Raindrop erosion is a significant materials limiting issue. It can affect materials for transportation and renewable energy converters such as wind turbines as well as all external structures used in the construction industries. In such cases, the raindrop effects can occur over a wide range of impact velocities and particles sizes. In understanding tribological variable effects, it is useful to study using reference materials. This is because the reference material is well characterized, from previous knowledge of the tribological and corrosion patterns. Further, the well established chemical composition and stochiometry of the corrosion products provide some background understanding of how effectively, during tribological action, the surface scale adheres to the substrate. In this study, a carbon steel was used as a reference to study the effects of velocity and drop diameter in a whirling arm erosion test rig. The results were used to establish the conditions where corrosion was accelerated and the environments where aerodynamic effects may have resulted in droplets being deflected the surfaces. Erosion maps were generated to illustrate such mechanisms based on the results.

It is widely, but not universally, believed that the lipids of the plasma membrane are not uniformly distributed, but that "rafts'' of sphingolipids and cholesterol float in a "sea'' of unsaturated lipids. The physical origin of such heterogeneities is often attributed to a phase coexistence between the two different domains. We argue that this explanation is untenable for several reasons. Further we note that the results of recent experiments are inconsistent with this picture. However they are quite consistent with an alternate explanation, namely that the plasma membrane is an emulsion of the two kinds of regions. To show this, we briefly review a simplified version of this theory and its phase diagram. We also explicate the dependence of the predicted domain size on four physical parameters. Among them are the spontaneous curvature of the membrane and its bending modulus and surface tension. Taking values of the latter two from experiment, we obtain domain sizes for several different cell types that vary from 58 to 88 nm.

In passing maneuvers on two-lane highways, assessing the needed distance and the potential power reserve to ensure the required speed mode of the passing vehicle is a critical task of speed planning. This task must meet several mutually exclusive conditions that lead to successful maneuver. The paper addresses three main aspects. First, the issues of rational distribution of the speed of the passing vehicle for overtaking a long commercial vehicle on two-lane highways are discussed. The factors that affect maneuver effectiveness are analyzed, considering safety and cost. Second, a heuristic algorithm is then proposed based on the rationale for choosing the necessary space and time for overtaking. The initial prediction's sensitivity to fluctuations of current measurements of the position and speed of the overtaking participants is examined. Third, an optimization technique for passing vehicle speed distribution over the overtaking time using the finite element method is presented. The adaptive model predictive control is applied for tracking the references being generated. The presented model is illustrated using simulation.

In order to reach the theoretical efficiency limits of lead-based metal halide perovskite solar cells, the voltage should be enhanced because it suffers from nonradiative recombination. Perovskite materials contain intrinsic defects that can act as Shockley-Read-Hall recombination centers. Several experimental and computational studies have characterized such defect states within the band gap. We give a systematic overview of compositional engineering by distinguishing the different defect reducing mechanisms. Doping effects are divided into influences on: (1) Crystallization; (2) Lattice properties. Incorporation of dopant influences the lattice properties by: (a) Lattice strain relaxation; (b) Chemical bonding enhancement; (c) Band gap tuning. The intrinsic lattice strain in undoped perovskite was shown to induce vacancy formation. The incorporation of smaller ions, such as Cl, F and Cd, increases the energy for vacancy formation. Zn doping is reported to induce strain relaxation but also to enhance the chemical bonding. The combination of computational studies using (DFT) calculations quantifying and qualifying the defect reducing propensities of different dopants with experimental studies is essential for deeper understanding and unraveling insights, such as the dynamics of iodine vacancies and the photochemistry of the iodine interstitials, and can eventually lead to a more rational approach in the search for optimal photovoltaic materials.

A unified presentation of a class of Humbert’s polynomials in two variables which generalizes the well known class of Gegenbauer, Humbert, Legendre, Chebycheff, Pincherle, Horadam, Kinnsy, Horadam-Pethe, Djordjević , Gould, Milovanović and Djordjević, Pathan and Khan polynomials and many not so called ’named’ polynomials has inspired the present paper and the authors define here generalized Humbert-Hermite polynomials of two variables. Several expansions of Humbert- Hermite polynomials, Hermite-Gegenbaurer (or ultraspherical) polynomials and Hermite- Chebyshev polynomials are proved.

The entropic gravity conception proposes that what has been traditionally interpreted as unobserved dark matter might be merely the product of quantum effects. These effects would produce a novel sort of positive energy that translates into dark matter via $E=mc^2$. In the case of axions, this perspective as been shown to yield quite sensible, encouraging results [DOI:10.13140/RG.2.2.17894.88641] . There, a simple Schrodinger mechanism was utilized, in which his celebrated equation is solved with a potential function based on the microscopic Verlinde's entropic force advanced in [Physica A {\bf 511} (2018) 139]. In this effort we revisit such technique with regards to fermions' behavior (specifically, baryons).

The stiffness of the myosin cross-bridges is a key factor in analysing possible scenarios to explain myosin head changes during force generation in active muscles. The seminal study of Huxley and Simmons (1971: Nature 233: 533) suggested that most of the observed half-sarcomere instantaneous compliance (=1/stiffness) resides in the myosin heads. They showed with a so-called T₁ plot that, after a very fast release, the half-sarcomere tension reduced to zero after a step size of about 60Å (later with improved experiments reduced to 40Å). However, later X-ray diffraction studies showed that myosin and actin filaments themselves stretch slightly under tension, which means that most (at least two-thirds) of the half sarcomere compliance comes from the filaments and not from cross-bridges. Here we have used a different approach, namely to model the compliances in a virtual half sarcomere structure in silico. We confirm that the T₁ curve comes almost entirely from length changes in the myosin and actin filaments, because the calculated cross-bridge stiffness (probably greater than 0.4 pN/Å) is higher than previous studies have suggested. In the light of this, we present a plausible modified scenario to describe aspects of the myosin cross-bridge cycle in active muscle. In particular, we suggest that, apart from the filament compliances, most of the cross-bridge contribution to the instantaneous T₁ response comes from weakly-bound myosin heads, not myosin heads in strongly attached states. The strongly attached heads would still contribute to the T₁ curve, but only in a very minor way, with a stiffness that we postulate could be around 0.1 pN/Å, a value which would generate a working stroke close to 100 Å from the hydrolysis of one ATP molecule. The new program can serve as a tool to calculate sarcomere elastic properties for any vertebrate striated muscle once various parameters have been determined (e.g. tension, T₁ intercept, temperature, X-ray diffraction spacing results).

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

This paper presents the robotic platform, PiBot, that has been developed and that is aimed at improving the teaching of Robotics with vision to secondary students. Its computational core is the Raspberry Pi 3 controller board, and the greatest novelty of this prototype is the support developed for the powerful camera mounted on board, the PiCamera. An open software infrastructure written in Python language was implemented so that the student may use this camera, or even a WebCam, as the main sensor of this robotic platform. Also, higher level commands have been provided to enhance the learning outcome for beginners. In addition, a PiBot 3D printable model and the counterpart for the Gazebo simulator were also developed and fully supported. They are publicly available so that students and educational centers that do not have the physical robot or can not afford the costs of these, can nevertheless practice and learn or teach Robotics using these open platforms: DIY-PiBot and/or simulated-PiBot.

The increasing variability in power plant load, in response to a wildly uncertain electricity market and the need to to mitigate CO₂ emissions, lead power plant operators to explore advanced options for efficiency optimization. Model-based, system-scale dynamic simulation and optimization are useful tools in this effort, and the subject of the work presented here. In prior work, a dynamic model validated against steady-state data from a 605 MW subcritical power plant was presented. This power plant model is used as a test-bed for dynamic simulations, in which the coal load is regulated to satisfy a varying power demand. Plant-level control regulates plant load to match an anticipated trajectory of the power demand. The efficiency of the power plant operating at varying load is optimized through a supervisory control architecture that performs set point optimization on the regulatory controllers. Dynamic optimization problems are formulated to search for optimal time-varying input trajectories that satisfy operability and safety constraints during the transition between plant states. An improvement in time-averaged efficiency of up to 1.8% points is shown feasible with corresponding savings in coal consumption of 184.8 tons/day and carbon footprint decrease of 0.035 kg/kWh.

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.

We present an exact expression for the upscaled dynamic dispersion coefficient (D) for one-dimensional transport by Hagen-Poiseuille flow which is the basis for modeling transport in porous media idealized as capillary tubes. The theoretical model is validated by comparing the breakthrough curves (BTCs) from a 1D advection-dispersion model with dynamic D to that from direct numerical solutions utilizing a 2D advection-diffusion model. Both Taylor dispersion theory and our new theory are good predictors of D at lower Peclet Number (Pe) regime, but gradually fail to capture most parts of BTCs as Pe increases. However, our model generally predicts the mixing and spreading of solutes better than Taylor’s theory since it covers all transport regimes from molecular diffusion, through anomalous transport, and to Taylor dispersion. The model accurately predicts D based on the early part of BTCs even at relatively high Pe regime (~62) where the Taylor’s theory fails. Furthermore, the model allows for calculation of the time scale that separates Fickian from non-Fickian transport. Therefore, our model can readily be used to calculate dispersion through short tubes of arbitrary radii such as the pore throats in a pore network model.

