a crack follows a sine wave shape. A customised accelerated finite element method solver programmed in MATLAB is adopted to simulate the performance of the designed sensor probe which can significantly improve the computation efficiency due to the small crack perturbation. The experiments have also been carried out to validate the simulations. It is found that the ratio between the z and x components of the magnetic field remains stable under various rotation angles. It shows the potential to estimate the depth of the crack from the ratio detected by combining the magnetic fields from both receiving coils (i.e., the x and z components of the magnetic field) using the rotated ACFM technique.

Instead of the conventional 0 and 1 values, bipolar reasoning uses -1, 0, +1 to describe double-sided judgements in which neutral elements are halfway between positive and negative evaluations (e.g., “uncertain” lies between “impossible” and “totally sure”). We discuss the state-of-the-art in bipolar logics and recall two medieval forerunners, i.e., William of Ockham and Nicholas of Autrecourt, who embodied a bipolar mode of thought that is eminently modern. Starting from the trivial observation that “once a wheat sheaf is sealed and tied up, the packed down straws display the same orientation”, we work up a new theory of the bipolar nature of networks, suggesting that orthodromic (i.e., feedforward, bottom-up) projections might be functionally coupled with antidromic (i.e., feedback, top-down) projections via the mathematical apparatus of presheaves/globular sets. When an entrained oscillation such as a neuronal spike propagates from A to B, changes in B might lead to changes in A, providing unexpected antidromic effects. Our account points towards the methodological feasibility of novel neural networks in which message feedback is guaranteed by backpropagation mechanisms endowed in the same feedforward circuits. Bottom-up/top-down transmission at various coarse-grained network levels provides fresh insights in far-flung scientific fields such as object persistence, memory reinforcement, visual recognition, Bayesian inferential circuits and multidimensional activity of the brain. Implying that axonal stimulation by external sources might backpropagate and modify neuronal electric oscillations, our theory also suggests testable previsions concerning the optimal location of transcranial magnetic stimulation’s coils in patients affected by drug-resistant epilepsy.

Objectives: Low and Middle Income Countries (LMICs) are experiencing a fast-paced epidemiological rise in clusters of non-communicable diseases (NCDs) such as diabetes and cardiovascular disease, forming an imminent rise in multimorbidity (MMD). However, preventing MMD has received little attention in LMICs, especially in Sub-Saharan African Countries. Design: Narrative review which scoped the most recent evidence in LMICs about MMD determinants and appropriated them for potential MMD prevention strategies. Methods: MMD in LMICs is affected by several determinants including increased age, female gender, environment, lower socio-economic status, obesity, and lifestyle behavious, especially poor nutrition and physical inactivity. Results: MMD public health interventions in LMICs, especially Sub-Saharan are currently impeded by local and regional economic disparity, underdeveloped healthcare systems, and concurrent prevalence of communicable diseases. However, lifestyle interventions that are targeted towards preventing highly prevalent MMD clusters, especially hypertension, diabetes and cardiovascular disease, can provide an early prevention of MMD, especially within Sub-Saharan African countries with emerging economies and socio-economic disparity. Conclusion: Future public health initiatives should consider targeted lifestyle interventions and appropriate policies and guidelines in preventing MMD in LMICs.

Being able to ascertain the physiological condition of the buds on a young apple tree before bud burst could help farmers manage their orchards more efficiently, especially if they could do so without destroying the buds in the process. The experiments carried out in this study were conducted with the aim of distinguishing shoot from non-shoot buds before bud burst using a visible/near-infrared spectrometer, a device that does not destroy the buds being tested. Tests on spring-planted (April 30, 2021) trees were conducted to check shoot and non-shoot bud physiology and the winter dormancy of young ‘Jonagold’, ‘Miyabi Fuji’ and ‘Orin’ apple trees. The light absorbance of the shoot buds before bud burst was much lower than the light absorbance of the non-shoot buds as checked on the visible/near-infrared spectrometer. The highest first factor effect was determined by a PCA test conducted on shoot and non-shoot ‘Jonagold’ buds (99.9%) at a range of 640-652 nm, ‘Miyabi Fuji’ buds (99.7%) at 654-680 nm and ‘Orin’ buds (99.6%) at 704-766 nm seven days before bud burst. We also found that the highest level of accuracy, using the Classifier analysis, between shoot and non-shoot ‘Jonagold’ buds (76.6%) was one day before bud burst, for ‘Miyabi Fuji’ buds (82.1%) it was three days before and for ‘Orin’ buds (76.3%) it was two days before. These findings suggest that growers can more effectively manage the development of the young trees in their orchards with a visible/near-infrared spectrometer.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

