Diabetic retinopathy (DR), a major complication of prolonged diabetes, poses a significant risk of vision loss. Early detection is critical for effective treatment, yet traditional diagnostic methods by ophthalmologists are time-consuming, costly, and subject to variability. This study introduces a novel approach employing a hybrid Convolutional Neural Network-Radial Basis Function (CNN-RBF) classifier integrated with Multi-Scale Discriminative Robust Local Binary Pattern (MS-DRLBP) features for enhanced DR detection. We implemented advanced image preprocessing techniques, including noise reduction, morphological operations, and Otsu’s thresholding, to optimize blood vessel segmentation from retinal images. Our method demonstrates exceptional performance in screening DR, achieving an average of 96.10% precision, 95.35% sensitivity, 97.06% specificity, and 96.10% accuracy. These results significantly outperform traditional methods and offer a promising tool for remote and efficient screening of DR. Applied to publicly available datasets, this research contributes to the development of accessible, accurate diagnostic methods in ophthalmology, potentially reducing the global burden of diabetic vision loss.

Obesity is associated with serious comorbidities and economic implications. Bariatric surgery, most commonly Roux-en-Y gastric bypass and sleeve gastrectomy, are effective options for weight loss and improvement of obesity-related comorbidities. With the growing obesity epidemic, there has been a concomitant rise in bariatric surgeries, particularly in sleeve gastrectomy, which has been the most widely performed bariatric surgery since 2013. Gastroesophageal reflux disease (GERD) is highly prevalent in obese individuals, can significantly impact quality of life and may lead to serious complications. Obesity and GERD both improve with weight loss. However, as the incidence of sleeve gastrectomy rises, recent data has revealed a risk of exacerbation of pre-existing GERD or the development of de novo GERD following sleeve gastrectomy. We performed a detailed review of GERD post-sleeve gastrectomy, including its overall incidence, pathophysiology and current treatment paradigms.

Postpartum depression (PPD) can interfere with the establishment of affective bonds between infant and mother, which is important for the cognitive, social-emotional, and physical development of the child. Rates of PPD have increased during the COVID-19 pandemic, likely due to the added stress and limited support available to new parents. The present study examined whether parenting-related stress, perceived bonding impairments, quality of observed mother-infant interactions and salivary oxytocin levels differ between depressed and non-depressed mothers, along with differential impacts of COVID-19 on depressed mothers. Participants included 70 mothers (45 depressed, 25 controls) with infants aged 2-6 months. All data were collected remotely to ease participant burden during the pandemic. Depression was associated with experiences of heightened parenting-related stress and bonding difficulties. These differences were not observed during mother-infant interactions or in salivary oxytocin levels. Differences in COVID-related experiences were minimal, though depressed mothers rated slightly higher stress associated with returning to work and financial impacts of the pandemic. Findings highlight the importance of early intervention for PPD to mitigate long-term effects on mothers, children, and families. Additionally, they underscore the need for an early intervention to support the developing mother-infant dyad relationship during this crucial time.

In this paper, we present a new parametric class of optimal fourth-order iterative methods to estimate the solutions of nonlinear equations. After the convergence analysis, we study the stability of this class by using the tools of complex discrete dynamics. This allows us to select those elements of the class with lower dependence on initial estimations. We verify by means of numerical tests that the stable members on quadratic polynomials perform better than the unstable ones, when applied to other non-polynomial functions. We also compare the performance of the best elements of the family with known methods, such as the schemes by Newton or Chun, among others, showing robust and stable behaviour.

Natural Fibre Composites (NFC) are eco-friendly, sustainable alternatives to synthetic polymers. However, some intrinsic natural fillers´ properties hinder their widespread implementation as re-inforcement in polymeric matrices and require further investigation. In the scope of this study, the thermal, rheologic, mechanical (tension and flexural modes), morphological properties, water ab-sorption and dimensional stability of the NF polypropylene (PP) based injection moulded compo-sites with the rice husk (rh) and olive pits (op) of 20 wt% and 30% wt%, were investigated. The results suggest that the higher content of the rice husk and olive pits led to a similar reduction of the Melt Flow Index (MFI), independent of the additive type compared to virgin polypropylene (PPv). The melting and crystallization temperatures of the PPrh and PPop composites did not change with statistical significance. The composites are stiffer than the PP matrix by up to 49% and possess higher mechanical strength in what concerns the tension mode at the expense of de-creased ductility. PPrh and PPop have superior flexural modulus in the bending mode, while the flexural strength improvement was accomplished for the PP30%rh. The dimensional stability of the composites was improved as the linear shrinkage in the flow direction was decreased by 49% for PPrh and 30% for PPop, positively correlating with an increase in the filler content and stiff-ness. PPop was less susceptible to water sorption than PPrh due to fibres' composition and larger surface-to-area volume ratios.

A partial or complete pulpotomy is a type of vital pulp therapy (VPT) that aims to remove the in-flamed, infected pulp, leaving behind healthy, vital pulp that is capable of healing. VPT has gained renewed popularity as a treatment option in permanent mature posterior teeth with irre-versible/moderate-severe pulpitis, its high success rates matching that of root canal treatment (RCT). There is currently no consensus regarding diagnostic and prognostic predictors of success of pulpotomies for managing such cases. Therefore, we conducted a scoping review to identify and analyze how these factors affect the outcome of treatment. A literature search using the PRISMA guidelines was undertaken using PubMed and Scopus on July 7, 2023. A total of 22 studies met the inclusion criteria and were qualitatively analyzed by two reviewers. The follow-ing diagnostic and prognostic factors were recognized and discussed; presenting signs and symptoms, periapical diagnosis, bleeding time, indicators of inflammation (bleeding time, con-centration of inflammatory biomarkers), patient age and medical status, the depth, activity and location of caries, and restorative factors. Based on the studies assessed, there is limited evidence to support their prognostic value. Further research is necessary to identify solid predictors of outcome.

Raman scattering has been employed to study in detail the concentration dependence of the vibrational modes for the hexamethylenetetramine (HMTA) aqueous solutions. The formation of protonated and/or aggregated species has been clarified by comparing the experimental with the theoretically predicted vibrational spectra by means of quantum mechanical calculations. The analysis has shown that the vibrational modes of the solutions arise from a contribution of the vibrational modes of the HMTA self-aggregates and hetero-aggregates of HMTA with water molecules that are formed in the low- and intermediate-concentration region, respectively. The protonation of HMTA is ruled out due to the large differences between the experimental and the theoretically calculated spectra of the protonated molecules of HTMA in the fingerprint region. In the low-concentration solutions, the hetero-aggregation reaction of HMTA with water is the dominant mechanism, while at higher concentrations a self-aggregation mechanism occurs. Ultrasonic absorption and velocity measurements were carried out for hexamethylenetetramine aqueous solutions. The acoustic spectra reveal the presence of only one single Debye-type relaxation process that is assigned to the aggregation mechanism of HMTA. The sound absorption data follow two different dependencies on HMTA mole fraction. The crossover 0.018 mole fraction signifies two separate regions with distinct structural characteristics. The relaxation mechanism observed in dilute solutions is attributed to hetero-association of HMTA with water molecules, while at higher concentrations the observed relaxation process is assigned to the self-association reaction of HMTA molecules. This structural transformation is also reflected in several physicochemical properties of the system, including the kinematic viscosity, the mass density, the sound speed, and the adiabatic compressibility of the HMTA aqueous solutions. The combination of vibrational and acoustic spectroscopies with molecular orbital calculations allowed us to disentangle the underlying processes and to elucidate the observed relaxation mechanism in the HMTA aqueous solutions.

Age-related macular degeneration, a leading cause of visual loss and dysfunction in the devel-oped world, is a disease initiated by genetic polymorphisms that impairs negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of SIGLEC medi-ated glyco-immune checkpoint parainflammatory homeostasis as a main determinant for the vi-sion impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte derived macrophages (PBMDM) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring gly-co-immune checkpoint control with a sialic acid mimetic nanoparticle targeting microgli-al/macrophage SIGLECs to regain retinal para inflammatory homeostasis is a promising thera-peutic that could halt the progression of and improve visual function in all stages of macular de-generation.

We report on the study of the temperature dependence of the response of a BSO crystal based polarimetric current sensor with spectral interrogation. Two possible interrogation schemes are discussed. The spectral dependence of the optical rotation along the crystal caused by temperature and current changes has been investigated and approximate dependences for the sensitivities to current SI and temperature ST have been derived. A mixed term in the response with spectral interrogation has been revealed, the elimination of which is done by tracking wavelength shifts of two distinct extrema in the polarimetric response. A temperature independent second degree equation for the current changes as a function of the spectral shifts has been derived and tested.

Antimicrobial resistance (AMR) poses a global public health threat, with rates directly linked with consumption. The World Health Organization (WHO) AWaRе-classification aims to guide antibiotic use, which is influenced by drug availability, affordability, and economic policies. In Jordan, a high proportion of consumed antibiotics belong to the 'Watch' category. Data from the WHO-AWaRе classification, the Essential Medicines List, and the Jordan Food and Drug Administration were analyzed. Antibiotics for adults were classified and their cost per Defined Daily Dose (DDD) was determined, then affordability was assessed. In 2023, 43 injectable and 43 oral antibiotics for adults were registered in Jordan. 'Watch' antibiotics were the most common. 'Access' antibiotics had the lowest cost/DDD. 'Rеsеrvе' antibiotics were the most expensive with few generics. Injectable antibiotics had a negative correlation between cost and the number of alternatives. Affordability was higher for oral antibiotics compared to injectable ones. 'Rеsеrvе' antibiotics were generally unaffordable. This study highlights the need to promote 'Access' antibiotics over other categories by encouraging registration of missing ‘Access’ antibiotics and adjusting 'Watch' and 'Rеsеrvе' antibiotic prices. Competition among generics can lead to lower prices, increasing affordability and accessibility. We emphasize the importance of the AWaRе-classification in guiding antibiotic use in Jordan.

Lifelong learning has been integral to advancement of the nutrition and dietetics profession and its practitioners. Both the Commission on Dietetic Registration (CDR) and the Academy of Nutrition and Dietetics (Academy) advocate for continuous skill development and professional growth. Responding to evolving environmental trends and diverse practice perspectives, CDR joined the Joint Accreditation for Interprofessional Continuing Education organization in 2020 and CDR is transforming its own continuing professional education (CPE) requirements and prior approval program. This paper, a historical perspective and current state review, chronicles past and recent developments in nutrition and dietetics CPE, including opportunities for reflective learning and interprofessional continuing education (IPCE). Also explored are the establishment and expansion of the Joint Accreditation organization and its standards, as well as applicable case examples. Additionally, the paper outlines CDR’s and the Academy's strategies to advance inclusion, diversity, equity, and access (IDEA) within the profession and identifies how CPE advancements may facilitate accessible and equitable CPE for an increasingly diverse membership of practitioners. Nutrition and dietetics professionals stand to benefit from a more comprehensive understanding of CPE changes and the opportunities they may bring to the future of the profession.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have been attracted attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. This review explores the emerging role of omega-3 FAs and their specialized pro-resolving mediators (SPMs) in the context of macrophage polarization, with a focus on chronic liver diseases. Omega-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have promising effects in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. SPMs, such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties. These mediators modulate the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLD, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3 and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. However, the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment require further investigation. Understanding the intricate relationship among SPM and macrophage polarization holds unlimited potential for the development of novel therapeutic strategies for chronic liver diseases.