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Abstract: This study aims to analyze the physico-mechanical properties and dynamic models of tissue-simulating hydrogels, specifically the photoacoustic (PA) response signals, by varying the concentrations of polyvinyl alcohol (PVA) and molecular weight (MW). A state space model (SSM) is proposed to study the PVA hydrogels to retrieve the PA-related signal's damping ratio and nat-ural frequency. Nine box-shaped PVA hydrogels containing saline solution were used, with five concentrations of PVA (7, 9, 12, 15, 20%) for MW1 and four for MW2. The results indicated that the concentration of PVA and MW played an important role in the PA wave's amplitude, arrival time, and speed of sound over the hydrogels. The SSM parameters showed that increasing PVA and MW concentrations improved the hydrogels' ability to absorb and transfer energy under the PA effect. These parameters were also found to be correlated with density and modulus of elasticity. Addi-tionally, the concentrations of PVA and MW affected the absorption and optical scattering coeffi-cients. The physical-mechanical properties, including porosity, density, and modulus of elasticity, improved as the concentration of PVA and MW increased. The ultimate goal of this study is to develop hydrogels as phantoms that can be used for tissue simulation and imaging.

Insecticidal toxins from Bacillus thuringiensis (Bt) are valuable tools for pest management worldwide, contributing to the management of human disease insect vectors and phytophagous insect pests of agriculture and forestry. Here, we report the effects of dual and triple Bt toxins expressed in transgenic cotton cultivars on the fitness and demographic performance of Helicoverpa zea (Boddie), a noctuid pest known as cotton bollworm and corn earworm. Life-history traits were determined for individuals of three field populations from a region where H. zea overwintering is likely. Triple-gene Bt cotton cultivars expressing Cry and Vip3Aa toxins killed 100% of the larvae in all populations tested. In contrast, dual-gene Bt cotton expressing Cry1Ac+Cry1F and Cry1Ac+Cry2Ab2 allowed population growth with the intrinsic rate of population growth (rm) 38% lower than on non-Bt cotton. The insects feeding on Bt cotton plants expressing Cry1Ac+Cry2Ab2, Cry1Ac+Cry1F, or Cry1Ab+Cry2Ae exhibited reduced larval weight, survival rate, and increased development time. Additionally, fitness parameters varied significantly among the insect populations, even on non-Bt cotton plants, likely because of their different genetic background and/or previous Bt toxin exposure. This is the first report of the comparative fitness of H. zea field populations on dual-gene Bt cotton after the recent reports of field resistance to certain Bt toxins. These results document the population growth rates of H. zea from an agricultural landscape with 100% Bt cotton cultivars. Our results will help to refine models designed to predict resistance evolution and improve insect resistance management for Bt crops.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Laser-induced fluorescence spectroscopy (LIFS) is actively used for remote sensing of atmospheric aerosols and currently is one of the most sensitive and selective techniques for determining small concentrations of substances inside particles. The use of high-power femtosecond laser sources for LIFS-based remote sensing of aerosol contributes to the development of new-generation fluorescence atmospheric lidars since it makes it possible overcoming the energy threshold for the nonlinear-optical effects of multiphoton absorption in particles and receiving the emission signal at long distances in the atmosphere. Our study is aimed to the development and experimental demonstration the technique of nonlinear laser-induced fluorescence spectroscopy (NLIFS) based on the remote excitation of aerosol fluorescent emission stimulated by a spatially-structured high-power femtosecond laser pulse. Importantly, for the first time to our knowledge, we demonstrate the advances of using stochastically-structured plasma-free intense light channels (postfilaments) specially formed by propagation of femtosecond laser radiation through a turbulent air layer for improving NLIFS efficiency. A multiple increase in the received signal of two-photon-excited fluorescence of polydisperse dyed aqueous aerosol by the structured postfilaments is reported.

Background: Although endoscopic submucosal dissection (ESD) can provide a high rate of curative resection, remaining gastric mucosa after ESD is at risk of metachronous recurrence. We investigated risk factors for metachronous superficial gastric epithelial neoplasms (MSGENs) following ESD. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. The primary endpoint was to identify clinicopathological risk factors for the occurrence of MSGENs. The secondary endpoint was to evaluate the association of Helicobacter pylori (Hp) eradication with the MSGENs. Results: Twenty-seven MSGENs were occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in upper or middle part (INUM) in the MSGEN group. The HIM group and INUM group had significantly higher cumulative incidence of MSGENs. We compared the 27 patients of MSGEN group and 27 patients of matched not-MSGEN (Mnot-MSGEN) group that was matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of Hp spontaneous eradication in the MSGEN group. Conclusion: HIM, INUM and Hp spontaneous eradication may be clinicopathological risk factors for developing MSGENs after ESD.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

The emergence of novel coronavirus (SARS-CoV-2) in marked as the highest pathogenic coronavirus that has crossed from the hosts to the human population in the twenty-first century. The spreading of COVID-19 in different chinese cities and around the world is travel-related viral spread with the unprecedented nosocomial outbreaks. It has also shown with high case-fatality rates, indeed to urgent prophylactic and therapeutic settings. Scientific advancements of the SARS-CoV-2 pandemic allowed for rapid progress to understand the epidemiology and pathogenesis of SARS-CoV-2. This review highlights the the genomic structure of SARS-CoV-2 with the proposed roles of genotype and phenotype of SARS-CoV-2 in pathogenesis and discuss recent results supporting treatment strategies of COVID-19 with a special focus on how these new insights may facilitate rational development of SARS-CoV-2 for targeted therapies in the future.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. Besides, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

Since December 2019, the world is fighting against coronavirus disease (COVID-19). This disease is caused by a novel coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work focuses on the applications of machine learning algorithms in the context of COVID-19. Firstly, regression analysis is performed to model the number of confirmed cases and death cases. Our experiments show that autoregressive integrated moving average (ARIMA) can reliably model the increase in the number of confirmed cases and can predict future cases. Secondly, a number of classifiers are used to predict whether a COVID-19 patient needs to be admitted to an intensive care unit (ICU) or semi-ICU. For this, classification algorithms are applied to a dataset having 5644 samples. Using this dataset, the most significant attributes are selected using features selection by ExtraTrees classifier, and Proteina C reativa (mg/dL) is found to be the highest-ranked feature. In our experiments, random forest, logistic regression, support vector machine, XGBoost, stacking and voting classifiers are applied to the top 10 selected attributes of the dataset. Results show that random forest and hard voting classifiers achieve the highest classification accuracy values near 98%, and the highest recall value of 98% in predicting the need for admission into ICU/semi ICU units.

We study the deterministic dynamics of N point particles moving at constant speed in a 2D table made of two polygonal urns connected by an active rectangular channel, which applies a feedback-control on the particles, inverting the horizontal component of their velocities, when their number in the channel exceeds a fixed threshold. Such a bounce--back mechanism is non-dissipative: it preserves volumes in phase space. An additional passive channel closes the billiard table forming a circuit in which a stationary current may flow. Under specific constraints on the geometry and on the initial conditions, the large N limit allows nonequilibrium phase transitions between homogeneous and inhomogeneous phases. The role of ergodicity in making a probabilistic theory applicable is discussed both for rational and irrational urns. The theoretical predictions are compared with the numerical simulation results. Connections with the dynamics of feedback-controlled biological systems are highlighted.

This paper presents a case study of Fulani herdsmen in Nigeria, whose traditional ethnoveteri-nary practices risk being lost as the country transitions to more intensive and enclosed livestock practices. We use a planetary health framing to make visible the value of indigenous practices that are less damaging to the environment, animal welfare and human health. Through ethnographic observation, focus group discussions (FGD) and key stakeholder interviews, we show that the Fulani use a complex system of herbal medicines and traditional herding practices to maintain herd health, manage and treat animal disease when it arises. However, their traditions often sit uncomfortably with commercial farming practices. As traditional Fulani grazing lands are eroded, dispossessed Fulani take employment from businessmen farmers but both parties’ inex-perience with shed hygiene, artificial feed and less environmentally resilient crossbreeds leads to increased incidence of infectious disease. This in turn drives higher use of antibiotics. There is a ‘causal chain’ of underlying drivers that leads, through poorer environmental, animal and hu-man health, to increased use of antibiotics. The antibiotic resistance that emerges from this chain threatens human health now and into the future. Through a planetary health framing we advocate for more respect for Fulani herdsmen and their traditional ethnoveterinary practices as an alter-native to increasing antibiotic use.

While referral-level medicine is important in the veterinary curriculum, students also need a solid base knowledge of clinically relevant routine surgery and diagnostic skills. Veterinary hospitals must maintain a steady caseload that provides wellness cases and commonly encountered conditions. Shelter Medicine programs can create the opportunities to meet these challenges. Students can gain quantifiable surgical experience in spay/neuter with measured growth in surgical efficiency and competency while providing needed community service for animal shelters. Students can directly interact with shelter animals by performing examinations, diagnostic testing, and development of treatment protocols and recommendations for commonly encountered problems. Furthermore, students can obtain a working knowledge of biosecurity on a population level to minimize risk of infectious diseases spreading to healthy populations.

Anion doping of tungsten trioxide by nitrogen is used to obtain electrochrome cathode material, the spectral transmittance of which can be controlled by the doping level. A series of samples was synthesized by reactive magnetron sputtering of a metal tungsten target in a mixture of argon, nitrogen and oxygen gases. Warm-colored tungsten oxynitride films were prepared at higher doping levels and characterized using scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy techniques. Optical properties were measured making use of transmission spectrophotometry and spectroscopic ellipsometry. These extensive experimental studies revealed an increase in absorption towards shorter wavelengths with increasing the doping level. At the same time, it was found that with increasing the doping level, the fraction of non-stoichiometric oxygen also steadily increases to half the total oxygen content. The imperfection of the doped material can stimulate its intercalation with electrolyte ions, accelerating the coloring/bleaching process and increasing the dynamical range between the dark and clear states, thus improving the consumer qualities of electrochemical materials and devices.

