Background: Deficiency of alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic a priority issue. We investigate the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. Methods: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of Alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those subjects displaying concentrations below 100 mg/dL. Results: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 subjects (91%). Heterozygous mutations were detected in 7 patients; 3 had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), 2 the c.863A>T mutation (p.Glu288Val; Pi*S), one the c.221_223delTCT mutation (p.Phe76del; Pi*Malton) having the last one the c.1066G>A (p.Ala356Thr) mutation not previously described. Finally one patient had the c.863A>T mutation in homozygosis whereas two double heterozygous patients c.863A> T/ c.1096G>A were detected. Conclusions: an altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the Alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

The COVID-19 pandemic has resulted in a wide range of spatial interventions to slow down the spread of the virus. The spatial limitations of narrow public circulation spaces within informal settlements, which house over one billion people around the world, make it impossible for pedestrians to practice physical distancing (or social distancing). In this paper, we propose a flexible mathematical method, named the Cluster Lane Method, for turning a planar circulation network of any size or complexity into a network of unidirectional lanes, making physical distancing possible in narrow circulation spaces by limiting face-to-face interactions. New notions and theorems about oriented graphs in graph theory are introduced. The paper ends with a discussion of the potential implementation of this cost-efficient, low-tech, sustainable solution, and with the introduction of a novel unidirectional tactile paving for the visually impaired.

This paper is a detailed study on radio frequency identification (RFID) technology focused on its application for warehouse traceability in the company FRUMECAR. It highlights the importance of controlling the traceability of items in warehouses or logistics companies, highlighting the need for reliable, real-time information to effectively manage inventory and resolve incidents quickly. The paper discusses in depth what RFID is, its types, main components such as tags, readers, and antennas, as well as discussing how it works, advantages, disadvantages, and specific applications. It also examines factors such as return on investment, cost feasibility, and environmental factors that influence the implementation of RFID systems. The paper presents a practical approach, proposing RFID-based solutions to improve traceability in FRUMECAR, analyzing the current state of the company and its warehouses, with the aim of implementing an efficient system that allows real-time tracking of products.

The differential distribution, size, and quality of urban green spaces (UGS) among localities generate a differential distribution of benefits provided to users. We analyzed the spatial distribution of five size categories of UGS among 15 municipalities of Mexico City, compared their total surface per capita and associated them with the social marginality index. We found 1,353 UGSs accessible for public use with a total area of 2,643 ha. Seventy-four percent of them had <1 ha of surface area, and 51% were located in only three municipalities that were mostly middle- and high-income. These municipalities concentrated a higher area of green spaces per capita. We found a negative correlation between the marginality index and the area of UGS per municipality; the lower the marginality index, the higher the area of green spaces. We consider this a situation of environmental injustice since urban environmental services are distributed unequally with respect to marginalized populations.

In studies of dynamic stability and power quality, it is necessary to know the mechanical parameters that determine the transient response of a wind turbine. The exact value of these parameters is not as decisive as the power curve can be, but an estimate that is far from reality can distort or even invalidate the simulation results. Despite its importance, this information, especially the inertia, but also the stiffness and damping constant of the drive-train, is hardly available for the turbine model under investigation. In this work, the different bibliographical sources that provide values of blade inertia in kg·m2 will be reviewed, and above all, those that provide a distribution of masses along the span of the blade. With this, different reliable relations will be obtained that allow calculating the inertia of the turbine rotor, based on the mass and length of the blade. When the center of gravity is also available, a very correlated expression is provided to obtain the inertia. The even rarer references to the stiffness and damping constant of the drive-train will also be reviewed.

Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rate during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare maternal and obstetric complications between women who seroconverted in the first versus the third trimester. This is an observational, cohort study carried out at Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11-13 weeks scan between January 1st and May 15th, 2020, were included and monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from the first and third trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester.

A new layout optimization method for offshore wind farms is proposed to minimize power deficits due to wake effect. The main engine of the algorithm is a gradient-descent method, in which an analogy is established between power deficit and repulsive electrostatic potential energy. To achieve a maximum dispersion in the initial solution, throughout the optimization process, new turbines are included in the centre of the concession area, and quickly expand outward looking for areas with less potential, in turn pushing the previous ones. When the optimization process ends, to avoid local maximums, it enters into a process of suppression of the set of locations that cause the greatest potential (power deficit). Then, a potential map of the entire area is created and a greedy algorithm includes new turbines to complete the layout with the final number of turbines. To speed up the search process and the creation of the potential map, two simplifications have been validated and added: the spatial distribution of velocities has been converted into its equivalent with point symmetry; and, for turbines affected by multiple wakes, the power deficit has been calculated by using a linear aggregation of powers, instead of the usual linear (or quadratic) aggregation of speeds. Owing to this type of aggregation, the process is accelerated in a factor of 90.

Trace metals are essential elements that play key roles in a number of biochemical processes governing human visual physiology in health and disease. Several trace metals, such as zinc, have been shown to play important roles in the visual phototransduction process. In spite of this, there has been little research conducted on the direct effect of trace metal elements on the visual pho-toreceptor rhodopsin. In the current study, we have determined the effect of several metal ions, such as iron, copper, chromium, manganese, and nickel on the conformational stability of rho-dopsin. To this aim, we analyzed, by means of UV-visible and fluorescence spectroscopic methods, the effects of these trace elements on the thermal stability of dark rhodopsin, the stability of its active Metarhodopsin II conformation, and its chromophore regeneration. Our results show that copper prevented rhodopsin regeneration and slowed down the retinal release process after il-lumination. In turn, Fe3+, but not Fe2+, increased the thermal stability of the dark inactive con-formation of rhodopsin, whereas copper ions markedly decreased it. These findings stress the important role of trace metals in retinal physiology at the photoreceptor level, and may be useful for the development of novel therapeutic strategies to treat retinal disease.

One of the biggest threats we face globally is the emergence of antimicrobial resistant (AMR) bacteria, which runs in parallel with a lack in the development of new antimicrobials. Among these AMR bacteria, pathogens belonging to the ESKAPE group can be highlighted (Enterococcus spp, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) due to their profile of drug resistance and virulence. Therefore, innovative lines of treatment must be developed for these bacteria. In this review, we summarize the different strategies for the treatment and study of molecular mechanisms of AMR in the ESKAPE pathogens based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins' technologies: loss of plasmid or cellular viability, random mutation or gene deletion as well directed mutations that lead to a gene's loss of function.

The aim of this study was to evaluate patients' knowledge and perception of the use of systemic antibiotics in the treatment of endodontic infections and to determine the possible contribution of patients to the development of bacterial resistance. Five hundred and fifty patients were asked to respond to a survey on the perception of systemic antibiotic use in the treatment of endodontic infections and antibiotic resistance during January 2022 and March 2023. Data were analyzed using descriptive statistics and Pearson's Chi-square test. 514 patients were included in the study, 65.9% of whom were women. While 34.6% of the population studied thought that it was always necessary to take antibiotics prior to endodontics, 49.4% considered that they were necessary after endodontics, regardless of the clinical symptoms (p>0.05). The prevalence of self-medication was 17.3% and women self-medicate more than men, with significant differences (p<0.05), although they have greater knowledge of antibiotic resistance than men (p>0.05). Forty-four percent of the population expect to take antibiotics when faced with dental pain, mainly women (p<0.05). The general population is contributing to the serious problem of bacterial resistance. It is necessary to promote educational strategies focused on the correct use of antibiotics in the community.

The focus of this research is to analyze the results of encrypting audio using various authenticated encryption algorithms implemented in the Python cryptography library for ensuring authenticity and confidentiality of the original contents. The Advanced Encryption Standard (AES) is used as the underlying cryptographic primitive in conjunction with various modes including Galois Counter Mode (GCM), Counter with Cipher Block Chaining Message Authentication Code (CCM), and Cipher Block Chaining (CBC) with Keyed-Hashing for encrypting a relatively small audio file. The resulting encrypted audio shows similarity in the variance when encrypting using AES-GCM and AES-CCM. There is a noticeable reduction in variance of the performed encodings and an increase in the amount of time it takes to encrypt and decrypt the same audio file using AES-CBC with Keyed-Hashing. In addition, the corresponding encrypted using this mode audio spans a longer duration. As a result, AES should either have GCM or CCM for an efficient and reliable authenticated encryption integration within a workflow.

The repeated application of herbicides has led to the development of herbicide resistance. Models are useful for identifying key processes and understanding the evolution of resistance. This study developed a spatially explicit model at a landscape scale to examine the dynamics of Lolium rigidum populations in dryland cereal crops and the evolution of herbicide resistance under var-ious management strategies. Resistance evolved rapidly under repeated herbicide use, driven by weed fecundity and herbicide efficacy. Although fitness costs associated with resistant plants re-duced resistance evolution, they did not affect the speed of spread. The most effective strategies to slow resistance involved diversifying cropping sequences (e.g., crop rotation) and the herbicide applications (e.g., rotating different herbicide modes of action). Pollen flow was the main disper-sal vector, with seed dispersal also contributing significantly. Strategies limiting seed dispersal effectively decreased resistance spread. However, the use of a seed-catching device at harvest could unintentionally enrich resistance in the area. It would be beneficial to optimise the move-ment of harvesters between fields. The model presented here is a useful tool that may assist in the exploration of novel management strategies within the context of site-specific weed management at the landscape scale, as well as in the advancement of our understanding of resistance dynamics.

On 2013 the Villonaco wind farm (16.5 MW), the first wind farm in continental Ecuador near the city of Loja, began operations. The power generated is delivered to the National Interconnected System (SNI), which services the city. This research confronts two sets of real data, the electricity use of the urban area of Loja, and the power generated by the Villonaco Wind Farm. Electricity use follows clearly defined daily and weekly cycles, and wind power has a seasonal behaviour. The study shows that wind power integration cannot be a long-term stable power source regardless power or generation surplus. Another essential finding is that time series can be used as a statistical source to determine the need for short- (seconds) and long- (days, weeks) term energy storage. Strategies to further the energy autonomy of the urban area through the expansion of the wind farm by a factor of 2 are discussed.