The aim of this study is to examine an efficient and environmental friendly process for hydrolyzing starch, an industrial-derived by-product of the potato processing industry, and to use the produced hydrolysates as substrates for methane production. A full factorial experiment was designed and the optimal concentrations of FeSO4·7H2O, H2O2 and temperature were determined obtaining a yield of 99.5%, with a total carbohydrates content equal to 28.65 g, when the input parameters were at their high level: FeSO4·7H2O 1.00g/L, H2O2 0.51 g/L and temperature 70.0oC. The hydrolysis kinetics were also examined revealing that temperature was the most important factor among the three optimization parameters. Furthermore, biodegradability tests were carried out to measure the methane production potential from the produced hydrolysates. The specific methanogenic activity was reached 0.669 g CODCH4/gVSS-day proving the effectiveness of the hydrolysis process and highlighting the potential of this food manufacturing by-product for bioenergy production. A preliminary cost analysis showed that a small investment for utilizing the starch in an existing wastewater treatment facility of a potato processing industry becomes profitable before the end of the 3rd year obtaining a NPV 37.5% higher than the NPV of the current utilization scenario.

: Sulfate presence is of great importance for anaerobic digestion as its addition can control the anaerobic microbial community. In this study, the effect of sulfuric acid addition on the perfor-mance of an UASB reactor fed with hydrolyzed starch was investigated. TOC, Fe and SO4-2 re-moval as well as the methane production were monitored under various COD/ SO4-2 ratios, HRTs and OLRs. When HRT was 16 hours and OLR equal to 2 g COD/LUASB-d the methane production was 0.24 L CH4/LUASB-day. After the sulfuric acid addition, TOC removal reached 95%. At HRT, OLR, and COD/ SO4-2 ratio equal to 16 hours, 2 g COD/ LUASB-d and 3.72 respectively, the methane production was 0.267 L CH4/LUASB-d. When the OLR was increased to 5.94 g COD/LUASB-d and COD/SO4-2 ratio was equal to 12.5, the methane production was 3 times higher (0.84 L CH4/LUASB-d) with a methane content in the produced biogas greater than 70%. 16s rRNA gene analysis demonstrated that after the sulfate addition, SRB were enriched and methane was mainly produced by Methanosaeta sp. This study indicates that appropriate sulfate concentrations in the feed in combination with the presence of iron in the UASB reactor lead to enhanced me-thane yields.

Information on how bacteria in plants and soil, along with extracellular enzymes, affect nutrient cycling in Encephalartos villosus growing in nutrient-poor and acidic scarp forests is lacking. Bacteria in coralloid roots, rhizosphere, and non-rhizosphere soils were isolated to determine the potential role of soil bacterial communities and their associated enzyme activities in nutrient contributions in rhizosphere and non-rhizosphere soils. The role of soil characteristics and associated bacteria on E. villosus nutrition and nitrogen source reliance was investigated. Encephalartos villosus leaves, coralloid roots, rhizosphere, and non-rhizosphere soils were collected at two scarp forests. Leaf nutrition, nitrogen source reliance, soil nutrition and extracellular enzyme activities were assayed. A phylogenetic approach was used to determine the evolutionary relationship between identified bacterial nucleotide sequences. Twenty, twelve and seven different bacterial genera were isolated from rhizosphere, non-rhizosphere, and coralloid roots, respectively. Phosphorus and nitrogen cycling enzyme activities in E. villosus rhizosphere and non-rhizosphere soils were insignificant. More than 70% of the leaf nitrogen was derived from the atmosphere. This study revealed that plant-associated bacteria with plant growth-promoting functions, soil bacteria, and associated extracellular enzymes play a role in E. villosus nutrition and nitrogen source reliance and contribute to E. villosus rhizosphere and non-rhizosphere soil nutrition.

We examine here the conductance changes associated with the change in spin state in a variety of different structures, using the example of the spin crossover complex [Fe(H2B(pz)2)2(bipy)] (pz= (pyrazol-1-yl)-borate and bipy = 2,2’-bipyridine) and [Fe(Htrz)2(trz)](BF4)] (Htrz = 1H-1,2,4-triazole) thin films . This conductance change is highly variable depending on the mechanism driving the change in spin state, the substrate and the device geometry. Simply stated, the choice of spin crossover complex used to build a device is not the only factor in determining the change in conductance with the change in spin state.

Purpose of the study: to reveal how the transfusion and the refraining from it affects the neuro-vascular unit in the congenital heart defects correction with cardiopulmonary bypass. Materials and methods: in vitro research, we formed a model of a neurovascular unit, which contains neu-rons, astrocytes and endothelial cells. This cellular model was cultivated in hypoxia conditions with the oxygen saturation levels of 1, 2, 3, 4%. In addition, this unit was cultivated with the pa-tient's serum adding in two different groups - with minimal and maximal levels of system in-flammatory response that we estimated by IL-6 level. Results: We found that during incubation in hypoxic conditions, the level of transendothelial resistance changed in groups with oxygen levels of 1% and 2% only after 4 hours. When we cultivated neurovascular unit cells with patients' sera, we found a minimal level of transendothelial resistance at 4 hours that increased after 24 hours. Permeability analysis showed that its level significantly decreased in the 1% and 2% oxygen group at 60- and 90-minutes relative to the control group. Conclusion: the system inflammatory response has more expressed but less long effect on the neurovascular unit model than hypoxia.

Various studies on the physical characteristics of the canopy gaps in tropical and subtropical regions but that in the mangrove swamp forest in Malaysia is little known. The objectives of this study are to assess the canopy gaps physical characteristics (size, form, direction), to assess the changes in soil physical characteristics and microenvionment in and around the canopy gaps. Five canopy gaps were selected formed by lightning strikes, gaps size and shapes were determined using the portable Global Positioning System and photographic images were analysed using ForestCrown. Result shows that canopy gap opening has increased the total light reaching the forest floor, changed the canopy gap microenvironment. Strong correlation between canopy opening percentage and temperature of gaps explains the changes of canopy gaps characteristics. These changes have contributed to new seedling germination, regeneration and maintaining the canopy gap dynamics.

Shear deflection effects are traditionally neglected in most structural system identification methods. Unfortunately, this assumption might lead to significant errors in some structures, like deep beams. Although some inverse analysis methods based on the stiffness matrix method including shear deformation effects have been presented in the literature, none of these methods is able to deal with actual rotations in their formulations. Recently, the observability techniques, one of the first methods for the inverse analysis of structures included the shear effects into the system of equations. In this approach, the effects of shear rotation are neglected. When actual rotations on site are used to estimate the mechanical properties in the inverse analysis, it can result in serious errors in the observed properties. This characteristic might be especially problematic in structures such as deep beams where only rotations can be measured. To solve this problem and increase the observability techniques' applicability, this paper proposes a new approach to include shear rotations into the inverse analysis by observability techniques. This modification is based on the introduction of a new iterative process. To illustrate the applicability and potential of the proposed method, the inverse analysis of several examples of growing complexity is presented.

The present analysis deals with the study of the $f(Q, T )$ theory of gravity which was recently considered by many cosmologists. In this theory of gravity, the action is taken as an arbitrary function $f(Q, T )$ where $Q$ is non-metricity and $T$ is the trace of energy-momentum tensor for matter fluid. In this study, we have taken three different forms of the function $f(Q, T )$ as $f(Q,T)=a_1Q+a_2 T$ and $f(Q,T)=a_3 Q^2+a_4 T$ and discussed some physical properties of the same. Also, we have obtained the various cosmological parameters towards Friedmann-Lemaitre-Robertson-walker (FLRW) Universe by defining the transit form of scale factor which yields the Hubble parameter in redshift form as $H(z)=\frac{H_{0}}{(\lambda+1)} \left(\lambda+ (1+z)^{\delta}\right)$. %We have obtained the approx best-fit values of model parameters using the least square method for observational constraints on available datasets like Hubble dataset $H(z)$, Supernova dataset SNe-Ia, etc., by applying the Root Mean Squared Error formula (RMSE). By applying the Root Mean Squared Error formula (RMSE), we were able to determine the approximate best-fit values of model parameters using the least square approach for observational constraints on the datasets Hubble dataset $H(z)$, Supernova dataset SNe-Ia, etc. We have observed that the deceleration parameter $q(z)$ exhibits a signature-flipping (transition) point within the range $0.623 \le z_{0} \le 1.668$ through which it changes its phase from the decelerated to the accelerated expanding universe with $\omega = -1$ at $z=-1$ for the approximate best-fit values of the model parameters. %For obtained approx best-fit values of model parameters we have observed that the deceleration parameter $q(z)$ shows a signature-flipping (transition) point within the range $0.623 \le z_{0} \le 1.668$ through which it changes its phase from decelerated to the accelerated expanding universe with $\omega = -1$ at $z=-1$.

Deciding when to replace dairy bulls presents a complex challenge for artificial insemination (AI) companies. These decisions encompass multiple factors, including a bull's age, predicted semen production, and estimated genetic merit. This study's purpose was to provide a practical, objective tool to assist in these decisions. We utilized a Markov Chain model to calculate the economic valuation of dairy bulls, incorporating key factors such as housing costs, collection and marketing expenses, and the bull's probable tenure in the herd. Data from a leading AI company were used to establish baseline values. The model further compared a bull's net present value to that of a potential young replacement, establishing a relative valuation (BullVal$). The range of BullVal$ observed spanned from -$316,748 to $497,710. Interestingly, the model recommended culling for 49% of the bulls based on negative BullVal$. It was found that a bull's net present value was primarily influenced by market allocation and pricing, coupled with the interaction of semen production and genetic merit. This study offers a robust, data-driven model to guide bull replacement decisions in AI companies. Key determinants of a bull's valuation included market dynamics, semen production rates, and genetic merit.