The sensitivity of exercise ECG is marginally sufficient for detection of mild reduction of coronary blood flow in patients with early coronary atherosclerosis. Here we describe the application of new technique of ECG registration/analysis – ultrahigh resolution ECG (UHR ECG) – for early detection of myocardial ischemia (MIS). The utility of UHR ECG vs. conventional ECG (C ECG) was tested in anesthetized rats and pigs. Transmural MIS was induced in rats by the ligation of the left coronary artery (CA). In pigs, subendocardial ischemia of variable extent was produced by stepwise inflation of balloon within the right CA causing 25-100% reduction of its lumen. In rats, a reduction in power spectral density (PSD) in high-frequency (HF) channel of UHR ECG was registered at 60 s after ischemia (power 0.81±0.14 vs. 1.25±0.12 mW at baseline, p<0.01). This was not accompanied by any ST segment elevation on C ECG. In pigs, PSD in HF channel of UHR ECG was significantly decreased at 25% reduction of CA lumen, while ST segment on C ECG remained unchanged. In conclusion, UHR ECG enabled earlier detection of transmural MIS compared to C ECG. PSD in HF-channel of UHR ECG demonstrated greater sensitivity in the settings of subendocardial ischemia.

An open source computational fluid dynamics (CFD) solver has been incorporated into the WindNinja modeling framework widely used by wildland fire managers as well as researchers and practitioners in other fields, such as wind energy, wind erosion, and search and rescue. Here we describe incorporation of the CFD solver and evaluate its performance compared to the conservation of mass (COM) solver in WindNinja and previously published large-eddy simulations (LES) for three field campaigns conducted over isolated terrain obstacles of varying terrain complexity: Askervein Hill, Bolund Hill, and Big Southern Butte. We also compare the effects of two important model settings in the CFD solver and provide guidance on model sensitivity to these settings. Additionally, we investigate the computational mesh and difficulties regarding terrain representation. Two important findings from this work are: (1) the choice of discretization scheme for advection has a significantly larger effect on the simulated winds than the choice of turbulence model and (2) CFD solver predictions are significantly better than the COM solver predictions at windward and lee side observation locations, but no difference was found in predicted speed-up at ridgetop locations between the two solvers.

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein gene vp3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential for infectivity. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

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.

The plantar plate (PP) tear of the second metatarsophalangeal joint (MTPJ) is the most common reason for forefoot pain in clinical practice. PP is the main stabilizing structure of the joint and, together with collateral ligaments, is the key to maintaining the stability of MTPJ. Many surgical procedures have been described to repair PP tears. Currently, there is still controversy regarding which is the surgical superior option (direct versus indirect PP repair techniques). Transfer of the flexor digitorum longus tendon to the dorsum of the proximal phalanx is one of the surgical techniques described to treat PP tears associated with MTPJ instability. We present two cases that developed instability of the second MTPJ secondary to chronic PP tear with symptoms resolved after transfer of the flexor digitorum longus (FDL). Currently, the literature review shows that the procedure seems to be the most consistent surgical option in chronic cases of PP tears.

Good hand hygiene has proven to be essential in reducing the uncontrolled spread of human pathogens. Cold atmospheric plasma (CAP) may provide an alternative to disinfecting hands with ethanol-based handrubs when hand washing facilities are unavailable. CAP can be safely applied to the skin if the energy is well controlled. In this study, RF and DC plasma sources was built with a pin-to-mesh electrodes configuration inside a fused silica tube of 5 mm of inner diameter. Microbiological assays based on EN 13697:2015+A1:2019 using Escherichia coli DSM 682 or Staphylococcus epidermidis DSM 20044 were used to examine the antimicrobial effect of various plasma conditions. Metal and silicone disks that model skin were used as inoculation matrices. The prototype air radio frequency (RF) CAP achieved significant disinfection in the MHz range on stainless steel and silicone substrates. This is equivalent to half the performance of direct current CAP, which is only effective on conductive substrates. Using only electricity and air CAP could, with further optimization, replace or complement current hand disinfection methods, and mitigate the economic burden of public health crises in the future.

New developments in broadcast technology, such as the ad hoc wireless network and the detection devices that work, enable daily connections to the Internet, commonly referred to as the Internet of Things (IoT). IoT saw this as a support for the development of creative and contextual services and applications. The service can respond to the user's environment and preferences. Finite state machines are recently making waves when the issue of self-controlling systems come into the picture of designs. This research focuses on the design of a fault tolerant system that controls random failures impressed on the network. The method comprises of diodes, Resistors, Optocouplers, ESP8266 WI-FI Module Webpage with button, and two Arduinos which in effect will determine iteratively who to handle a failure at hand modelled as when the button on the webpage is pressed. In this work, a Heartbeat Detection and Monitoring System will be made using Arduino that detect the electrical state using the Pulse Sensor and show the readings in Beats Per Minute on the LED connected a microcontroller. It sends the texts to the server using the Wi-Fi module ESP8266 to signals can be monitored from the monitoring zone via the internet. This is reflected by the declaration of a master state by either of two Arduinos whenever the push button is pressed as observed on the codes. The result obtained from the research shows apparently, the state of the fault tolerance system none power deny of heartbeat condition connected to the LED.

Recently, fasting has been spotlighted from a healthcare perspective. However, the de-tailed biological mechanisms and significance by which the effects of fasting confer health benefits are not yet clear. Due to certain advantages of zebrafish, as a vertebrate model widely utilized in biological studies, we used mRNA-sequencing and bioinformatics analysis to examine comprehensive gene expression changes in skeletal muscle tissues during fasting-refeeding. Our results produced a novel set of nutrition-related genes under a fasting-refeeding protocol. We found five dramatically upregulated genes in each fasting (for 24 hours) and refeeding (after 3 hours), exhibiting a rapid response to the provided conditional changes. The assessment of the gene length revealed, the gene set whose expression was elevated only after 3 hours of refeeding had a shorter length, suggesting that nutrition-related gene function is associated with gene length. Taken together, our results from bioinformatics analyses provide new insights into biological mechanisms induced by fasting-refeeding conditions within zebrafish skeletal muscle.

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

C-X-C motif chemokine receptor 3 (CXCR3, CD183) is a G-protein-coupled receptor for CXCL9, CXCL10, and CXCL11. CXCR3 signaling induces chemotaxis of immune cells to inflammation sites and promotes inflammation in inflammatory diseases. Various mouse models to mimic the pathogenesis of each disease have been developed to understand mechanisms and evaluate therapeutics for these diseases. Although CXCR3 is an attractive target to suppress inflammation, anti-CXCR3 therapeutic agents have not been approved. In this study, we established a novel anti-mouse CXCR3 (mCXCR3) monoclonal antibody, Cx₃Mab-4 (rat IgG₁, kappa), using the Cell-Based Immunization and Screening method. Flow cytometric analysis demonstrated that Cx₃Mab-4 bound to mCXCR3-overexpressed Chinese hamster ovary-K1 (CHO/mCXCR3) cells, but did not react to parental CHO-K1 cells. The dissociation constant of Cx₃Mab-4 was determined as 1.3 × 10^-9 M, indicating that Cx₃Mab-4 possesses a high affinity to mCXCR3-expressing cells. Cx₃Mab-4 could be useful for targeting CXCR3-expressing cells in preclinical mouse models.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC with peritoneal metastasis exhibits a poor prognosis due to the lack of diagnostic biomarkers and effective therapy. A comprehensive analysis of malignant ascites identified the genomic alterations and significant amplifications of cancer driver genes, including CD44. CD44 and its splicing variants are overexpressed in tumors, and play crucial roles in the acquisition of invasiveness, stemness, and resistance to treatments. Therefore, the development of CD44-targeting monoclonal antibodies (mAbs) is important for GC diagnosis and therapy. In this study, we immunized mice with CD44v3–10-overexpressed PANC-1 cells and established several dozens of clones that produce anti-CD44v3–10 mAbs. One of the clones (C44Mab-94; IgG1, kappa) recognized the variant-8-encoded region and peptide, indicating that C44Mab-94 is a specific mAb for CD44v8. Furthermore, C44Mab-94 could recognize CHO/CD44v3–10 cells, oral squamous cell carcinoma cell line (HSC-3), or GC cell lines (MKN45 and NUGC-4) in flow cytometric analyses. C44Mab-94 could detect the exogenous CD44v3–10 and endogenous CD44v8 in western blotting and stained the formalin-fixed paraffin-embedded gastric cancer cells in immunohistochemistry. These results indicate that C44Mab-94 is useful for detecting CD44v8 in various applications and is expected to be useful for the application of GC diagnosis and therapy.