A temperature-modulated pyroelectricity measurement system for a small single crystal is developed and applied to standard sample measurements performed on a thin single crystal of lithium niobate. The modulation measurement is based on the AC technique, in which the temperature of the sample is periodically oscillated, and the synchronized pyroelectric signal is extracted using a lock-in amplifier. Temperature modulation is applied by irradiating periodic light on the sample placed in the heat exchange gas. To apply this technique to the transparent reference sample, a commercially available black resin is coated on the sample’s surface to absorb the light energy and transmits it to the specimen. The experimental results are analyzed using a two-layer heat transfer model to verify the effect of the light-absorbing layer as well as the non-contact temperature modulation system.

Sweet cherry pomace is a by-product that can be a source of bioactive phenolic compounds. Usually, polyphenols have been extracted using conventional extraction methodologies. However, a significant fraction, called non-extractable polyphenols (NEPs), remains retained in the conventional extraction residues. Therefore, this work is aimed, for the first time, to investigate the release of NEPs from cherry pomace combining pressurized liquid extraction (PLE) and enzyme-assisted extraction (EAE) using Promod enzyme. A response surface methodology was employed to study the influence of temperature, time, and pH on the NEPs extraction. The response variables were the total phenolic content (TPC) measured by Folin-Ciocalteu method, total proanthocyanidin (PA) content evaluated by vanillin, DMAC, and butanol/HCl assays, and total antioxidant capacity determined by Trolox equivalent antioxidant capacity and inhibition of hydroxyl radical assays. The results indicated that PLE-EAE was more suitable and selective to obtain NEPs from sweet cherry pomace than PLE alone. In fact, the extracts obtained by PLE-EAE displayed higher TPC, PA content, and bioactivity than the extracts obtained by PLE under the same extraction conditions, and those obtained by conventional methods. Moreover, size-exclusion chromatography profiles showed that the combination of PLE and EAE enabled the recovery of NEPs with higher molecular weight than PLE without EAE treatment.

Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) could be negatively associated with thwarted belongingness and perceived burdensome. To date, no studies have analyzed whether thwarted belongingness and perceived burdensomeness could be associated with the frequency of NSSI in adolescents. On the other hand, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of NSSI. Aims: a) to test whether thwarted belongingness and perceived burdensomeness are associated with NSSI frequency; b) to test whether MIL moderates the association between thwarted belongingness and NSSI frequency; and c) to test whether MIL moderates the association between perceived burdensomeness and NSSI frequency. Method: The sample consisted of N = 1531 participants between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescents Version, and Interpersonal Needs Questionnaire. Moderation analysis were performed. Results: Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of NSSI, and between perceived burdensomeness and the frequency of NSSI. Conclusion: Thwarted belongingness and perceived burdensomeness could be a risk factor for NSSI and MIL could be a protective factor against NSSI, and adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve the assessment and treatment protocols for adolescents with NSSI.

There must exist a reformulation of quantum field theory which does not refer to classical time. We propose a pre-quantum, pre-spacetime theory, which is a matrix-valued Lagrangian dynamics for gravity, Yang-Mills fields, and fermions. The definition of spin in this theory leads us to an eight dimensional octonionic space-time. The algebra of the octonions reveals the standard model; model parameters are determined by roots of the cubic characteristic equation of the exceptional Jordan algebra. We derive the asymptotic low energy value 1/137 of the fine structure constant, and predict the existence of universally interacting spin one Lorentz bosons, which replace the hypothesised graviton. Gravity is not to be quantized, but is an emergent four-dimensional classical phenomenon, precipitated by the spontaneous localisation of highly entangled fermions.