Purpose: Inducible Slc4a11 KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH3-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study is to investigate the link between oxidative stress and failure of pump and barrier functions and test different approaches to revert the process. Methods: Mice homozygous for Slc4a11 Flox and Estrogen receptor –Cre Recombinase fusion protein alleles at 8 weeks of age were fed Tamoxifen (Tm) enriched chow (0.4 g/Kg) for 2 weeks, and controls were fed normal chow. During the initial 14 days, Slc4a11 expression, corneal thickness (CT), stromal [lactate], Na+-K+ ATPase activity, mitochondrial superoxide levels, expression of lactate transporters, and activity of key kinases were assessed. In addition, barrier function was assessed by fluorescein permeability, ZO-1 tight junction integrity, and cortical cytoskeleton F-actin morphology. Results: Tm induced a rapid decay in Slc4a11 expression that was 84% complete at 7 days and 96% at 14 days of treatment. Superoxide levels increased significantly by day 7; CT and fluorescein permeability by day 14. Tight junction ZO-1 distribution and cortical cytoskeleton were disrupted at day 14 concomitant with decreased expression of Cldn1 yet an increase in tyrosine phosphorylation. Stromal lactate increased by 60%, Na+-K+ATPase activity decreased by 40%, and expression of lactate transporters MCT2 and MCT4 significantly decreased, but MCT1 was unchanged at 14 days. Src kinase was activated but not Rock, PKCα, JNK, or P38Mapk. Mitochondrial antioxidant Visomitin (SkQ1, mitochondrial targeted antioxidant) or Src kinase inhibitor eCF506 significantly slowed the increase in CT, with concomitant decreased stromal lactate retention, improved barrier function, reduced Src activation and Cldn1 phosphorylation, and rescued MCT2 and MCT4 expression. Conclusions: Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that results in perturbation of pump components and barrier function of the CE.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

Severe combined immunodeficiency (SCID) is a primary inherited immunodeficiency that could be fatal, usually due to opportunistic infections caused by bacteria, viruses, fungi, and protozoa if left untreated. Opportunistic infections are the most common presentation of SCID these include viral, fungal, or intracellular bacteria, and infection should prompt immunological investigation. This review aimed to provide a comprehensive approach to the microrganisms associated with severe combined immunodeficiency (SCID) and its management. The authors described SCID as a syndrome and summarized the different microorganisms that affect children and how they are managed.

This paper attempts to develop a Dynamic Mode Decomposition (DMD) based Reduced Order Model (ROMs) which can quickly but accurately predict the forces and moments experienced by a road vehicle such that they be used by an on-board controller to determine the vehicle's trajectory. DMD can linearize a large dataset of high-dimensional measurements by decomposing them into low-dimensional coherent structures and associated time-dynamics. This ROM then also can be applied to predict the future state of the fluid flow. Existing literature on DMD is limited to low Reynolds number applications. This paper presents DMD analyses of the flow around an idealized road vehicle, called the Ahmed body, at a Reynolds number of 2.7E6. The high dimensional dataset used in this paper was collected from a computational fluid dynamics (CFD) simulation performed using Menter's shear stress transport (SST) turbulence model within the context of Improved Delayed Detached Eddy Simulations (IDDES). The DMD algorithm, as available in literature, was found to suffer nonphysical dampening of the medium-to-high frequency modes. Enhancements to the existing algorithm were explored, and a modified DMD approach is presented in this paper which includes: (a) a requirement of higher sampling rate to obtain higher resolution of data, and (b) a custom filtration process to remove spurious modes. The modified DMD algorithm thus developed was applied to the high Reynolds number, separation dominated flow past the idealized ground vehicle. The effectiveness of the modified algorithm was tested by comparing future predictions of force and moment coefficients as predicted by the DMD-based ROM to the reference CFD simulation data, and found to offer significant improvement.

In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This review summarizes the evidence on strategies that can be applied to treat both long and vaccine injuries based on similar mechanisms of action.

In recent years, there has been a growing interest in the preoperative modeling of fluid-structure interaction in the treatment of cerebral aneurysms. In this study, we investigate two cases involving laminar incompressible fluid flow interacting with hyperelastic materials (a vertical flap and aneurysm walls) under the effect of fluid flow. We present a finite element method (FEM) for these prototypical two-dimensional ($2D$) configurations, taking into account the complex flows and deformation of the variant's structure models. We use an Arbitrary Lagrangian-Eulerian (ALE) formulation in a continuum, fully monolithic coupled way, and discretize the fluid and solid domains using the quadratic LBB stable $P_2P_1$ finite element pair to approximate the displacement, velocity, and pressure spaces independently. The resulting discretized form of the nonlinear algebraic system is linearized using a variant of Newton's procedure, and the Jacobian matrices are approximated via the divided difference method. The resulting linear systems are solved using a direct solver MUMPS. We evaluate hydrodynamic forces such as drag and lift coefficients for nonlinear elastic material models, including Saint-Venant Kirchoff, Neo-Hookean, and Mooney-Rivlin (2 parameters) separately. To gain more physical insight into the problem, we verify the computed results by comparing the velocity, viscosity, and pressure fields. Our aim is to qualitatively analyze the changes in the mechanics of the wall behavior of the elasticity of the flap vs. the complexity of deformation, interface, details for prototypical flow situations, corresponding displacement, and deformation. We also provide a physical interpretation of blood flow magnitude and basic hemodynamic phenomena of wall shear stresses (WSS) in aneurysma and the range of deformation. Overall, this study presents a comprehensive approach to modeling fluid-structure interaction in cerebral aneurysms, which could help in the development of more effective treatment strategies.

Information about molecular mechanism of pesticide resistance in the rust-red flour beetle, a major pest destroying grains and flour across Nigeria is grossly lacking, hindering evidence-based con-trol. Here, we identified to species level three populations of the red-flour beetle from Kano, Ni-geria, as Tribolium castaneum, and investigated the mechanism driving their insecticide resistance. IRAC susceptibility bioassays established high cypermethrin resistance, with LC50s of 4.35-5.46mg/ml in the three populations, NNFM, R/Zaki and Yankaba. High DDT and malathion resistance was observed in NNFM, with LC50s of 15.32- and 3.71mg/ml, respectively. High sus-ceptibility was observed towards dichlorvos in all three populations with LC50s of 0.17-0.35mg/ml, respectively. Synergist bioassay with piperonylbutoxide significantly restored cypermethrin sus-ceptibility, with mortality increasing almost threefold, from 24.8% obtained from 1.25mg/ml of cypermethrin, to 63.3% in synergised group (p=0.013), suggesting a preeminent role of P450s. The two major knockdown resistance (kdr) mutations, T929I and L1014F in the IIS4 and IIS6 fragments of voltage-gated sodium channel were not detected in both cypermethrin-alive and cyperme-thrin-dead beetles, suggesting lesser role of target-site insensitivity. These findings highlight the need to explore alternative control tools for this pest and/or explore incorporation of synergists, like piperonylbutoxide as additional chemistries into pesticides formulations to improve their ef-ficacy.

We use a recently proposed formulation of quantum mechanics based, not on potential functions but rather, on orthogonal energy polynomials. In this context, the most important building block of a quantum mechanical system, which is the wavefunction at a given energy, is expressed as pointwise convergent series of square integrable functions in configuration space. The expansion coefficients of the series are orthogonal polynomials in the energy; they contain all physical information about the system. No reference is made at all to the usual potential function. We consider, in this new formulation, few representative problems at the level of undergraduate students who took at least two courses in quantum mechanics and are familiar with the basics of orthogonal polynomials. The objective is to demonstrate the viability of this formulation of quantum mechanics and its power in generating rich energy spectra illustrating the physical significance of these energy polynomials in the description of a quantum system. To assist students, partial solutions are given in an appendix as tables and figures.

Marine seaweeds are nature’s largesse resource in human well-being. Seaweed’s contribution to the food industry is being widened for its rich source of essential vitamins, minerals, and PUFA. ‘Nori’ is a dried sheet of red seaweed Porphyra sp. used to make ‘sushi’ a renowned cuisine in Japan, and other Southeast Asian countries. In this present study, commercial-grade ‘Nori’ was extracted and fractionated with different solvents, and subjected to evaluate the cytotoxic activity on human ovarian tetracarcinoma cells (PA1). As a result, the ethyl acetate fraction was found effective in inhibiting the proliferation of human ovarian cancer cells with an IC50 value of 41.1 µg/mL. The main component responsible for anticancer activity was determined as a sesquiterpene lactone Tatridin B (3h-cyclodeca[b]furan-2-one, 4,9-dihydroxy-6-methyl-3,10-dimethylene-). Moreover, it was found effective in inhibiting NSD2, an important and recently proposed biomarker for several types of cancer. This is a hitherto report on the presence of this compound in ‘Nori’ showing potent anticancer activity on human ovarian tetracarcinoma (PA1).

Sensing Technology (ST) plays a key role in Structural Health Monitoring (SHM) systems. ST focuses on developing sensors, sensory systems or smart materials that monitor a wide variety of materials properties aiming to create smart structures and smart materials, using Embedded Sensors (ESs), and allowing continuous and permanent measurements of the structural integrity. The integration of ESs is limited to the processing technology to embed the sensor due to its high-temperature sensitivity and the possibility of damage during its insertion into the structure. In addition, the technological process selection is dependent on the base material composition, either metallic or composite parts. The selection of smart sensors or the technology underlying them is fundamental to the monitoring mode. This paper presents a critical review of the fundaments and applications of sensing technologies for SHM employing ESs, focusing on the actual developments and innovation of these, as well as analysing the challenges that these technologies present, to build a path that allows a connected world through distributed measurement systems.

Glutamate dehydrogenase (GDH) plays a key role in the metabolism of glutamate, an important compound at a cross-road of carbon and nitrogen metabolism and a relevant neurotransmitter. Despite being one of the first discovered allosteric enzymes, GDH still poses challenges for structural characterization of its allosteric sites. Only the structures with ADP, and at low (3.5 Å) resolution, are available for mammalian GDH complexes with allosteric activators. Here we aim at deciphering structural basis for the GDH allosteric activation, using bovine GDH as a model. For the first time we report a mammalian GDH structure in a ternary complex with the activators leucine and ADP, co-crystallized with potassium ion. An improved 2.4 Å resolution of the GDH complex with ADP is also presented. The ternary complex with leucine and ADP differs from the binary complex with ADP by the conformation of GDH C-terminus, involved in the leucine binding and subunit interactions. The potassium site, identified in this work, may mediate interactions between the leucine and ADP binding sites. Our data provide novel insights into the mechanisms of GDH activation by leucine and ADP, linked to the enzyme regulation by (de)acetylation.

Uranium (U) is enriched in the waters of the southern Colorado Plateau, including waters of the Navajo Nation. The region has naturally occurring U in rocks and a history of U mining which may increase U concentrations in waters. Despite prior research into the concentration of U in the waters of the Navajo Nation, a framework has not been established to understand the variation of U in the region’s groundwater. To this end, we examined data from five studies to establish where and why U is likely to be enriched in waters of the southern Colorado Plateau. We show that U concentrations are related to the presence of U-rich rock bodies, surface elevation, and local aquifer salinity. Additionally, we show that the distance to the nearest mine is a significant predictor of U in water sources. Our work can act as a guide for local water withdrawal, regional water remediation and mitigation efforts, and provides a means for understanding the geographical patterns of U concentration in waters of the southern Colorado Plateau.