CD44 is a cell surface glycoprotein, and its isoforms are produced by the alternative splicing with the standard and variant exons. The CD44 variant exon containing isoforms (CD44v) are overexpressed in carcinomas. CD44v6 is one of the CD44v, and its overexpression predicts poor prognosis in colorectal cancer (CRC) patients. CD44v6 plays critical roles in CRC adhesion, proliferation, stemness, invasiveness, and chemoresistance. Therefore, CD44v6 is a promising target for cancer diagnosis and therapy for CRC. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO) cells. We then characterized them using enzyme-linked immunosorbent assay, flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-9; IgG1, kappa) reacted with a peptide of variant 6-encoded region, indicating that C44Mab-9 recognizes CD44v6. Furthermore, C44Mab-9 reacted with CHO/CD44v3-10 cells or CRC cell lines (COLO201 and COLO205) by flow cytometry. The apparent KD of C44Mab-9 for CHO/CD44v3-10, COLO201, and COLO205 was 8.1 × 10−9 M, 1.7 × 10−8 M, and 2.3 × 10−8 M, respectively. C44Mab-9 detected the CD44v3-10 in western blotting, and partially stained the formalin-fixed paraffin-embedded CRC tissues in immunohistochemistry. Collectively, C44Mab-9 is useful for detecting CD44v6 in various applications.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

Ischemia/reperfusion (I/R) injury results in cell death by inducing apoptosis. During I/R, early generation of mitochondrial reactive oxygen species (mtROS) can induce neighboring mitochondria to release additional ROS, a toxic cycle resulting in significant mitochondrial and cellular injury. Oxidative damage in the mitochondria contributes to various pathologies, including I/R injury. Accordingly, preventing mitochondrial oxidative damage should be therapeutically relevant for many disorders, including cardiovascular diseases. We recently discovered an Indole-Peptide-Tempo Conjugate (IPTC) that served as a novel bifunctional agent with both antioxidant and autophagy-modulating capacity. Here, we demonstrate that IPTC can protect H9C2 cardiomyocytes from hypoxia/reoxygenation (H/R) injury that results from mtROS overproduction due to impaired mitophagy and resultant mitochondrial dysfunction. We hypothesize that the mechanism of action of IPTC involves the capacity to decrease mtROS combined with induction of mitophagy.

CD44 is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. CD44 is involved in cell adhesion, migration, proliferation, survival, stemness, and chemo-resistance. Therefore, CD44 is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10 ectodomain and screening using enzyme-linked immunosorbent assay. We then characterized them using flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-46; IgG1, kappa) reacted with CD44s-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44s) or esophageal squamous cell carcinoma (ESCC) cell lines (KYSE70 and KYSE770). The KD of C44Mab-46 for CHO/CD44s, KYSE70, and KYSE770 was 1.1×10-8 M, 4.9×10-8 M, and 4.1×10-8 M, respectively. C44Mab-46 detected CD44s of CHO/CD44s and KYSE70, and CD44v of KYSE770 in western blot analysis. Furthermore, C44Mab-46 strongly stained esophageal squamous carcinoma cells in immunohistochemistry using formalin-fixed paraffin-embedded ESCC tissues. Taken together, C44Mab-46 is very useful for detecting CD44 in various applications.

C-C motif chemokine receptor 1 (CCR1/CD191) is a member of G-protein-coupled receptors, and is expressed on myeloid cells, such as neutrophils and macrophages. Because the CCR1 signaling promotes tumor expansion in the tumor microenvironment (TME), the modification of TME is an effective strategy for cancer therapy. Although CCR1 is an attractive target for solid tumors and hematological malignancies, anti-CCR1 therapeutic agents have not been approved. Here, we established a novel anti-mouse CCR1 (mCCR1) monoclonal antibody (mAb), C₁Mab-6 (rat IgG_2b, kappa), using the Cell-Based Immunization and Screening (CIBS) method. Flow cytometry and Western blot analyses showed that C₁Mab-6 recognizes mCCR1 specifically. The dissociation constant of C₁Mab-6 for mCCR1-overexpressed Chinese hamster ovary-K1 was determined as 3.9×10^-9 M, indicating that C₁Mab-6 possesses a high affinity to mCCR1. These results suggest that C₁Mab-6 could be a useful tool for targeting CCR1 in preclinical mouse models.

Copper-nitride (Cu3N) material is attracting much attention as a potential next-generation thin-film solar-light absorber. In this work, polycrystalline Cu3N thin films were prepared using reactive-RF-magnetron sputtering, at room temperature,onto glass and silicon substrates. The optical properties of the Cu3N thin layers were studied by spectroscopic ellipsometry and transmission, to achieve a low-cost absorber material to replace conventional silicon. The reactive-RF-sputtered Cu3N films were also investigated by FIB-SEM microscopy and FTIR spectroscopy.

To meet an ever global population's food demand, crop yields must be sustained and increased. Drought, which is getting harsher as a result of global warming, is largely impeding the agricultural productivity. Maize is widely used as food and animal feed in many regions of the world, but its yields are largely effected by drought and heat stress. Historical data on climate change predicts that drought and heat stress becoming major threat for maize cultivation in coming years, which will have huge impact on food security of the world especially in Africa and Asia. Thus there is an immense necessary to develop drought tolerant and climate resilient maize to feed the predicted population of the world. Availability and accessibility of crop genetic resources plays a huge role in development of drought-tolerant maize cultivars. A huge genetic resources of maize, including its landraces and crop wild relatives (CWR) have been reported naturally and many of them have stored in National and International gene banks globally. Conventional breeding methods have been tremendously increased maize yields, but these methods frequently fall short of achieving the demand for improved drought stress resistance. In this article, we have briefly discussed about impact of climate variability on crop production, maize yield losses due to drought, drought tolerance in maize landraces and CWR, and origin and evolution of Mexican landraces. This information may help in utilization of these potential resources in various pre-breeding programs.

Background: Antiplatelet medications such as aspirin and clopidogrel are used following thrombotic stroke or transient ischemic attack (TIA) to prevent a recurrent stroke. However, the antiplatelet treatments fail frequently, and patients experience recurrent stroke. One approach to lower the rates of recurrence, may be the individualized antiplatelet therapies (antiplatelet therapy modification (ATM)) based on the results of platelet function analysis (PFA). This review was undertaken to gather and analyse the evidence about the effectiveness of such approaches. Methods: We searched Medline, CINAHL, Embase, Web of Science and Cochrane databases to 7 January 2020. Results: Two observational studies involving 1136 patients were included. The overall effects of PFA-based ATM on recurrent strokes (OR 1.05; 95% CI 0.69 to 1.58), any bleeding risk (OR 1.39; 95% CI 0.92 to 2.10) or death hazard from any cause (OR 1.19; 95% CI 0.62 to 2.29) were not significantly different from the standard antiplatelet therapy without ATM. Conclusions: The two studies showed opposite effects of PFA-guided ATM on the recurrent strokes in aspirin non-responders, leading to an insignificant difference in the subgroup meta-analysis (OR 1.59; 95% CI 0.07 to 33.77), while the rates of any bleeding events (OR 1.04; 95% CI 0.49 to 2.17) or death from any cause (OR 1.17; 95% CI 0.41 to 3.35) were not significantly different between aspirin non-responders with ATM and those without ATM. There is a need for large randomized controlled trials which account for potential confounders such as ischemic stroke subtypes, technical variations in the testing protocols, patient adherence to therapy, and pharmacogenetic differences.

Water scarcity challenges have necessitated the adoption of water-saving techniques in protected and nom-protected farming. This study aimed to assess the performance of a water-saving soil-less cultivation technique and to compare it with conventional soil-based cultivation in protected farming. The soilless technique used local gravel and a mixture of peat-moss, humin-substrate, and perlite in ratios of 4:3:1.5. Three irrigation regimes were imposed using emitters 8Lh-1 design discharge (D1) emitters with 6Lh-1 design discharge (D0.75) and 4Lh-1 de-sign discharge (D0.5) for the two cultivation methods during the growth cycle of tomato by drip irrigation. The vegetative growth, fruit yield and water consumption were measured and water productivity was determined. Moreover, an economic assessment was carried out by estimating and comparing economic coefficients for the two cultivation methods. Estimated coefficients include revenues, net profit, benefit-cost ratio, break-even levels of production and prices, revenues over variable cost, and revenues on investment. The tomato fruit yield under soil-based cultivation overtopped the yield under soilless cultivation. The water productivity under the soilless cultivation was almost twice that (24.3 kg m-3) of the soil-based cultivation (15.5 kg m-3). The soilless cultivation saved 50% of irrigation water applied by the conventional soil-based method, saving energy and soil from deterioration. Revenues and net profits stimulated by higher yield coupled with lower variable cos supported the soil-based cultivation. The economic assessment showed that both cultivation methods were economically viable. However, the soil-based cultivation method was more profitable due to its higher fruit yield. Overall, the results of this study suggest that the soilless cultivation technique is a viable option for wa-ter-saving cultivation. However, the soil-based cultivation method is still more profitable due to its higher fruit yield

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism of action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis,and antiviral mechanism of action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanism of actions as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.

Originally developed to image the shadow region of the central black hole in Sagittarius A* and in the nearby galaxy M87, the Event Horizon Telescope (EHT) provides deep, very high angular resolution data on other AGN sources too. The challenges of working with EHT data have spurred the development of new image reconstruction algorithms. This work briefly reviews the status of the EHT and its utility for observing AGN sources, with emphasis on novel imaging techniques that offer the promise of better reconstructions at 1.3 mm and other wavelengths.

