The study, conducted at the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, aimed to investigate the prevalence of iron deficiency anaemia among anaemic overweight and obese individuals. Fifty participants were included after screening and consent, undergoing socio-demographic assessment, clinical evaluation, and laboratory investigations. Middle to old-aged individuals predominated (Mean ± SD: 54.54 ± 11.32 years), with females comprising 62%. All subjects were obese (mean BMI: 37.27 ± 5.71 kg/m²), with common comorbidities including hypertension (68%), diabetes (36%), and obstructive sleep apnea-hypopnea syndrome (32%). Nutritional deficiencies, particularly iron deficiency, were prevalent, affecting 62% of subjects, with 48% having iron deficiency alone. Anemia of chronic illness was observed in 38%. Laboratory parameters showed low hemoglobin (8.53 ± 1.23 g/dL), MCV (78.75 ± 10.13 fL), and elevated ESR (20.56 ± 21.47 mm/hour) and CRP levels (4.71 ± 3.32 mg/dL), indicating inflammation. Correlation analyses revealed negative associations between BMI and serum iron/ferritin and positive associations with serum hepcidin. The study underscores the significance of addressing nutritional deficiencies and monitoring iron status in obese populations, suggesting potential associations between obesity and iron metabolism. Further research is needed to explore these relationships for clinical management implications.

While the mobile phone is the world’s most popular media device, it is actually not one single medium, but is effectively used as a different medium by different user groups. The article characterizes polymodal differences in mobile apps usage among different user groups, including gender, education, occupation, screen size, and price. We monitored the complete app usage of 10,725 smartphone users for one month each (56 million sessions, recording almost 1 million hours). Our key contribution consists in developing and analyzing a theoretical framework to classify the over 16,000 apps used into five categories. Exploring nine research questions we provide a broad characterization by asking who, with which characteristics, uses which kinds of apps in what extensity and intensity? For example, it is not the young and high occupational grades that use the mobile phone as a human-to-machine computer (including gaming and artificial intelligence tools). Large screen size is related to extensive long sessions, while a small screen size is related to intensive frequent usage. The results go beyond providing ample empirical evidence for the inherently polymodal nature of the mobile phone, but also proposes a framework on how to possibility deal with it analytically.

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor usage of COVID-19 therapeutics in hospital and community settings and inform stewardship. Three antiviral therapies: nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®); and two neutralising monoclonal antibody therapies (nMAbs): sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®); were in use in England between July 2020 to April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report 2022 to 2023 also discusses the epidemiological surveillance of these five directly-acting antiviral COVID-19 therapeutics use in England between 2022 to 2023.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

In the recent years, tubular nanostructures have been related with immense advances in various fields of science and technology. Considerable research efforts have been centered on the theoretical prediction and manufacturing of non-carbon nanotubes (NTs), which meet modern requirements for the developing of novel devices and systems. In this context, diatomic inorganic nanotubes formed by atoms of elements from the 13th group of the periodic table (B, Al, Ga, In, Tl) and nitrogen (N), have received much research attention. In the present work, the elastic properties of single-walled boron nitride, aluminium nitride, gallium nitride, indium nitride and thallium nitride nanotubes were numerically evaluated using the nanoscale continuum modelling approach (also called molecular structural mechanics). The elastic properties (rigidities, surface Young´s and shear moduli, and Poisson´s ratio) of nitride nanotubes are discussed with respect to the bond length of the corresponding diatomic hexagonal lattice. The results obtained contribute to a better understanding of the mechanical response of nitride compound-based nanotubes, covering a broad range from the well-studied boron nitride NTs to the hypothetical thallium nitride NTs.

In this study, we prove the norm separating property for the composition of Cesàro 1 and Gamma matrices with their transpose. As a result, we compute the ℓp-norms of six classes of operators that commute with the infinite Hilbert operators. Additionally, we find the norm of 3 Hilbert’s commutants on some well-known sequence spaces.

Tree ordinances can be an effective means of preserving urban forests in the face of development pressures. Despite this, they also have the potential to be divisive among the public - especially when applied to privately-owned land. In this study we surveyed 1,716 Florida urban residents to understand how they value regulation and management of the urban forest. Specifically, we asked about: tree protection ordinances, incentive programs to manage or plant trees, justification for tree removal, and development. Most respondents supported tree protections, even when applied to trees on their own property or when they had the potential to limit development activities. Additionally, there was limited support for removing healthy trees for development. Respondents supported the use of funds for urban forestry efforts – particularly at the local or state level.

Let $(Omega, mu)$ be a measure space and $\{\tau_\alpha\}_{\alpha\in \Omega}$ be a normalized continuous Bessel family for a real Hilbert space $\mathcal{H}$. If the diagonal $\Delta \{(\alpha, \alpha):\alpha \in \Omega\}$ is measurable in the measure space $\Omega\times \Omega$, then we show that \begin{align}\label{CRBA} \sup _{\alpha, \beta \in \Omega, \alpha\neq \beta}\langle \tau_\alpha, \tau_\beta\rangle \geq \frac{-(\mu\times\mu)(\Delta)}{(\mu\times\mu)((\Omega\times\Omega)\setminus\Delta)}. \end{align} We call Inequality (1) as continuous Rankin bound. It improves 76 years old result of Rankin [Ann. of Math., 1947]. It also answers one of the questions asked by K. M. Krishna in the paper [Continuous Welch bounds with applications, Commun. Korean Math. Soc., 2023]. We also derive Banach space version of Inequality (1).

Interest on psychosocial predictors of doping has been increasing as a way of finding new approaches to reduce use of performance-enhancing drugs. This investigation aimed to test the psychometric properties of an instrument to asses doping attitudes in Brazilian athletes. The PEAS was validated to Brazilian sports through a process of translation, back-translation and content validity assessment, presenting satisfactory evidences based on its content (CVC>0.80). Then, 994 athletes, from different sexes, types of sports and competitive levels, answered to the Brazilian version of the PEAS. Results showed satisfactory evidences of validity based on its response process, internal structure [X2/df = 2.04; RMSEA = 0.032 (0.026-0.038); CFI = 0.96; TLI = 0.95] and reliability (Cronbach’s α, McDonald’s ω, and CR > 0.70). Network analysis was also used to further explore PEAS’s internal structure. Overall results provide support for the adoption of the PEAS for Brazilian athletes and possibly other Portuguese-speaking countries.

The aim of this paper is to determine a suitable definition for the concept of fuzzy Hilbert space. In order to achieve this, we firstly focused on various approaches from the already-existent literature. Then we considered another approach to the notion of fuzzy inner product and analysed its properties.

The conformations of trifluoroacetyl triflate, CF3C(O)OSO2CF3, were investigated through vibrational experimental methods (gas-phase FTIR, liquid-phase Raman, and Ar-matrix FTIR spectroscopy) and Density Functional Theory (DFT) calculations. A potential energy surface was computed using the B3P86 /6-31+g(d) approximation as a function of the dihedral angles τ1 = CCOS and τ2 = COSC. The surface reveals three minima, which were further optimized using the B3LYP method with various basis sets (6-31++G(d), 6-311++G(d), tzvp and cc-pvtz). The global minimum corresponds to a syn-anti conformer (the CO double bound syn with respect the O−S single bond and the C−O single bond anti with respect to de S−C single bond). The other two minima represent enantiomeric syn-gauche forms. The Ar-matrix FTIR spectrum exhibited clear evidence of the presence of two conformers. Furthermore, the randomization process observed following broad-band UV-visible irradiation facilitated the identification of the IR absorption of each conformer. Based on the Ar-matrix FTIR experiments, the vapour phase of trifluoroacetyl triflate at room temperatures was composed of approximately 60-70% of the syn-anti conformer and 30-40% of the syn-gauche form.

The fractional Hilbert transform, a generalization of the Hilbert transform, has been extensively studied in the literature because of its extensive use in optics, engineering, and signal processing. In the present work, we aimed to expand the fractional Hilbert transform to a space of generalized functions known as Boehmians. We introduce a new fractional convolution operator for the fractional Hilbert transform to prove a convolution theorem similar to the classical Hilbert transform and also to extend the fractional Hilbert transform to Boehmians. We also construct a suitable Boehmian space on which the fractional Hilbert transform exists. Further, we investigate convergence of the fractional Hilbert transform for the class of Boehmians and discuss the continuity of the extended fractional Hilbert transform.

Discrete Double Hilbert Exponential sums along polynomials. This is preprint version (not peer reviewed) And we now check the proof of (ii) of Lemma 3.2 whether it is really true.

In a previous paper (https://dx.doi.org/10.2139/ssrn.3648127 ), an elementary and thoroughly arithmetical proof of Fermat’s last theorem by induction has been demonstrated if the case for “n = 3” is granted as proved only arithmetically (which is a fact a long time ago), furthermore in a way accessible to Fermat himself though without being absolutely and precisely correct. The present paper elucidates the contemporary mathematical background, from which an inductive proof of FLT can be inferred since its proof for the case for “n = 3” has been known for a long time. It needs “Hilbert mathematics”, which is inherently complete unlike the usual “Gödel mathematics”, and based on “Hilbert arithmetic” to generalize Peano arithmetic in a way to unify it with the qubit Hilbert space of quantum information. An “epoché to infinity” (similar to Husserl’s “epoché to reality”) is necessary to map Hilbert arithmetic into Peano arithmetic in order to be relevant to Fermat’s age. Furthermore, the two linked semigroups originating from addition and multiplication and from the Peano axioms in the final analysis can be postulated algebraically as independent of each other in a “Hamilton” modification of arithmetic supposedly equivalent to Peano arithmetic. The inductive proof of FLT can be deduced absolutely precisely in that Hamilton arithmetic and the pransfered as a corollary in the standard Peano arithmetic furthermore in a way accessible in Fermat’s epoch and thus, to himself in principle. A future, second part of the paper is outlined, getting directed to an eventual proof of the case “n=3” based on the qubit Hilbert space and the Kochen-Specker theorem inferable from it.