Nowadays, technological advancement has transformed traditional vehicles into Au-tonomous Vehicles (A.V.s). In addition, in our daily lives, A.V.s play an important role since they are considered an essential component of smart cities. A.V. is an intelligent vehicle capable of main-taining safe driving by avoiding crashes caused by drivers. Unlike traditional vehicles, which are fully controlled and operated by humans, A.V.s collect information about the outside environment using sensors to ensure safe navigation. Furthermore, A.V.s reduce environmental impact because they usually use electricity to operate instead of fossil fuel, thus decreasing the greenhouse gasses. However, A.V.s could be threatened by cyberattacks, posing risks to human life. For example, re-searchers reported that Wi-Fi technology could be vulnerable to cyberattacks through Tesla and BMW AVs. Therefore, more research is needed to detect cyberattacks targeting the components of A.V.s to mitigate their negative consequences. This research will contribute to the security of A.V.s by detecting cyberattacks at the early stages. First, we inject False Data Injection (FDI) attacks into an A.V. simulation-based system developed by MathWorks. Inc. Second, we collect the dataset generated from the simulation model after integrating the cyberattack. Third, we implement an intelligent symmetrical anomaly detection method to identify FDI attacks targeting the control system of the A.V. through a compromised sensor. We use long short-term memory (LSTM) deep networks to detect FDI attacks in the early stage to ensure the stability of the operation of A.V.s. Our method classifies the collected dataset into two classifications: normal and anomaly data. The ex-perimental result shows that our proposed model's accuracy is 99.95%. To this end, the proposed model outperforms other state-of-the-art models in the same study area.

This paper introduces a multi-class hand gesture recognition model developed to identify a set of defined hand gesture sequences in two-dimensional RGB video recordings. The work presents an action detection classifier that looks at both appearance and spatiotemporal parameters of consecutive frames. The classifier utilizes a convolutional-based network combined with a long-short-term memory unit. To leverage the need for a large-scale dataset, the model uses an available dataset to then adopt a technique known as transfer learning to fine-tune the model on the hand gestures of relevance. Validation curves performed over a batch size of 64 indicate an accuracy of 93.95% (± 0.37) with a mean Jaccard index of 0.812 (± 0.105) for 22 participants. The presented model illustrates the possibility of training a model with a small set of data (113,410 fully labelled frames). The proposed pipeline embraces a small-sized architecture that could facilitate its adoption.

Inconsistent results published in previous studies make it difficult to determine the precise effect of consumer knowledge on their acceptance of functional foods, which were developed to improve consumers’ health status by providing adequate nutrition. We conducted a systematic review and meta-analysis by identifying and collecting relevant literature from three databases. Of the 1050 studies we reviewed, we included 40 in the systematic review and 18 in meta-analysis. Based on the focus of each included study, we operationally defined knowledge as knowledge of the functional food concept, nutritional-related knowledge, and knowledge of specific functional products. Results from the systematic review indicate that most participants from the included studies had a low level of knowledge, especially nutrition-related knowledge associated with consuming functional foods, and they were generally not familiar with the concept of functional foods. It is possible that participants’ level of knowledge was influenced by their demographic characteristics (e.g., age, gender, educational level, marital status, nationality). Results from the meta-analysis generated a summary effect size (r = 0.14, 95% CI [0.05; 0.23]), measured by the correlation coefficient r, which indicates that a small positive relationship exists between consumers’ level of functional foods knowledge and their acceptance of functional foods.

Yemen is a water-scarce country with inadequate fresh water and considerable groundwater depletion, as well as a lack of adequate surface water. The study region is considered an arid region, and there is insufficient water to meet the needs of the region's yearly population growth rate of 4 %. This study aims to assess the water resources in the Sana'a region and to identify the current water situation and forecast for the future. Rainfall changes spatial and temporal in very few quantities and an annual average of 267 mm. Water harvesting facilities are entirely filled by 75% of the total water facilities in the rainy seasons. The groundwater level in Sana’a Basin decreases about 6-8 meters annually due to the increase in the number of wells, the abundance of abstraction, and the lack of recharge. The amount of abstraction exceeds 400% of the recharge in the Sana'a basin. The water per capita is 70 - 85 m³ annually. It is an abstraction from the aquifers by private wells. The crop cultivated area decreased from 184217 hectares in 2007 to 122583 hectares in 2018 due to lack of water. The sewage treatment plant treats 18.25 Mm³ annually, with less than 70 % efficiency. The water deficit is about 500 to 723 Mm³ annually; it is an abstraction from the aquifers by private wells. The current water situation in the Sana'a region is catastrophic, and the planning and management must ensure a water balance in the future.

The yellow-legged Asian hornet (Vespa velutina Lepeletier 1836 (Hymenoptera: Vespidae)) is naturally distributed in China, Southeast Asia and India; however it has since detected outside of its native area, confirmed as being established in South Korea, Europe and Japan. Health risks and deaths caused by the invasive Vespa velutina stings have become a public health concern, being the most common cause of anaphylaxis due to hymenopterans in some European regions. This in turn has led to increased demand from medical practitioners and researchers for Vespa velutina venom for diagnostic and therapeutic purposes. In this study, a straightforward, quick and inexpensive method for obtaining Vespa velutina venom by electric stimulation is described. The venom extracts were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), confirming the composition of the obtained material. The availability of Vespa velutina venom will lead to improved diagnostic and therapeutic methods, mainly by venom immunotherapy (VIT), in patients allergic to this invasive species.

Organophosphate pesticides are used in large quantities. However, they exhibit toxic effects on non-target organisms. Dimethoate and its oxo-analog omethoate inhibit acetylcholinesterase and are toxic for mammals. Moreover, they show extreme toxicity for bees. Once in the environment, they undergo chemical transformations and decomposition. We show that dime-thoate and omethoate decompose rapidly in alkaline aqueous solutions (half-lives 5.7 and 0.89 days) but are highly stable in acidic solutions (half-lives 124 and 104 days). These differences are explained using quantum chemical calculations, indicating that a weaker P–S bond in omethoate is more susceptible to hydrolysis, particularly at a high pH. The toxicity of these pesticides solutions decreases over time, indicating that no or very little highly toxic omethoate is formed during hydrolysis. Presented data can be used to predict dimethoate and omethoate concentrations in contaminated water depending on pH. Presented results suggest that alkaline hydrolysis of organophosphates has an advantage over other techniques for their removal since there is no risk of omethoate accumulation and increased toxicity of contaminated water.

Aedes albopictus is an invasive mosquito species responsible for local transmission of chikungunya and dengue viruses in Europe. In the absence of available treatments, insecticides-based control is one of the most important viable strategies to prevent emerging problems. Diflubenzuron (DFB) and Bacillus thuringiensis var. israelensis (Bti) are among the most commonly used larvicides for Ae. albopictus control which pose major concerns for potential resistance development. Studies on the resistance emergence of Ae. albopictus to both DFB and Bti and its persistence in the wild are essential for the efficient and sustainable planning of the control programs. In this concept, larvae from a recently laboratory established population were subjected to increasing selective pressure for nine successive generations against both DFB and Bti. At the end of this process, the resistance levels and the overwintering success of the selected populations relative to control (colonies that received no selection) were determined. Results revealed a substantial and a moderate increase on the resistance levels following selection with DFB and Bti respectively. Interestingly, the selection process to both larvicides had no apparent impacts on the overwintering capability relative to control suggesting the successful persistence of the resistant individuals in the wild from year to year.

Pathogenic Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea. N. gonorrhoeae has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally-competent commensal Neisseria species. At present, little is known about the antimicrobial resistance profiles of commensal Neisseria. Here, we characterized the phenotypic resistance profile of four commensal Neisseria species (N. lactamica, N. cinerea, N. mucosa, and N. elongata) against 10 commonly used antibiotics, and compared their profiles to 4 N. gonorrhoeae strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic N. gonorrhoeae strains. Next, we compared the penicillin-binding-protein 2 (PBP2) sequences between commensal and N. gonorrhoeae strains. We found mutations in PBP2 known to confer resistance in N. gonorrhoeae also present in commensal Neisseria sequences. Our results suggest that commensal Neisseria have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic N. gonorrhoeae, possibly impairing drug development and clinical treatment.

Objectives: A wealth of literature has established risk factors for social isolation among older people, however much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.

The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess n and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity P from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with n = 24, there are two other competing contributions that enable increasing n under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. In vitro cytotoxicity/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cancer cells, and low activity against non-tumorigenic MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.

By the use of the tertiary amine A327 and 1 M HCl solution as precursors, the ionic liquid A327H+Cl- was generated and used to investigate its performance in the transport of Au(III) form hydrochloric acid medium. The influence of the stirring speed (600-1800 min-1), ionic liquid concentration (1.25-50% v/v) in the membrane phase and gold concentration (0.01-0.15 g/L) in the feed phase on metal transport have been investigated. An equation which included both equilibrium and kinetics parameters was derived, and the membrane diffusional resistance (Δm) and feed phase diffusional resistance (Δf) was estimated as 9.5x106 s/cm and 307 s/cm, respectively. At carrier concentrations in the 5-50% v/v range and gold concentrations in the 0.01-0.15 g/L range, metal transport is controlled by diffusion of metal species through the feed boundary layer, whereas at the lowest carrier concentrations, membrane diffusion is predominant. From the receiving solutions, gold can be recovered as gold nanoparticles.

Background: Developing patient-centric baseline standards that enable the detection of clinically significant outlier gene products on a genome-scale remains an unaddressed challenge required for advancing personalized medicine beyond the small pools of subjects implied by “precision medicine”. This manuscript proposes a novel approach for reference standard development to evaluate the accuracy of single-subject analyses of metabolomes, proteomes, or transcriptomes. Since distributional assumptions of statistical testing may inadequately model genome dynamics of gene products, the so-called significant results of previous studies may artefactually conflate with real signals. Model confirmation biases escalate when studies use the same analytical methods in the discovery sets and reference standards, as corroboration of results leads to an evaluation of reproducibility confounded with replicated biases rather than a measure of accuracy. We hypothesized that developing method-agnostic reference standards using effect-size and expression-level filtering of results, obtained from multiple discovery methods that are distinct from the one evaluated, would maximize the evaluation of clinical-transcriptomic signals and minimize statistical artefactual biases. We developed and released an R package “referenceNof1” to facilitate the construction of robust reference standards. Results: Since RNA-Seq data analysis methods often rely on binomial and negative binomial assumptions to non-parametric analyses, the differences create statistical noise and make the reference standards method dependent. In our experimental design, the accuracy of 30 distinct combinations of fold changes (FC) and expression levels (EL) were determined for five types of RNA analyses in two different datasets. This design was applied to two distinct datasets: breast cancer cell lines and a yeast study with isogenic biological replicates in two experimental conditions. In addition, the reference standard (RS) comprised all RNA analytical methods with the exception of the method testing accuracy. To mitigate for biased optimization of the RS parameters towards a specific analytical method, similarity between observed results of distinct analytical methods were calculated across all methods (Jaccard Concordance Index). The greatest differences were observed across diametric extremes. For example, filtering out differentially expressed genes (DEGs) using a fold change < 1.2 leads to a 50% increase in concordance between techniques when compared to results with FC > 1.2. Combining this FC cutoff with genes with mean expressions > 30 counts leads to a 65% increase in concordance in comparison to genes with expression levels < 30 counts and with FC < 1.2. Conclusions: We have demonstrated that comparing accuracies of different single-subject analysis methods for clinical optimization requires a new evaluation framework. Reliable and robust reference standards, independent of the evaluated method, can be obtained under a limited number of parameter combinations: fold change (FC) ranges thresholds, expression level cutoffs, and exclusion of the tested method from the RS development process. When applying anticonservative reference standard frameworks (e.g., using the same method for RS development and for prediction), a majority of the concordant signal between prediction and Gold Standard (GS) cannot be confirmed by other methods, which we conclude as biased results. Statistical tests to determine DEGs from a single-subject study generate many biased results that require subsequent filtering for increasing their reliability. Conventional single-subject studies pertain to one or a few measures in one patient over time [1]and need a substantial conceptual framework extension in order to address the tens of thousands of measures in genome-wide analyses of gene products. The proposed referenceNof1 framework addresses some of the inherent challenges in improving transcriptome scale single-subject analyses by providing a robust approach to constructing reference standards. Github: https://github.com/SamirRachidZaim/referenceNof1