Results of geological and geophysical investigations of the Siljan Ring impact structure (central Sweden) revealed complicated relationships between Paleozoic sedimentary succession and the Precambrian basement. Tectonic and depositional evolution caused complex geology. Studies of a new drill core from the C-C-1 well provide information necessary for the reconstruction of the geological setting in the southwestern part of Siljan Ring. The whole interval of the core section is from 32.60 to 634.90 m with almost no breaks. The sedimentary cover is 373.55 m thick in total. The sedimentary sequences are predominantly composed of wackestones, mudstones, and shales. In the lower part of the sedimentary section, limestone layers intercalate with black shales. In a result of the investigations, it has been suggested that sedimentary layers represent Late Ordovician and Silurian deposits and have disturbed stratigraphic relations. The basement section is composed of Precambrian meta-volcanic and meta-sedimentary rocks. The contact between the basement and the sedimentary cover is tectonic, not normal sedimentary, in origin. Tectonic processes caused intensive rock fracturing. Four generations of fractures were identified with analysis of fracture relations and mineralization sequence. Only two of them occur in sedimentary rocks that probably belong to the latest stages of tectonic activity. Highly fractured basement rocks in some cases contain open vugs developed along the fractures. Rock matrix is tight either in sedimentary and basement rocks and only micro-porosity space is recognized in cataclastic zones. Single evidence of bituminous filling of micro-porosity zone and partly cemented vug is established in limestone from the lower part of the sedimentary section. These findings are particularly valuable for stratigraphy refinement and tectonic setting reconstructions as well as oil and gas reservoir forecasts.

Ginkgolic acids (GA) have been reported to exhibit anticancer properties, however, the mechanisms remain unclear. This study aims to investigate the mechanisms of GA C13:0 that was isolated from Ginkgo biloba exocarp (GBE) for anti-proliferation, pro-apoptosis and anti-migration effects in human MCF-7 and mouse 4T-1 breast cancer cells. The cytotoxic effect, apoptosis induction and migration inhibition were measured using MTT, TUNEL and Wound healing assays. The expression of mRNA and protein were determined using qPCR and Western blot. Our results showed that no cytotoxicity was found at concentrations of C13:0 below 100µM. The effects of GA C13:0 was further demonstrated by up-regulation of the Bax/Bcl-2 apoptosis pathway and the expression of Apaf-1 protein in the mitochondria. In addition, GA C13:0 also suppressed cell migration and epithelial to mesenchymal transition (EMT) with the increase of E-cadherin expression accompanied by the decrease of Snail, MMP-2, MMP-9 and Vimentin expression. Moreover, GA C13:0 induced cytochrome P450 (CYP) 1B1 expression in aryl hydrocarbon receptor (AhR) pathway. Notably, the up-regulation of CYP1B1 also might play a pivotal regulatory role in mitochondrial and EMT pathways in MCF-7 and 4T-1 cells. Our results may have implications for the development of anticancer agents containing GA as functional additives.

African indigenous herbs and medicinal plants are extensively reported for their protective and therapeutic potential against Diabetes. However, most of the constituent phytochemicals that may account for the therapeutic activity are largely uninvestigated. Exploring novel phytochemical–target interactions in silico could help to provide useful insights into the mechanism underpinning the biological activities of these plants and their constituent phytochemicals. The aim of this study was to explore the interactions of terpene struc-tures previously reported from selected African antidiabetic with two emerging drug targets in diabetes. Structure-based virtual screening was used to screen 107 terpene structures against DPP-4 and PTP1B enzymes. The MD simulation, MM-GBSA free energy calculation and DFT were used to clarify the inter-actions of the in silico hits with the target enzymes. Molecular docking, post-docking Prime MM-GBSA analysis revealed the top terpenes with high binding affinity with the active site regions of DPP-4 and PTP1B. Ensemble docking revealed three triterpenes viz: cucurbitacin B (T1), 6-Oxoisoiguesterin (T4) and 20-Epi-isoiguesterinol (T2) as in silico hits which exhibit strong interaction potential with critical residues that define the catalytic triad (Ser630 and His740); oxyanion cavity (Ser631); hydrophobic S1 pocket (Tyr662) and the charged S2 pocket (Arg125) in the active site region of DPP-4. The interactions of these compounds with DPP-4 exhibited structural stability and conformational flexibility during 100 ns full atomistic MD simulation as indicated by the structure dynamics parameters including RMSD, RoG, SASA and hydrogen bond number. The post-MD MM/GBSA calculations further revealed the stability of the triterpene-DPP-4 complexes. Furthermore, Frontier molecular orbital calculations showed that, the triterpenes possess high interaction potential with the enzyme. The triterpenes showed desirable ADMET properties and drug-likeness. Therefore, cucurbitacin B, 6-Oxoisoiguesterin and 20-Epi-isoiguesterinol are recommended for experimental validation.

The burden of bacterial bloodstream infections (BSIs) is rapidly increasing in Africa including Rwanda. This is a retrospective study investigates the diversity, distribution, and antimicrobial susceptibility profiles of BSIs bacteria in three tertiary referral hospitals in Rwanda between 2020 and 2022. A total of 1,532 blood culture tests were performed for visiting patients. Overall, the proportions of Gram-negative and Gram-positive bacteria were 48.2% and 51.8, respectively. Staphylococcus aureus was the predominant species accounting for 25% of all Gram-positive BSIs species and Klebsiella species representing 41% of all Gram-negative BSIs species. Antimicrobial susceptibility testing revealed that Amikacin exhibited the highest activity against Enterobacter spp., Serratia spp. and Escherichia coli in &gt;92% of cases and Klebsiella spp. in 75.7%. Meropenem and Imipenem were highly efficacious to Salmonella spp. (100% susceptibility), Enterobacter spp. (96.2% and 91.7%, respectively), and Escherichia coli (94.7% and 95.5%, respectively). The susceptibility of Enterococcus spp., S. aureus, and Streptococcus spp. to Vancomycin was 100%, 99.5% and 97.1%, respectively. Klebsiella spp. was highly sensitive to Colistin (98.7%), Polymyxin B (85.6%), Imipenem (84.9%), and Meropenem (78.5%). We recommend strengthening the implementation of integrated transdisciplinary and multisectoral One Health including AMR-stewardship for the surveillance, prevention, and control of AMR in Rwanda.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O2), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, Oxygen nanoBubbles (OnB), an emerging versatile oxygen de-livery platform, implies to offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

The multidrug-resistant fungal pathogens belonging to the Candida haemulonii complex and the phylogenetically related species Candida auris are well-known for causing infections that are difficult to treat due to their multidrug-resistance profile. C. auris is even more worrisome due to its ability to cause outbreaks in healthcare settings. These emerging yeasts produce a wide range of virulence factors that facilitate the development of the infectious process. In recent years, the aggregative phenotype has been receiving attention, as it is mainly associated with defects in cellular division and its possible involvement in helping the fungus to escape from host immune responses. In this study, we initially investigated the aggregation ability of 18 clinical isolates belonging to the C. haemulonii species complex and C. auris. Subsequently, we evaluated the effects of physicochemical factors on the fungal aggregation competence. The results demonstrated that cell aggregation was a typically time-dependent event, in which almost all studied fungal isolates exhibited high aggregation after 2 h of incubation at 37°C. The aggregation was not impacted by pH, temperature, -mercaptoethanol (a protein-denaturing agent) and EDTA (a chelator agent). Conversely, proteinase K, trypsin and sodium dodecyl sulfate significantly diminished the aggregation. Collectively, our results demonstrated that the aggregation ability in these opportunistic yeast pathogens is time-dependent, and surface proteins and hydrophobic interactions seem to mediate cell aggregation, since the presence of proteases and anionic detergent affected the aggregation ability. However, further studies are necessary to better elucidate this phenomenon.

Advanced cutaneous melanoma is considered the most aggressive type of skin cancer with variable rates of treatment response. Nowadays, there are available some classes of immunotherapy and target therapy for its treatment. Immunotherapy can inhibit tumor growth and its recurrence by triggering host's immune system, while targeted therapy acts inhibiting specific molecules or signaling pathways. However, melanoma response to these treatments are highly heterogenous, and frequently become resistant. Epigenome (DNA/histone modification) contribute to cancer initiation and progression. Epigenetic alterations are divided into four levels of gene expression regulation: DNA methylation, histone modification, chromatin remodeling and non-coding RNAs regulation. The deregulation of lysine methyltransferase enzymes is associated with tumor initiation, invasion, development of metastases, changes in immune microenvironment and drug resistance. The study of lysine histone methyltransferase (KMT) inhibitors is important to cancer epigenetic mechanisms understanding and to biological processes. In addition to immunotherapy and target therapy, the research and development of KMT inhibitors is ongoing. Many studies are exploring the therapeutic implications and possible side effects of these compounds, besides their adjuvant potential to the approved current therapies. Importantly, as with any drug development, safety, efficacy, and specificity are crucial considerations when developing KMT inhibitors for clinical applications.

Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports proposed that the black spots (called melanized focal changes (MFC)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFC, and also of red pigment (called red focal changes (RFC)), of salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis. This revealed that the MFC contain 3,4-dihydroxyphenylalanine (DOPA)-derived eumelanin whereas the RFC only contain trace amounts of eumelanin. Therefore, probably, the black color of MFC can be explained by the presence of eumelanin from accumulated melanomacrophages. For the red pigment, we could not find a significant signature of either eumelanin or pheomelanin, and the red color is probably predominantly hemorrhagic in nature. However, we found that in RFC the level of pigmentation did increase together with some melanogenic metabolites. Comparison with a “mimicking experiment,” in which a mixture of a salmon homogenate + DOPA was oxidized with tyrosinase, suggested that the RFC include conjugations of DOPAquinone and/or DOPAchrome with salmon muscle tissue proteins. In short, the results suggest that melanogenic metabolites in MFC and RFC derive from different chemical pathways, which would agree with the two different colorations deriving from distinct cellular origins, namely melanomacrophages and red blood cells, respectively.