Let G be a connected Lie group with Lie algebra g. This review is devoted to studying the fundamental dynamic properties of elements in the normalizer NG of G. Through an algebraic characterization of NG we analyze the different dynamics inside the normalizer. NG contains the well-known left-invariant vector fields and the linear and affine vector fields on G. In any case, we show the shape of the solutions of these ordinary differential equations on G. We give examples in low-dimensional Lie groups. It is worth saying that these dynamics generate the linear and bilinear control systems on Euclidean spaces and the invariant and linear control systems on Lie groups. Moreover, the Jouan Equivalence Theorem shows how to extend this theory to control systems on manifolds.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

This paper presents a practical case illustrating how the Sustainable Development Goals (SDGs) of the 2030 Agenda have been designed and articulated in the context of the University of the Basque Country (UPV/EHU). Even though there is a widespread formal adherence of universities to the SDGs, there is a lack of solid commitment to go beyond the compartmentalization of their implementation and to contribute to a holistic approach. The EHUagenda 2030 is a roadmap to move towards an integrated, verifiable and pragmatic contribution to this international agenda. It describes the UPV/EHU's contribution to 12 of the 17 SDGs, with the addition of its own commitment to linguistic and cultural diversity (SDG 17 + 1), along with the three sectoral plans: the Equality Campus, the Inclusion Campus and the Planet Campus. It also describes the refocus of its education model IKD i3; i3 is ikaskuntza x ikerketa x iraunkortasuna, Basque for learning x research x sustainability. Additionally, it includes the UPV/EHU’s Panel of Sustainable Development Indicators, which addresses the technical aspects of monitoring the implementation of the SDGs. The systematic methodology used in this process (mapping; mainstreaming; diagnosis and definition and, finally, estimation) and presented in this paper could be replicated in other universities yet to embark on this integration. The steps and findings presented here can also be applied to other organizations and help the integration process.

Water recycling and reuse are corner stones in the water management that may be compromised by the presence of pollutants. Among them, pharmaceuticals can overcome the standard water treatments and require sophisticated approaches to remove them. Sorption is an economically affordable alternative limited by the need of sorbents that exhibit sorption coefficient (Kd) higher than 500 L/kg to be useful in wastewater treatment plants (WWTPs). We report that th cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU, Kd higher than 600 L/kg for ciprofloxacin (CIP) and ofloxacin and an outstanding Kd higher than 4000 L/kg for erythromycin (ERY), when assayed against a cocktail of 6 drugs. The characterization of the polymers by XRPD, TGA and SEM reveals that both pDx1 and pDx5 share similar features, with an ERY Kd of 13 x 103 for pDx1 and 6.4 x 103 for pDx5. The facts that new affinities and improvements in Kd can be achieved by cross-linking Dx in presence of other molecules that promote a pre-organization, broaden the applications of DVS cross-linked polysaccharide as sustainable and eco-friendly sorbents.

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non- melanoma skin cancer and the second cause of death by skin cancer in caucasian population. However, at present it is difficult to predict patients with worst SCC prognosis. Objective: To identify proteins whose expression level could predict SCC infiltration in SCC arising from actinic keratosis (AC). Methods: A total of 20 biopsies of 20 different patients were studied, 10 were from SCC-AK samples and 10 from normal skin. Early infiltrated SCC-AK were selected on histological examination and to determine the expression of proteins fresh skin samples were processed by 2DE-electrophoresis Results: The expression levels of three proteins namely alpha-hemoglobin, heat shock protein (Hsp)-27 and 70 were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immnunohistological examination suggested that the increased expression of Hsp70 proteins seems to mainly occur in the keratinocytes cytoplasm. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western-blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be potential biomarker of early infiltration of SCC arising from an AK. Keywords: actinic keratosis, cutaneous squamous cell carcinoma; cytoplasm, skin cancer; heat shock protein.

In this paper, the existence of two nontrivial stationary solutions for the nonlinear Gilpin Ayala two species competition model is given by using the mountain pass lemma, and the local stability criterion of the trivial solution is given by using Lyapunov function method. Based on the local stability criterion, we give some suggestions on how to avoid the population extinction. This is, when the population is on the verge of extinction, we should try our best to avoid the diffusion behavior and reduce the diffusion coefficient, otherwise the species are easy to go extinct. Numerical example shows the effectiveness of the proposed method.

This work presents an innovative application of optimal control theory to the strategic scheduling of battery storage in the day-ahead electricity market, with a focus on enhancing profitability while factoring in battery degradation. The study incorporates in the optimisation framework the cost of battery capacity degradation, the effects of capacity degradation and internal resistance degradation into dynamics. We employ a continuous-time representation of the dynamics, in contrast with many other studies that use a discrete-time approximation with rather coarse intervals. We adopt an equivalent circuit model coupled with empirical degradation parameters to simulate a battery cell’s behaviour and degradation mechanisms with good support from experimental data. Utilising direct collocation methods with mesh refinement allows for precise numerical solutions to the complex, nonlinear dynamics involved. Through a detailed case study of Belgium’s day-ahead electricity market, we determine the optimal charging and discharging schedules under varying objectives: maximizing net revenues, profits considering capacity degradation, and profits considering both capacity degradation and internal resistance increase due to degradation. The results demonstrate the viability of our approach and underscore the significance of integrating degradation costs into the market strategy for battery operators, alongside its effects on the battery’s dynamic behaviour. Our methodology extends previous work by offering a more comprehensive model that empirically captures the intricacies of battery degradation, including a fine and adaptive time domain representation, focusing on the day-ahead market, and utilising accurate direct methods for optimal control. The paper concludes with insights into the potential of optimal control applications in energy markets and suggestions for future research avenues.

The field of applied behavior analysis has been directly involved in both research and applications of behavioral principles to improve the lives of captive zoo animals. Thirty years ago, Forthman and Ogden (1992) wrote one of the first papers documenting some of these efforts. Since that time, considerable work has been done using behavioral principles and procedures to guide zoo welfare efforts. The current paper re-examines and updates Forthman and Ogden’s original points, with attention to the five categories they detailed: (1) promotion of species-typical behavior, (2) reintroduction and repatriation of endangered species, (3) animal handling, (4) pest control, and (5) animal performances. In addition, we outline three current and future directions for behavior analytic endeavors: (i) experimental analyses of behavior and the zoo, (ii) applied behavior analysis and the zoo, and (iii) within-subject methodology and the zoo. The goal is to provide a framework that can guide future behavioral research in zoos, as well as create applications based on these empirical evaluations.

In this paper, the author utilizes Saddle Theorem and variational methods to deduce existence of at least six stationary solutions for reaction-diffusion Gilpin-Ayala competition model (RDGACM). To obtain the global stabilization of the positive stationary solution of the RDGACM, the author designs a suitable impulsive event triggered mechanism (IETM) to derive the global exponential stability of the the positive stationary solution. It is worth mentioning that the new mechanism can exclude Zeno behavior and effectively reduce the cost of impulse control through event triggering mechanism. Besides, compared with existing literature, the restrictions on the parameters of the RDGACM are relaxed so that the methods used in existing literature can not be applied to the relaxed case of this paper, and so the author makes comprehensive use of Saddle Theorem, orthogonal decomposition of Sobolev space $H_0^1(\Omega)$ and variational methods to overcome the mathematical difficulty. Numerical examples show the effectiveness of the methods proposed in this paper.

The current study aims to first, isolate H. pylori in cultures from gastric biopsy samples and test their susceptibility. Secondly, we aim to assess the efficacy of the standard triple therapy from patients coming of the western central region of Colombia. Patients with H. pylori positive re-ceived standard triple therapy with PPI [40 mg b.i.d.], clarithromycin [500 mg b.i.d.], amoxicillin [1g b.i.d.] for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Resistance to metronidazole, levofloxacin, rifampicin, clarithromycin and amoxicillin was 81, 26.2, 23.9, 19 and 9.5%, respectively. No resistance was found for tetracycline. 54 patients received standard triple therapy, 48 attended follow-ups testing and of them, 30 had resistance test reports. Overall eradication rate was 81.2%, 4 patients underwent second-line management and only one patient remained H. pylori positive by urea breath test during the follow-up [six weeks]. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains [95.6% vs. 42.8% p= 0.001]. The updated percentages of resistance to clarithromycin in this geographical area have increased, so this value must be considered when choosing the treatment regimen.

Glioblastoma is a central nervous system cancer type with a poor prognosis. One of its main features is the constant change of metabolism phenotype to support its development and progression. Mitochondria play a critical role in cellular metabolism. Acetylation on lysine residues of mitochondrial enzymes is a mechanism for regulating protein function. This modification negatively affects the mitochondrial proteome function and is counteracted by the enzyme sirtuin 3 (SIRT3). To better understand how SIRT3 regulates mitochondrial metabolism, we inhibited SIRT3 and examined by high-resolution mass spectrometry analysis the proteome and acetylome of two glioblastoma cell lines with different metabolic preferences. Our results indicate that protein synthesis machinery is regulated by lysine acetylation and plays a role in the metabolic phenotype. We also identified new SIRT3 targets not previously associated with specific functions, highlighting their potential as future targets for further study. This study shed light on the role of SIRT3 in mitochondria and its implication for cellular metabolism. We have generated knowledge at the proteome and acetylome levels on the dynamics between two glioblastoma cell lines with opposing metabolic phenotypes. Our results might guide in searching for biomarkers at both proteome and acetylome levels in glioblastoma.

We analyse recent contradictory results and conclusions about the spectrum of the screened Coulomb potential $V(r)=-r^{-1}e^{-C/r}$. The well known Hellmann-Feynman theorem shows that all the bound states of the Coulomb potential ($C=0$) remain bounded as $C$ increases. We derive a simple approximate analytical expression for the eigenvalues for sufficiently small values of the screening parameter $C$ and an approximate asymptotic expression for the asymptotic behaviour of the s-state eigenvalues when $C\rightarrow \infty $. Present results are expected to resolve the discrepancy about the spectrum of the quantum-mechanical model just mentioned.