An activated carbon manufacturing process using winemaking waste is analyzed and designed at industrial scale. Starting from experimental research, the chemical transformations and thermodynamics during pruning wood conversion are studied as a basis for plant design. In this way, mass and energy balances of hydrothermal carbonization and physical activation are fulfilled and a thermoeconomic methodology is applied to develop an energy-integrated plant. To achieve this target, a network of heat exchangers is allocated to minimize heat consumption and supply hot domestic water, while a cogeneration cycle is designed to provide electricity and satisfy the remaining heat demand. Furthermore, a sensitivity analysis is carried out to determine the influence of the production scale and other operation parameters, such as annual workload, service life, and capital and feedstock costs, on the economic viability of the plant. The energy balance of the plant indicates that the energy integration design manages to provide 48.9% of the overall process energy demand by crossing hot and cold streams and recovering heat from residual flue gas. On the other hand, the exergy cost analysis identifies the combustion of pruning wood used to provide heat demands as the main source of exergy destruction, confirming the suitability of integration to improve the thermodynamic performance. Including activated carbon production, electricity, and hot domestic water, the exergy efficiency of the plant stands at 11.5%.

Spin crossover (SCO) complexes are in the forefront of image, memory and sensing devices, with applications already established since for thirty years. In order to reach magnetic multistability conditions, the high-spin (HS) and low-spin (LS) states have to be carefully balanced by ligand field stabilization and spin pairing energies. Both of these effects could be effectively modelled by electronic structure theory, if the description would be accurate enough to describe these concurrent influences to within a few kJ/mol. Such a milestone would allow for the in silico-driven development of SCO complexes. However, so far, the ab initio simulation of such systems has been dominated by general gradient approximation density functional calculations. The latter can only provide the right answer for the wrong reasons, given that the LS states are grossly stabilized. In this contribution, we explore different venues for the parameterisation of hybrid functionals. A fitting set is provided on the basis of explicitly correlated coupled cluster calculations, with single- and multi-dimensional fitting approaches being tested to selected classes of hybrid functionals (hybrid, range separated and local hybrid). Promising agreement to benchmark data is found for a rescaled PBE0 hybrid functional and a local version thereof, with a discussion of different atomic exchange factors.

A theoretical nonlocal thermoelastic model for studying the effects of the thermal conductivity variability on a rotating nanobeam has been described in the present article. The theory of thermal stress is employed using the Euler–Bernoulli beam model and generalized heat conduction with phase lags. It is believed that the thermal conductivity of the current model varies linearly according to temperature. Due to variable harmonic heat, the considered nanobeam excited and was subjected to a time-varying exponential decay load. Using the Laplace transform process, the analytical solutions for displacement, deflection, thermodynamic temperature and bending moment of rotating nanobeams are provided in final forms and a numerical example has been taken to address the problem. A comparison of the stated results was displayed and additionally, the influences of non-local parameters and varying load were analyzed and examined. We also investigate how the linear changes in the temperature of physical properties can influence both the static and dynamic responses to the rotating nanobeam.

Mankind faces a coronavirus pandemic originating from a seafood market in Wuhan, China since December 2019. The pathogen was named novel coronavirus (n-CoV) and bats are the identified key reservoir. The coronavirus disease 2019 (COVID-19) quickly spread over China across the globe, turned into a pandemic with exponentially increasing numbers of cases and significant mortality rate. China reacted with lockdowns and strict control measurements to prevent spreading the virus. The treatment of severe cases was hampered by lack of specific vaccines. Vaccine-development and production is a painstaking process and can only be enforced by international cooperation. Different supportive treatment options surfaced due to combinations of antiviral agents with antibiotic drugs. Elderly, male, immune-suppressed patients with co-morbidities showed a high mortality rate. Health literacy, strong immune system, adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations and healthy life style choices can support fast recovery. Antibiotic resistance needs to be addressed by development of new generation antimicrobials against nosocomial infections in preparation for future outbreaks. Plant-biosynthesis of nanomaterials and antiseptics may help in prevention and recovery rate. Prevalence of COVID-19 maybe inversely related to BCG vaccination, endemicity of malaria, humidy and temperature but directly with latitude. Recommendations to prevent the spread of COVID-19 should be followed strictly.

Androgen receptor signaling is crucial for prostate cancer growth and is positively regulated in part by intratumoral CYP3A5. As African American (AA) men often carry the wild type CYP3A5 and express high level of CYP3A5 protein, we blocked the wild type CYP3A5 in AA origin prostate cancer cells and tested its effect on androgen receptor signaling. q-PCR based profiler assay identified several AR regulated genes known to regulate AR nuclear translocation, cell cycle progression and cell growth. CYP3A5 processes several commonly prescribed drugs and many of these are CYP3A5 inducers or inhibitors. In this study, we test the effect of these commonly prescribed CYP3A5 inducers/inhibitors on AR signaling. The results show that the CYP3A5 inducers promoted AR nuclear translocation, downstream signaling and cell growth whereas CYP3A5 inhibitors abrogated them. The observed changes in AR activity is specific to alterations in CYP3A5 activity. Both the inducers tested demonstrated increased cell growth of prostate cancer cells, whereas the inhibitors showed reduced cell growth. Further, characterization and utilization of the observation that CYP3A5 inducers and inhibitors alter AR signaling may provide guidance to physicians prescribing CYP3A5 modulating drugs to treat comorbidities in elderly patients undergoing ADT, particularly AA.

The objective of this study was to assess the ability of producing laminated edible films manufactured using the following proteins; gelatin (G), whey protein isolate (WPI), and polysaccharide; sodium alginate (SA), and to evaluate their physical properties. Additionally, films’ preparation employing these ingredients was optimized through the addition of corn oil (O), Overall, 8-types of laminated films (G-SA, G-WPI, SA-WPI, SA-G-WPI, GO-SAO, GO-WPIO, SAO-WPIO, SAO-GO-WPIO were developed in this study. The properties of the prepared films were characterized through the measurement of; tensile strength (TS), elongation at break point (EB), puncture resistance (PR), tear strength (TT), water vapour permeability (WVP) and oxygen permeability (OP). The microstructure of cross-sections of laminated films was investigated by scanning electron microscopy (SEM). Mechanical properties of films were dramatically enhanced through the addition of film layers. GO-SAO laminate showed the best barrier properties to water vapour (22.6 ± 4.04 g mm/kPa d m2) and oxygen (18.2 ± 8.70 cm3 mm/kPa d m2). SAO-GO-WPIO laminate film was the strongest of all laminated films tested, having the highest TS of 55.77 MPa, PR of 41.36 N and TT of 27.32 N. SA-G-WPI film possessed the highest elasticity with an EB value of 17.4%.

Henry’s constants for different existing compounds in water have great importance in transfer calculations. Measurement of these constants face different difficulties including high costs of experiment and low accuracy of measurement apparatus. Due to these facts, proposing a low cost and accurate approach becomes highlighted. To this end, adaptive neuro-fuzzy inference system (ANFIS) and least squares support vector machine (LSSVM) have been used as Henry’s constant predictor tools. The molecular structure of compounds has been used as inputs of models. After training the models, the visual and mathematical studies of outputs have been done. The coefficients of determination of LSSVM and ANFIS algorithms are 0.999 and 0.990 respectively. According to the comprehensiveness of databank and accurate prediction of algorithms, it can be concluded that LSSVM and ANFIS algorithms are accurate methods for prediction of Henry’s constant in wide range of chemical structure of compounds in water.

Since the 1960s Rare earths (REs) applications gradually have expanded to everyday life. REs have great strategic importance in industrial and technological development, so it is expected an increase in their demand. Among the REs the European Commission considered Cerium and Lanthanum as critical raw materials. This research article studies the adsorption of Ce and La onto two carbon nanomaterials, multiwalled carbon nanotubes (MWCNT) and carboxylic functionalized multiwalled carbon nanotubes (MWCNT_ox). The latter has slightly more affinity for REs than MWCNT. The recovery percentage for Ce were 89 and 98% and in the case of for La were 99 and 92% using 0.8 g of MWCNT and 0.2 g of MWCNT_ox respectively. The adsorption process fits a pseudo second-order kinetic model and the Langmuir isotherm best represented the metal uptake.

Directed evolution methods are becoming increasingly popular, as they are extremely powerful toward developing new biomolecules with altered/novel activities, e.g., proteins with new catalytic functions or substrate specificities, and nucleic acids that recognize an intended target. Especially useful are systems that have incorporated continuous evolution, where the protein to be evolved undergoes continuous mutagenesis to evolve a desired trait with little to no input from the researcher once the system is started. However, continuous evolution methods can be challenging to implement in the lab and daunting for researchers to invest time and resources. Our intent is to provide basic information and helpful suggestions that we have gained from our experience with bacterial phage-assisted continuous evolution (PACE). Specifically, we review factors to consider before adopting PACE for a given evolution scheme, different types of selection circuits that can be utilized with particular focus on the PACE-B1H selection system, what optimization of a PACE selection circuit may look like using directed evolution of ME47 as a case study, and additional techniques that may be incorporated into a PACE experiment. With this information, researchers will be better equipped to determine if PACE is a valid strategy to use to evolve their proteins and how to set up a valid selection circuit.

This article presents the copper ions adsorption process using an activated carbon from winemaking wastes. The pH, temperature, activated carbon amount and initial copper concentration were varied based on a full factorial 2^k experimental design. Kinetic and thermodynamic studies were also carried out. The adsorption kinetics was found follow a pseudo-second-order model. The adsorption data fit better to the Langmuir isotherm. The ANOVA demonstrated that both pH of the solution and activated carbon dosage had the greatest influence on copper adsorption. The activation energy was -32 kJ·mol^-1 suggesting that the copper adsorption is a physic-sorption process. The best fit to a linear correlation was the moving boundary equation that controls the kinetics for the adsorption copper ions onto the activated carbon. The X-ray photoelectron spectroscopy (XPS) results reveal the existence of different copper species (Cu²⁺, Cu⁺ and or Cu⁰) on the surface of the carbonaceous adsorbent after the adsorption, which could suggest a simultaneous reduction process.

Traditionally it has been thought necessary to lose 2% of body mass due to dehydration, before functioning is disrupted, although recently adverse effects have been reported with a loss of 0.5-0.7%. It is, however, unclear whether the response to small decreases in mass reflects dehydration, mechanisms that help to adapt to a loss of bodily fluid, or a placebo effect. Individuals were therefore subject to a temperature of 30°C for three hours, and mood and cognition monitored. To explore the possibility of a placebo response, the consumption of plain or coloured water was compared. To consider changes in hydration status, drinks known to differ in their ability to rehydrate were contrasted. Not drinking was disruptive, although a combination of plain water and electrolyte’s most effectively prevented a decline in functioning, indicating a role for rehydration after a loss of 0.52% body mass. There was, however, also evidence of a placebo response: a combination of plain water and electrolytes was better able to prevent a decline in functioning than coloured plain water and electrolytes. As increased anxiety was a robust response, it was discussed whether the renin–angiotensin–aldosterone system might be part of the mechanism.

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. In cases of hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. As a result, a measure related to skin tissue oxygenation is likely to be more sensitive to inadequate breathing during sleep than pulse oximetry. Energy Conversion Monitoring (ECM) provides a method for measuring skin tissue oxygen-dependent energy conversion and, as such, is promising for more sensitively detecting sleep disordered breathing (SDB) events compared to pulse oximetry. We hypothesized that ECM would detect hypoxia occurring with SDB events associated with drops in SpO₂ but also would detect hypoxic challenge occurring with SDB events not associated with drops in SpO₂ (hypopneas defined by a drop in nasal pressure occurring in conjunction with an arousal, respiratory-related arousals, and primary snoring). Primary snoring is of particular interest with respect to the potential of ECM because it is statistically associated with co-morbidities of SDB, such as hypertension, but is not considered pathological because of the lack of a proximal measure of pathology occurring with PSG. In this article we review ECM technology and methodology, present preliminary data indicating that it detects hypoxia occurring in the skin during SDB events that is not detected as blood desaturation by pulse oximetry, and make the case that it is a promising tool for identifying pathology occurring at the mild end of the SDB spectrum.

Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, i.e. Mycobacterium tuberculous complex and Mycobacterium leprae, respectively. The latter group is undoubtedly the most infamous, with TB infecting an estimated 10 million people and causing over 1.2 million deaths in 2017 alone (1). TB and leprosy also differ from NTM in that they are only transmitted from person to person and have no environmental reservoir, whereas NTM infections are commonly acquired from the environment (2) (3). It took until the 1950's for NTM to be recognised as a potential lung pathogen in people with underlying pulmonary disease and another 3 decades for NTM to be widely recognised by the medical community when NTM, particularly Mycobacterium avium complex (MAC) was recognised as the most common group of opportunistic pathogens in AIDS patients (4). This review focusses on an emerging NTM called Mycobacterium abscessus (M. abs). M. abs is a rapidly growing (RGM) NTM that is responsible for opportunistic pulmonary infections in patients with structural lung disorders such as cystic fibrosis (CF) and bronchiectasis (5), as well as a wide range of skin and soft tissue infections (SSTIs) in humans (6) (7). M. abs is a weakly staining Gram-positive mycobacterium that is neverand is, like other NTM, most often seen in soil and aquatic environments (8). The bacillus-shaped bacterium is 1-6µm long and 0.2-0.5µm in diameter, with curved ends and the presence of cord factor, or trehalose 6-6'-dimycolate, a glycolipid found in the cell wall of virulent species of mycobacteria that results in "serpentine cord" cell morphology is sometimes observed (8) (9). On solid growth medium, M. abs can display either a rough (M. abs-R) or smooth (M. abs-S) morphotype, with the rough morphotype displaying a more virulent phenotype than its smooth variant (10). The rough morphotype is characterised by irregular parallel filaments that form ridges across the colony, whereas a smooth morphology is displays a wet, smooth colony with no filaments or ridges (79). This morphology is driven by cell wall glycopeptidolipid (GPL); a loss of GPL results in the reversion from rough to smooth morphotype (80) (81). Moreover, it has been shown using human tissue culture models of infection that M. abs-R is able to persist and multiply within the host macrophage whereas M. abs-S lacks this capacity, hence its role in virulence (82). Like all other mycobacteria, M. abs are aerobic, non-motile and acid-fast organisms with a characteristically thick, lipid-rich cell wall that is hydrophobic. Due to their unusually impermeable, thick cell wall, mycobacteria are notoriously resistant to many antibiotics, disinfectants and heavy metals (11). When the genome of M. abs became available in 2009, elucidation of the resistance mechanisms of M. abs became an area of focus for scientific research, as the considerable threat it poses to public health became more apparent (12) (13) (14). In this review we will discuss how we came to understand the pathogen, how it is currently treated, as well as a discussion of drug resistance mechanisms and novel treatments currently in development.

We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Understanding ecological interactions is a key in managing phytopathology. Although entomologists rely mostly on both traditional molecular methods and morphological characteristics to identify pests, next-generation sequencing is becoming the go-to avenue for scientists studying fungal and oomycete phytopathogens. These organisms sometimes infect plants together with insects. There are many relationships yet to be discovered and much to learn about how these organisms interact with one another. Considering the growing number of exotic insect introductions in Canada, a high-throughput strategy for screening those insects is already implemented by the Canadian Food Inspection Agency (CFIA). However, no plan is deployed to investigate the phytopathogenic fungal and oomycete species interacting with insects. Metagenomics analysis was performed on the preservation fluids from CFIA’s insect traps across Canada. Using the Ion Torrent PGM technology and fusion primers for multiplexing and indexing, community profiling was conducted on the different semiochemicals used in the insect traps and the various areas where these traps were placed. Internal transcribed spacer 1 (fungi and oomycetes) and adenosine triphosphate synthase subunit 9-nicotinamide adenine dinucleotide dehydrogenase subunit 9 spacer amplicons were generated. Although direct links between organisms could not be established, moderately phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis) and oomycetes (mainly Peronospora spp. and Pythium spp.) unique to every type of semiochemical were discovered. The entomopathogenic yeast Candida michaelii was also detected. This project demonstrated our ability to screen for unwanted species faster and at a higher scale and throughput than traditional pathogen diagnostic techniques. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields.

The Hedgehog (Hh) signaling pathway plays an important role in embryonic and postnatal vascular development and in maintaining the homeostasis of organs. Under physiological conditions, Sonic Hedgehog (Shh), a secreted protein belonging to the Hh family, regulates endothelial cell growth, promotes cell migration, and stimulates the formation of new blood vessels. The present review highlights recent advances made in the field of Shh signaling in endothelial progenitor cells (EPCs). The canonical and non-canonical Shh signaling pathways in EPCs and endothelial cells (ECs) related to homeostasis, Shh signal transmission by extracellular vesicles (EVs) or exosomes containing single-strand non-coding miRNAs, and impaired Shh signaling in cardiovascular diseases are discussed. As a promising therapeutic tool, the possibility of using the Shh signaling pathway for the activation of EPCs in patients suffering from cardiovascular diseases is further explored.

We describe electron temperature measurements in the SSX MHD wind tunnel using two different methods. First, we estimate T_e along a chord by measuring the ratio of the C__III 97.7 nm to C_IV 155 nm line intensities using a vacuum ultraviolet monochrometer. Second, we record a biasing scan to a double Langmuir probe to obtain a local measurement of T_e. The aim of these studies is to increase the Taylor state lifetime, primarily by increasing the electron temperature. Also, a model is proposed to predict magnetic lifetime of relaxed states and is found of predict the lifetime satisfactorily. Furthermore, we find that proton cooling can be explained by equilibration with the electrons.

Although there are extensive literature reports on the use of gold nanoparticle (AuNP) based homogeneous assays for detection of biomolecules, very few experimental description and procedures involving their preparation are described. In this study, AuNPs conjugated to Bovine Serum Albumin or Envelope protein from Dengue II were developed as a homogeneous immunoassay for antibody detection. We report here optimization of key parameters to prepare an immunoassay like conjugation protein concentration, centrifugation time, electrolyte addition and assay temperature. We determined that saturating protein concentrations improved AuNPs surface coverage and uniformity of the assay and addition of sodium chloride improved sensitivity of the antibody detection method and assay stability. Furthermore, we showed that dynamic light scattering can be used to monitor changes in gold nanoparticles in the preparation and detection steps. Additionally, numerical simulations of the plasmonic optical response of AuNPs were carried out to scan for size-dependent response of the AuNPs. The AuNPs homogeneous immunoassay developed was further used in the detection of antibodies in vitro to detect Dengue virus infection.

Several studies have quantified the responses of Eucalyptus globulus plantations to weed control on its early development (2-3 years after establishment). However, long-term results of competing vegetation effects have been rarely incorporated into growth and yield models that forecast the long-term effects of reducing the intensity of competing vegetation control and its interaction with site resource availability on stem volume production close to rotation age. We compared several models predicting stand stem volume yield of Eucalyptus globulus plantations established across a water and fertility gradient growing under different intensity levels of free area of competing vegetation maintained during the first 3 years of stand development. Four sites were selected encompassing a gradient in rainfall and amount of competing vegetation. Treatments were applied at stand establishment and were monitored periodically until age 9 years. Competing vegetation control intensity levels considered 0, 5, 20, 44 and 100% weed-free cover around individual E. globulus seedlings. Maximum competing vegetation biomass production during the first growing season were 2.9, 6.5, 2.2 and 12.9 Mg ha^-1, for sites ranging from low to high annual rainfall. As expected, reductions in volume yield at age 9 years were observed as competing vegetation control intensity decreased during the first growing season. A strong relationship was established between stem volume yield loss and the intensity of competing vegetation control, the amount of competing vegetation biomass produced during the first growing season and mean annual rainfall. The slope of the relationship was different among sites and was related mainly to water and light limitations. Our results, suggest that the biomass of competing vegetation (intensity of competition) affecting site resource availability, contribute to observed long-term effects on E. globulus plantations productivity. The site with the lowest mean annual rainfall showed the highest volume yield loss at age 9 years. Sites with highest rainfall showed contrasting results related to the amount of competing vegetation biomass.

In this work, we report the magnetocaloric effect (MCE) in two systems of non-interactive particles, the first corresponds to the Landau problem case and the second, the case of an electron in a quantum dot subjected to a parabolic confinement potential. In the first scenario, we realize that the effect is totally different from what happens when the degeneration of a single electron confined in a magnetic field is not taken into account. In particular, when the degeneracy of the system is negligible, the magnetocaloric effect cools the system, while in the other case, when the degeneracy is strong, the system heats up. For the second case, we study the competition between the characteristic frequency of the potential trap and the cyclotron frequency to find the optimal region that maximizes the ΔT of the magnetocaloric effect, and due to the strong degeneration of this problem, the results are in coherence with those obtained for the Landau problem. Finally, we consider the case of a transition from a normal MCE to an inverse one and back to normal as a function of temperature. This is due to the competition between the diamagnetic and paramagnetic response when the electron spin in the formulation is included.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-ultra violet detection (FPSE-HPLC-UV) method for the simultaneous extraction and analysis of four phenyltin derivatives that include triphenyltin hydroxide, triphenyltin acetate, triphenyltin chloride and tetraphenyltin in environmental water (agricultural waste water and municipal waste water) and canned food samples. The selected analytes were well resolved by Waters Nova pack C18 column (3.9 x 150 mm, 4 µm particle size) in isocratic elution mode within 15 minutes. The new microextraction media has been analytically evaluated using phenyltin derivatives as model compounds. The factors affecting the extraction efficiency of FPSE have been evaluated and the optimum extraction conditions were determined. Under these optimum conditions, the limits of detection (LODs) for sol-gel C18 coated fabric phase sorptive extraction (FPSE) media in combination with HPLC-UV for the analysis of the phenyltin derivatives were in the range of 10-100 ng/mL with high precision (low relative standard deviation) at 10 ng/mL concentration with good absolute recoveries. To the best of our knowledge, this is the first FPSE extraction procedure applied to environmental water and canned food samples for the simultaneous determination of phenyltin derivatives and could be readily adopted as a rapid and robust green analytical tool for routine environmental and food analytical laboratories.

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. For several cancers, breast and prostate in particular, bone is the primary site of metastasis. Efforts to treat bone metastases have been stymied by a lack of models to study the progression and cellular players and signaling pathways driving bone metastasis. In this review, we examine the newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic and in silico computational models bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cell enter and escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

Observed sea surface Ka-band normalized radar backscatter cross section (NRCS) and Doppler velocity (DV) exhibit energy at low frequencies (LF) below the surface wave range. It is shown that non-linearity in NRCS-wave slope Modulation Transfer Function (MTF) and inherent NRCS averaging within the footprint account for the NRCS and DV LF variance with the exception of VV NRCS for which almost half of the LF variance is attributable to wind fluctuations. Although the distribution of radar DV is quasi-Gaussian suggesting virtually little impact of non-linearity, the LF DV variations arise due to footprint averaging of correlated local DV and non-linear NRCS. Numerical simulations demonstrate that MTF non-linearity weakly affects traditional linear MTF estimate (less than 10% for |MTF|< 20). Thus the linear MTF is a good approximation to evaluate the DV averaged over large footprints typical of satellite observations.

Assessing the economic supply of biomass in a geospatial context while accounting for risk from natural disasters was studied. Risk levels were estimated from a component of factors which included: population density, road density, federal ownership, U.S. Environmental Protection Agency ecoregions, and Presidential Disaster Declarations. The Presidential Disaster Declarations included risks due to: coastal storm, drought, fire, flood, freezing, hurricane, mud land slide, severe ices, severe storms, snow, tornado, and tropical storm. Presidential Disaster Declarations included summaries based on a short-term time period from 2000-2011, and on a long-term time period from 1964-2011. Risk categories were developed as a function of the number of disaster declarations, agricultural-to-forest land ratio, average road density, and average population density. A significant contribution of the research was the allocation of spatially explicit data using GIS technology at the 5-digit zip code tabulation area. The average area for 5-digit ZCTAs in the Eastern U.S. study region was approximately 169 kilometers². Long-term risk (1964-2011) from disaster declarations had a greater impact on the economic availability of biomass supply relative to short-term declarations (2000-2011). The greatest risk to biomass supply came from population density relative to the other risk factors studies. Of the 25,044 total ZCTAs, 12,256 ZCTAs were in locations that did not include population density ≥ 150/km², road density ≥ 14 km/km², federal ownership, and US Environmental Protection Agency Level III ecoregions. Of the remaining 12,256 ZCTAs, 26.8% were considered to be moderate-to-high risk based on short-term declarations (2000-2011) and 29.4% were considered to be moderate-to-high risk based on long-term declarations (1964-2011). Lower risk locations for procuring biomass supply for both short-term and long-term declarations, across all risk factors, were in southern Georgia, South Carolina, and Texas.

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [¹²³I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [¹²³I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [¹²³I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [¹²³I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [¹²³I]IAZA and total radioactivity (total[¹²³I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [¹²³I]IAZA data from healthy volunteers rest. Following exercise stress, both [¹²³I]IAZA and total[¹²³I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t_1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t_1/2β of 195 and 290 min, respectively]. Total body clearance (CL_TB) and the steady state volume of distribution (V_ss) were 0.647 L/kg and 185 mL/min, respectively, for [¹²³I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[¹²³I]. The t_1/2β, CL_TB and V_ss values were comparable to those reported previously for rested volunteers. The t_1/2α was approximately 4-fold shorter for [¹²³I]IAZA and approximately 3-fold shorter for total[¹²³I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [¹²³I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t_1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [¹²³I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [¹²³I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

This work deals with the numerical investigation of the delivery of potential therapeutic agents through dentinal discs (i.e. a cylindrical segment of the dentinal tissue) towards the dentin-pulp junction. The aim is to assess the main key features (i.e. molecular size, initial concentration, consumption rate, disc porosity and thickness) that affect the delivery of therapeutic substances to the dental pulp and consequently to define the necessary quantitative and qualitative issues related to a specific agent before its potential application in clinical practice. The CFD code used for the computational study is validated with relevant experimental data obtained using micro Laser Induced Fluorescence (μ-LIF) a non-intrusive optical measuring technique. As the phenomenon is diffusion dominated and strongly dependent on the molecular size, the time needed for the concentration of released molecules to attain a required value can be controlled by their initial concentration. Finally, a model is proposed which, given the maximum acceptable time for the drug concentration to attain a required value at the pulpal side of the tissue along with the aforementioned key design parameters, is able to estimate the initial concentration to be imposed and vice versa.

All-polyamide composite coated fabric (APCCF) materials were developed and used as the material of construction of textile bioreactors as a replacement of traditional costly steel-/concreate-based bioreactors. Then, APCCF-bioreactor was used to cultivate filamentous fungus Neurospora intermedia to produce ethanol and fungal biomass. The results showed similar performance of the fungus cultivated in stain-less steel bioreactors. Techno-economical analysis for a 5000-m³ APCCF bioreactor for fermentation facility would lead to a reduction of the annual production cost of the facility by $128,000,000 compared to similar stainless-steel processes. The comparative analyses (including mechanical and morphological analyses, density measurements and techno-economical analysis) revealed that the APCCF is a better candidate for material of construction of the textile bioreactor. The APCCF is a 100% recyclable single polymer composite which was prepared from textile production line waste.

Load transfer through orthopaedic joint implants is poorly understood. The longer-term outcomes of these implants are just starting to be studied, making it imperative to monitor contact loads across the entire joint implant interface to elucidate the force transmission and distribution mechanisms exhibited by these implants in service. This study proposes and demonstrates the design, implementation, and characterization of a 3D-printed smart polymer sensor array using conductive polyaniline (PANI) structures embedded within a polymeric parent phase. The piezoresistive characteristics of PANI were studied to characterize the sensing behaviours inherent to these embedded pressure sensor arrays. PANI's stable response to a continuous load, its stability throughout loading and unloading cycles, and its repeatable and linear response to incremental loading cycles together with the accuracy of these measurements were investigated. It is demonstrated that this specially developed multi-material additive manufacturing process for polyaniline is an attractive approach for the fabrication of implant components having embedded smart-polymer sensors for the measurement and analysis of joint loads in orthopaedic implants.

Continuous object tracking in WSNs, such as monitoring of mud-rock flows, forest fires etc., is a challenging task due to characteristic nature of continuous objects. They can appear randomly in the network field, move continuously, and can change in size and shape. Monitoring such objects in real-time generally require tremendous amount of messaging between sensor nodes to synergistically estimate object’s movement and track its location. In this paper, we propose a novel twofold-sink mechanism, comprising of a mobile and a static sink node. Both sink nodes gather information about boundary sensor nodes, which is then used to uniformly distribute energy consumption across all network nodes, thus helping in saving residual energy of network nodes. Numerous object tracking schemes, using mobile sink, have been proposed in the literature. However, existing schemes employing mobile sink cannot be applied to track continuous objects, because of momentous variation of network topology. Therefore, we present in this paper a mechanism, transformed from K-means algorithm, to find the best sensing location of the mobile sink node. It helps to reduce transmission load on the intermediate network nodes situated between static sink node and the ordinary network sensing nodes. The simulation results show that the proposed scheme can distinctly improve life time of the network, compared to one-sink protocol employed in continuous object tracking.

Phosphorylation reactions of glycerol were studied using different inorganic phosphates such as sodium phosphate, trimetaphosphate (a condensed phosphate), and struvite. The reactions were carried out in two non-aqueous solvents: formamide and a eutectic solvent consisting of choline chloride and glycerol in a ratio of 1:2.5. The glycerol reacted in formamide and in the eutectic solvent with phosphate to yield its phosphorylated derivatives in the presence of silicates such as quartz sand and kaolinite clay. The reactions were carried out by heating glycerol with a phosphate source at 85 °C for one week and were analyzed by 31P nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). The yield of the phosphorylated glycerol was improved by the presence of silicates, and reached 90% in some experiments. Our findings further support the proposal that non-aqueous solvents are advantageous for the prebiotic synthesis of biomolecules, and suggest that silicates may have aided in the formation of organophosphates on the prebiotic earth.

Peptidyl-prolyl cis/trans isomerases (PPIases) are present in a wide variety of microorganisms, including protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Trichomonas vaginalis, Leishmania major, Leishmania donovani, Plasmodium falciparum, Plasmodium vivax, Entamoeba histolytica, and Giardia intestinalis, all of which cause important neglected diseases. PPIases are classified as cyclophilins, FKBPs, or parvulins and play crucial roles in catalyzing the cis-trans isomerization of the peptide bond preceding a proline residue. This activity assists in correct protein folding. However, the biological structure‒function characterization of PPIases from these protozoan parasites is still incomplete. The recombinant production of these enzymes is highly relevant for this ongoing research. In this review, we explore the structural diversity, functions, recombinant production, and activity and inhibition of protozoan PPIases. We also highlight their potential as biotechnological tools for the in vitro refolding of other recombinant proteins from these parasites. These applications are invaluable for the development of diagnostic and therapeutic tools.

(1) Background: Most patients with atrial fibrillation, on warfarin therapy, are at higher risk of morbidity and mortality. However, data targeting patients with atrial fibrillation, who take warfarin therapy, are limited in Jordan. This study aimed to provide in-depth analysis of a cohort of patients with atrial fibrillation on warfarin regarding patients’ characteristics, atrial fibrillation related symptoms, interventions, comorbidities, and 12-months outcomes. (2) Methods: The study enrolled 645 patients with atrial fibrillation, on warfarin, from 28 health settings across Jordan. Standardized clinical data form was utilized to collect data upon enrollment, at one, six, and 12 months post initial assessment. Descriptive statistics were used for the description of variables. (3) Results: The most commonly reported symptoms were palpitation (41.4%) shortness of breath (39.1%) and fatigue (26.2%). The prevalent comorbidities associated with atrial fibrillation were congestive heart failure (22.5%), valvular heart diseases (16.6%), and cerebral vascular accident (16.3%). The embolic (32.4%) and thrombotic cerebral vascular accident (16.2%) were the most common type. Major bleeding associated with hospitalization was the most frequent type of bleeding (10 out of 24). (4) Conclusions: Jordanians, using anticoagulation, need to be constantly monitored in terms of their characteristics, symptoms, and any potential complications, to ensure its optimal therapeutic dose and prevent any potential health complications.

With the growing demand for personal protective equipment (PPE) in the face of the pandemic events caused by SARS-COV-2, the opportunity arises for the development of materials with characteristics such as antimicrobial, antiviral, antifungal activity, etc. The use of polymeric nanocomposites based on polyester/copper offers an alternative of great interest due to the versatility of the raw material and the high efficiency of copper as an antimicrobial additive. In this study, textile fibers prototypes with different Cu nanoparticles (CuNP) content were produced using melt-spinning to obtain bi-component multifilament fibers, and melt-blowing to obtain non-woven fabrics. The prototypes were tested against different pathogenic microorganisms such as S. aureus, E. coli, and C. albicans. It was shown that bi-component fibers offer more excellent protection against pathogens, while non-woven fabric only shows activity against E. coli. It was possible to identify that the CuNP were confined exclusively in the outer cover of the bi-component fibers, using different analytical techniques, which may be associated with the increase in antimicrobial activity, compared to the fibers present in the non-woven fabric, even when they present the same CuNP content.

The success rate of extracorporeal shock wave lithotripsy (ESWL) is influenced by various factors, including stone density, which is determined through computed tomography scans in Hounsfield Units (HU). Materials and method: This retrospective single-center study was conducted in King Fahad hospital. Sixty-seven adult patients with renal and ureteric stones were selected randomly and enrolled in the study. Their age ranged from 20 to 69 years. The patients were examined with non-contrast enhancement (NCCT) to assess the HU of stones, consequently, treated with ESWL. Results: of the 67 patients, 37.3% of the stones were completely fragmented, while 62.7% were partially fragmented. HU, location of the stone, a multiplicity of the stone, and patient age were significant factors contributing to stone fragility (p-values&lt; 0.05). The HU has a positive significant linear correlation with serum calcium (r= .28, p-value=.036), while serum acid has a negative correlation (r=-.55, p-value= &lt; .001). Thus, the probability of calcium-containing stones formation increased with increased HU. In contrast, uric acid stone formation is likely to develop with decreasing HU with serum uric acid. Renal stones in patients with diabetes mellitus and hypertension were not completely fragmented compared to those without clinical history. Conclusion: Mean HU, location of the stone, laterality, status of stone, and the number of ESWL sessions were the most significant factors affecting stone fragility. CT attenuation values can predict the composition of stones from serum calcium and uric acid examinations. Hypertension and Diabetes mellitus are risk factors for renal stone fragmentation.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

The objective of this study was to evaluate the glycemic index and the satiety response of three Mexican kinds of honey. The values of fructose ranged from 272.40-395.10 g/kg, while the glucose value ringed 232.20-355.50 g/kg. The ratio F/G of sample honey was 1.45, 1.00, and 1.17 for Highland, Multifloral, and Avocado honey, respectively. Twenty-six participants completed this study, which was previously approved by the ethics committee of the Facultad de Salud Pública y Nutrición (CE 2/2018-19). Highland and Avocado honey is classified as medium-GI (69.204.07 and 66.365.74, respectively), while Multifloral honey is classified as high-GI (74.245.98). The Highland honey presented the best satiety response. The difference in IG values and the effect of the satiety response of Highland honey could be explained by the different fractions of carbohydrates in samples and other components such as phytochemicals.

The dimorphic, soil-dwelling fungus Coccidioides is the causative agent of coccidioidomycosis and is a reemerging pathogen of human health concern. Despite increasing incidence and isolations of the organism outside of its theoretical environmental range, much of Coccidioides epidemiology, including complete host range, remains unknown. Feral swine (Sus scrofa) are an invasive species distributed throughout the United States that may play a role in fungal ecology due to their behavioral associations with soil. To address this, we evaluated seven feral swine for susceptibility to Coccidioides. After intranasal inoculation with 106.2 arthroconidia of C. posadasii, no pigs displayed signs of clinical disease, nor did any exhibit antibodies by AGID testing. Histopathologic evaluation did not reveal the presence granulomatous lesions, and fungal spherules or endospores were not observed in any of the tissue sections examined, although individuals had significant comorbidities, most notably Metastrongylus nematodes in the lungs. Despite the absence of lesions and organisms histologically, C. posadasii was isolated by culture from the lung and mediastinal lymph node of two pigs, indicating active infection. These results suggest that feral swine are mildly susceptible to acute Coccidioides infection and may aid in fungal dispersal due to the presence of spherules in tissues post-mortem.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

Botanical biopesticides have emerged as sustainable and eco-friendly alternatives to synthetic pesticides, whose indiscriminate use leads to several drawbacks to human and environment health. The present study reports on the evaluation of the roots extract from Magonia pubescens, species from the Cerrado (Brazilian savannah), on the phytopathogenic fungi, Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum. In addition, its insect antifeedant effect was assayed against Chrysodeixis chalcites. Thus, an in vitro test-assay was used to determine the fungicide potential (percentage growth inhibition, % GI) of the ethanolic extract of this plant species, whereas a leaf-disk bioassay on the 5^th instar larvae of C. chalcites was performed to evaluate the insecticide potential. The ethanolic extract was further fractionated by liquid-liquid extraction, using organic solvents of increasing polarity. The hexane/dichloromethane fraction exhibited a moderated potency, and similar to the ethanolic extract on the three assayed fungi (around % GI 30 at 1 mg/mL), whereas the n-butanol fraction showed a slight improvement of the fungicide effect against B. cinerea (% GI 39.18 at 1 mg/mL). Moreover, the etanolic extract exhibited a strong antifeedant activity, with a refusal rate (FR) higher than 90% in both choice and non-choice assays against C. chalcites, while the ethyl acetate and n-butanol fractions behaved as appetite suppressors. These results highlight M. pubescens as a promising source of biopesticides and deserve further investigations to optimize extraction procedures.

The results of experimental studies of ohmic conductivity degradation in the ensembles of nanostructured anatase bridges under long-term effect of direct current are presented. Stochastic sets of interelectrode partially conducting bridges consisting of close-packed anatase nanoparticles were formed by the seeding particles from drying aqueous suspensions on the surfaces of silica substrates with interdigital platinum electrodes. Multiple-run experiments at room temperature have shown that ohmic conductivity degradation in these systems is irreversible. It is presumably due to accumulated capture of conduction electrons by deep traps in anatase nanoparticles. The scaling analysis of voltage drops across the samples at the final stage of degradation gives a critical exponent for ohmic conductivity as 1.597. This value satisfactorily agrees with the reported model data for percolation systems. At an early stage of degradation, the spectral density of conduction current fluctuations wihin the frequency range of 0.01 Hz - 1 Hz decreases approximately as , while near the percolation threshold the decrease trend changes to . This transition is interpreted in terms of an increasing contribution of blockages and subsequent avalanche-like breakdowns of part of the local conduction channels in the bridges into electron transport near the percolation threshold.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

People with diabetic foot frequently exhibit poor gait and balance. However, there is no review to inform digital biomarkers of poor gait and balance related to diabetic foot, measurable by wearables outside traditional gait laboratories. Such information could assist in designing remote patient monitoring platform to track changes in gait and balance dysfunction among people with diabetic foot for timely referral and intervention. Accordingly, we conducted a web-based review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, measured by wearables, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our review, we recommend establishing appropriate strategies to successfully implement wearable-based assessment into clinical practice for diabetic foot care.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently pose a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carries mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n=586). mcr-1 genes were detected using a previously developed qPCR assay and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological background.

In horses, there is an increasing interest in developing long-lasting drug formulations, with bi-opolymers as viable carrier alternatives in addition to their use as scaffolds, suture threads, screws, pins, and plates for orthopedic surgeries. This communication focuses on the prolonged biocompatibility and biodegradation of PLA, prepared by hot pressing at 180 ºC. Six samples were implanted subcutaneously on the lateral surface of the neck of one horse. The polymers remained implanted for 24 to 57 weeks. Physical examination, plasma fibrinogen, and the mechanical noci-ceptive threshold (MNT) were performed. After 24, 28, 34, 38, and 57 weeks, the materials were removed for histochemical analysis using hematoxylin-eosin and scanning electron microscopy (SEM). There were no essential clinical changes. MNT decreased after the implantation procedure, returning to normal after 48h. A foreign body response was observed by histopathologic evalua-tion up to 38 weeks. At 57 weeks, no polymer or fibrotic capsules were identified. SEM showed surface roughness suggesting a biodegradation process, with an increase in the average pore di-ameter. As in the histopathological evaluation, it was not possible to detect the polymer 57 weeks after implantation. PLA showed biocompatible degradation and these findings may contribute to future research in the biomedical area.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

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.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

We improved a magnetic scanning microscope for measuring the magnetic properties of minerals in thin sections of geological samples at submillimeter scales. The microscope is comprised of a 200 µm diameter Hall sensor that is 142 µm from the sample; an electromagnet capable of applying to the sample up to 500 mT dc magnetic fields over a 40 mm diameter region; a second Hall sensor arranged in a gradiometric configuration to cancel the background signal applied by the electromagnet and reduce overall noise in the system; a custom-designed electronics to bias the sensors and provide adjustment for background signal cancelation; and a scanning XY stage with micrometer resolution. Our system achieves a spatial resolution of 220 µm with noise at 6.0 Hz of »300 nT_rms/(Hz)^1/2 in an unshielded environment. The magnetic moment sensitivity is 1.3 × 10⁻¹¹ Am².^1/2 We successfully measured the representative magnetization of a geological sample using an alternative model that takes into account the sample geometry and identified different micrometric characteristics in the sample slice.

Bimetallic nanoparticles are of interest since they lead to many interesting electrical, chemical, catalytic, and optical properties. They are particularly important in the field of catalysis since they show superior catalytic properties than their monometallic counterparts. The structures of bimetallic nanoparticles depend mainly on the synthesis conditions and the miscibility of the two components. In this work, PdPt alloyed-bimetallic nanoparticles (NPs) were synthesized through the polyol method, and characterized using spherical aberration (Cs) corrected scanning transmission electron microscopy (STEM). High-angle annular dark-field (HAADF)-STEM images of bimetallic nanoparticles were obtained. The contrast of images shows that nanoparticles have an alloy structure with an average size of 8.2 nm. Together with the characterization of nanoparticles, a systematic molecular dynamics simulations study, focused on the structural stability and atomic surface segregation trends in 923-atom PdPt alloyed-bimetallic NPs was carried out.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.