Background: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, France) is a microscope that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. Objective: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two fol-low-up appointments: one and two years after the study, beginning with rtx1 image acquisition, visual acuity assessment, macular OCT scans and blood measurements. Results: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements have shown decreased photoreceptor and microvascular parameters in the DR group compared to the control group. Furthermore, in the 2-year follow-up, both groups' rtx1-acquired morphological changes were statistically significant. Conclusions: Rtx-1 technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study has revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.

Aims: This study aims to evaluate the impact of family-centered empowerment on Jordanian adolescents with type 1 diabetes (T1DM), focusing on their HbA1c levels, self-efficacy, and quality of life (QOL). Background: Poor glycemic management in adolescents with type 1 diabetes increases complications. Improved control is linked to various variables, but few studies focus on Middle Eastern populations. Methods: An experimental study involved 68 adolescents with T1DM visiting Jordanian Royal Medical Services' clinics. Two sets of participants were created: control (n = 34) and intervention (n = 34). Data was collected through face-to-face interviews and medical records. Results: The study found significant differences in self-efficacy scores between the intervention and control groups, with the intervention group experiencing a significant decrease in HbA1c readings and a significant difference in QOL between pre-program and post-program phases. Discussion: Family empowerment can significantly improve the lives of Jordanian teenagers with type 1 diabetes. This strategy leads to improved glycemic management, increased self-efficacy, and improved quality of life. Future treatments and health policies should recognize and value the critical role families play in the care of this population. Conclusion: The study suggests that patients with T1DM should receive continuous care education sessions, including self-care training, to improve their health. Nurses should also incorporate these training into treatment plans and educational programs for adolescents to enhance their QOL.

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease characterized by mature B-cell neoplasms. The standard immunochemotherapy for DLBCL is R-CHOP, which includes rituximab, cyclophosphamide, doxoru-bicin, vincristine, and prednisone. Up to 30-40% of patients with DLBCL either exhibit primary refractory disease to standard treatment or experience relapse after the initial response. A 72-year-old man diagnosed with DLBCL involving chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) showed primary refractory disease after the fourth cycle of R-CHOP. The patient ultimately experienced cardiac involvement by the lymphoma and received salvage chemotherapy. He passed away about 15 months away after the diagnosis of DLBCL. We conducted fluorescence in situ hybridization (FISH) for further analysis of the chromosomal translocations. The breakpoint of chromosome 1q21 was located at a distance of around 151 Mb from the telomeric end of chromosome 1p. The breakpoint in chromosome 22q11 contains the immunoglobulin lambda locus. Furthermore, the breakpoint of chromosome 6p was in the telomeric region of chromosome 6p21. The breakpoint of chromosome 18q21 contains BCL2. This case report presents the first documented co-occurrence of chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) in a patient with DLBCL. These chromosomal translocations may indicate a worse clinical outcome.

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention to prevent malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change of amino acid leading to non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014-2021. Criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of IR mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

The renin-angiotensin system (RAS) plays a role in cardiovascular homeostasis and hydro-electrolyte balance influencing organ function throughout the body. The classical view of RAS focused on a single biologically active metabolite, the octapeptide angiotensin (Ang)ll, created by the Angiotensin-converting enzyme (ACE). The past two decades have revealed new functions for intermediate products of the RAS beyond their role as substrates. Angiotensin 1-7 (Ang-(1—7), a RAS peptide product with actions at the Mas receptor, reportedly prevents cardiovascular disease-induced cognitive decline and cancer-induced bone pain (CIBP). However, Ang-(1—7) has a short half-life in vivo; here, we hypothesized that activating the MasR1 with a lactoside Ang-(1—7) analogue- PNA6-would attenuate inflammatory, cancer pain confined to the long bones, and chemotherapy-induced peripheral neuropathy (CIPN) for a longer-lasting efficacious therapeutic effect. PNA6, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-Lact)-amide, was successfully synthesized on solid phase peptide synthesis (SPPS). PNA6 significantly reversed inflammatory pain induced by 2% carrageenan in mice. In a second study modeling a complex pain state, E0771 breast adenocarcinoma cells were implanted into the femur of female C57BLK/6J wild-type mice to induce cancer-induced bone pain (CIBP). Both acute and chronic dosing of PNA6 significantly reduced the spontaneous pain behaviors associated with CIBP. A third murine model of platinum drug-induced painful peripheral neuropathy was established using oxaliplatin. Mice in the oxaliplatin-vehicle treatment groups demonstrated significant mechanical allodynia compared to oxaliplatin- PNA6 treatment group mice. These data suggest that PNA6 is a viable lead candidate for treating chronic inflammatory and complex neuropathic pain.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

The main question proposed in this research is if different types of organizational approach, adapted from rapidly changing disciplines — such as IT industry, and software engineering in particular — could help overcome this gap by shortening the response time needed to analyze advanced solutions in accordance with changed circumstances, thus allowing for architectural programming to obtain different positions in the timeline of project planning and realization. We propose a novel methodology of architectural design as a self-reliant instrument inspired by Agile Manifesto and some of its instantiations, most notably by the Scrum Framework.

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed transcriptomic changes observed in epidermal PPARγ deficient mice (Pparg-/-epi). Gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis and cell survival. Single cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and or mouse actinic keratoses (AK) and cutaneous squamous cell carcinomas (SCCs) revealed strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AK and SCC. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably. these changes are not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes while Ppard was highly expressed in myofibroblasts, suggesting a role for PPARδ in myofibroblast differentiation. In conclusion, these data indicate PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs.

Ready-to-eat fresh fruit have an increasing presence in international markets due to its convenience and health benefits. However, these produces are highly perishable and efficient technologies to increase their shelf life are needed. In the present research, different citrus fruit species and cultivars from organic farming were assayed to obtain enzymatically citrus segments. The best results in terms of segment quality were observed for ‘Hernandina’ clementine which was chosen to make a new ready-to-eat produce based on peeled citrus segments packaged in glass jars with slight syrup made on citrus juice and organic sugar cane. The most appreciated syrup was those containing 50-50 (v/v) of ‘Fino’ lemon juice and ‘Hernandina’ clementine based on the sensory scores given by the panellists. In addition, different pasteurization treatments were assayed to preserve the new produce safety and nutritional and sensory quality properties during storage at cold temperature. Results showed that pasteurization treatment at 50 °C for 45 min could be enough to avoid microbial contamination with mesophilic and psychrophilic aerobic bacteria or yeast and mould and to maintain sensory properties until five weeks of storage at 4 °C. In addition, only a 10 % reduction of vitamin C was observed from fresh segments or syrup until the end of storage period, showing that the new ready-to-eat produce would conserve high bioactive compound content and health benefits after pasteurization and prolonged cold storage.

Originating in the 1970s, Magnetic Compression Anastomosis (MCA) has lately been revisited with a focus on minimal invasive surgery (MIS). The aim of this report is to reappraise our earlier experience with MCA with the intention of facilitating future MCA advancement. A retrospective review was conducted regarding preclinical experiments and clinical trials at a single institution from 1980 through 1995. The reviewed information was compiled and appraised to generate proposals for future MCA use. The experimental studies, including 250 MCA cases in gastrointestinal and urinary tract animal models, demonstrated the technical versatility of MCA as well as the superior biomechanical characteristics in comparison to hand-sewn anastomoses. Clinical trials encompassed 87 MCA procedures in 86 children, 2 to 10 years of age, involving the following techniques: non-operative esophageal recanalization (n=15), non-operative ileostomy undiversion (n=46), Swenson pull-through (n=10), non-operative urethral recanalization (n=5), and extravesical ureterocystoneostomy (n=11). Clinical MCA was found to be successful in over 87% of cases. MCA limitations concerning anastomotic failure and scarring were thought to be mostly due to inadequate magnetic compression. Based on our historic experience, we propose further research on the technical aspects of MCA, along with the biologic aspects of anastomotic tissue remodeling. Magnets should be designed and manufactured for a wide spectrum of pediatric surgical indications, particularly in combination with novel MIS techniques.

Calcium-activated potassium channels (KCa) are the important participants in calcium signaling pathways due to their ability to be activated by increase of the intracellular free calcium concentration. KCa channels are involved in the regulation of various processes in the cells under normal, as well as pathophysiological conditions, including oncotransformation. Previously, with the use of patch-clamp method, we registered the KCa activity in the plasma membrane of human myeloid leukemia K562 cell line. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of leukemia cells that express functionally active KCa channels in the plasma membrane.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleo-side antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with inhibition of cancer cell growth and progression of tumors. Thus, TM can be considered a potent antitumor drug in various cancers and may promote chemosensitivity. Mechanistically, TM impedes the role of the UDP-HexNAc enzyme in the biosynthesis of oligosaccharides, specialized macromolecules instrumental in N-linked glycosylation. Further, like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and Cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Despite TM's antitumor effectiveness, its lack of cell-type specific cytotoxicity impedes its anticancer efficacy. Thus, various nanoencapsulation techniques and materials have been considered for use in experiments to reduce TM's cytotoxicity and improve efficacy as a targeted therapy. The current review is a profound audit of the benefits and pitfalls of TM in various cancers, focusing on breast, colon, and pancreatic cancers. Additional progressive studies have also discussed the use of TM in immune checkpoints and other unique pathways. Cytotoxicity and other possibly adverse effects of TM are highlighted based on the data from in vitro and in vivo assays. In addition, the recent advances in nano-based drug delivery systems regarding TM have been emphasized. However, the potential of this nucleoside inhibitor re-quires thorough investigation and research to determine its likeliness as a viable chemotherapeutic.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

In the present work, the interactions between hydrocortisone and cyclodextrins were investigated. The cyclodextrins selected for this study were hydroxypropyl-α-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin. The study was carried out using density measurements, 1H-NMR and FT-IR spectroscopy. Preliminary studies show that hydroxypropyl-α-cyclodextrin has a low affinity for hydrocortisone, while hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin have a good affinity for hydrocortisone in both solid state and solution. The study was carried out at two temperatures: 298.15 K and 310.15 K. The results suggest that at both temperatures, the system 2-HP-β-CD + HC induces an increase in the solvent structure, with increasing the solute concentration in the solution, while on the contrary the system 2-HP-γ-CD + HC induces a decrease in the solvent structure when the concentration of the solute in the system increases.