Firstly, the author do dynamic analysis for reaction-diffusion Gilpin-Ayala competition model with Dirichlet boundary value, involved in harmful species. Existence of multiple stationary solutions is verified by way of Mountain Pass lemma, and the local stability result of the null solution is obtained by employing linear approximation principle. Secondly, the author utilize variational methods and LMI technique to deduce the LMI-based global exponential stability criterion on the null solution which becomes the unique stationary solution of the ecosystem with delayed feedback under a reasonable boundedness assumption on population densities. Particularly, LMI criterion is involved in free weight coefficient matrix, which reduces the conservatism of the algorithm. In addition, a new impulse control stabilization criterion is also derived. Finally, two numerical examples show the effectiveness of the proposed methods. It is worth mentioning that the obtained stability criteria of null solution presented some useful hints on how to eliminate pests and bacteria.

Ferulic acid has numerous beneficial effects for human health, which are frequently attributed to its antioxidant behavior. In this report many of them are reviewed and 185 new ferulic acid derivatives are computationally designed, using the CADMA-Chem protocol. For the later, the chemical space was sampled and evaluated. To that purpose selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes, directed related with the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and alpha-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directed related with the etiologies of Parkinson’s and Alzheimer’s diseases. They are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.

In the coming years, digital applications and services that continue to use the country's native cloud systems will be huge. By 2023, that will exceed 500 million, according to IDC. This corresponds to the sum of all applications developed in the last 40 years. If you are the one you answered, yes! This article is for you!

The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-Protein Interactions (PPIs) of the nucleocapsid protein of MERS-CoV has been reported as a valid strategy to inhibit viral replication. In this study, the applicability of this unexplored mechanism of action against SARS-CoV-2 is analyzed. During our research, we were able to find three inducible interfaces of SARS-CoV-2 N protein NTD, compare them to the previously reported MERS-CoV stabilized dimers, and identify those residues that are responsible for their formation. A drug discovery protocol implemented consisting of docking, molecular dynamics and MM-GBSA enabled us to find several compounds that might be able to exploit this mechanism of action. In addition, a common catechin skeleton was found among many of these molecules, which might be useful for further drug design. We consider that our findings could motivate future research in the fields of drug discovery and design towards the exploitation of this previously unexplored mechanism of action against COVID-19.

Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.

Digital twins are an emerging technology that could be harnessed for the digitalization of the industry. Steel industry systems contain a large number of electro-hydraulic components, as proportional valves. An input-output model for a novel water proportional cartridge valve is derived from physical modelling based on fluid mechanics, dynamics, and electrical principles. The valve is a two-stage valve with two 2/2-way water proportional valves as the pilot stage and a marginally stable poppet-type cartridge valve as the main valve. The orifice equation, which is based on Bernoulli principles, is approximated by a polynomial which makes parameter estimation easier and makes modelling possible without measuring pressure of the varying control volume situated in the pilot stage part of the valve. Data were collected when the valve was operating as a component in a closed-loop system as part of a press-mill machine in a steel manufacturing plant. Parameter estimation was made by convex optimization with physical constraints to overcome problems caused by poor system excitation. For comparison, a simple linear model was derived and the least squares method used for parameter estimation. A thorough estimation of the parameters relative errors is presented. The model contains 5 parameters related to the design parameters of the valve. The modelled position output is in good agreement with experimental data for training and test data. The model can be used for real time monitoring of the valve’s status by the model parameters. One of the model parameters varies linearly with production cycles. Thus, aging of the valve can be monitored.

Elliptic scator algebra is possible in 1+n dimensions, n∈N. It is isomorphic to complex algebra in 1+1 dimensions, when the real part and any one hypercomplex component are considered. It is endowed with two representations: an additive one, where the scator components are represented as a sum; and a polar representation, where the scator components are represented as products of exponentials. Within the scator framework, De Moivre’s formula is generalized to 1+n dimensions in the so called victoria equation. This novel formula is then used to obtain compact expressions for the integer powers of scator elements. A scator in S1+n can be factored into a product of n scators that are geometrically represented as its projections onto n two dimensional planes. A geometric interpretation of scator multiplication in terms of rotations with respect to the scalar axis is expounded. The powers of scators, when the ratio of their director components is a rational number, lie on closed curves. For 1+2 dimensional scators, twisted curves in a three dimensional space are obtained. Collecting previous results, it is possible to evaluate the exponential of a scator element in 1+2 dimensions.

In 1948, Skinner described the behavior of pigeons under response-independent schedules as “superstitious,” and proposed that the responses were reinforced by contiguous, adventitious food deliveries. Subsequently, response-independent schedules have been of interest to both basic and applied researchers, first to understand the mechanisms involved, and later, as “noncontingent reinforcement” (NCR) to reduce undesirable behavior. However, the potential superstitious effects produced by these schedules have been challenged, with some researchers arguing that antecedent variables play a significant role. This paper examines the evidence for adventitious reinforcement from both laboratory and applied research, the results of which suggest that antecedent, non-operant functions may be important in fully understanding the effects of NCR. We propose an applied-basic research synthesis, in which attention to potential non-operant functions could provide a more complete understanding of response-independent schedules. We conclude with a summary of the applied implications of the non-operant functions of NCR schedules.

The present research project entitled "Development of a method for predicting the optimal maturity level of avocado using machine learning" aims to establish an accurate and efficient approach to assess the maturity of avocados using machine learning methodologies. This research specifically focuses on identifying the relevant physical and chemical characteristics of avocados, creating a dataset containing categorized images of maturity levels, and creating machine learning models capable of accurately predicting fruit maturity. The studies reveal that the application of machine learning, in particular convolutional neural networks and multisensor models, has the potential to transform the prediction of avocado maturity and thus improve product quality and customer satisfaction. The findings indicate that the proposed techniques achieve an accuracy rate of over 90%, demonstrating their viability for integration into mobile applications that can benefit growers and suppliers in their decision-making processes.

Currently, a large part of the wells for agricultural use located in the state of Sonora are overexploited, which generates a high degree of saline intrusion and abandonment by nearby communities. In this paper the temperature effect on the final concentration of permeate water was evaluated through voltage and intel concentration variations in a batch electrodialysis reversal process (EDR), in order to identify optimal operating conditions with emphasis on the reduction of energy consumption and cost of desalinated water. Thirty-six samples were prepared: eighteen 2,000 mg/L total dissolved solids (TDS) samples and eighteen 5,000 mg/L TDS samples; brackish well water of 639 mg/L TDS and synthetic salt were mixed to obtain those concentrations. 3 different temperatures (25, 30, 35 °C) and 2 different voltages (10 and 20 V) were tested for each sample. The best salt removal occurred in the 20 V arrays, with 18.34% higher removal for 2,000 mg/L TDS experiments and 25.05% for 5,000 mg/L experiments (average between the 25 to 35 °C tests). Temperature positively affected EDR, especially in the experiments at 10 V voltage, where increasing 10 °C increased its efficiency by 10.83% and 24.69% for 2,000 and 5,000 mg/L TDS, respectively. Energy consumption was lower with increasing temperature (35 °C), as it decreased by 1.405% and 1.613% for 2,000 and 5,000 mg/L TDS concentrations, respectively (average between 10 and 20 V tests), decreasing the cost per m3 of water.

During the last decades West Nile Virus (WNV) outbreaks have continuously occurred in the Mediterranean area. In August 2020 a new WNV outbreak affected 71 people with meningoencephalitis in Andalusia and 6 more cases in Extremadura (south-west of Spain), causing a total of eight deaths. The whole genomes of four viral isolates were obtained and phylogenetically analyzed in the context of recent outbreaks. The Andalusian viral samples belonged to the lineage 1 and were relatively similar to previous outbreaks occurred in the Mediterranean region. Here we present a detailed analysis of the outbreak, including an extensive phylogenetic study.

Scientific literature shows increased interest in the aged and the aging phenomenon. The Aging Attitudes Questionnaire - AAQ was validated for the Portuguese population to understand the importance of attitudes towards old age and their impact on the subjective well-being of the elderly. A sample of 400 subjects (from 18 to 93 years) answered a socio-demographic questionnaire, and the AAQ was composed of three subscales (psychosocial losses, physical change, and psychological growth). The CFA confirmed the tri-factorial structure with very good adjustment of the model to the data with the Cronbach alpha of the total scale scoring .84 and ranging from .65 to .77 for each factor. A total of 9 items were omitted both for poor factor loadings (<0.50. Notwithstanding, 3 items below the criteria were maintained, as they conceptually fit into the factor. Of the final 15 AAQp items, 5 belong to the Psychosocial Loss factor, 6 to Physical Change, and 4 to Psychosocial Growth. This tree factor model explained 50.1 % of the total variance. In conclusion, this study supports that AAQ has acceptable validity, confirming the composite reliability and the discriminant validity, but not the convergent validity. Through multi-group analysis, the invariance of the scale was confirmed. This validation is of pivotal importance once it allows measuring the attitudes towards aging, thus facilitating the promotion of wellbeing across the lifespan.

Regulatory T cell master transcription factor, Forkhead box P3 (Foxp3) has been detected in cancer cells, but its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumor administration of Ad.P60 in breast tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells, and that gene therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

Byers Peninsula (62°34’-62°40’S-60°54’61°13’W), 60 km2 in size, is considered one of the largest ice-free areas in Antarctica. Since 2006, the Spanish Polar Program has taken part in a large number of environmental studies involving effects of climate changes, limnology and microbiology, live cycles, but not albedo. Surface albedo is one of the key physical parameters in the surface energy budget of polar regions. Most of Antarctica is covered by ice sheets; only about 0.44% of the area is permanently ice-free. However, in maritime Antarctica, the ice-free areas, corresponding to small islands, peninsulas, and coastal beaches, account for about 3% of the territory. To incorporate the contribution of these areas into global albedo models, it is necessary to relate the soil properties of the ice-free areas to the surface albedo response. Also, mapping soil properties and albedo have and special interest in these ice-free areas. Image classification using machine learning methods trained with georeferenced soil data could be useful for mapping soil properties and albedo in multispectral optical satellite images. A shallow neural network implemented using the Keras Python module was used to define and train models of soil properties using 15 explanatory variables corresponding to bands and spectral indices of a Sentinel image and a population of 49 soil samples taken from the top 5 centimeters of the soil profile. The soil samples were analyzed in the laboratory and a spectral library in the Vis-Nir range (350-2500 nm) was created. The albedo of the samples was integrated from the ADS spectra. At the same time, a linear regression model of albedo using the soil properties as explanatory variables was performed. The R2 fit of this new model was about 0.82 and the error of estimation was 4.1. The model was extended to the entire Byers Peninsula using the ML soil property models as explanatory variables. The RMSE of the extended models increased up to 8.2. We think that the main cause of this increase (2.6 points) is related to the error propagation, phenomenon due to the use of models as explanatory variables. However, another important part of the error increase could be due, among other reasons, to the use of an image that, although corrected, is not completely free of clouds.

The broad bean plant contains L-DOPA, a compound that is essential for patients with Parkin-son’s disease. However, little has been reported on other broad bean compounds that have bene-ficial effects on health. The objective was to evaluate plants of four Mexican broad bean varieties to determine the content and yield of total phenolic compounds (TPC), total flavonoids (TF), and L-DOPA, as well as to analyze the flavonoid profile and antioxidant (AA) and anti-inflammatory (AANTI) activity in vitro. Broad bean seeds were sown in the field and plants were harvested 20 days after emergence. The analyses were performed with visible UV spectrophotometry and HPLC. The variety José María produced the highest yield of TPC (9.30 g m-2), TF (8.08 g m-2) and L-DOPA (5.64 g m-2) per unit of area. The highest yields per plant were obtained with the Rojita variety: TPC (0.25 g plant-1), TF (0.21 g plant-1) and L-DOPA (0.17 g plant-1). This variety also had the highest antioxidant (CI50= 87.68 µg mL-¹) and anti-inflammatory (CI50= 74.40 mg mL-1) activi-ty, which was attributed to the L-DOPA compounds and to rutin and isoorientins, respectively. The flavonoid profile revealed the presence of rutin and isoorientins, which had not been previ-ously detected in the broad bean plant.

Physical rehabilitation aims to help people recover their mobility and strength after an injury or illness. One way to evaluate progress in rehabilitation is through isokinetic prototype tests that describe the dynamic characteristics of an isokinetic leg extension device for rehabilitation and control action. These tests use an isokinetic system to assess muscle strength and performance in a patient during isometric or isokinetic contraction. An experimental prototype allows the performance of the device to be evaluated in a controlled environment prior to use by the patient. In order to achieve physical recovery from musculoskeletal injuries in the lower limbs and achieve the reintegration of the affected subject into society as an independent and autonomous individual in their daily activities, a control model is presented that introduces a medical isokinetic rehabilitation protocol, where the element that allows carrying out such protocol consists of a magnetic particle brake whose control action is strongly influenced by the dynamics of the system when in contact with the end user, specifically the patient's legs in the stretch from the knee to the ankle. The results of these tests are valuable for health professionals seeking to measure their patient’s progress during the rehabilitation process and determine when it is safe and appropriate to advance in their treatment.

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

Currently, the use of medications during pregnancy in Latin America is common; studies with Latin American samples find that nearly 90% of pregnant women use some medication at least once during pregnancy. Furthermore, approximately 21% of the respondents self-medicated. Worldwide, the prevalence of this disease is 32%. The most common medications are nonsteroidal anti-inflammatory drugs and analgesics. Many of these drugs are available over the counter without a prescription. For this reason, a systematic review of the literature on the adverse effects on the woman and the fetus was performed. Objective: To determine the adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on pregnant women and fetuses during pregnancy. Methods: Systematic literature review. The following search strategy was used for the databases: Science Direct, PubMed, Scopus and Web of Science, through September 3, 2022. The population of pregnant women without previous comorbidities was defined. The intervention of interest was the use of NSAIDs during pregnancy. The outcomes of interest were adverse effects for the mother or fetus (weight of the newborn, congenital malformations present in the fetus, systemic effects in the pregnant woman during her gestation period). The types of studies included clinical trials, cohort studies and case‒control studies. Results: 1 study included 2,985 pregnant women without previous comorbidities. The use of aspirin more frequently during pregnancy stands out. The adverse effects on the fetus were preterm birth <37 weeks, low birth weight < 2500 g and increased admission to the neonatal intensive care unit. No adverse effects were found for the mother. Conclusions: There are not enough data indicating that the use of NSAIDs during pregnancy is safe. Some studies show that the use of NSAIDs during pregnancy could be related to problems in the development and growth of the fetus and health effects for the mother during pregnancy, so it is advisable to use these drugs under medical prescription and for the shortest possible time. in the gestation stage.

Ixodes scapularis is the major vector of Lyme disease in the eastern United States. Each active life stage (larva, nymph, and adult) takes a blood meal either for developing and molting to the next stage (larvae and nymphs) or for oviposition (adult females). This protein-rich blood meal is the only food taken by Ixodes ticks and therefore blood digestion is very important for tick survival. Most studies on blood digestion in ticks have shown that the initial stages of digestion are carried out by cathepsin proteases within acidic digestive cells. However, most of these studies have focused on partially engorged ticks. In other hematophagous arthropods, the serine proteases play an important role in blood protein degradation. In this study, we determined transcript expression of four I. scapularis serine proteases with previously characterized roles in blood digestion. RNA interference was used for functional analysis and a trypsin-benzoyl-D, L-arginine 4-nitoanilide assay was used to measure active trypsin levels. An in vitro hemoglobinolytic assay was performed with or without serine protease inhibitor. Our data suggest that trypsin levels increase significantly after blood feeding and peaked in larvae, nymphs, and adults at 3, 1, and 1 day post host detachment, respectively. The knockdown of three previously identified serine proteases by RNAi negatively impacted blood intake, survival, fecundity, levels of active trypsin in the gut and resulted in lower hemoglobin degradation in vitro. A trypsin inhibitor, PMSF, blocked the action of trypsin in the gut extract resulting in 65% lower hemoglobin degradation. We provide evidence of the serine proteases as digestive enzymes in fully engorged, replete females. Our data also demonstrated that in addition to blood digestion, these serine proteases might have a role in blood feeding success in I. scapularis.

Shewanella spp. are gram-negative bacteria that thrive in aquatic niches and also cause infectious diseases as opportunistic pathogens. Chromosomal integrons (CI) and mobile integrons (MI) were previously described in some Shewanella isolates. Here, we evaluated the occurrence of integrase genes, the integron systems and their genetic surroundings in the genus. We identified 22 integrase gene types, 17 of which were newly described, in different Shewanella species, evidencing multiple gain and loss events. Phylogenetic analysis showed that most of them were strain-specific, except for Shewanella algae, which seem to have co-evolve within the host as typical CIs. Noteworthy, co-existence of up to 5 different integrase genes, as well as their wide dissemination to Alteromonadales, Vibronales, Chromatiales, Oceanospirillales and Enterobacterales was observed. Identification of novel MIs suggests that lateral genetic transfer may have occurred resembling the behavior of class 1 integrons. The constant emergence of determinants associated to antimicrobial resistance worldwide, concomitantly with novel MIs in strains capable to harbor several types of integrons may be an alarming threat for the recruitment of novel antimicrobial resistance gene cassettes in the genus Shewanella, and its evolution towards the multidrug resistance.

Use of porous titanium (Ti) and Ti alloys in orthopedic implants or in light structures requires processing routes that could generate an as-much-as possible control in the pores amount, shape, size and connectivity. In this work, a colloidal approach to the processing of Ti porous structures by the inside foaming of a porogen into a gelled high solid content aqueous suspension of Ti powders, is presented. The prepared slurries contained different amounts of Methyl Cellulose (MC) as gelling agent (8, 10 and 12 g/L) and ammonium bicarbonate (BA) as porogen (15, 20, 25 wt. %). The gel-casted samples were heated at mild temperatures ranging (60, 70 and 80 °C) to promote the gelation and produce, at the same time, the porosity by the thermal decomposition of the ammonium bicarbonate. Different structures are obtained depending on the combination of the study variables

Compared to other 2D materials, MBenes are at an early stage in both experimental and theoretical approaches. However, the wide range of possible 2D structures leads to novel and challenging properties and their consequent applications. From all the possible stoichiometries, we have performed a theoretical study of orthorhombic and hexagonal M2B2 MBenes in the framework of the Density Functional Theory. We have found that both symmetries of Cr2B2, Fe2B2, and Zr2B2 show a metallic behavior and could be grown under certain conditions, as they are demonstrated to be dynamically stable. Moreover, the values of the magnetic moment, in specific ferromagnetic cases exceeding 2.5 μB/M2B2, make them suitable as robust 2D magnets. All our findings represent an important step in the understanding of MBenes and open several windows to future research in fields like energy conversion and storage, sensing, catalysis, biochemistry, or nanotechnology, among others.

We propose an approach for estimating the error in depth data provided by generic 3D sensors, which are modern devices capable of generating an image (RGB data) and a depth map (distance) or other similar 2.5D structure (e.g. stereo disparity) of the scene. Our approach starts capturing images of a checkerboard pattern devised for the method. Then proceed with the construction of a dense depth map using functions that generally comes with the device SDK (based on disparity or depth). The 2D processing of RGB data is performed next to find the checkerboard corners. Clouds of corner points are finally created (in 3D), over which an RMS error estimation is computed. We come up with a multi-platform system and its verification and evaluation has been done, using the development kit of the board nVIDIA Jetson TK1 with the MS Kinects v1/v2 and the Stereolabs ZED camera. So the main contribution is the error determination procedure that does not need any data set or benchmark, thus relying only on data acquired on-the-fly. With a simple checkerboard, our approach is able to determine the error for any device. Envisioned application is on 3D reconstruction for robotic vision, with a series of 3D vision sensors embarked in robots (UAV of type quadcopter and terrestrial robots) for high-precision map construction, which can be used for sensing and monitoring.

American Sign Language is a popular language for deaf individuals. Communication is made easier for these people through sign language. However, in a digital era like today, there is a need for these people to be able to communicate online, and even get help from technology to communicate in person with non sign language speakers. This research will present a program able to translate American sign language to plain English. This study aims to use the OpenCV library to recognize hand signals, also a trained model to identify images so that the program can then translate them to words and letters. The program uses a data set of over 2000 images which will be in this case the largest data set available. With over 90\% of accuracy it results in a basic computer program with the largest data set available that would make possible for users to communicate with a wide variety of words and expressions.

Peru has one of the highest informal employment rates in Latin America (73%). Previous studies have shown higher prevalence of poor self-perceived health (P-SPH) in informal workers compared to formal. The study’s aim is to analyse the role of working conditions in the association between informality and SPH in urban working population in Peru. We conducted a cross-sectional study based on 3098 workers from the working conditions survey of Peru 2017. Prevalence of P-SPH and exposure to poor working conditions were calculated separated by formal and informal employment and stratified by sex. Poisson regression models were used to assess the association between P-SPH and informal employment, with its prevalence ratios (PR) crude and adjusted for working conditions. Informal employment was 76% in women and 66% in men. Informal workers were more exposed to poor working conditions than formals and reported worse SPH. Workers in informal employment showed higher risk of P-SPH than formals: PR 1.38 [95% CI: 1.16 – 1.64] in women and PR 1.27 [95% CI: 1.08 – 1.49] in men. Adjustment by working conditions weakened the association in both sexes. In women, this association was only partially explained by worse working conditions 1.23 [95% CI: 1.04 – 1.46]. The negative effect on informal workers’ health is partially explained by poor working conditions. However, there is a part of the effect explained by informality per se.

We compare the well known Rayleigh-Ritz variational method (RRVM) with a recently proposed approach based on supersymmetric quantum mechanics and the Gram-Schmidt orthogonalization method (SSQMGS). We apply both procedures to a particular class of double-well harmonic oscillators that had been conveniently chosen for the application of the latter approach. The RRVM eigenvalues converge smoothly from above providing much more accurate results with less computational effort. Present results show that the unproved SSQMGS upper bounds do not hold.

The archival Rossi X-ray Timing Explorer (RXTE) Proportional Counter Array (PCA) observations of HZ Her/Her X-1 are analyzed here. The time periods for Anomalous Low States are refined. The 35-day X-ray lightcurve of Her X-1 is produced using 35-day phases determined with RXTE All-Sky Monitor (ASM) and Swift Burst Altert Telescope (BAT) data, with adjustments based on the RXTE/PCA data. The result is the highest sensitivity 35-day lightcurve of Her X-1. The RXTE/PCA data were separated into 8 differents states of the 35-day cycle: Main High (MH) turn-on, MH, MH decline, Low State (LS) 1, Short High (SH) turn-on, SH, SH decline, and LS2. Orbital lightcurves were created for each state, and the different states are compared. Eclipse data was extracted for each state to determine the changes of eclipse shape with 35-day phase. A scattering corona model was fit to the eclipses for the different 35-day states: this shows that the corona is present at all 35-day phases with similar intensity. We carried out a search for previously-reported dips with no absorption, but did not find any.

An impaired healing response underlies diabetic foot wounds chronicity, frequently translating in amputation, disability, and early mortality. In addition, diabetics frequently suffer of the underappreciated episode of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high; so that the ulcer is considered in “remission” and not healed for the time it remains epithelialized. Recurrence may result from the conspiracy of behavioral and biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, the role of endogenous biological signalers that prime the residual scar tissue to recurrence has remained elusive. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts, and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblasts-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers, induce the onset of “at-risk phenotypes” as premature skin cells aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cells demise. Unfortunately, post epithelialization recurrence rates data are missing in clinical studies of accepted ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first line chemoimmunotherapy. In recent years there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell therapies (CAR T-cells) and monoclonal antibodies as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are under investigation to treat R/R DLBCL.

In the field of robotics education, introductory courses would ideally utilize heavy industrial arms for hands-on learning. This would provide students with valuable experience in joint programming, which involves direct control of each joint motor in the arm to accomplish desired path planning and differential movements. This practice requires consideration of the physical dynamics of the arm. However, the use of heavy industrial arms has several drawbacks. They are large and expensive, require specialized maintenance, can pose safety risks, and they typically do not allow for direct control of the joint motors. One solution is to use a small, lightweight, toy-like arm. While these are cost-effective and provide direct access to the joint motors without posing safety risks, their lightweight construction means they exhibit minimal dynamic behavior, which limits their educational value. Another solution involves a robotic arm simulator that uses a virtual arm. However, a virtual arm doesn't offer the same level of hands-on engagement and excitement as a physical arm. We propose a hybrid solution that combines a small physical arm with a virtual arm. This approach provides students with the experience of working with an industrial arm, but without the associated difficulties. We demonstrate how this approach successfully improved the completion rate of joint programming assignments, offering a promising solution for practical robotics education.

In this review, we aimed to understand the relationship between SARS-CoV-2 infection and preeclampsia severity in infected pregnant women. Pregnant women with SARS- CoV-2 infection have been shown to have a significantly increased risk of maternal death, ICU admission, preterm delivery, and stillbirth compared with those without infection. The risk of preeclampsia also increases in pregnant women infected with SARS-CoV-2, particularly in those with severe symptoms. We emphasize the im-portance of specialized clinical management to prevent poor pregnancy outcomes in this situation. The association between COVID-19 and preeclampsia (PE) is likely due to multiple mechanisms, including the direct effects of the virus on trophoblast function and the arterial wall, acute atherosis, local inflammation leading to pla-cental ischemia, exaggerated inflammatory responses in pregnant women, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microan-giopathy. Emphasis has been placed on the potential impact of COVID-19 on pregnant women, specifically in relation to thrombotic complications, placental dysfunction, and cardiovascular dysfunction. Undoubtedly, one of the diagnostic tools to differentiate between COVID-19-induced preeclampsia-like syndrome and true preeclampsia is the use of biomarkers, such as the sFlt-1/PlGF ratio. We wish to highlight the potential for COVID-19-induced myocardial injury in pregnant women and the associated in-crease in maternal mortality rate. Vaccination against COVID-19 in the general population and in pregnant women in particular, drastically reduced the severity of the disease. There is an urgent need to continue the follow-up of these women and their children to detect the appearance of sequelae of the disease or peristent COVID 19

Quantitative evaluation of the musical timbre and its variations is important for the analysis of audio recordings and computer-aided music composition. Using the FFT acoustic descriptors and their representation in an abstract timbral space, variations of a sample of monophonic sounds of chordophones (violin, cello) and aerophones (trumpet, transverse flute, and clarinet) sounds are analyzed. It is concluded that the FFT acoustic descriptors allow us to distinguish the timbral variations of the musical dynamics, including crescendo and vibrato. Furthermore, using the Random Forest algorithm, it is shown that the FFT-Acoustic provides a statistically significant classification to distinguish musical instruments, family of instruments, and dynamics. We observed a better behavior for the FFT-Acoustic descriptors when classifying pitch compared to some timbral features of Librosa.

The objective of this study is to analyze the assessment practices in primary education and how they relate to the valuation of the learning process. It seeks to understand the perceptions of teachers and students regarding assessment and to observe classroom activities, as well as to analyze the assessment instruments used. The method used is a mixed approach that combines qualitative interpretations of the participants’ realities with a phenomenological analysis to reflect on the evaluative practices. The results indicate a contradiction between what is said and what is done in terms of evaluation, with a tendency to use written tests and traditional exams instead of a combination of techniques that allow for a significant evaluation of student learning. In addition, significant differences are observed among teachers regarding the importance they give to evaluation within their practices and evaluative models.

Generative AI has gained enormous interest nowadays due to new applications like chatGPT, DALL E, Stable Difussion and Deep Fake. Particularly DALL E, Stable Difussion and others (Adobe Firefly, ImagineArt...) are able to create images from a text prompt and are also able to recreate real photographs. Due to this fact, intense research has arisen to create new image forensics applications able to distinguish between real captured images and videos and artificial ones. Detecting forgeries made with Deep Fake is one of the most researched issues. This paper is about another kind of forgery detection. The purpose of this research aims to detect photo realistic AI created images versus real photos coming from a physical camera. For this purpose, techniques that perform a pixel level feature extraction are used. First one is Photo Response Non-Uniformity (PRNU). PRNU is a special noise due to imperfections on the camera sensor that is used for source camera identification. The underlying idea is that AI images will have a different PRNU pattern. Second one is Error level analysis (ELA). This is other type of feature extraction traditionally used for detecting image editions. In fact, ELA is being used nowadays by photographers to detect manually AI created images. Both kinds of features are used to train Convolutional Neural Networks to differentiate between AI images and real photographs. Good results are obtained achieving accuracy rates over 95%. Both extraction methods are carefully assessed by computing precision/recall and F1-score measurements.

(1) Background: Painful nervus intermedius neuropathy (e.g., geniculate neuralgia) involves continuous or near-continuous pain affecting the distribution of the intermedius nerve(s). The diagnosis of this entity is challenging, particularly when the clinical and demographic features do not resemble the typical presentation of this condition. To the best of our knowledge, only three case reports have described the occurrence of nervus intermedius neuropathy in young patients. (2) Case Description: A 13-year-old female referred to the Orofacial Pain clinic with a complaint of pain located deep in the right ear and mastoid area. The pain was described as a constant throbbing and dull, with an intensity of 7/10 on numerical rating scale, characterized by superimposed brief paroxysms of severe sharp pain. The past treatments included ineffective pharmacological and irreversible surgical approaches. After a comprehensive evaluation, a diagnosis of idiopathic painful nervus intermedius neuropathy was given, which was successfully managed with the use of gabapentin. (3) Conclusions and Practical Implications: The diagnosis and treatment of neuropathic pain affecting the nervus intermedius can be challenging due to the complex nature of the sensory innervation of the ear. The diagnosis can be even more challenging in cases of atypical clinical and demographic presentations, which in turn may result in unsuccessful, unnecessary, and irreversible treatments. Multidisciplinary teams and constant knowledge update are fundamental to provide good quality of care to our patients and to not overlook any relevant signs or symptoms.

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants < 12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients under-went clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 hours of hospital admission. The existence of significant correlation between car-diac and respiratory parameters was the primary outcome. The association of different cardio-pulmonary variables with the need of respiratory support higher than O2, the length of stay hos-pitalization, the PICU stay, and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bron-chiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction. Up to 36 (32%) infants required respira-tory support during the hospitalization. This group presented with higher lung ultrasound score (p<0.001), and increased values of Tei index (p<0.001) and pulmonary artery pressures (p<0.001). All the analyzed respiratory and cardiac variables showed moderate to strong correlations with the LOS hospitalization and the time of respiratory support. Lung ultrasound and echocardiog-raphy showed a moderate to strong predictive accuracy for the need of respiratory support in the ROC analysis, with AUC varying from 0.74 to 0.87. Conclusion: Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ul-trasonography could be a good strategy to easily identify high-risk population for a complicated acute bronchiolitis hospitalization.

The distribution of Mexican Magnolia species´ occur under restricted climatic conditions. As many other tree species from the tropical montane cloud forests (TMCF), Magnolia species appear to be sensitive to drought. Through the use of dendrochronological techniques, this study aims to determine the climate influence on the vessel traits of M. vovidesii and M. schiedeana which are endangered tree species that are endemic to the Sierra Madre Oriental in eastern Mexico. Because most of the tree species in TMCFs are sensitive to climate fluctuations, it is necessary to investigate the differences in the climatic adaptability of the vessel architecture of these trees. This could allow us to further understand the potential peril of climate change on TMCFs. We compared vessel frequency, length and diameter in drought and non–drought years in two Mexican Magnolia species. We used tree–rings width and vessel traits to assess the drought effects on Magnolias’ diffuse–porous wood back to the year 1929. We obtained independent chronologies for M. vovidesii with a span of 75 years (1941–2016), while for M. schiedeana we obtained a span of 319 years (1697–2016). We found that temperature and precipitation are strongly associated with differences in tree–ring width (TRW) between drought and non–drought years. Our results showed anatomical differences in vessel trait response between these two Magnolia species to climatic variation. We suggest that our approach of combining dendroclimatic and anatomical techniques is a powerful tool to analyse anatomic wood plasticity to climatic variation in Magnolia species.

The use of Learning Management Systems (LMS) has had a rapid growth over the last decades. Great efforts have been recently made to assess the level of performance of the students online due to the COVID-19 pandemic. Faculty members with limited experience in the use of LMS such as Moodle, Edmodo, MOOC, Blackboard and Google Classroom can have some problems creat-ing online tests. In this work, a new plugin for Moodle is presented: FastTest PlugIn. This plugin is based on a Microsoft® Excel spreadsheet and it can be used to export questions to Moodle. Us-ers of FastTest PlugIn can create question pools in an easy and intuitive way. A literature review about plugins used to import/export questions in Moodle is carried out. Then, the characteristics of FastTest PlugIn are presented. At the end, the characteristics of the main plugins found in the literature are discussed and compared with the ones of FastTest PlugIn.

Malignant tumors behave dynamically as cell communities governed by ecological principles. Massive sequencing tools are unveiling the true dimension of the heterogeneity of these communities along their evolution in most human neoplasms, clear cell renal cell carcinomas (CCRCC) included. Although initially thought to be purely stochastic processes, very recent genomic analyses have shown that temporal tumor evolution in CCRCC may follow some deterministic pathways that give rise to different clones and sub-clones randomly spatially distributed across the tumor. This fact makes each case unique, unrepeatable and unpredictable. Precise and complete molecular information is crucial for patients with cancer since it may help in establishing a personalized therapy. Intratumor heterogeneity (ITH) detection relies on the correctness of tumor sampling and this is part of the pathologist’s daily work. International protocols for tumor sampling are insufficient today. They were conceived decades ago, when ITH was not an issue, and have remained unchanged until now. Noteworthy, an alternative and more efficient sampling method for detecting ITH has been developed recently. This new method, called multisite tumor sampling (MSTS), is specifically addressed to large tumors that are impossible to be totally sampled, and represent an opportunity to improve ITH detection without extra costs.

Engineers make things, make things work, and make things work better and easier. This kind of knowledge is crucial for innovation, and much of the explicit knowledge developed by engineers is embodied in scientific publications. In this paper, we analyze the evolution of publications and citations in Engineering in a middle-income country such as Mexico. Using a database of all Mexican publications in Web of Science from 2004 to 2017, we explore the characteristics of publications that tend to have the greatest impact; this is the highest number of citations. Among the variables studied are the type of collaboration (no collaboration, domestic, bilateral, or multilateral), the number of coauthors and countries, the language of the article, controlling for a coauthor from the USA and the affiliation institution of the Mexican author(s). Our results emphasize the overall importance of joint international efforts and suggest that publications with the highest number of citations are those with multinational collaboration (coauthors from three or more countries), written in English, and when one of the coauthors is from the USA.

Although the influence of climate on the fire regime is unanimously recognized, most publications are studies on this influence are at the global scale. Therefore, this study aims to demonstrate the role of climate in the incidence of wildfires at the country and regional scale using statistical analysis and machine learning methods. Mainland Portugal was chosen as a case study due to its climate and because it is the European region most affected by wildfires. Results demonstrate the climate signature in the spatial and temporal distribution of the wildfire incidence. The conclusions of the study include (i) the existence of two pyro-regions, with different types of climate (Csb and Csa) composed of NUTS II regions: the northern region composed of the Norte and Centro regions and the southern region composed of Alentejo and Algarve; (ii) the intra-annual variability in the incidence of wildfires, characterized by two peaks, one in spring and the other in summer, are a consequence of the country's type of climate; and, (iii) how the annual cycle of wildfire incidence varies over the years depends on the weather conditions throughout each year. These results are of fundamental importance for wildfire managers, especially in the context of climate change.

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.

Chagalapoli fruit (Ardisia compressa) is similar to Vaccinium myrtillus (berries) with high-polyphenol content. The objective of this study was to evaluate the physicochemical properties of Chagalapoli fruit and to determine the conditions for the preparation of a fermented beverage using Saccharomyces cerevisiae yeast, evaluating the impact on sensory properties. The fermentation process lasted 4 days at 27 °C, with absence of light and a fixed pH of 3.8. The phenolic contents obtained in samples according to chromatograms were 1.27 mg(EPI)/mL in filtered juice, 1.59 mg(EPI)/mL in filtered fermented beverage, 1.91 mg(EPI)/mL in partially filtered juice and 3.19 mg(EPI)/mL in partially filtered fermented beverage. An affective test was carried out to determine the sensory acceptability of the final product, evaluating the flavor, color and aroma parameters. The fermented beverage with the greatest preference on color and flavor attributes was the partially filtered fermented beverage.

Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. However, few genera of FLA are linked to human infections. Within these genera, Acanthamoeba spp., classified by genotypes (T1-T23), being T1, T2, T4, T5, T10, T12, and T18 as capable of causing granulomatous amoebic encephalitis (GAE) in immunocompromised patients mostly and Acanthamoeba keratitis related to genotypes T2, T3, T4, T5, T6, T10, T11, T12 and T15 in apparently healthy patients. Meanwhile, Naegleria fowleri is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while Balamuthia mandrillaris, like some Acanthamoeba genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; Sappinia pedata is responsible for one case of amoebic encephalitis; Vermamoeba vermiformis has been found in cases of ocular damage, and its extraordinary capacity as endo-cytobiont for microorganisms of public health importance such as Legionella pneumophila, Bacillus anthracis, Pseudomonas aeruginosa, among others. In this review, issues related to the epidemiology of each one are addressed, updating their geographic distribution and cases reported in recent years for pathogenic FLA.

Sensors and actuators are fundamental units in Cyber-Physical and Internet of Things systems. Because they are included in a variety of systems, using many technologies, it is very useful to characterize their functions abstractly by describing them as Abstract Entity Patterns (AEPs), that are patterns that describe abstract conceptual entities. For concreteness, we study them here in the context of autonomous cars. An autonomous car is a complex system because, in ad-dition to its own complex design, it interacts with other vehicles and with the surrounding in-frastructure. To handle these functions, it must incorporate various technologies from different sources. An autonomous car is an example of a Cyber-Physical System, where some of its func-tions are performed by Internet of Things units. Sensors are extensively used in autonomous cars to measure physical quantities; actuators are commanded by controllers to perform appro-priate physical actions. From AEPs we can derive concrete patterns, a structure combining re-lated AEPs is an Entity Solution Frame (ESF). Both sensors and actuators are susceptible to mali-cious attacks due to the large attack surface of the system where they are used. Our work is in-tended to make autonomous cars more secure, which also increases their safety. Our final objec-tive is to build a Security Solution Frame for sensors and actuators of autonomous cars that will facilitate their secure design. A Security Solution Frame is a solution structure that groups to-gether and organizes related security patterns. This article is the first stage of a secure unit that can be used to design not only secure autonomous cars but also any system where sensors and actuators are used. This paper concentrates on AEPs and ESFs for sensors and actuators; that is, on the functional aspects of these devices.

Generative adversarial networks (GANs) have become a recent and rapidly developing research topic in Machine Learning. Since their inception in 2014, a significant number of variants have been proposed to address various topics across many fields, and has particularly excelled not only in image and language processing, but also in the medical and data science domains. In this paper, we aim to highlight the significance and advance that these GAN models can introduce in the field of Business Economics, where they have yet to be fully developed. To this end, a review of the literature of GANs is presented in general together with a more specific review in the field of Business Economics wherein only a few papers can be found. Furthermore, the most relevant papers are analysed in order to provide an approach the opportunity to research into GANs in the field of Business Economics.

The innate immune system is the first line of defense against pathogens. It’s composition includes barriers, mucus and other substances as well as phagocytic and other cells. The purpose of the paper is to analyze in general grounds the immune system and the body immunity to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen’s average rate of growth. When nonlinearities are added, a reference value for the number of pathogens is set, and a stability condition emerges, which relates strength of regular threats, barrier height and annihilation rate. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The stability condition allows a comparison of immunity in different tissues. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. These statements are formulated at the qualitative level, but may and deserve to be quantitatively checked.

Through a partnership with three Federally Qualified Health Centers (FQHCs), the local health department in Los Angeles County implemented a produce prescription program (PPR) to increase fresh fruit and vegetable purchases among patients with diabetes or prediabetes. The PPR, which began in 2020, provided eligible patients with a $40 voucher every month for 6 months to promote the purchase of fresh produce at large chain grocery stores. This qualitative assessment describes staff experiences with the PPR, documenting the facilitators and barriers they encountered while implementing the program. Fifteen clinic staff (i.e., PPR implementers) were interviewed for this assessment. Thematic analysis and coding were conducted using the ATLAS.ti software; the coding was carried out by two separate coders. Interviewees discussed the importance of having preexisting partnerships and programs to support the PPR at their clinic site. Hidden costs related to implementing the program included a large and unexpected amount of staff time devoted to enrolling patients into the program. Collecting quality data and having limited expertise to rigorously evaluate the program were other challenges. Because patients often share their food with their family, the monthly $40 incentive was generally not enough to support their needs; interviewees suggested giving a higher inventive amount to those with a larger household. Future PPR efforts and similar food incentive programs should consider these and other facilitators and barriers to implementation and sustainability, especially when making adjustments to these programs to improve services and access to food resources.

In a constantly transforming retail financial sector, TCS has established a strategic alliance with Cencosud Scotiabank, expanding its role beyond consultancy to become an essential partner in the journey of growth and transformation. This collaboration reflects a shared commitment to advancing together in the competitive world of retail financial services, driving significant strategic change at Cencosud Scotiabank. As part of this effort, TCS has co-designed a series of practical workshops aimed at fostering and expanding the culture of innovation within the organization. These practical workshops are fundamental in the transformation process, providing deep and practical learning that serves as a solid foundation for the desired change. Each workshop session, carefully designed and executed according to an innovation playbook, aligns visual thinking tools with practical techniques to ensure smooth and effective execution of the work. The goal of these efforts is twofold: on the one hand, to strengthen the culture of innovation at Cencosud Scotiabank through collaboration; on the other, to firmly center the organization around the customer. The workshops are not just meetings; rather, they are collaborative spaces where creativity, deep user understanding, and agility converge to shape innovative solutions.

Mycobacteria can be one of the main contaminants of biological products, and their presence can have serious consequences on patients’ health. Thus, specific testing is necessitated by regulations such as the European Pharmacopoeia. The current pharmacopeial reference i.e., microbial culture method cannot ensure an exhaustive detection of mycobacteria due to their growth characteristics. Additionally, the method is time-consuming and requires a continuous supply of culture media, which could be further challenging. Thus, to overcome these challenges, pharmaceutical industries need to consider alternative non-microbiological techniques to detect these fastidious, slow-growing contaminating agents. This review provides an overview of alternative methods, which could be applied within a quality control environment of biological products, and underlines advantages and limitations of these methods. Nucleic acid amplification techniques or direct measurement of mycobacteria stands out as the most suitable alternatives for mycobacterial testing in biological products.

The review aims to assess fifteen (15) academic literature sources, highlighting the application of machine learning algorithms in the maintenance operations of optical fiber networks. It exhibits the collection of data using PRISMA methodology—Preferred Reporting Item for Systems Review and Meta-Analyses. The application, results, and performance metrics are discussed based on the collected observations, computations, and statistics in the studies, which revealed records of high accuracy degrees ranging from 86% to 98% on average and quality ML models including Neural Networks (NNs), Support Vector Machines (SVMs), and LSTM, as well as deep learning models that disclosed effective results of determining challenges and problems within the optical fiber lines. The review mainly centralized on superior machine learning technologies that surpass traditional techniques in fault detection and localization for improved optical fiber networks’ operations while providing insights into the limitations and challenges encountered in real-world applications of these models, offering a comprehensive perspective on the optical fiber network’s domain.

There are different ways to analyse energy absorbance (EA) in the human auditory system. In previous research, we developed a complete finite element model (FEM) of the human auditory system. In this mentioned work, the external auditory canal (EAC), middle ear, and inner ear (spiral cochlea, vestibule, and semi-circular canals) were modelled based on human temporal bone histological sections. Multiple acoustic, structure and fluid-coupled analyses were conducted using the FEM to perform harmonic analyses in the 0.1–10 kHz range. Once the FEM had been validated with published experimental data, the FEM numerical results were used to calculate the EA or energy reflected (ER) by the tympanic membrane. This EA was also measured in clinical audiology tests which were used as a diagnostic parameter. A mathematical approach was developed to calculate the EA and ER, with numerical and experimental results showing adequate correlation up to 1 kHz. Another published FEM had adapted its boundary conditions to replicate experimental results. Here, we recalculated those numerical results by applying the natural boundary conditions of human hearing and found that the results almost totally agreed with our FEM. This boundary problem is frequent and problematic in experimental hearing test protocols: the more invasive they are, the more the results are affected. One of the main objectives of using FEMs is to explore how the experimental test conditions influence the results. Further work will still be required to uncover the relationship between the middle ear structure and EA to clarify how to best use FEMs. Moreover, the FEM boundary conditions must be more representative in future work to ensure their adequate interpretation.

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from the oxidative damage and the coexistence of different sources of energy production, such as mitochondrial and glycolytic ATP, allows faster adaptative mechanisms to situations of high energy demand and may help in the maintenance of neuronal function in stress situations. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of Multiple Sclerosis. This work has been performed in a model of oxidative damage on neuronal cell cultures exposed to menadione, in presence or absence of fingolimod phosphate. We have studied the mitochondrial function and several pathways related with glucose metabolism, including oxidative, glycolytic and pentose phosphate in neuronal cells cultures. Our results showed a beneficial effect on neuronal survival probably based in the recovery of all, oxidative balance, glycolysis and pentose phosphate, promoted by fingolimod phosphate. These effects are mediated, at least in part by the interaction with its specific receptor. These actions would make this drug a potential tool to the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.

The objective of this study was to analyze the effects of a pulmonary telerehabilitation (TR) program in young adults with post-COVID-19 syndrome. The information of sixteen students' medical files were analyzed and allocated to one of two groups (control=CG/experimental=EG). Twelve TR sessions were performed distantly and asynchronously at the EG patients' homes during 4-weeks. The program included diaphragmatic pattern breathing and aerobic exercises. The parameters: i) vital signs (oxygen saturation "SpO2", heart rate "HR", respiratory rate "RR" and blood pressure "BP"; ii) physical capacity “Sit-to-stand test”; iii) cardiorespiratory capacity “6-Minute Walk Test”; and iv) perceived effort "Borg scale" were assessed in both groups. The statistical analyses showed a significant decrease of RR and HR (p < 0.012) accompanied by a significant increase in SpO2 (p < 0.042), physical (p < 0.012) and respiratory (p < 0.028) capacity. The perceived effort decreased significantly in both groups (CG: p < 0.006; EG p < 0.001) only for physical but not for cardiorespiratory capacity (p < 0.106). There were no statistical changes registered in BP (p > 0.05). The current study suggests that a TR program that involves breathing and aerobics exercises is feasible and effective in treating post-COVID-19 syndrome in young patients.

Background Oral anticoagulation (OAC) for atrial fibrillation (AF) patients is administered frequently. Vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs) prevent thromboembolic events, but information about the quality of life (QoL) and patient satisfaction, related to both anticoagulants, is limited. Methods REGUEIFA is an observational and multicentre study that included patients with AF diagnosis treated by cardiologist. Those on OAC, VKA, and DOACs were selected. The EuroQol-5D (EQ-5D) questionnaire evaluated QoL, and the ACTS (Anti-Clot Treatment Scale) questionnaire investigated patient satisfaction with OAC. Results From a total of 1007 patients, 904 patients were on OAC, 532 on VKA and 372 on DOACs. In total, 846 patients completed the EQ-5D questionnaire, with results significantly worse in patients on VKA than on DOACs: (1) mobility limitations (37.6% vs. 24.2%, p

Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one third of global population and became the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) also remain significant challenges to liver health even in the 21st century. The coexistence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. Thorough understanding of the pathobiological interlink and interactions between MAFLD and these two chronic viral hepatitis infections are crucial for appropriate management of patients. We update these interlinks in this comprehensive clinical review.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

In this work a new method is proposed to tackle down the multiple objective optimization problem of the calculation of cation distribution in spinels structure, through the difference of intensity ratios between experimental and calculated intensities of cation sensitive Bragg planes, by introducing a new factor, Rabs, in Bertaut method. This factor is introduced as the sum of absolute R factors, and it is minimized by varying cation distribution. To test this method aluminate manganese spinel where synthesized though modified Pechini method and characterized though XRD. The results show to be in agreement with literature for the aluminum inversion in tetrahedral sites, which is near to the reported value of 10%. Also, it was noticed that the manganese atoms are present in octahedral sites with a mixed valence state of +2 and +3. Which might be an indicator that oxygen vacancies are present in the structure, so the vacancies value of oxygen is proposed considering the total charge of cations and thus proposing the value of 3.678 mol per formula unit of the spinel, thus having the next stoichiometry considering normalized Al and Mn, MnAl2O3.678. Finally, the last cation distribution proposed was [Mn0.867^(+2) Al0.129^(+3) ][Mn0.034^(+2) Mn0.098^(+3) Al1.871^(+3) ] O3.678 with a Rabs factor value of 0.6466, which considers the cation distribution and oxygen vacancies.

Academic interest in social and human capital is growing significantly. Similarly, their relationship with sustainability is increasing, especially compared to sustainability’s relationship with natural capital and financial and economic capital. Bibliometric and visualization research on these relationships is nonetheless insufficient. This study analyzes the evolution of the literature on natural capital, financial and economic capital, and social and human capital related to sustainability. On the other hand, the study presents a bibliometric analysis on social capital and human capital (SHC) related to sustainability. The article studies 635 references collected from the Web of Science (WoS) Core Collection database and utilizes visualization of similarities (VOS) viewer program to graphically map the material. The analysis involves co-occurrence of keywords, co-citation, and co-authorship. The results reveal not only the state of the art and the leading trends, but also the evolution regarding impact, main journals, documents, topics, authors, institutions, and countries. The study provides researchers and practitioners with a visual and schematic frame of the research on this topic.

Abstract: Understanding the reliability and sensitivity of jump testing is essential to determine the neuromuscular progress of athletes and make informed decisions. This study aimed to assess the reliability and sensitivity of countermovement jump (CMJ) and drop jump (DJ) tests metrics in female volleyball players. Sixteen semi-professional female volleyball players participated in the study. Intrasession and intersession reliability of CMJ and DJ metrics were evaluated using a randomized cross-over design. Dual force platform was used to collect data, and several dependent variables were calculated using forward dynamics. Intraclass correlation coefficients (ICC), coefficients of variation (CV) and minimum difference (MD) were calculated. The third attempt presented the highest values for both test, and changes in jump strategy in DJ. CMJ is consistent across sessions, while DJ also shows intersession differences (p<0.05) in 11 out of 15 variables. Most CMJ variables exhibit excellent reliability while DJ variables have lower reliability and higher variability. Concentric and eccentric impulses for DJ showed excellent reliability. Most CMJ variables showed excellent reliability and variability, DJ had lower reliability, higher variability, and lower sensitivity. These findings provide valuable information when assessing athletes' performance and highlight the reliability, sensitivity, and variability in jump performance for CMJ and DJ tests.

Social media has become more popular in the last few years. It has been used in public health development and healthcare settings to promote healthier lifestyles. Given its important role in today's culture, it is necessary to understand its current trends and future directions in public health. This review aims to describe and summarize how public health professionals have been using social media to improve population outcomes. Additionally, it discusses potential future directions on how social media can be used to improve population health. The findings showed how social media has been used as a tool for research, designing and implementing health campaigns, messaging, and health promotion. In addition, social media integration with Artificial Intelligence (AI) and Generative Pre-Trained transformers (GPT) can have a big impact and offer an innovative approach to tackle the problems and difficulties in health informatics. These innovations might improve patient participation, individualized assistance, and care experiences. The research showed how likely social media will keep growing and evolving and, if used effectively, have the potential to help close public health gaps across different cultures and improve population health.

This study presents the validation process of the Questionnaire on Academic Stress in Secondary Education –QASSE-, designed to assess the wide variety of school sources and situations related to academic stress in adolescence, and their relationship with students’ physical and psychological well-being. Participants were 860 Spanish high school students (52.9% girls) with an average age of 14.62 years (SD = 1.8). Through a cross-validation process, EFA and CFA supported QASSE multifactorial structure with four first-order factors -academic overload, interaction with classmates, family pressure, and future-oriented perspective- and a second-order factor of academic stress, showing a significant and intense relationship with adolescents’ psychological and physical well-being. Results also highlight the effects of the gender*educational level interaction on the students’ stress, with girls showing higher levels of stress in the transition courses between educational phases (sophomore and junior years). The QASSE demonstrates good validity and reliability, showing potential for both research and educational application. The results show the high impact of the QASSE dimensions on psychological and physical well-being in adolescence, highlighting its special usefulness for designing and adjusting educational prevention and intervention actions in this area to the students’ specific characteristics and needs

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

The concept of geostationary VHTS (Very High Throughput Satellites) is based on multibeam coverage with intensive frequency and polarization reuse in addition to the use of larger bandwidths in the feeder links, in order to provide high capacity satellite links at a reduced cost per Gbps in orbit. The dimensioning and design of satellite networks based on VHTS imposes the analysis of multiple trade-offs to achieve an optimal solution in terms of cost, capacity and figure of merit of the user terminal. In this paper, we propose a new method for sizing VHTS satellite networks based on an analytical expression of the forward link CINR (Carrier-to-Interference-plus-Noise Ratio) that is used to evaluate the trade-off of different combinations of system parameters. The proposed method considers both technical and commercial requirements as inputs including the constraints to achieve the optimum solution in terms of the user G/T, the number of beams and the system cost. The cost model includes both satellite and ground segments. Exemplary results are presented with feeder links using Q/V bands, DVB-S2X and transmission methods based on CCM and VCM (Constant and Variable Coding and Modulation, respectively) in two scenarios with different service areas.

Compound parabolic concentrators are relevant systems used in solar thermal technology. With adequate tailoring, they can be used as an efficient and low-cost alternative in residential water applications. This work presents a simulation study using a ray tracing methodology. With this technique we simulate the interaction between solar rays and solar concentrator to quantify the amount of energy that impinges on the receiver at a particular time. Energy availability is evaluated in a comparison of two configurations: stationary at 21° throughout the year and multi position setup; tilted with respect to the horizontal depending on three seasonal positions: 0° for summer, 16° for spring / autumn and 32° for winter, with the objective of increasing the amount of available energy in each season. The fact that a tracking system can be dispensed with also represents an economical option for the proposed application. The results showed that at 21°, the proposed system works satisfactorily; however, by carrying out the selected angular adjustments, the overall energy availability increased by 22%, resulting in a more efficient option. The methodology developed herein proved to be a valuable tool for prototype design and performance evaluation.

In this work, an embroidered textile moisture sensor is presented. The sensor is based on a capacitive interdigitated structure embroidered on a cotton substrate with an embroidery conductor yarn composed by 99% pure silver plated nylon yarn 140/17 dtex. In order to evaluate the sensor sensitivity, the impedance of the sensor has been measured by means of a LCR meter from 20 Hz to 20 kHz on a climatic chamber with a sweep of the relative humidity from 25% to 65% at 20 ºC. The experimental results show a clear and controllable dependence of the sensor impedance with the relative humidity. Moreover, the reproducibility of the sensor performance subject to the manufacturing process variability and washing process is also evaluated. The results show that the manufacturing variability introduce a moisture measurement error up to 4%. The washing process impact on the sensor behavior after applying the first washing cycle implies a sensitivity reduction higher than 14%. Despite these effect, the textile sensor keeps its functionality and can be reused in standard conditions. Therefore, these properties point out the usefulness of the proposed sensor to develop wearable applications on health and fitness scope including the user needs to have a life cycle longer than one-time use

In vertebrates, oligodendrocytes (OLs) are glial cells of the central nervous system (CNS) responsible for the formation of the myelin sheath that surrounds the axons of neurons. The myelin sheath plays a crucial role in the transmission of neuronal information by promoting the rapid saltatory conduction of action potentials and providing neurons with structural and metabolic support. Saltatory conduction, first described in the peripheral nervous system (PNS), is now generally recognized as a universal evolutionary innovation to respond quickly to the environment: myelin helps us think and act fast. However, the function of myelin in the CNS, particularly in the brain, is not necessarily to act quickly, but rather to act correctly. In this respect, myelin should primarily play a role in synchronizing the different neuronal networks, a synchrony that occurs in the form of oscillations (or rhythms) relevant for specific information processing. Interestingly, myelin has been directly involved in different types of cognitive processes relying on brain oscillations, and myelin plasticity is currently considered to be part of the fundamental mechanisms for memory formation and maintenance. However, despite ample evidence showing the involvement of myelin in cognition and neurodevelopmental disorders characterized by cognitive impairments, the link between myelin, brain oscillations, cognition and disease is not yet fully understood. In this review, we aim to highlight what is known and what remains to be explored to understand the role of myelin in high order brain processes.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used for cognitive measurement. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider that it is crucial to expand the knowledge we have about the neurocognitive development of premature infants both in specific cognitive domains and in age ranges so that the information obtained helps to predict the probability of presenting cognitive alterations from early stages and, therefore, to implement intervention strategies and programs based on scientific evidence and complemented in their design by clinical experience, empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. Examination of tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some of the neuronal ceroid lipofuscinosis (NCL) diseases. The also dog exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband’s DNA revealed a homozygous C to T substitution that altered the intron 3 – exon 4 splice site of CLN6. Other mutations in CLN6 cause NCL diseases in humans and animals including dogs. CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog is classified as an NCL resulting from the absence of CLN6 protein. Screening the dog’s genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed breed dogs and at least some of the ancestral breeds.

We advance the notion that much, like artificial nanoparticles, relatively more complex biological entities with nanometric dimensions such as pathogens (viruses, bacteria and other microorganisms) may also acquire a biomolecular corona, upon entering the blood circulation of an organism. We view this biomolecular corona as a component of a much broader non-cellular blood interactome that can be highly specific to the organism, akin to components of the innate immune response to an invading pathogen. We review published supporting data and generalize these notions from artificial nanoparticles to viruses and bacteria. Characterization of the non-cellular blood interactome of an organism may help explain apparent differences in the susceptibility to pathogens among individuals. The non-cellular blood interactome is a candidate therapeutic target to treat infectious and non-infectious conditions.