Eddy current testing can be used to interrogate steels but it is hampered by the lift-off distance of the sensor. Previously, the lift-off point of intersection (LOI) feature has been found for the pulsed eddy current (PEC) testing. In this paper, a lift-off invariant inductance (LII) feature is proposed for the multi-frequency eddy current (MEC) testing, which merely targets the ferromagnetic steels. That is, at a certain working frequency, the measured inductance signal is found nearly immune to the lift-off distance of the sensor. Such working frequency and inductance are termed as the lift-off invariant frequency (LIF) and LII. Through simulations and experimental measurements of different steels under the multi-frequency manner, the LII has been verified to be merely related to the sensor parameters and independent of different steels. By referring to the LIF of the test piece and using an iterative inverse solver, one of the steel properties (either the electrical conductivity or magnetic permeability) can be reconstructed with a high accuracy.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

In many advanced industrial applications, the thickness is a critical index, especially for metallic coatings. However, the variance of lift-off spacing between sensors and test pieces affects the measured voltage or impedance, which leads to unreliable results from the sensor. Massive research works have been proposed to address the lift-off issue, but few of them applies to the thickness measurement of planar metallic films with finite-size circular (disk) geometry. Previously, a peak-frequency feature from the swept-frequency inductance was used to compensate the measurement error caused by lift-offs, which was based on the slow-changing rate of impedance phase term in the Dodd-Deeds formulas. However, the phase of measured impedance is nearly invariant merely on a limited range of sample thicknesses and working frequencies. Besides, the frequency sweeping is time-consuming, where a recalibration is needed for different sensor setups applied to the online real-time measurement. In this paper, a single-frequency algorithm has been proposed, which is embedded in the measurement instrument for the online real-time retrieval of thickness. Owing to the single-frequency measurement strategy, the proposed method does not need to recalibrate for different sensor setups. The thickness retrieval is based on a triple-coil sensor (with one transmitter and two receivers). The thickness of metallic disk foils is retrieved from the measured electrical resistance of two transmitter-receiver sensing pairs. Experiments on materials of different electrical conductivities (from direct current), thicknesses and planar sizes (radii) have been carried out to verify the proposed method. The error for the thickness retrieval of conductive disk foils is controlled within 5 % for lift-offs up to 5 mm.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Electromagnetic sensors have been used for inspecting small surface defects of metals. Based on the eddy-current thin-skin regime, a revised algorithm is proposed for a triple-coil drive-pickup eddy-current sensor scanning over long surface crack slots (10 mm) with different rotary angles. The method is validated by the voltage measurement of the designed EC sensor scanning over a benchmark (ferromagnetic) steel with surface defects of different depths and rotary angles. With an additional sensing coil for the designed EC sensor, the defect angle (or orientation) can be measured without spatially and coaxially rotating the excitation coil. By referring to the voltage change (due to the defect) diagram (voltage sum versus voltage different) of two sensing pairs, the rotary angle of the surface crack is retrieved with a maximum residual deviation of 3.5 %.

Recently, there is a trend among food manufacturers in producing functional foods containing fruit and milk. On the other hand, there is an increasing demand for buffalo milk as an alternative to cow milk. Therefore, the aim of this study was to investigate the impact of adding bael fruit extract on microbial, physiochemical and sensory characteristics of buffalo yoghurt containing the EPS-producing probiotic Lactobacillus rhamnosus GG (LGG) during 21 days of refrigerated storage. Four formulations of buffalo yoghurt: a control yoghurt manufactured with conventional yoghurt culture (CON); a probiotic yoghurt containing Lb. rhamnosus GG plus yoghurt culture (PY); a probiotic yoghurt containing 5% (w/v) bael (PY5); and 10% (w/v) bael (PY10) were evaluated for changes in pH, syneresis, hardness, probiotic viability and sensory attributes during the storage. Control yoghurt experienced significant post acidification and a higher rate of syneresis. Addition of probiotics had a positive effect on post acidification and syneresis rate. Addition of bael did not affect post-acidification, but significantly decreased the level of syneresis. All probiotic formulations maintained LGG counts of >107 cfu/mL and the highest counts were observed in 5% (w/v) bael incorporated yoghurt. Results showed that buffalo yoghurt is an ideal matrix to deliver LGG and 5% bael incorporation would be ideal or symbiotic product development.

For the electromagnetic eddy current testing, various methods have been proposed for reducing the lift-off error on the measurement of samples. In this paper, instead of eliminating the measurement error caused by the lift-off effect, an algorithm has been proposed to directly measure the lift-off distance between the sensor and non-magnetic conductive plates. The algorithm is based on a sample-independent inductance (SII) feature. That is, under high working frequencies, the inductance is found sensitive to the lift-off distance and independent of the test piece under an optimal single high working frequency (43.87 kHz). Furthermore, the predicted lift-off distance is used for the thickness prediction of the non-magnetic conductive samples using an iterative method. Considering the eddy current skin depth, the thickness prediction is operated under a single lower frequency (0.20 kHz). As the inductance has different sensitivities to the lift-off and thickness, the prediction error of the sample thickness is different from that of the lift-off distance. From the experiments on three different nonmagnetic samples – aluminium, copper, and brass, the maximum prediction error of the lift-off distance and sample thickness is 1.1 mm and 5.42 % respectively at the lift-off of 12.0 mm.

Complex diseases such as cancer are caused by changes in the Gene Regulatory Networks. Systems that model the complex dynamics of these networks along with adapting to real gene expression data are closer to reality and can help understand the creation and treatment of cancer. In this paper, for the first time, modelling of gene regulatory networks is performed using delayed nonlinear variable order fractional systems in the state space by a new tool called GENAVOS. This tool uses gene expression time series data to identify and optimize system parameters. This software has several tools for analyzing system dynamics. The results show that the nonlinear variable order fractional systems have very good flexibility in adapting to real data. We found that regulatory networks in cancer cells actually have a larger delay parameter than in normal cells. It is also possible to create chaos, periodic and quasi-periodic oscillations by changing the delay, degradation and synthesis rates. Our findings indicate a profound effect of time-varying order on these networks, which may be related to a type of cellular memory due to epigenetic and environmental factors. We showed that by changing the delay parameter and the variable order function for a normal cell system, its behavior changes and becomes quite similar to the behavior of a cancer cell. This work also confirms the effective role of the miR-17-92 cluster in the cancer cell cycle. GENAVOS is available at https://github.com/hanif-y/GENAVOS with its user guide and MATLAB codes.

In this paper, we introduce a non-invasive approach for monitoring bridge infrastructure with ground-based interferometric radar. This approach is called the mirror mode, since it utilises the flat surface of the bridge underside as a mirror to reflect the signal to a corner reflector on the ground placed opposite of the radar sensor. For proving the feasibility of this approach, a measurement campaign has been carried out at an exemplary bridge in Karlsruhe (Germany) including a radar sensor in mirror mode, a second radar sensor in the default mode and a laser profile scanner. We investigate the potential of this approach to monitor the bridge displacement in vertical direction and compare the results with the two other sensors. The derived results reveal the potential for monitoring bridge infrastructure. Finally, we propose further research aspects of this approach to analyse its capabilities and limitation in the context of non-invasive infrastructure monitoring.

Biological invasions represent a threat to ecosystems, through competition and habitat destruction, which may result in significant changes of the invaded community. Asparagopsis armata is a red macroalgae (Rodophyta) globally recognized as an invasive species. It is found from the intertidal to shallow subtidal areas, on rock or epiphytic, forming natural vegetation belts on exposed coasts. This study evaluated the variations on native intertidal seaweed and macroinvertebrate assemblages inhabiting rock pools with and without the presence of the invasive macroalgae A. armata. To achieve this, manipulation experiments on Atlantic (Portugal) rock pools were done. Three rock pools were maintained without A. armata by manual removal of macroalgae, and three others were not experimentally manipulated during the study period and A. armata was freely present. In this study the variations between different rock pools were assessed. Results showed different patterns in the macroalgae composition of assemblages but not for the macrobenthic communities. Ellisolandia elongata was the main algal species affected by the invasion of A. armata. Invaded pools tended to show less species richness, showing a more constant and conservative structure, with lower variation of its taxonomic composition than the pools not containing A. armata, where the variability between samples was always higher. Despite the importance of the achieved results, further data based on observation of long-term series are needed, in order to further understand more severe effects of the invader A. armata on native macroalgal assemblage.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

Previously, various techniques have been proposed for reducing the lift-off effect on the thickness measurement of the non-magnetic films, including the peak-frequency feature and phase feature in the Dodd-Deed analytical formulation. To realise a real-time feedback response on the thickness monitoring, the phase term in the Dodd-Deeds formulation must be taken off the integration. Previous methods were based on the slow change rate of the phase term when compared to the rest of the term – the magnitude term. However, the change rate of the phase term is still considerable for a range of working frequencies. In this paper, a high-frequency feature has been found. That is, the ratio between the imaginary and real part of the phase term is proportional to the integral variable under high frequencies. Based on this proportion relationship, the phase term has been taken out; and a thickness algorithm has been proposed. By combing the measured impedance from the custom-built sensor (three coils), the thickness of the metallic film can be reconstructed. Experiments have been carried out for the verification of the proposed scenario. Results show that the thickness of the metal film can be reconstructed with a small error of less than 2 %, and immune to a reasonable range of lift-offs.

This paper presents a new approach of eddy current methods for determining the size of the co-axial hole in the metallic circular disk. In recent decades, for the air-cored sensor probe, the impedance change due to the presence of an infinite metal plate can be calculated by the Dodd-Deeds model. However, in practical measurements, the sample cannot match with the condition required - ‘infinite’, thus the Dodd-Deeds model could not be applied to the disk with finite size and certainly not a co-axial hole in the center. In this paper, a dual-constraint analytical method is proposed. That is, the upper and lower limits of the integration are substituted with specific values instead of the original 0 and . Besides, it is found that, once the outer radius of the disk is fixed (i.e. the lower limit of integration is fixed), the upper limit reduces linearly as the size of the coaxial hole increases. Both the FEM simulation and experiments have been carried out to validate this method. The radius of the hole can be estimated based on the dual-constraint integration feature.

The expanding use of devices emitting Pulsed Telecommunication Signals (PTS) has launched a serious debate over the possible effects of electromagnetic radiation (EMR) on living organisms. Our previous work has indicated that PTS exposure alters Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) metabolism in human cells of neural origin, providing a possible connection between exposure and neurodegeneration. This investigation aimed to reveal, in vitro in human non-neural cells (HEK293), the aftermath of the same exposure on the processing of APP and α-syn. Data presented here, indicate changes in APP metabolism, acquisition of different cellular topologies of the newly generated APP fragments, changes in monomeric α-syn accumulation and multimerization, indicating that APP and α-syn processing is possibly altered in the periphery by EMR. These effects are accompanied by a substantial increase in the levels of Reactive Oxygen Species (ROS). Further investigation is required in order to provide insights into the interaction of PTS with non-neural cells affecting the peripheral systemic functional stability. This is necessary because nowadays whole body human exposure from various EMR sources is a fact in normal life with the valid estimation that they may be increased in view of the forthcoming 5G telecommunications network implementation.

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

Although wheat is used worldwide as a staple food, it can give rise to adverse reactions, for which the triggering factors have not been identified yet. These reactions can be caused mainly by kernel proteins, both gluten and non-gluten proteins. Among these latter, -amylase/trypsin inhibitors (ATI) are involved in baker’s asthma and realistically in Non Celiac Wheat Sensitivity (NCWS). In this paper, we report characterization of three transgenic lines obtained from the bread wheat cultivar Bobwhite silenced by RNAi in three ATI genes CM3, CM16 and 0.28. We have obtained transgenic lines showing an effective decrease of the activity of target genes that, although showing a higher trypsin inhibition as a pleiotropic effect, generate a lower reaction when tested with sera of patients allergic to wheat, accounting for the important role of the three target proteins in wheat allergies. Finally, these lines show unintended changes differences in high molecular weight glutenin subunits (HMW-GS) accumulation, involved in technological performances, but do not show differences in terms of yield. The development of new genotypes accumulating a lower amount of proteins potentially or effectively involved in such pathologies, not only offers the possibility to use them as a basis for the production of varieties with a lower impact on adverse reaction, but also to test if these proteins are actually implicated in those pathologies for which the triggering factor has not been established yet.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

This paper aims to investigate the criteria of behaviour of certain type of third order neutral generalized difference equations with distributed delay. With the technique of generalized Riccati transformation and Philos-type method, some oscillation criteria are obtained to ensure convergence and oscillatory solution of suitable example is listed to illustrate the main result.