This study reports on allelic and genotypic frequencies of OCT1, OCT2, OCT3 polymorphisms among metformin-treated DMT2 patients. It also reports the association with HbA1c control on 59 DMT2 patients. They were genotyped through real-time PCR (TaqMan assays). Metformin plasmatic levels were determined through mass spectrometry. Neither the analysis of HbA1c control by SNPs in SLC22A1, SLC22A2, and SLC22A3, nor the dominant genotypic model analysis yielded statistical significance across genotypes in polymorphisms rs72552763 (p=0.4678), rs622342 (p= 0.2215), rs316019 (p=0.2209), and rs2076828 (p=0.215). HbA1c levels were different in rs72552763 (p= 0.0220) and rs622342 (p=0.0093) genotypes. The dominant genotypic model found the lowest HbA1c levels by GAT/GAT (p= 0.0058) and A/A (p=0.0108), in rs72552763 and rs622342 respectively. We may conclude that rs72552763 and rs622342 polymorphisms in SLC22A1, exercise a relevant effect in metformin response determined by HbA1c levels among Mexican-Mestizo DMT2 patients.

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

In 2014, the International Union for Conservation of Nature adopted the Red List of Ecosystems (IUCN RLE) criteria as the global standard for assessing risks to terrestrial, marine, and freshwater ecosystems. Identifying and quantifying the impacts of biodiversity assessments on the status of nature is key to justifying continued investment in assessments and enabling strategic planning to maximize future impact. In this policy perspective, we use an established impact evaluation framework to identify the impacts of the IUCN RLE since its inception. To date, 1,397 ecosystem units in 100 countries have been assessed following the IUCN RLE protocol. Systematic assessments are complete or underway in more than 25 countries and two continental regions (the Americas and Europe). Countries with established ecosystem red lists have already used them to inform legislation, land-use planning, protected area expansion, monitoring and reporting, and ecosystem management. IUCN RLE indices based on systematic assessments have high potential to inform global biodiversity reporting for the Aichi Targets and the United Nations Sustainable Development Goals. Expanding the coverage of IUCN RLE assessments, building capacity to undertake them, and establishing stronger policy instruments to manage red-listed ecosystems will be key to maximizing conservation impacts over the coming decades.

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

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets have been implicated in the etiology of the disease, along with their protein composition, mainly perilipins. These proteins have garnered increasing attention as a pivotal regulator, since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications in the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis, and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis chaperone mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.

The rapid technological progress has ushered in a new era of human-computer interaction, where the distinction between the physical and virtual realms is becoming increasingly blurred. This research paper explores the profound and multifaceted intersection of Human-Data Interaction (HDI) and Data Virtualization (DV), examining how emerging technologies can significantly enhance the exploration, comprehension, and utilization of complex, multidimensional data sets. Informed by the insights gleaned from prior research in this domain , the present study delves into the potential of DV techniques to improve HDI, with a particular focus on three experimental investigations conducted within the realms of education, healthcare, and retail. The findings reveal the benefits and potential challenges associated with the implementation of DV in these diverse contexts, offering valuable guidance for the design and development of future HDI systems. Drawing upon a diverse array of authoritative sources, this paper presents a holistic, forward-looking perspective on the future of HDI, underscoring the critical role that DV will play in shaping the next generation of human-computer interfaces and facilitating a deeper, more intuitive understanding of the digital world. Furthermore, the paper presents a preliminary framework for integrating HDI principles into standard design practices. This framework outlines key considerations and guidelines to help designers and developers incorporate HDI techniques more effectively into the development of data-driven applications and interfaces.The proposed framework outlines key considerations for enhancing data accessibility and comprehension, empowering users to exercise greater control over their data, and cultivating transparent dialogues between data providers and end-users. By establishing this conceptual foundation, the paper aims to facilitate the seamless integration of HDI principles into standard design practices, ultimately leading to more intuitive, user-centric, and ethically-grounded approaches to data interaction and utilization.

In this paper, we study the convergence of new implicit iterations dealing with n-tupled fixed point results for nonlinear contractive-like mappings on W-hyperbolic metric spaces. Herein, we demonstrate that our newly implicit iteration schemes have faster rate of convergence than implicit S-iteration process, implicit Ishikawa and Mann type iteration processes. Furthermore, a numerical simulation to improve our theoretical results is obtained.

Honey bee colonies rapidly decline when confined to greenhouses, increasing pollination rental costs as they need to be replaced frequently. We tested a hive system with entrances that can be manipulated to direct bees to inside or outside greenhouses containing a zucchini crop. In one greenhouse, the bees could only forage inside for 15 days; in another, bees were directed to the inside from 5 to 9 AM, after which they foraged outside. This procedure was repeated two more times in each greenhouse with new hives. Data was collected on how the number of bee flower visits affected fruit production, the frequency of flower visits, and the amount of bee brood and food in the hives. Flowers visited by bees four times or more set more and larger fruit. The frequency of flower visits by bees from the hives confined to the greenhouse was reduced after eight days; it was not reduced in the greenhouse with bees that could forage outside. Bee brood area was reduced in the colonies that were confined to the greenhouse, while it was maintained in the semiconfined hives. The hive system with controllable entrances proved effective for pollination, while causing less damage to the bees.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

Hospitals are perpetually challenged by the dual requirements of concurrently improving the quality of healthcare and maintaining financial solvency. Both issues are among the top concerns for hospital executives across the United States, yet some have questioned if the efforts to enhance quality are financially sustainable. led us to examine if improving quality in the hospital setting impacts revenue. Using multivariate regression, we assessed if numerous quality measures were associated with our targeted measure of hospital profitability: the net patient revenue per adjusted discharge. The independent variables included the HCAHPS Summary Star Rating, Hospital Compare Overall Rating, All-Cause hospital-wide Readmission Rate, Total Performance Score, Clinical Outcomes Domain Score, Safety Domain Score, Person and Community Engagement Domain Score, and the Efficiency and Cost Reduction Score. Our results indicated that improving quality was significantly associated with improved net patient revenue per adjusted discharge for seven of the eight of these quality measures at the hospital level. It is clear that failing to address quality and patient safety issues is costly for US hospitals, thus we believe our findings support the premise that increased attention to the quality of care delivered as well as patients’ perceptions of care may allow hospitals to accentuate profitability and advance a hospital’s financial position.

In the application of classical nucleation theory (CNT) and all other theoretical models of crystallization of liquids and glasses it is always assumed that nucleation proceeds only after the supercooled liquid or the glass have completed structural relaxation processes towards the metastable equilibrium state. Only employing such assumption, the thermodynamic driving force of crystallization and the surface tension can be determined in the way it is commonly performed. The present paper is devoted to the theoretical treatment of a different situation when nucleation proceeds concomitantly with structural relaxation. To treat the nucleation kinetics theoretically for such cases, we need adequate expressions for the thermodynamic driving force and the surface tension accounting for the contributions caused by the deviation of the supercooled liquid from metastable equilibrium. In the present paper, such relations are derived. They are expressed via deviations of structural order parameters from their equilibrium values. Relaxation processes result in changes of the structural order parameters with time. As a consequence, the thermodynamic driving force and surface tension, and basic characteristics of crystal nucleation, such as the work of critical cluster formation and the steady-state nucleation rate, also become time-dependent. We show that this scenario may be realized in the vicinity and below the glass transition temperature, and it may occur only if diffusion (controlling nucleation) and viscosity (controlling the alpha-relaxation process) in the liquid decouple. Analytical estimates are illustrated and confirmed by numerical computations for a model system. The theory is successfully applied to the interpretation of experimental data. Several further consequences of this newly developed theoretical treatment are discussed in detail. In line with our previous investigations, we reconfirm that only when the characteristic times of structural relaxation are of similar order of magnitude or longer than the characteristic times of crystal nucleation, elastic stresses evolving in nucleation may significantly affect this process. Completing the analysis of elastic stress effects, for the first time expressions are derived for the dependence of the surface tension of critical crystallites on elastic stresses. As the result, a comprehensive theoretical description of crystal nucleation accounting appropriately for the effects of deviations of the liquid from the metastable states and of relaxation on crystal nucleation of glass-forming liquids, including the effect of simultaneous stress evolution and stress relaxation on nucleation, is now available. As one if its applications, this theoretical treatment provides a new tool for the explanation of the low-temperature anomaly in nucleation in silicate and polymer glasses (the so-called \breakdown" of CNT at temperatures below the temperature of the maximum steady-state nucleation rate). We show that this anomaly results from much more complex features of crystal nucleation in glasses caused by deviations from metastable equilibrium (resulting in changes of the thermodynamic driving force, the surface tension, and the work of critical cluster formation, in the necessity to account of structural relaxation and stress effects) than assumed so far.