While many practitioners and experts understand the risks associated with low urban tree diversity, they often lack the ability to rectify issues they encounter on their own. The current system of tree production and procurement is complex – shaped by market pressures, nursery and site constraints, local governance, and differing professional objectives among those who grow, specify, and plant trees. To understand this complexity as well as constraints to- and opportunities for increasing urban tree diversity, we conducted a series of focus groups comprised of nursery growers, landscape architects, and urban foresters. Our results highlight a significant list of considerations and constraints to diversity (both shared among green industries and some specific to growers or purchasers). More importantly, in discussing our findings we outline actionable strategies for increasing urban tree diversity.

Hemoglobinopathies are a group of disorders in which the hemoglobin molecule has abnormal production or structure. The hemoglobin molecules in red blood cells (RBC) are impacted by the blood disease known as sickle cell disease (SCD), and Thalassemia is one of the major monogenic disorders that reduces hemoglobin production( Kohne et al ., 2011). This disorder results in a large number of red blood cells being destroyed, leading to anemia. India bears a huge burden of hemoglobinopathies; thalassemia is the most prevalent (Mondal SK et al., 2016). A key component of thalassemia prevention is a successful screening procedure to identify Thalassemia carriers. Effective screening programs have numerous obstacles, especially in environments with limited resources. Machine learning (ML) has been used to solve technical and domain-specific problems in a variety of prognostic and diagnostic medical jobs. In this work, we aimed to identify and analyze the most common mutation of β--thalassemia and sickle cell disease from the north Indian population by employing Machine learning-based algorithms. To accurately predict the carrier state from a simple blood test, and to predict pathogenic hemoglobin variants in a group of individuals, these results demonstrate the application of integrated bioinformatics and machine learning approaches. This study contributes to the validation of the models based on data from several individuals and hemoglobinopathies.

The paper is a continuation of another paper (https://philpapers.org/rec/PENFLT-2) published as Part I. Now, the case of “n=3” is inferred as a corollary from the Kochen and Specker theorem (1967): the eventual solutions of Fermat’s equation for “n=3” would correspond to an admissible disjunctive division of qubit into two absolutely independent parts therefore versus the contextuality of any qubit, implied by the Kochen – Specker theorem. Incommensurability (implied by the absence of hidden variables) is considered as dual to quantum contextuality. The relevant mathematical structure is Hilbert arithmetic in a wide sense (https://dx.doi.org/10.2139/ssrn.3656179), in the framework of which Hilbert arithmetic in a narrow sense and the qubit Hilbert space are dual to each other. A few cases involving set theory are possible: (1) only within the case “n=3” and implicitly, within any next level of “n” in Fermat’s equation; (2) the identification of the case “n=3” and the general case utilizing the axiom of choice rather than the axiom of induction. If the former is the case, the application of set theory and arithmetic can remain disjunctively divided: set theory, “locally”, within any level; and arithmetic, “globally”, to all levels. If the latter is the case, the proof is thoroughly within set theory. Thus, the relevance of Yablo’s paradox to the statement of Fermat’s last theorem is avoided in both cases. The idea of “arithmetic mechanics” is sketched: it might deduce the basic physical dimensions of mechanics (mass, time, distance) from the axioms of arithmetic after a relevant generalization, Furthermore, a future Part III of the paper is suggested: FLT by mediation of Hilbert arithmetic in a wide sense can be considered as another expression of Gleason’s theorem in quantum mechanics: the exclusions about (n = 1, 2) in both theorems as well as the validity for all the rest values of “n” can be unified after the theory of quantum information. The availability (respectively, non-availability) of solutions of Fermat’s equation can be proved as equivalent to the non-availability (respectively, availability) of a single probabilistic measure as to Gleason’s theorem.

Inspired by works of W. H. Zurek and others, a mathematical, physical theory, entirely within a quantum mechanical formalism, is proposed for cognitive processes in terms of an abstract Hilbert-space for the conscious state that is an exact replica of the Hilbert-space for the neuronic physical state. Thus, any actual state of consciousness arises by its formal alignment (identification) with some-one in the set of the neuronic states, with the latter undergoing perpetual changes in the wake of life-long experiences. It is posited that these changes become expressed by an increase in the number of ordered, coherent neuronic states at the expense of the pre-ordinal random neuronic states. Changes, transitions between states are induced by a Gorini-Kossakowski-Sudarshan-Lindblad formalism, which is also instrumental in the effect of the conscious state on bodily actions. The paradigmatic findings of R.N. Shepard (1958 - 2011) and of S. Sternberg (1966 - 2016) for long- and short-term recalls are interpreted within the model.

The standard approach to integrable nonlinear evolution equations (NLEE) usually uses the following steps: 1) Lax representation $[L,M]=0$; 2)~construction of fundamental analytic solutions (FAS); 3) reducing the inverse scattering problem (ISP) to a Riemann-Hilbert problem (RHP) $\xi^+(x,t,\lambda) =\xi^-(x,t,\lambda) G(x,t\lambda)$ on a contour $\Gamma$ with sewing function $G(x,t,\lambda)$; 4) soliton solutions and possible applications.Step 1) involves several assumptions: the choice of the Lie algebra $\mathfrak{g}$ underlying $L$, as well as its dependence on the spectral parameter, typically linear or quadratic in $\lambda$. In the present paper we propose another approach which substantially extends the classes of integrable NLEE.Its first advantage is that one can effectively use any polynomial dependence in both $L$ and $M$. We use the following steps: A) Start with canonically normalized RHP with predefined contour $\Gamma$; B) Specify the $x$ and $t$ dependence of the sewing function defined on $\Gamma$; C) Introduce convenient parametrization for the solutions $ \xi^\pm(x,t,\lambda)$ of the RHP and formulate the Lax pair and the nonlinear evolution equations (NLEE); D) use Zakharov-Shabat dressing method to derive their soliton solutions. This needs correctly taking into account the symmetries of the RHP. E) Define the resolvent of the Lax operator and use it analyze its spectral properties.

Motivated from the theory of Hilbert-Schmidt morphisms between Hilbert C*-modules over commutative C*-algebras by Stern and van Suijlekom [J. Funct. Anal., 2021], we introduce the notion of p-absolutely summing morphisms between Hilbert C*-modules over commutative C*-algebras. We show that an adjointable morphism between Hilbert C*-modules over monotone closed commutative C*-algebra is 2-absolutely summing if and only if it is Hilbert-Schmidt. We formulate version of Pietsch factorization problem for p-absolutely summing morphisms and solve partially.

Here we present Hilfer-Polya, psi-Hilfer Ostrowski and psi-Hilfer-Hilbert- Pachpatte types fractional inequalities. They are univariate inequalities involving left and right Hilfer and -Hilfer fractional derivatives. All estimates are with respect to norms ||.||p, 1 <_ p <_infinite. At the end we provide applications.

We investigate \texorpdfstring{$L_2$}{}-approximation problems in the worst case setting in the weighted Hilbert spaces \texorpdfstring{$H(K_{R_{d,\a,\g}})$}{} with weights \texorpdfstring{$R_{d,\a,{\bm \ga}}$}{} under parameters \texorpdfstring{$1\ge \ga_1\ge \ga_2\ge \cdots\ge 0$ and $1<\az_1\le \az_2\le \cdots$}{}. Several interesting weighted Hilbert spaces \texorpdfstring{$H(K_{R_{d,\a,\g}})$}{} appear in this paper. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. Multivariate approximation; information complexity; tractability; weighted Hilbert spacesWe discuss tractability of \texorpdfstring{$L_2$}{}-approximation problems for the involved Hilbert spaces, which describes how the information complexity depends on \texorpdfstring{$d$}{} and \texorpdfstring{$\va^{-1}$}{}. As a consequence we study the strongly polynomial tractability (SPT), polynomial tractability (PT), weak tractability (WT), and \texorpdfstring{$(t_1,t_2)$}{}-weak tractability (\texorpdfstring{$(t_1,t_2)$}{}-WT) for all \texorpdfstring{$t_1>1$}{} and \texorpdfstring{$t_2>0$}{} in terms of the introduced weights under the absolute error criterion or the normalized error criterion.

In this paper we survey some recent results due to the author concerning various inequalities and approximations for the finite Hilbert transform of a function belonging to several classes of functions, such as: Lipschitzian, monotonic, convex or with the derivative of bounded variation or absolutely continuous. More accurate estimates in the case that the higher order derivatives are absolutely continuous, are also provided. Some quadrature rules with error bounds are derived. They can be used in the numerical integration of the finite Hilbert transform and, due to the explicit form of the error bounds, enable the user to predict a priory the accuracy.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

In this article, we establish some new generalized inequalities of Hilbert-type on time scales delta calculus which considered as similar formulas for inequalities of Hilbert type proved by Chang-Jian, Lian-Ying and Cheung [7]. These inequalities will proved by applying Hölder’s inequality, chain rule on time scales and the mean inequality. As special cases of our results (when T = N and T = R), we get the discrete and continuous inequalities. Also, we can obtain other inequalities in different time scale, like T = q^Z, q > 1.

Integrated Kerr micro-combs, a powerful source of many wavelengths for photonic RF and microwave signal processing, are particularly useful for transversal filter systems. They have many advantages including a compact footprint, high versatility, large numbers of wavelengths, and wide bandwidths. We review recent progress on photonic RF and microwave high bandwidth temporal signal processing based on Kerr micro-combs with spacings from 49-200GHz. We cover integral and fractional Hilbert transforms, differentiators as well as integrators. The potential of optical micro-combs for RF photonic applications in functionality and ability to realize integrated solutions is also discussed.

Sesquiterpene lactones (STLs) are a large group of terpenoids most commonly found in plants of the Asteraceae family, e. g. in chicory plants, displaying a wide range of interesting biological activities. However, further studies on the biological potential of chicory derived STLs and analogues are challenging as only four of these molecules are commercially available (as analytical standards), and to date there are no published or patented simple extraction-purification processes capable of large scale STLs isolation. In this work we describe a novel three-step large scale extraction and purification method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and lactucin (Lc) starting from a chicory genotype rich in these STLs and in the corresponding glycosyl and oxalyl conjugated forms. After a small-scale screening on 100 mg of freeze-dried chicory root powder, the best results were achieved with a 17 h water maceration at 30°C. With these conditions we managed to increase the content of DHLc and Lc, at the same time favouring the hydrolysis of their conjugated forms. On a larger scale, the extraction of 750 g of freeze-dried chicory root powder, followed by a liquid-liquid extraction step and a reversed-phase chromatography, allowed the recovery of 642.3 ± 76.3 mg of DHLc and 175.3 ± 32.9 mg of Lc. The two pure STLs were subsequently used in the context of semi-synthesis to generate analogues for biological evaluation as antibacterial agents. In addition, other described chicory STLs that are not commercially available were also synthesized or extracted to serve as analytical standards for the study. In particular, lactucin-oxalate and 11,13-dihydrolactucin-oxalate were synthesized in two steps starting from Lc and DHLc, respectively. On the other hand, 11β,13-dihydrolactucin-glycoside was obtained after a MeOH/H₂O (70/30) extraction, followed by a liquid-liquid extraction step and a reversed-phase chromatography. Together, this work will help facilitate the evaluation of the biological potential of chicory derived STLs and their semisynthetic analogues.

Hilbert arithmetic in a wide sense, including Hilbert arithmetic in a narrow sense consisting by two dual and anti-isometric Peano arithmetics, on the one hand, and the qubit Hilbert space (originating for the standard separable complex Hilbert space of quantum mechanics), on the other hand, allows for an arithmetic version of Gentzen’s cut elimination and quantum measurement to be described uniformy as two processes occurring accordingly in those two branches. A philosophical reflection also justifying that unity by quantum neo-Pythagoreanism links it to the opposition of propositional logic, to which Gentzen’s cut rule refers immediately, on the one hand, and the linguistic and mathematical theory of metaphor therefore sharing the same structure borrowed from Hilbert arithmetic in a wide sense. An example by hermeneutical circle modeled as a dual pair of a syllogism (accomplishable also by a Turing machine) and a relevant metaphor (being a formal and logical mistake and thus fundamentally inaccessible to any Turing machine) visualizes human understanding corresponding also to Gentzen’s cut elimination and the Gödel dichotomy about the relation of arithmetic to set theory: either incompleteness or contradiction. The metaphor as the complementing “half” of any understanding of hermeneutical circle is what allows for that Gödel-like incompleteness to be overcome in human thought.

To enhance the overall reliability of the power system, engineers have redirected their focus toward health monitoring and early detection of faults in transformers. Among these faults, transformer core defects demand particular attention. While fault simulation using software has traditionally been the preferred approach, these methods suffer from data inaccuracies in real-world conditions. Consequently, conducting actual experimental setups with induced faults is imperative to investigate core issues. This study uses Hilbert Transform (HT) as a signal processing technique to extract crucial data characteristics, thereby enhancing the performance of the classifier model. The research involves analyzing electric current signals from a single-phase 1kVA transformer. A comparative assessment of our proposed model was conducted using raw data and Fast Fourier Transform (FFT), evaluating accuracy, precision, recall, F1-score, and computational time. The results demonstrate a significant improvement in all metrics for the classifier models, particularly the k-nearest neighbor (KNN) algorithm, which exhibited values of 83.89%, 84.39%, 83.89%, 83.79%, and 0.0156 seconds, respectively. Future work aims to extend this analysis under different loading conditions.

A major task in Functional Time Series Analysis is measuring the dependence within and between processes, for which lagged covariance and cross-covariance operators have proven to be a practical tool in well-established spaces. This article deduces estimators and asymptotic upper bounds of the estimation errors for lagged covariance and cross-covariance operators of processes in Cartesian products of abstract Hilbert spaces for fixed and increasing lag and Cartesian powers. We allow the processes to be non-centered, and to have values in different spaces when investigating the dependence between processes. Also, we discuss features of estimators for the principle components of our covariance operators.

We consider a stationary inclusion in a real Hilbert space X, governed by a set of constraints K, a nonlinear operator A and an element f∈X. Under appropriate assumptions on the data the inclusion has a unique solution, denoted by u. We state and prove a covergence criterion, i.e., we provide necessary and sufficient conditions on a sequence {un}⊂X which guarantee its convergence to the solution u. We then present several applications which provide the continuous dependence of the solution with respect to the data K, A and f, on one hand, and the convergence of an associate penalty problem, on the other hand. We use these abstract results in the study of a frictional contact problem with elastic materials which, in a weak formulation, leads to a stationary inclusion for the deformation field. Finally, we apply the abstract penalty method in the anlysis of two nonlinear elastic constitutive laws.

Despite the abundance of tree diversity in the natural world, and generally high tree species richness in urban areas, urban forests continue to be dominated by a limited number of species. As socio-ecological systems, urban forests are shaped by historical and current management efforts and decision-making of a wide range of human actors. Drawing on past research, we offer a conceptual framework for describing the complex interactions among tree producers and consumers as trees are selected, grown, specified, and planted in private and public urban areas. We illustrate how multiple layers of selection criteria filter down the entirety of potential local tree diversity to a handful of commonly used and accepted tree species. We detail the actors and decision makers who impact tree composition and diversity across several land types. Finally, we identify research, education and outreach needs as they relate to creating more diverse and resilient urban forest ecosystems.

In this paper, a generic fractional derivative is defined as a set of the linear operators left-inverse to the Riemann-Liouville fractional integral. Then the theory of the left-invertible operators developed by Przeworska-Rolewicz is applied for derivation of its properties. In particular, we characterize its domain, null-space, and projector operator, establish the interrelations between its different realisations, and present a generalized fractional Taylor formula involving the generic fractional derivative. Then we consider the fractional relaxation equation containing the generic fractional derivative, derive a closed form formula for its unique solution, and study its complete monotonicity.

Safe water is a global public health concern amid increasing scarcity and pollution. Bottled water production and consumption contribute to these problems. This study examines tap water consumption in Italy, assessing associated sociodemographic factors and related health outcomes such as obesity and self-perceived health status. Data from the Italian National Statistics Institute's "Aspects of daily life" survey (N=45,597) were analyzed. Covariates included education, age, gender, economic status, region, concerns about waste and climate change, consumption of carbonated drinks excluding water, alcohol consumption, consumption of vegetables, consumption of snacks, body mass index, and self-perceived health status. Bivariate analyses and mixed-effect logistic regression models explored the associations. People who drink tap water were 19,674 with a higher prevalence in people aged 45 to 59 old, people with a graduate/post-graduate degree diploma, with optimal economic resources, and concerned about waste production and climate change, coming from the North-East regions of Italy. Underweight people showed a higher prevalence of TW assumption as well as those who drink less than occasionally carbonated drinks, drink alcohol, consume vegetables more than once a day, and snacks less than once a week with a satisfying level perceived health status. Regressions showed that all age classes are less likely to drink tap water than people younger than 20 years old. The category with “inadequate” economic resources is more likely to consume tap water. Low educational classes show a low likelihood of consuming tap water as well as Islands. A concern about waste production and climate change is associated with an increased likelihood of assuming tap water. Tap water consumption was negatively associate with obesity but not with a satisfactory Self-perceived health status. Insights from this study can inform public health strategies.

BACKGROUND AND OBJECTIVE: The use of biomass for cooking carries significant health implications and can lead to adverse environmental issues such as deforestation, greenhouse gas emissions, and erosion. Despite these concerns, there is a lack of information about the nature and extent of cooking emissions in many developing countries. To address this gap, a study was conducted to assess cooking emission levels and their associated health effects among households in Dodoma City, Tanzania. METHODS: A descriptive cross-sectional design was conducted, involving 285 households in the peri-urban area of Dodoma City, Tanzania. A combination of questionnaires, observational checklists, and sampling devices (Aeroqual series 500 for Carbon Monoxide and Temptop PMD 351 for Particulate Matters) were employed for data collection, adhering to established protocols. Additionally, lung function tests were conducted with consent from the primary household cooks. Collected data were entered into an Excel spreadsheet and analyzed using STATA 17 software. FINDINGS: Out of 285 participants, 74.7% predominantly use charcoal for cooking, with 68.4% having outdoor kitchen setups. Significant differences in pollutant concentrations were observed across various fuel types (P=0.0001), with firewood emitting higher levels of particulate matter and carbon monoxide. Carbon monoxide concentrations during cooking were 6 times higher for firewood, 5 times higher for charcoal-gas, and 3 times higher for charcoal compared to WHO daily average limits. Additionally, a positive correlation between pollutant concentrations was noted (P-value = 0.0000). Lung problems 17.8% followed by eye irritation 15.7% were mentioned by those who claimed to know the health effects associated with cooking emissions. In addition, the spirometry test indicated that the majority of the participants had % predicted >80 while only 19% had % predicted below 50. CONCLUSION: Charcoal and firewood remain the primary cooking fuels in the study area despite their significant negative impacts. Our findings highlight a lack of awareness among community members regarding the health effects of biomass cooking emissions and insufficient guidance on constructing healthy kitchens. To address this, enforcing building standards, raising health awareness, and ensuring affordable access to modern fuels are crucial steps. These measures are essential for promoting healthier cooking practices and mitigating the adverse effects on households.

One of the most important agrotechnical factors that influence the growth conditions of crops is plant density. Alterations in habitat conditions result in the emergence of phytophagous organisms, whose development is closely associated with host plants. The objective of this study was to assess the abundance and species composition of thrips (Thysanoptera) collected in soybean plants of different varieties cultivated under different plant arrangements (row spacing, number of seeds sown differed). The research was conducted at two locations in southwestern Poland between 2015 and 2018. The herbivores that inhabit plants were caught using an entomological net. The experiments were carried out using the complete randomised block design, with four replications. Regardless of location and treatment, thrips were the most numerous group of pests. Thrips tabaci and T. fuscipes were the dominant species within the collected material. A total of 24 species of thrips were identified and their dietary specialisation was determined. The assemblages of studied insects were also analysed due to the density of the plants and the stage of development. The increase in the sowing density of soybean (90 seeds per m2) resulted in a greater total number of thrips compared to a lower sowing density (50 seeds per m2). The number of thrips significantly increased during the flowering period and shortly after the flowering time, which made them a significant threat to the plants. Therefore, it is crucial to develop innovative pest management strategies tailored to effectively grow soybean to mitigate potential pest-related challenges.

Selenium is essential for the synthesis and function of various selenoenzymes, such as glutathione peroxidases, selenoprotein P, and thioredoxin reductase, which play an important role in both antioxidant defense and limiting oxidative damage. Associations between serum selenium concentration and obstetric complications as well as pregnancy outcomes has been reported in many studies. The aim of this study was to determine whether the dietary intake of selenium, its concentration in serum and the activity of glutathione peroxidase in subsequent trimesters of pregnancy affect the birth condition of newborns assessed on the basis of the Apgar score in the 1st and 5th minute of life, birth weight, body length and head and chest circumference in physiological and complicated pregnancy course. Twenty-seven pregnant women at a mean age 29.6 ± 4.8 years from the Lower Silesia region of Poland were recruited to the study, 55% of studied group had pregnancy complications. The mean reported Se intake and serum selenium content for Polish pregnant women was in the first trimester – 56.53 μg/day and 43.75 μg/l, the second trimester – 61.79 μg/day and 41.77 μg/l and the third trimester – 58.37 μg/day and 42.13 μg/l, respectively. In the subgroup of pregnant women with a physiological pregnancy course, a weak, although statistically significant, positive correlation was found in the first trimester between Se intake and the length (R=0.48, p=0.019) and birth weight of newborns (R=0.472, p=0.022), and in the second trimester with the APGAR score at 1 (R=0.680, p=0.005) and 5 minutes (R=0.55, p=0.033), as well as in the third trimester with th APGAR score at 1 minut (R=0.658, p=0.019). The GPX value had a strong positive correlation with the APGAR score at 1 min. (R=0.650, p=0.008) in the second trimester and with the birth weight of the newborns (R=0.598, p=0.039) in the third trimester. There was no correlation between newborns' birth measurements and serum selenium concentration. In the subgroup of pregnant women with pregnancy complications, a strong, statistically significant, negative correlation was found between Se intake in the second trimester and gestational age (R=-0.618, p=0.032), and in the third trimester, a positive correlation between Se concentration in serum and head circumference (R=0.587, p=0.021). The obtained results indicate that there is a relationship between the maternal selenium status during pregnancy, both in terms of the intake of this element, its serum concentration as well as the glutathione peroxidase activity, and the anthropometric parameters of the newborn, such as birth weight, length and APGAR score, especially in the group with physiological course of pregnancy, but when pregnancy complications occur, these relationships lose their importance.

Introduction: Most industrialized and developed countries now working to implement more advanced transportation systems. These include autonomous vehicle(AV) systems of various forms, such as delivery vehicles, which eliminate the crashes, injuries, and fatalities associated with human-operated machinery. Self-driving vehicles have the potential to make roads safer, but some safety concerns need to be addressed. Before AV systems become commonplace in developing countries, society needs to determine how safe they truly are. Objectives: This paper provides brief descriptions and examines the realities for AV in developing countries using results from infrastructure-based assessment of countries worldwide and from a questionnaire-based survey. Methods: Relevant research papers, articles, reports, and departmental websites were used as the main data sources. Ethiopia was chosen as a representative case. Different aspects of AV infrastructure, its current status in developing countries, and perspectives on AV systems are explored through interviews with approximately 1500 randomly selected individuals. The main variables in the assessment were physical infrastructure, digital infrastructure, and societal perceptions on AV systems. Results: Surprisingly, the results indicated that 55.82%, 78.58%, 87.78%, and 86.09% of Ethiopian interviewees agreed with statements regarding high ease of use, usefulness, positive attitude, and benefits, respectively, of AV. However, it should be noted that some interviewees did not provide a response to certain questions.

Development and redevelopment are important drivers of tree removal and canopy loss in urban landscapes. Local ordinances are often used to curtail tree removal, but punitive regulations alone may not be enough to reduce urban tree canopy loss in land development. In Florida (US), efforts to balance trees and development have so far focused on fees and fines, but with a recent backlash against tree regulations and the fast pace of urban growth, we explored the possible role of incentives in urban tree policies. We interviewed 20 land developers across Florida to understand their perspectives on current barriers and potential incentives for tree preservation and planting. We collected data from developers, whose perspectives on tree preservation are often unknown or overlooked, despite their significant role in tree planting, removal, and retention in and around cities. Our results show that major barriers to tree preservation and planting include requirements to grade sites for stormwater management, site constraints, and monetary costs. Most developers did not know of any existing incentives beyond intrinsic motivations but said that financial incentives would be most appealing to them. Top incentive suggestions include increasing building density, reducing impact fees and tax liability, and changing tree mitigation policies. Another promising finding is that developers are willing to work with regulators to find solutions that benefit both parties. Future research should consider evaluating the level of support and viability of different incentives by gathering feedback from policymakers, land developers, and the public.

As urban development increases in density, the space to grow urban trees becomes more constrained. In heavily developed areas, small stature trees can be planted to reduce both above- and below-ground conflicts with infrastructure elements. However, even these species have their limits when placed in extremely confining conditions. In this study, we build on past work to determine the minimum planting widths of small stature urban trees. We found that species, stem diameter, and the height at which stem diameter measurements occurred were all strong predictors of trunk flare diameter (adjusted R² of 0.843). Additionally, we modelled the relationship between planting space and the presence or absence of hardscape conflicts – using the predictions derived from this effort to project the potential cost savings in two United States cities. Study results provide a guideline to create sufficient space for urban trees and minimize infrastructure damage and associated cost savings.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

We demonstrate an RF photonic fractional Hilbert transformer based on an integrated Kerr micro-comb source featuring a record low free spectral range of 49 GHz. By programming and shaping the comb lines according to calculated tap weights for up to 39 wavelengths across the C-band, we achieve tunable bandwidths ranging from 1.2 to 15.3 GHz as well as variable center frequencies from baseband to 9.5 GHz, for both standard integral and arbitrary fractional orders. We experimentally characterize the RF amplitude and phase response of the tunable bandpass and lowpass Hilbert transformers with 90 and 45-degree phase shifts. The experimental results show good agreement with theory, confirming the effectiveness of our approach as a powerful way to implement standard and fractional order Hilbert transformers with broad and variable bandwidths and center frequencies, with high reconfigurability and greatly reduced size and complexity. Tan, and D. J. Moss are with the Optical Sciences Centre, Swinburne University of Technology, Hawthorn, VIC 3122, Australia. (Corresponding e-mail: [email protected]). Xu is with the Electro-Photonics Laboratory, Department of Electrical and Computer System Engineering, Monash University, Clayton, 3800 VIC, Australia

COVID-19 infection is extremely dangerous for persons with comorbidities such as kidney disease and diabetes. Although many people of all ages and socioeconomic backgrounds have suffered due to this pandemic, those with underlying medical conditions like kidney disease and diabetes are more vulnerable to becoming infected with COVID-19 related to weak immunity. However, the role of vaccination in the co-infection of COVID-19 with diabetics is not available in the literature. Therefore, we examine the unique challenges presented by the co-infection of COVID-19 in individuals with diabetes, focusing on its disease transmission dynamics. A mathematical modelling technique is to be employed in this work to analyse the dynamics of COVID-19 outbreaks with seven compartments, including vaccination with comorbidities such as diabetes. We also investigated analytically by displaying the solutions' existence, boundedness, positivity and sensitivity. After calculating the basic reproduction numbers, the stability analysis of model equilibrium points is also covered. If the reproduction numbers are less than unity, the disease-free equilibrium points of the model appear to be both locally and globally stable. The findings of this study are that as the vaccination rate rises, the incidence of COVID-19 and its co-infections with diabetes decreases. Effective disease treatment strategies may be based partly on the possible impact of vaccination on the co-infection of COVID-19 related to diabetic disease insights.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

The paper is concerned with a class of stochastic differential equations in infinite dimensional Hilbert space with random coefficients driven by Teugel's martingales which are more general processes. and its optimal control problem. Here Teugels martingales are a family of pairwise strongly orthonormal martingales associated with L\'{e}vy processes (see Nualart and Schoutens). There are three major ingredients. The first is to prove the existence and uniqueness of the solutions by continuous dependence theorem of solutions combining with the parameter extension method. The second is to establish the stochastic maximum principle and verification theorem for our optimal control problem by the classicconvex variation method and dual technique.The third is to represent an example of a Cauchy problem for a controlled stochastic partial differential equation driven by Teugels martingales which our theoretical results can solve.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

Low-energy cosmic rays (LECRs) play a crucial role in the formation of planetary systems, and detecting and reconstructing the properties of early LECRs is essential for understanding the mechanisms of planetary system formation. Given that LECRs interact with the surrounding medium to produce nuclear de-excitation line emissions with energy mainly within 0.1–10 MeV, which are unaffected by stellar wind modulation, these gamma-ray emissions can accurately reflect the properties of LECRs. This study introduces an innovative method for using gamma-ray emissions to infer LECR properties. We employed the Parker transport equation to simulate the propagation and spectral evolution of LECRs in a protoplanetary disk and calculated the characteristic gamma-ray emissions resulting from interactions between LECRs and disk material. These gamma-ray emissions encapsulate the spectral information of LECRs, providing a powerful tool to reconstruct the cosmic ray environment at that time. This method, supported by further theoretical developments and observations, will fundamentally enhance our understanding of the impact of CRs on the origin and evolution of planetary systems and address significant scientific questions regarding the cosmic ray environment at the origin of life.

Lewis Carroll, both logician and writer, suggested a logical paradox containing furthermore two connotations (connotations or metaphors are inherent in literature rather than in mathematics or logics). The paradox itself refers to implication demonstrating that an intermediate implication can be always inserted in an implication therefore postponing its ultimate conclusion for the next step and those insertions can be iteratively and indefinitely added ad lib, as if ad infinitum. Both connotations clear up links due to the shared formal structure with other well-known mathematical observations: (1) the paradox of Achilles and the Turtle; (2) the transitivity of the relation of equality. Analogically to (1), one can juxtapose the paradox of the Liar (for Lewis Carroll’s paradox) and that of the arrow (for “Achilles and the Turtle”), i.e. a logical paradox, on the one hand, and an aporia of motion, on the other hand, suggesting a shared formal structure of both, which can be called “ontological”, on which basis “motion” studied by physics and “conclusion” studied by logic can be unified being able to bridge logic and physics philosophically in a Hegelian manner: even more, the bridge can be continued to mathematics in virtue of (2), which forces the equality (for its property of transitivity) of any two quantities to be postponed analogically ad lib and ad infinitum. The paper shows that Hilbert arithmetic underlies naturally Lewis Carroll’s paradox admitting at least three interpretations linked to each other by it: mathematical, physical and logical. Thus, it can be considered as both generalization and solution of his paradox therefore naturally unifying the completeness of quantum mechanics (i.e. the absence of hidden variables) and eventual completeness of mathematics as the same and isomorphic to the completeness of propositional logic in relation to set theory as a first-order logic (in the sense of Gödel (1930)’s completeness theorems).

To characterize the fecal microbiota of lactating Bactrian camels, this study employed a random selection of camels, assigning them to three groups: the first parity group, the third parity group, and the fifth parity group. The fecal microbial community of lactating camels was assessed using 16S rRNA amplicon sequencing, and the resulting library was sequenced on an Illumina NovaSeq platform. The first parity group was characterized by Verrucomicrobiaceae as a distinctive bi-omarker, whereas Clostridiaceae exhibited a similar role to the third parity group. In terms of functional analysis, the relative abundance of the Steroid biosynthesis pathway was highest in the first parity group, whereas the fifth parity group demonstrated a higher relative abundance of the Tuberculosis pathway compared to the other groups. The first parity group exhibited the greatest presence of seven types of enzymes, whereas the fifth parity group displayed the highest levels of two specific enzymes. Additionally, a positive association was observed between the relative abundance of the Steroid biosynthesis pathway and Verrucomicrobiaceae. Furthermore, the relative abundance of the Tuberculosis pathway displayed positive correlations with 14 enzymes. In conclusion, this study revealed that different parity was associated with distinct fecal microbial ecologies in lactating Bactrian camels.

Background: Public engagement is needed to make sure urban forestry management efforts align with the values of the public being served. Noting this, we determined current and desired urban forest access of Florida (United States) residents using the criteria from the 3-30-300 rule (i.e., 3 trees visible from home, 30% canopy in neighborhood, and a green space within 300 meters of home). Methods: A survey of 1,716 Florida residents was conducted to assess canopy coverage and green space access. Respondents were then asked if this level of urban forest access was sufficient for their needs. We also asked their perceptions of the benefits and drawbacks of urban trees and whether they had any negative interactions with trees in the past. Results: We found that 37.3% of Florida residents met all three criteria of the 3-30-300 rule. Despite this, half the respondents would prefer more trees in their neighborhoods. When asked to name the top benefits provided by trees, the most common responses were shade, beauty, and attracting wildlife. The most common drawbacks to urban trees included risk to property, leaves/debris, and fears regarding storms and hurricanes. Conclusions: Florida residents largely value their urban forest and would like to see it maintained or enhanced. Improving access to greenspaces for recreation is the most pressing concern for urban forest managers in Florida looking to meet the requirements of the 3-30-300 rule. Results from this study can inform and test urban forest management at national and global scales.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Healthcare personnel must face two problems of growing importance: violence in the workplace and the loss of work ability due to ageing of the workforce. Studying the relationship between these two phenomena can help to prepare effective prevention measures. In a public health company, we asked nurses to self-assess their work ability using the Work Ability Index (WAI) and we analysed the relationship between this indicator and the violence experienced in the previous and following years. 321 out of 344 nurses (99.3%) participated. In a logistic regression model, the WAI score was a significant protective factor for violence experienced in the previous year (OR=0.94 CI95%=0.90; 0.98 p&lt;0.01) and in the following year (OR=0.88 CI95%=0.84; 0.92 p&lt;0.01). In a hierarchical logistic regression model, social support acted as a protective factor (OR = 0.87 CI95% = 0.79; 0.95 for violence experienced in the previous year), while occupational stress was a significant determinant of the risk of aggression (OR=3.65 CI95%=1.90; 7.03 in the previous year, OR=3.54 CI95%=1.801; 6.947 in the following year). The difficulties that nurses encounter in carrying out their growing work demands in an environment that is not promptly adapted to their changing physical and mental conditions can lead to an increased risk of violence. Prevention of workplace violence should include organizational and ergonomic measures that reduce stress and increase staff support and work ability.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

The Marun-Keu complex plays a significant role in understanding the geological evolution of the Ural orogen; however, it remains poorly understood. This study aims to provide insights into the complex's age, protolith composition, rock formation conditions, and its position in the region's history. The zircons from the host granitic gneisses are characterized by magmatic cores with an age of 470 Ma and metamorphic rims with an age of approximately 370 Ma. We suggest that the metamorphic rims were formed during eclogite metamorphism and that the metagranitoids hosting the eclogites experienced eclogite metamorphism simultaneously with the basic and ultrabasic rocks that are common in this area. Heterogeneous zircons were also isolated from the selvage of a pegmatite vein, in which four domains are distinguished, two to three of which can be identified within single grains, as follows: 1) igneous cores with an age of approximately 470 Ma and the geochemical characteristics of zircon crystallized in basic rocks; 2) zircons recrystallized during eclogite metamorphism with geochemical characteristics intermediate between those of the magmatic cores and true eclogitic zircon; 3) pegmatitic zircon, exhibiting the most sharply differentiated REE spectra of all four domains, characterized by a prominent positive Ce anomaly and a weakly expressed negative Eu anomaly; and 4) eclogitic zircon, observed in the form of veins and rims, superimposed in relation to the other three domains. The age of the latter three domains is within the error range and is estimated to be approximately 370 Ma. This indicates that the processes of eclogite metamorphism and the formation of pegmatites occurred at approximately the same time in the studied area.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

In recent years, the abundance of streaming data has posed significant challenges for traditional machine learning algorithms due to the dynamic nature and high volume of data. To address these challenges, this paper presents an adaptive supervised learning framework designed for data streams, leveraging the power of reproducing kernel Hilbert spaces (RKHS) while incorporating a data sparsity constraint. The proposed framework aims to adaptively update the model to efficiently handle the continuous arrival of streaming data while ensuring accurate and reliable predictions. The primary objective is to exploit the RKHS framework, which provides a rich mathematical structure for learning in high-dimensional feature spaces. By utilizing RKHS, the model can capture complex patterns and nonlinear relationships in the streaming data. Furthermore, the framework incorporates a data sparsity constraint to address the issue of limited resources and computational efficiency. The constraint promotes the selection of a subset of relevant features, reducing the dimensionality of the problem and enhancing the scalability of the learning algorithm. This constraint not only improves computational efficiency but also mitigates the effects of noisy or irrelevant features, leading to more robust and accurate predictions. To achieve adaptability, the proposed framework employs an online learning approach that incrementally updates the model parameters as new data arrives. This allows the model to adapt to concept drift and changing data distributions, ensuring its relevance and effectiveness over time. The adaptation process is guided by a mechanism that balances the exploitation of current knowledge with the exploration of new information, enabling the model to gradually evolve and refine its predictions. Experimental evaluations on various benchmark datasets demonstrate the efficacy of the proposed framework in handling streaming data. The results indicate that the adaptive supervised learning approach in RKHS with a data sparsity constraint outperforms traditional batch learning methods and exhibits superior accuracy, scalability, and adaptability in dynamic data stream scenarios. Overall, this research contributes to the development of adaptive supervised learning methods for data streams, highlighting the effectiveness of RKHS and the significance of incorporating a data sparsity constraint. The proposed framework offers a promising solution to handle the challenges posed by streaming data, paving the way for real-time, efficient, and accurate learning in diverse application domains.

Eight lesions were analyzed using some algorithms of Intelligence Artificial: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (MEL), actinic keratosis (AK), benign keratosis (BKL), dermatofibromas (DF), melanocytic nevi (NV), and vascular lesions (VASC). This manuscript presents the possibility of using concatenated signatures (instead of images) obtained from different integral transforms, such as Fourier, Mellin, and Hilbert, to classify skin lesions. Eleven other Artificial Intelligence models were applied so that eight skin lesions could be classified by analyzing the particular signatures of each lesion. The database was randomly divided into 80%–20% for the training and test datasets images, respectively. The metrics that are being reported are accuracy, sensitivity, specificity, and precision. Each case was repeated 30 times to avoid bias, according to the central limit theorem in this work, and the average and ±standard deviation were reported. Although all the results were very satisfactory, the best average mark for the eight lesions analyzed was obtained using the Subspace KNN model, where the metrics for the test were 99.98% accuracy, 99.96% sensitivity, 99.99% specificity, and 99.95% precision.

In this paper we introduce the hypo-q-norms on a Cartesian product of algebras of bounded linear operators on Hilbert spaces. A representation of these norms in terms of inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar reverses of Cauchy-Buniakowski-Schwarz inequality are also given. Several bounds for the norms δ_p, ϑ_p and the real norms η_r,p and θ_r,p are provided as well.

The COVID-19 pandemic struck unexpectedly, emergency services and chronic care institutions, including dialysis centers, were overloaded. An important problem was the care of positive COVID patients, but also the care of chronically dialyzed patients who presented emergencies. In our Hospital, which has become a COVID support for dialysis patients with severe forms of the disease, we had to care for PD patients with dialysis-related emergencies. We presented 2 cases of patients managed on an outpatient basis or 1 day hospitalization, treated successfully and without compromising the quality of the care provided. We used remote monitoring, we worked in a multidiscipli-nary team, we shortened the hospitalization of patients (and implicitly the risk of contact). In pandemic conditions, the advantage of PD was represented by the possibility of patient isolation, so that in the first 6 months of the pandemic, we recorded no deaths in this category of patients. In case of hemodialysis patients, in-fection and mortality rates were high. Although we expected an increase in the number of peritoneal dialysis patients in the post-pandemic period, this did not happen. We continue to plead for the popularization of the PD method among patients and doctors, which has proven its advantages under the conditions of the pandemic.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Presently, Jordan confronts a double substantial challenge of enhancing energy security and mitigating greenhouse gas emissions. One of the most encouraging avenues to attain the objectives of sustainable development, energy security, and environmental conservation is to enhance the integration of renewable energy into the generation of electricity. In pursuit of this goal, the Jordanian government intends to expand investments in the green energy sector, with solar and wind energy poised to play a key role in satisfying energy demands and cultivating an environmental sustainability. This paper aims to examine the distinctive dynamics, challenges, obstacles, and potential solutions corresponding to the establishment of community solar and wind farms in Jordan suburban areas. It aims to highlight the opportunities and barriers influencing the track of sustainable energy adoption in the country. Through a comprehensive analysis of the Jordanian context, the goal is to extract insights that can guide policies and practices. Additionally, the findings may serve as a valuable benchmark for other regions confronting similar challenges on their pursuit for a sustainable energy future.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

The main goal of our scientific study is to determine the particular characteristics of the endo-scopic image of the otorhinolaryngologic pathology of nasopharynx, which is called chronic rhinosinusitis in association with gastroesophageal acid reflux disease. Background/Objectives: to identify a specific features in the endoscopic picture of chronic rhinosinusitis associated with acid gastroesophageal reflux disease symptoms. Methods: there were selected 521 adult patients, from this sample as a main group we have selected only 95 patients with the highest scores on the Reflux Symptom Index (RSI) (>20) and Reflux Symptom Score-12 (RSS-12) (>130) questionnaires. As a control group we have selected 41 adult patients only with chronic rhinosinusitis and 10 healthy patients. Results: there were significant changes in the nasopharyngeal mucosa. In-creased vascularity of the nasopharyngeal mucosa was noted in 91 patients (95,7%). Hypertrophy of the nasopharyngeal mucosa was found in 83 patients (87,4%). In 77 (81,1%) patients, mucus was found in the nasopharynx with different characteristics of color and consistency, and no mucus or other secretions were found in the middle nasal passages in these patients. In 62 pa-tients (65,3%) asymmetric hypertrophy of the mucosa of the oropharynx was noted. Conclusions: the presence of specific features of the endoscopic picture of the nose and nasopharynx of pa-tients with chronic rhinosinusitis associated with gastroesophageal disease symptoms and pro-posed a method for assessing the degree of influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. The possible influence of symptoms of gas-tro-oesophageal reflux disease on the course and severity of clinical manifestations of exacerba-tions of chronic rhinosinusitis needs further investigation.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

The previous two parts of the paper (correspondingly, https://philpapers.org/rec/PENFLT-2 and https://philpapers.org/rec/PENFLT-3) demonstrate that the interpretation of Fermat’s last theorem (FLT) in Hilbert arithmetic meant both in a narrow sense and in a wide sense can suggest a proof by induction in Part I and by means of the Kochen - Specker theorem in Part II. The same interpretation can serve also for a proof FLT based on Gleason’s theorem and partly similar to that in Part II. The concept of (probabilistic) measure of a subspace of Hilbert space and especially its uniqueness can be unambiguously linked to that of partial algebra or incommensurability, or interpreted as a relation of the two dual branches of Hilbert arithmetic in a wide sense. The investigation of the last relation allows for FLT and Gleason’s theorem to be equated in a sense, as two dual counterparts, and the former to be inferred from the latter, as well as vice versa under an additional condition relevant to the Gödel incompleteness of arithmetic to set theory. The qubit Hilbert space itself in turn can be interpreted by the unity of FLT and Gleason’s theorem. The proof of such a fundamental result in number theory as FLT by means of Hilbert arithmetic in a wide sense can be generalized to an idea about “quantum number theory”. It is able to research mathematically the origin of Peano arithmetic from Hilbert arithmetic by mediation of the “nonstandard bijection” and its two dual branches inherently linking it to information theory. Then, infinitesimal analysis and its revolutionary application to physics can be also re-realized in that wider context, for example, as an exploration of the way for physical quantity of time (respectively, for time derivative in any temporal process considered in physics) to appear at all. Finally, the result admits a philosophical reflection of how any hierarchy arises or changes itself only thanks to its dual and idempotent counterpart.

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-age women. Women with PCOS are at higher risk of pregnancy complications including gestational diabetes (GDM). The prevalence of PCOS and GDM varies according to the diagnostic criteria used. The mechanism for the occurrence of GDM in women with PCOS is still unclear. Materials &amp; Methods- A systematic search of the electronic database was done using keywords like PCOS, and GDM to include studies between April 2008 and March 2023 where uniform diagnostic criteria were used. Studies were excluded with high-risk of bias after the assessment of bias, and meta-analysis was done with relative risks and confidence intervals. Results &amp; Discussion-Out of 1896 search results, 95 were selected for full-text. The quality of the studies was scrutinized and a total of 28 studies were included as they fulfilled the inclusion criteria. The incidence of GDM in women with PCOS was found to be 10.55 % (2.9- 54.9%) from pooled data involving 1,280,245. The prevalence of PCOS in women diagnosed with GDM was found from pooled data of 36,351 women in retrospective studies to be 2.47% (1.5- 50.1%). Selection predominantly included cohort studies, most commonly from China. The meta-analysis reported the risk of GDM is higher in women with PCOS than in those without PCOS (HR: 1.59, 95% CI: 1.27–1.91, p &lt; 0.001). Family history of diabetes, ethnicity, pre-pregnancy BMI, insulin resistance, gestational weight gain, use of assisted reproductive techniques, and multifetal gestation were the risk factors for GDM in women with PCOS. Conclusion- The prevalence of GDM in patients with PCOS is high, but the causality is complex. The newer predictive models are promising in clarifying the causative relationships, yet use various parameters at different cut-offs. There is a need for the development of universally acceptable parameters for the early prediction of GDM in women with PCOS.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Fusarium species are agriculturally important fungi with a broad host range and can be found as endophytic, pathogenic, or opportunistic parasites in many crop plants. This study aimed to identify Fusarium species in bare-rooted, dormant plants in Turkish grapevine nurseries using molecular identification methods and assess their pathogenicity. Asymptomatic dormant plants were sampled from grapevine nurseries (43) in different regions of the country, and fungi were isolated from plant roots and internal basal tissues. The Fusarium isolates were identified by performing gene sequencing (TEF1-α, RPB2) and phylogenetic analyses. Pathogenicity tests were carried out by inoculating mycelial agar pieces of isolates onto the stem or conidial suspensions into the rhizosphere of vines (1103 Paulsen rootstock). Laboratory tests revealed that Fusarium species were highly prevalent in Turkish grapevine nurseries (41 out of 43). Gene sequencing and phylogenetic analyses unraveled that 12 Fusarium species (F. annulatum, F. brachygibbosum, F. clavum, F. curvatum, F. falciforme, F. fredkrugeri, F. glycines, F. nanum, F. nematophilum, F. nirenbergiae, F. solani, and Fusarium spp.) existed in the ready-to-sale plants. Some of these species (F. annulatum, F. curvatum and F. nirenbergiae) consistently caused wood necrosis of seedling stems, rotting of the basal zone and roots, and reduced root biomass. Although the other nine species also caused some root rot and root reduction, their virulence was not as severe as the pathogenic ones, and they were considered opportunistic parasites or endophytic species. This study is the first detailed investigation of Fusarium species in grapevine nurseries in Türkiye and emphasizes the need to consider pathogenic species in producing healthy grapevine seedlings.

Increasing population size and income growth are causing and increasing demand for food and protein of animal origin. Insects are an interesting alternative to conventional animal source proteins as they can convert by-products from the agricultural industry to biomass for commercial feed for livestock and potentially as a food source for human consumption. Microorganisms have been found to affect insects and can be accumulated via horizontal and vertical transmission. This study aimed to identify if the removal of egg- and substrate-associated microorganisms impact larval performance through the following parameters: development of biomass, final biomass, and the survival rate of house fly (Musca domestica) larvae. Four treatments were tested on substrate consisting of 10.81% alfalfa (Medicago sativa), 21.62% wheat bran (Triticum aestivum), and 67.57% water: (A) disinfected eggs and non-autoclaved substrate, (B) non-disinfected eggs and autoclaved substrate, (C) disinfected eggs and autoclaved substrate, and (D) a control without any removal of microbiota. The results showed a significant decrease in final biomass for the treatments with only disinfected eggs, only autoclaved substrate and both when comparing to the control, and a significant decrease in survival rate for B and D. Moreover, the development of biomass showed a significant difference between days within all treatments. Together this suggest that microorganisms of housefly eggs and the growth substrate plays an important role for growth, which is critical in commercial insect production. Further studies must be performed to examine these parameters in more commercially relevant substrates.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

The morphological and compositional complexities of keratinized components make feathers ingenious skin appendages adapted to diverse ecological needs. Frizzling feathers, characterized by their distinct curling phenotypes, offer a unique model to explore the intricate morphogenesis in developing a keratin-based bioarchitecture over a wide range of morphospace. Here, we investigated the heterogeneous allocation of α- and β-keratins in flight feather shafts of homozygous and heterozygous frizzle chickens by analyzing the medulla-cortex integrations using quantitative morphology characterizations across scales. Our results reveal intriguing construction of frizzling feather shaft through modified medulla development, leading to a perturbed balance of the internal biomechanics and, therefore, introducing the inherent natural frizzling compared to those from wild-type chickens. We elucidate how the localized developmental suppression of the α-keratin in the medulla interferes with the growth of the hierarchical keratin organization by changing the internal stress in the frizzling feather shaft. This research not only offers insights into the morphogenetic origin of the inherent bending of frizzling feathers but also facilitates our in-depth understanding of the developmental strategies toward the diverse integuments adapted for ecological needs.

Background: Condoms have proven to be an effective contraceptive barrier method of family planning and have played a vital role in preventing sexually transmitted diseases including HIV. However, existing evidence shows that utilization of condoms still remains low, especially among youth and adolescents. We aimed to determine the prevalence of condom use and associated factors among the students of Gulu university in Uganda. Methods: A cross-sectional study was conducted among undergraduate students of Gulu University between June and December 2023. The students were accessed from their respective faculties and chosen using a simple random sampling method. Data were collected using a pretested self-administered structured questionnaire. Condom use was defined as use of either male or female condom in the last sexual encounter in the previous six months. Results: A total of 404 participants, with a median age of 23 years (interquartile range (21.5-24) years) were enrolled in the study, 54.2%(n=219) of whom were male. Overall, 81.4%(n=329) of the participants were in senior classes (year 2,3,4, and 5) and 18.6%(n=75) were in their first year of study. The prevalence of condom use was 53.7%(n=217). Prevalence of condom use was 50.2%(n=109) among male and 49.8%(n=108) among female students. Year of study (senior class)(aPR = 1.4, 95% CI = 1.59, 3.54), having a sexual partner (aPR = 2.4, 95% CI = 1.89, 2.94), having a sexual partner within campus (aPR = 2.0, 95% CI = 1.69, 2.45), experience of condom bursting (aPR = 1.3, 95% CI = 1.08, 1.61), having sex in absence of condoms (aPR = 0.6, 95% CI = 0.44, 0.70), alcohol use (aPR = 1.2, 95% CI = 1.01, 1.45) were independently associated with condom use. Conclusion: Just over half of undergraduate students of Gulu university used condoms during sexual encounters. There should be heighten campaigns on condom use to prevent unintended pregnancies and sexually transmitted infections.

Human disturbance, such as trampling, is an integral component of global change, yet we lack a comprehensive understanding of its effects on alpine ecosystems. Many alpine systems are seeing a rapid increase in recreation, and in understudied regions, such as the Coast Mountains of British Columbia, disturbance impacts on alpine plants remain unclear. We surveyed disturbed (trail-side) and undisturbed (off-trail) transects along elevational gradients of popular hiking trails in the T’aḵ’t’aḵ’múy̓in tl’a In̓inyáx̱a7n region (Garibaldi Provincial Park), Canada, focusing on dominant shrubs (Phyllodoce empetriformis, Cassiope mertensiana, Vaccinium ovalifolium) and graminoids (Carex spp). We used a hierarchical Bayesian framework to test for disturbance by elevation effects on total plant percent cover, maximum plant height and diameter (growth proxies), and buds, flowers, and fruits (reproduction proxies). We found that trampling reduces plant cover and impacts all species, but that effects vary by species and trait, and disturbance effects only vary with elevation for one species’ trait. Growth traits are more sensitive to trampling than reproductive traits, which may lead to differential impacts on population persistence and species level fitness outcomes. Our study highlights that disturbance responses are species-specific, and this knowledge can help land managers minimize disturbance impacts on sensitive vegetation types.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Abstract Introduction: Although ankle fractures and Achilles tendon injuries are among the most common traumatic presentations when they occur individually, concomitant Achilles tendon rupture and ipsilateral ankle fractures are quite unusual. To our knowledge this is the first report of acute Achilles tendon rupture associated with missed ipsilateral closed bimalleolar ankle fracture. Case Presentation: A 34 years old male patient presented with a traumatic right Achilles tendon rupture after sustaining road traffic accident one day prior. There was an open wound over the tendon substance with absent active plantaflexion of the involved leg. After confirming complete Achilles tendon rupture with positive Thompson test, the patient was prepared for emergency debridement and possible tendon repair differing imaging studies, which missed ipsilateral closed bimalleolar ankle fracture. Conclusion: Routine anteroposterior and lateral X-rays should be used in conjunction with a complete history and physical examination to detect any concomitant fracture with open Achilles tendon rupture.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

In China, preschool teachers have a significant influence on the development of young children aged 3-6. It is imperative to understand their mental health and the factors associated with it to inform policies, optimize their mental well-being, and support their job performance. This study aimed to investigate the factors contributing to anxiety symptoms among preschool teachers. A sample of 393 Chinese preschool teachers (279 females, 114 males) aged 21-56 completed online questionnaires collecting their socio-demographic and work-related information and assessing anxiety symptoms, interpersonal difficulties, personality traits, perceived stress, resilience, and inner strength. Pearson correlation and multiple linear regression analyses identified significant predictors of anxiety symptoms. The prevalence of anxiety symptoms among the studied cohort was found to be 12.2%. Statistically significant factors positively correlated with anxiety symptoms included objective work-related stress (B=0.149, p<.001), interpersonal difficulties (B=0.921, p<.001), perceived stress (B=0.108, p=.001), and neuroticism (B=0.071, p=.002). The findings highlight the urgent need for measures to reduce work-related stress and anxiety. However, when negative mental health predictors were included, the effect of positive psychological factors became nullified. Positive mental health might have a moderating role in such a negative mental health outcome as anxiety. Therefore, further research is required to understand the impact of positive mental health factors more clearly.

In this review, we have included current information on the use of photodynamic therapy in the treatment of gliomas. We mainly focused on the discussion and regarding the use of photodynamic therapy in patients with genetically determined syndromes that are associated with an increased risk of glioma. The review also uses information on genetic syndromes that are associated with an increased risk of glioma.

The effect of land use on sandy soils of southern Botswana was carried out by comparing the composition and properties of soil organic matter. Virgin and disturbed soils were sampled from savanna ecosystems (Central District and Kweneng District). The biodegradability of organic matter was evaluated by incubation in the laboratory. Humic fractions were quantified and humic acids were analyzed by visible and infrared spectroscopy. The results indicate that continued disturbance, whether due to grazing or subsistence farming, has resulted in small significant changes in the concentration of available nutrients and organic matter in the soil. Nevertheless, substantial changes could be established in soil C/N ratio, humic acid/fulvic acid ratio and in the biodegradability of soil organic matter and the structural characteristics of humic acids. The increased aromaticity of humic acid (visible and IR spectroscopies) following disturbance, suggests increased biogeochemical activity and/or the impact of abiotic processes (such as periodic fires) selectively removing aliphatic constituents. The overall results indicate a low potential soil fertility, the sustainable preservation of which depending more on features related to quality than to the total amount of the soil organic matter, which shows considerable aromatization parallel to its degree of association with the mineral fraction.

The nutrient absorption and utilization efficiency in the roots of seedlings are beneficial for increasing crop yield. Creating marker assisted selection for wheat root traits can assist wheat breeders in choosing robust roots to maximize nutrient uptake. Exploring and identifying the effect of different nitrogen applications on RSA is of great significance for breeding nitrogen efficient wheat varieties. In this study, A total of 243 wheat varieties native to the Yellow and Huai Valley regions of China were utilized for genome-wide association studies (GWAS). Furthermore, a recombinant inbred line (RIL) population of 123 lines derived from the cross between Avocet and Chilero was utilized for linkage examination and confirmation of the hereditary loci distinguished by GWAS. Five RSA traits include the relative number of root tips (RNRT); relative total root length (RTRL); relative total root surface area (RTRS); relative total root volume (RTRV) and relative average root diameter (RARD) where evaluated under two N conditions—normal N (NN) supply and low N (LN)—to characterize the NUE of each accession. GWAS and linkage analysis were performed by integrating data from the wheat 660k single nucleotide polymorphism (SNP) chip and diversity arrays technology (DArT) to identify genetic loci associated with RSA. The results showed that based on the ratio of RSA related traits under two N supply conditions, a total of 598 SNP markers, which are significantly associated with RSA related traits, were detected at 160 genetic loci by GWAS. A total of 10 QTL loci related to RSA were dis-covered and identified by linkage mapping. In which, three significant RSA related Quantitative Trait Locus (QTL) were identified, namely qRtrl-3D, qRnrt-3D, and qRtrl-7D. The study has the potential to enhance the effectiveness of selecting root traits in wheat breeding programs, offering valuable insights into the genetic underpinnings of nitro-gen use efficiency (NUE) in wheat. This could lead to the creation of NUE wheat varieties by implementing focused breeding strategies.

Consumption of ultra-processed foods is associated with abdominal obesity, but this association has not yet been investigated in individuals on hemodialysis. This cross-sectional study, developed with 1014 individuals, aimed to analyze the prevalence of abdominal obesity and its association with the consumption of ultra-processed foods in individuals on hemodialysis. Consumption of ultra-processed foods was measured using a questionnaire, whose list of foods was based on the Surveillance System of Risk and Protective Factors for Chronic Non-Communicable Diseases through Telephone Enquiry. Waist circumference was used to determine the presence of abdominal obesity. The difference in proportions between the independent variables and the outcome was verified using Pearson's chi-square test. Hierarchical logistic regression was used to determine the association between the outcome and the independent variables. The prevalence of abdominal obesity was 77.22%. In the final model, higher consumption of ultra-processed foods, be male and an adult, have between 8 and 11 years of schooling and practice physical activity below the recommended level increased the chances of having abdominal obesity. The research provides a basis for the creation and improvement of public policies that promote improvements in these health determinants.

Abstract Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medications used to treat type 2 diabetes by mimicking the actions of incretin hormones in the body. These hormones are responsible for promoting insulin release from the pancreas in response to nutrient intake, as well as decreasing glucagon secretion, slowing gastric emptying, and promoting satiety. By imitating these actions, incretin mimetics help to regulate blood sugar levels in individuals with diabetes and glucose intolerance. One of the key benefits of incretin mimetics is its ability to lower blood sugar levels without causing hypoglycemia. This is especially important for individuals with diabetes who may experience dangerous drops in blood sugar levels when using other medications. Additionally, incretin mimetics have been shown to promote weight loss in some individuals, making them a valuable option for those struggling with obesity in addition to diabetes. Incretin mimetics are administered by injection, once or twice daily, depending on the specific medication. They are often combined with other diabetes medications, such as metformin or insulin, for optimal blood sugar control. These medications are generally well-tolerated, with common side effects including nausea, vomiting, and diarrhea, which usually diminish over time as the body adjusts to the medication. Studies have shown that incretin mimetics can help improve cardiovascular outcomes in individuals with diabetes, including reducing the risk of heart attacks and strokes. This is particularly significant given the increased risk of cardiovascular disease in individuals with diabetes. Incretin mimetics also have been shown to preserve pancreatic beta-cell function, which is responsible for producing insulin. This can help slow the progression of diabetes and reduce the need for higher insulin doses over time. Despite their many benefits, incretin mimetics are not without limitations. They can be expensive compared to other diabetes medications, which may make them less accessible for some individuals. Additionally, there have been concerns about the potential risk of pancreatitis and pancreatic cancer associated with the use of these medications. However, more research is needed to fully understand these risks. It is important for healthcare providers to carefully assess each individual's unique needs and medical history when considering the use of incretin mimetics. They may not be appropriate for everyone, particularly those with a history of pancreatitis or pancreatic cancer. Patients should also be educated about these medications' proper administration and potential side effects to ensure their safety and efficacy. Overall, incretin mimetics have emerged as an important therapeutic option for individuals with type 2 diabetes, offering a unique mechanism of action that can help improve blood sugar control, promote weight loss, and reduce cardiovascular risk. With ongoing research and development in this field, incretin mimetics continue to show promise as valuable tools in managing diabetes and its associated complications and comorbidities.

The early 2-factor (E2F) family of transcription factors, including E2F1-8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment.To predict the possibility of GBM patient survival and progression, we classified and comparedthe expression of E2Fs according to BVZ-responsive subtypes and employed a machine learning method-TreeBagger, one random forest algorithm. Multiple bioinformatics analyses have shown that the significant increased E2F8 post BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, indicating one of the mechanisms of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. Our findings suggest that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers and therapeutic targets and recommending precise BVZ treatment for GBM patients.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum from 36 MHO and 34 MUO women, who participated in a lifestyle intervention for weight loss were analyzed using an untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical and dietary intake parameters were assessed at both time points. Both groups showed differential metabolites profile at baseline and sixth month. Seven metabolites including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline and tyrosine significantly changed between group post-intervention, in which all showed a decreasing pattern in MHO. Significant reduction in body weight and BMI in the MUO correlated with changes in carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. Changes in carnitine and tyrosine levels in MUO correlated with weight loss, suggesting potential targets for therapeutic intervention.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Snakebite envenomation remains a major cause of morbidity and mortality in rural populations. This study aimed to identify factors associated with complications from snakebite envenomation reported in health facilities in the Cascades region of Burkina Faso. This cross-sectional study used routine data of patients admitted for snakebite envenomation in five health facilities between January 1, 2016, and December 31, 2021. Data were collected on sociodemographic, clinical, and therapeutic characteristics of patients showing signs of envenomation. Bivariate and multivariate analyses were conducted to determine factors associated with complications. Among the 846 patients with envenomation, 355 (42%) experienced complications. Local complications at the bite site included wounds (21.5%) and skin necrosis (12.5%). Systemic complications included hemorrhage (30.5%), shock (16.3%), and coma (4.3%), with a mortality rate of 3.2%. Factors significantly associated with complications were rural residence (AOR: 4.80; 95% CI: 2.21-11.4), incision at the bite site (AOR: 4.31; 95% CI: 2.51-7.52), tourniquet application (AOR: 5.52; 95% CI: 1.42-30.8), bleeding (AOR: 14.2; 95% CI: 8.80-23.4), abnormal vital signs (AOR: 14.3; 95% CI: 9.22-22.7), and non-administration of antivenom serum (AOR: 2.92; 95% CI: 1.8-4.8). These findings highlight the importance of antivenom availability and public awareness to reduce complications from snakebite envenomation.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Predictive studies are essential to establish fundamental data for monitoring and controlling Xylella fastidiosa infections in our country. Limited knowledge exists about how Xylella fastidiosa interacts with the plant host's immune system, leaving numerous unanswered questions regarding Xylella fastidiosa biology and its interactions with national plant hosts. Key inquiries include understanding of how the plant immune system interfaces with Xylella fastidiosa in the xylem and identifying the specific or shared mechanisms underlying the susceptibility of different hosts. Factors such as the presence of insect vectors, abundance of host plants, and climate suitability play pivotal roles in Xylella fastidiosa dispersal. We recommend that countries identified with relatively high risk, like Portugal, undertake thorough individual risk analyses. The implementation of preventive measures and, if necessary, the enhancement of surveillance systems for early detection of Xylella fastidiosa in plants and insect vectors are crucial steps. Additionally, raising awareness is of equal importance to mitigate socioeconomic and ecological impacts on their ecosystems.

An analysis of 1300+ existing ACE mutations revealed that 400+ are damaging and led us to hy-pothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer’s disease (AD) [Danilov, 2024]. Here we quantified blood ACE levels in EDTA-plasma from 41patients with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates. We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C and G325R are truly damaging and, likely, transport-deficient, with ACE levels in plasma only ~50% of controls. Another AD-associated ACE mutation, R1250Q, in the cytoplasmic tail, did not cause a decrease in ACE and, likely, did not affect surface ACE expression. We have also developed a method to identify patients with anti-catalytic mutations in the N domain. These mutations may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD. Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has potential to identify individuals at an increased risk of late-onset AD. These individuals may benefit from future preventive or therapeutic interventions involving a combination of chemical and pharmacological chaperones, as well as proteasome inhibitors, aiming to enhance ACE protein traffic. This approach has been previously demonstrated in a cell model of the transport-deficient ACE mutation, Q1069R [Danilov, 2010].

A joint analysis of solar wind, geomagnetic field, and earthquake catalog data showed that before the catastrophic M7.8 and M7.5 Kahramanmaras earthquake sequence on February 6, 2023, the closed strong magnetic storm occurred on November 7, 2022, SYM/H=-117 nT. Storm started at 08:04 UT. At this time, the high latitudinal part of Turkey's longitudinal region of future epicenters was located under the polar cusp, where the solar wind plasma would directly access the Earth's environment. The time delay between storm onset and earthquake occurrence was ~91 days. We analyzed all seven strong (M7+) earthquakes from 1967 to 2020 to verify the initial findings. A similar pattern has been revealed for all events. The time delay between magnetic storm onset and earthquake occurrence varies from some days to some months. To continue these investigations, a retrospective analysis of seismic and other geophysical parameters just after preceded geomagnetic storms in the epicenter areas is desirable.

Many studies have demonstrated hydrogen's therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. Sub-lethal WBI resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of lethal WBI, while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p