The transition to sustainability requires major behavioural changes. This requires a complete rethinking of ecosystems and their interconnections, reassessing environmental issues, and a behavior change manifesting. Thus, understanding how sustainability Knowledge, Attitudes, and Practices (KAP) change is essential to sustainability as they shape human behaviour. The main aim of this study was to investigate the constructs of sustainability KAP among university and non-university populations. Data were collected using a structured questionnaire of items measured on a five-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). The questionnaire was distributed to diverse participants, ensuring a broad representation of views on sustainability. There are ten sociodemographic variables, 344 respondents in UAE where the female (28.5%) and male (13.7%), (58.1%) participants did not belong to the UAE university and their age fall into the 18-24 years old. The mean scores indicate a positive orientation towards sustainability, with Knowledge (M = 4.2272), Attitudes (M = 4.2650), and Practices (M = 3.8198) all above the midpoint and the UAE university students showed more knowledge, attitude and practices scores ‎than others population. Associations between KAP were significant at a significant level of p &lt; 0.05. This indicates that the next generation will have more environmentally KAP.

Schinus terebinthifolius Raddi is a plant native to Brazil. The objective of this work was to analyze the chemical composition, antioxidant and antibacterial potential of essential oils (EOs) from the leaves, fruits and twigs of S. terebinthifolius aiming for their application in food safety. EOs were obtained by hydrodistillation and the chemical composition was determined by gas chromatog-raphy coupled to mass spectrometry. Phenolic compounds were quantified and antioxidant ac-tivity was evaluated using three different methods. The antibacterial activity was determined by the broth microdilution method against foodborne bacteria. In the chemical analysis, 22 com-pounds were identified in the leaves, 13 compounds in the fruits and 37 compounds in the twigs, revealing the presence of the main compounds germacrene D, caryophyllene, α-pinene, β-pinene and γ-gurjunene. EOs showed better antioxidant potential using the β-carotene/linoleic acid method with 40.74, 61.52 and 63.65% oxidation inhibition for leaves, fruits and twigs, respectively. The EO from the leaves showed greater antibacterial potential against Escherichia coli and Staphy-lococcus aureus with a minimum inhibitory concentration (MIC) of 0.62 mg mL-1, values lower than the MIC of sodium nitrite (5.00 mg mL-1), antimicrobial standard synthetic. The activities of pink pepper EOs suggest their potential as a biopreservative in foods.

This work is driven by a practical question, corrections of Artificial Intelligence (AI) errors. Systematic re-training of a large AI system is hardly possible. To solve this problem, special external devices, correctors, are developed. They should provide quick and non-iterative system fix without modification of a legacy AI system. A common universal part of the AI corrector is a classifier that should separate undesired and erroneous behavior from normal operation. Training of such classifiers is a grand challenge at the heart of the one- and few-shot learning methods. Effectiveness of one- and few-short methods is based on either significant dimensionality reductions or the blessing of dimensionality effects. Stochastic separability is a blessing of dimensionality phenomenon that allows one-and few-shot error correction: in high-dimensional datasets under broad assumptions each point can be separated from the rest of the set by simple and robust linear discriminant. The hierarchical structure of data universe is introduced where each data cluster has a granular internal structure, etc. New stochastic separation theorems for the data distributions with fine-grained structure are formulated and proved. Separation theorems in infinite-dimensional limits are proven under assumptions of compact embedding of patterns into data space. New multi-correctors of AI systems are presented and illustrated with examples of predicting errors and learning new classes of objects by a deep convolutional neural network.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in individuals with overweight, obesity, and type 2 diabetes (T2D). Literature search was conducted through databases including PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. The random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24-h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analysis was conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and disease status of participants. This study revealed significantly reduced glucose AUC (Hedges’ g = -0.317; SE = 0.057; p < 0.05) and 24-hour mean glucose levels (Hedges’ g = -0.328; SE = 0.062; p < 0.05) following PPE than CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min than ≤30 min. The reduction in 24-hour mean glucose levels was also greater (p < 0.05) following PPE initiated ≥60 min than <60 min post-meal and in those with T2D than those without T2D. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE represents a promising strategy, particularly for patients with T2D.

Otolith morphology analysis is one of the main tools used for fish or fish stock identification. Moreover, otolith shape can also be used in fish dietary studies (stomach content) for the identi-fication of prey fishes and their size according to the relationship between fish and otolith sizes. In the present study, the relationship between fish length and otolith morphological dimensions was investigated for the sabre squirrelfish, Sargocentron spiniferum (Forsskål, 1775) (family: Hol-ocentridae). Samples of 185 fish were collected from the coast of the Red Sea, Egypt. To analyze the relationship between fish and otolith, otolith morphometric measurements (length, width, area, perimeter, weight, sulcus, and ostium) and shape factors (aspect ratio, compactness, form factor, rectangularity, roundness, ellipticity, squareness) describing outline shape were extracted using image analysis. Generalized linear models were applied for the relationship between body length and each otolith morphology feature. From the relationships between the total length of fish and fourteen morphology features, only otolith length, caudal length, and squareness were significantly correlated with fish size. Our results provide more information for the relationship between fish length and otolith morphometric features.

Nonlinear loads, a crucial component of power systems grids, pose a challenge due to harmonics injection. Our research tackles this issue with a novel approach - a modified green plug / switched filter compensation scheme using fuzzy logic controllers. This innovative scheme, presented in the paper, utilizes dual action pulse width modulation to ensure switching functions from harmonic reduction and capacitive compensation for inrush nonlinear type AC loads.  The scheme's multi-loop regulations and online switching effectively handle dynamic type slow acting inrush, motorized and other rectifier type-nonlinear loads, enhancing power factor, power quality at source and load buses, and reducing total harmonic distortion at key source and sensitive nonlinear load buses. A simulation model in the MATLAB/SIMULINK software environment demonstrates the efficiency of the proposed FACTS technique. The results show that voltage, current, active power, reactive power, power factor regulation, and effective energy utilization are achievable with the designed FACTS-MFCC-SFC. The switched modulated AC green plug filter significantly improves power quality and enhances power factor in the case of inrush and nonlinear loads.

Hollow and concrete-filled steel tubes (CFSTs) are widely used as columns in many structural systems and local buckling can occur when they are subjected to axial compression loading. The critical regions for the local buckling of the columns are near the ends of the column where the moments are the highest. To strengthen the critical regions of the CFSTs the CFRP provides a simple and effective method which used previously as an enhancement for both of strength and ductility. So, this study suggests investigating the axial load behaviour of CFST strengthened with CFRP using FE method after a verification study and then a various parametric studies were carried out to cover the effect of the CFRP layers, number, confinement length and position. The FE results proved that, one CFRP sheet with thickness equal to 1.2 mm was strengthened the composite column by 8.5%, two CFRP sheets with total thickness equal to 2.4 mm was strengthened the composite column by 23.5%, three CFRP sheets with total thickness equal to 3.6 mm was strengthened the composite column by 35.1% and four CFRP sheets with total thickness equal to 4.8 mm was strengthened the composite column by 44.5%. Moreover, this study proved that by strengthened the composite columns with CFRP sheets with different lengths, the axial load resistance was improved by 8.5%, 4.6%, 0.1% and 0.0% for length percentages 100%, 75%, 50% and 25% respectively.

Background: As the only place in a store where all customers must pass through and wait, the checkout lane may be particularly influential over consumer purchases. Because most foods and beverages sold at checkout are unhealthy (e.g., candy/sweets, sugar-sweetened beverages, and salty snacks), policymakers and advocates have expressed growing interest in healthy checkout policies. To understand the extent to which such policies could improve nutrition equity, we as-sessed the prevalence and sociodemographic correlates of purchasing items from checkout. Methods: We assessed self-reported checkout purchasing and sociodemographic characteristics in a national convenience sample of adults (n=10,348) completing an online survey in 2021. Re-sults: Over one-third (36%) of participants reported purchasing foods or drinks from checkout during their last grocery shopping trip. Purchasing items from checkout was more common among men; adults <55 years of age; low-income consumers; Hispanic, non-Hispanic American Indian and Alaska Native, and non-Hispanic Black consumers; those with at least a bachelor’s degree; parents; and consumers diagnosed with type 2 diabetes or pre-diabetes (p-values<0.05). Conclusions: Purchasing foods or beverages from store checkouts is common and more prevalent among low-income and racial and ethnic minority groups. These results suggest that healthy checkout policies have the potential to improve nutrition equity.

The pride of power of the Spanish preachers of religious art is reflected in the church of Santo Domingo built between 1541 and 1688. This work of heritage architecture, one of the first to be built in the colonized city, was affected by multiple earthquakes, interventions, and constructions that do not have a clear record. A total of 13 samples were taken from the lining mortar inside the cloister, central nave, and side chapel, following the nondestructive testing protocols and standards suggested by the research team. The analysis included mineral characterization studies and quantitative analysis by X-ray diffraction and scanning electron microscopy with microanalysis of the samples. The results showed the presence of volcanic aggregates and lime lining and joint mortars, mortars of rustic composition and coarse manufacture. The resolution of the data of mineralogical composition and texture has allowed us to corroborate the historical information described by the chroniclers and to date relatively the studied sites and to establish a hypothesis of constructive stages.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of vaccination declines experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on impacts to routine childhood vaccinations in low-income countries from January 1, 2020 to February 8, 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations.