Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate endothelial cell proliferation and migration, while VEGF-B, VEGF-C, and VEGF-D interact with VEGFR-1 and VEGFR-3 to regulate tumor angiogenesis, lymphangiogenesis, and metastasis. The VEGF/VEGFR signaling pathway activates various downstream effectors, including phospholipase Cγ1, MAPK, and PI3K/Akt, which are essential for maintaining vascular homeostasis and promoting angiogenesis. In NSCLC, elevated serum VEGF levels have been observed, and the VEGF/VEGFR axis is frequently impaired, leading to irregular blood vessel formation and metastatic spread. Despite the development of anti-VEGF therapies, their impact on lung cancer outcomes has been limited. Further research is needed to optimize the effectiveness of these treatments and elucidate the potential of serum VEGF as a predictive biomarker in NSCLC.

In this paper, we succeed to discover the new exact wave solutions to the truncated M-fractional complex three coupled Maccari’s system by utilizing the Sardar sub-equation scheme. The obtained solutions are in the form of trigonometric and hyperbolic forms. These solutions have many applications in nonlinear optics, fiber optics, deep water-waves, plasma physics, mathematical physics, fluid mechanics, hydrodynamics and engineering where the propagation of nonlinear waves is important. Achieved solutions are verified with the use of Mathematica software. Some of the achieved solutions are also described graphically by 2-dimensional, 3-dimensional and contour plots with the help of Maple software. The gained solutions are helpful for the further development of concerned model. Finally, this technique is simple, fruitful and reliable to handle the nonlinear FPDEs.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was screened using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir, and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.

This article delves into the intersection of generative AI and digital twins within drug discovery, exploring their synergistic potential to revolutionize pharmaceutical research and development. Through various instances and examples, we illuminate how generative AI algorithms, capable of simulating vast chemical spaces and predicting molecular properties, are increasingly integrated with digital twins of biological systems to expedite drug discovery. By harnessing the power of computational models and machine learning, researchers can design novel compounds tailored to specific targets, optimize drug candidates, and simulate their behavior within virtual biological environments. This paradigm shift offers unprecedented opportunities for accelerating drug development, reducing costs, and, ultimately, improving patient outcomes. As we navigate this rapidly evolving landscape, collaboration between interdisciplinary teams and continued innovation will be paramount in realizing the promise of generative AI and digital twins in advancing drug discovery.

There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

We show that one of the two important uncertainty principles derived by Maccone and Pati \textit{[Phys. Rev. Lett., 2014]} can be derived for arbitrary maps defined on subsets of $\mathcal{L}^p$ spaces for $1< p<\infty$. Our main tool is the Clarkson inequalities. We also derive a nonlinear uncertainty principle for weak parallelogram spaces and Type-p Banach spaces.

Let $\mathcal{X}$ be a Banach space. Let $\{\tau_j\}_{j=1}^n, \{\omega_k\}_{k=1}^m\subseteq \mathcal{X}$ and $\{f_j\}_{j=1}^n$, $\{g_k\}_{k=1}^m\subseteq \mathcal{X}^*$ satisfy $ |f_j(\tau_j)|\geq 1$ for all $ 1\leq j \leq n$, $|g_k(\omega_k)|\geq 1 $ for all $1\leq k \leq m$. If $x \in \mathcal{X}\setminus \{0\}$ is such that $x=\theta_\tau\theta_f x=\theta_\omega\theta_g x$, then we show that \begin{align}\label{FKDB} \|\theta_fx\|_0\|\theta_gx\|_0\geq \frac{\bigg[1-(\|\theta_fx\|_0-1)\max\limits_{1\leq j,r \leq n,j\neq r}|f_j(\tau_r)|\bigg]^+\bigg[1-(\|\theta_g x\|_0-1)\max\limits_{1\leq k,s \leq m,k\neq s}|g_k(\omega_s)|\bigg]^+}{\left(\displaystyle\max_{1\leq j \leq n, 1\leq k \leq m}|f_j(\omega_k)|\right)\left(\displaystyle\max_{1\leq j \leq n, 1\leq k \leq m}|g_k(\tau_j)|\right)}. \end{align} We call Inequality (\ref{FKDB}) as \textbf{Functional Kuppinger-Durisi-B\"{o}lcskei Uncertainty Principle}. Inequality (\ref{FKDB}) improves the uncertainty principle obtained by Kuppinger, Durisi and B\"{o}lcskei \textit{[IEEE Trans. Inform. Theory (2012)]} (which improved the Donoho-Stark-Elad-Bruckstein uncertainty principle \textit{[SIAM J. Appl. Math. (1989), IEEE Trans. Inform. Theory (2002)]}). We also derive functional form of the uncertainity principle obtained by Studer, Kuppinger, Pope and B\"{o}lcskei \textit{[EEE Trans. Inform. Theory, (2012)]}.

In this paper we provide some important and significant observations on invo-regular rings appeared in Ann. Univ. Mariae Curie-Sklodowska Sect. A Mathematica (2018). In addition we exhibit that strongly invo-regular rings, invo-regular rings and quasi invo-regular rings all coincide with the well known and well characterized tripotent rings and all these rings further coincide with the well known unit regular rings.

In this note we consolidate and give a brief description of several recently published results in ring theory having disproof. These results have been published during 2016 to 2021 in the so called non-predatory reputed mathematical journals indexed in the well known database like Scopus. We have considered results on rings in which each element is a sum of two idempotents appeared in Canad. Math. Bull. (2016), weakly tripotent rings appeared in Bull. Korean Math. Soc. (2018) and Rendiconti Sem. Mat. Univ. Pol. Torino (2021), involution t-clean rings appeared in Eur. J. Pure Appl. Math (2022) and strongly 2-nil clean rings with units of order two appeared in Eur. J. Pure Appl. Math (2023).

Let $(\Omega, \mu)$, $(\Delta, \nu)$ be measure spaces. Let $(\{f_\alpha\}_{\alpha\in \Omega}, \{\tau_\alpha\}_{\alpha\in \Omega})$ and $(\{g_\beta\}_{\beta\in \Delta}, \{\omega_\beta\}_{\beta\in \Delta})$ be unbounded continuous 1-Schauder frames for a Banach space $\mathcal{X}$. Then for every $x \in ( \mathcal{D}(\theta_f) \cap\mathcal{D}(\theta_g))\setminus\{0\}$, we show that \begin{align}\label{UB} \mu(\operatorname{supp}(\theta_f x))\nu(\operatorname{supp}(\theta_g x)) \geq \frac{1}{\left(\displaystyle\sup_{\alpha \in \Omega, \beta \in \Delta}|f_\alpha(\omega_\beta)|\right)\left(\displaystyle\sup_{\alpha \in \Omega , \beta \in \Delta}|g_\beta(\tau_\alpha)|\right)}. \end{align} where \begin{align*} &\theta_f:\mathcal{D}(\theta_f) \ni x \mapsto \theta_fx \in \mathcal{L}^1(\Omega, \mu); \quad \theta_fx: \Omega \ni \alpha \mapsto (\theta_fx) (\alpha):= f_\alpha (x) \in \mathbb{K},\\ &\theta_g: \mathcal{D}(\theta_g) \ni x \mapsto \theta_gx \in \mathcal{L}^1(\Delta, \nu); \quad \theta_gx: \Delta \ni \beta \mapsto (\theta_gx) (\beta):= g_\beta (x) \in \mathbb{K}. \end{align*} We call Inequality (\ref{UB}) as \textbf{Unbounded Donoho-Stark-Elad-Bruckstein-Ricaud-Torr\'{e}sani Uncertainty Principle}. Along with recent \textbf{Functional Continuous Uncertainty Principle} (derived in [arXiv:2308.00312v1 [math.FA], 1 August 2023]), Inequality (\ref{UB}) also improves Ricaud-Torr\'{e}sani uncertainty principle \textit{[IEEE Trans. Inform. Theory, 2013]}. In particular, it improves Elad-Bruckstein uncertainty principle \textit{[IEEE Trans. Inform. Theory, 2002]} and Donoho-Stark uncertainty principle \textit{[SIAM J. Appl. Math., 1989]}.

The notion of quantum-mechanics-free subsystem (QMFS) was introduced by Tsang and Caves in 2012. They showed that it is possible to design the dynamics of coupled quantum systems in such a way that one can construct a subsystem in which a given classical dynamics is realized, thus avoiding the measurement back-action of quantum mechanics. Although they mention that the Heisenberg picture equations of motion for QMFS was first proposed by Koopman in 1931 as a formulation of classical Hamiltonian dynamics in Hilbert space, in fact the connection between QMFS and Koopmann-von Neumann mechanics is deeper. Namely, quantum-mechanics-free subsystem is nothing but the realization of Sudarshan's perspective on the Koopman-von Neumann mechanics.

Let $(\Omega, \mu)$, $(\Delta, \nu)$ be measure spaces. Let $(\{f_\alpha\}_{\alpha\in \Omega}, \{\tau_\alpha\}_{\alpha\in \Omega})$ and $(\{g_\beta\}_{\beta\in \Delta}, \{\omega_\beta\}_{\beta\in \Delta})$ be continuous 1-Schauder frames for a Banach space $\mathcal{X}$. Then for every $x \in \mathcal{X}\setminus\{0\}$, we show that \begin{align*} \mu(\operatorname{supp}(\theta_f x)) \geq \frac{1}{\displaystyle\sup_{\alpha \in \Omega, \beta \in \Delta}|f_\alpha(\omega_\beta)|}, \quad \nu(\operatorname{supp}(\theta_g x))\geq \frac{1}{\displaystyle\sup_{\alpha \in \Omega , \beta \in \Delta}|g_\beta(\tau_\alpha)|}. \end{align*} where \begin{align*} &\theta_f: \mathcal{X} \ni x \mapsto \theta_fx \in \mathcal{L}^1(\Omega, \mu); \quad \theta_fx: \Omega \ni \alpha \mapsto (\theta_fx) (\alpha):= f_\alpha (x) \in \mathbb{K},\\ &\theta_g: \mathcal{X} \ni x \mapsto \theta_gx \in \mathcal{L}^1(\Delta, \nu); \quad \theta_gx: \Delta \ni \beta \mapsto (\theta_gx) (\beta):= g_\beta (x) \in \mathbb{K}. \end{align*} This solves a problem asked by K. M. Krishna in the paper 'Functional Continuous Uncertainty Principle' \textit{[arXiv:2308.00312v1]}.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no GE product has been approved, as opposed to 22 GT products that cost up to millions of dollars per dose. The FDA has recently added a guideline specific to gene editing that should be understood to enable faster development of GE products; at the same time, the FDA also needs to bring more clarification and make several amendments to this guideline to make it more rational.

Let $(\Omega, \mu)$, $(\Delta, \nu)$ be measure spaces. Let $(\{f_\alpha\}_{\alpha\in \Omega}, \{\tau_\alpha\}_{\alpha\in \Omega})$ and $(\{g_\beta\}_{\beta\in \Delta}, \{\omega_\beta\}_{\beta\in \Delta})$ be continuous p-Schauder frames for a Banach space $\mathcal{X}$. Then for every $x \in \mathcal{X}\setminus\{0\}$, we show that \begin{align}\label{CUE} \mu(\operatorname{supp}(\theta_f x))^\frac{1}{p} \nu(\operatorname{supp}(\theta_g x))^\frac{1}{q} \geq \frac{1}{\displaystyle\sup_{\alpha \in \Omega, \beta \in \Delta}|f_\alpha(\omega_\beta)|}, \quad \nu(\operatorname{supp}(\theta_g x))^\frac{1}{p} \mu(\operatorname{supp}(\theta_f x))^\frac{1}{q}\geq \frac{1}{\displaystyle\sup_{\alpha \in \Omega , \beta \in \Delta}|g_\beta(\tau_\alpha)|}. \end{align} where \begin{align*} &\theta_f: \mathcal{X} \ni x \mapsto \theta_fx \in \mathcal{L}^p(\Omega, \mu); \quad \theta_fx: \Omega \ni \alpha \mapsto (\theta_fx) (\alpha):= f_\alpha (x) \in \mathbb{K},\\ &\theta_g: \mathcal{X} \ni x \mapsto \theta_gx \in \mathcal{L}^p(\Delta, \nu); \quad \theta_gx: \Delta \ni \beta \mapsto (\theta_gx) (\beta):= g_\beta (x) \in \mathbb{K} \end{align*} and $q$ is the conjugate index of $p$. We call Inequality (\ref{CUE}) as \textbf{Functional Continuous Uncertainty Principle}. It improves the Functional Donoho-Stark-Elad-Bruckstein-Ricaud-Torr\'{e}sani Uncertainty Principle obtained by M. Krishna in \textit{[arXiv:2304.03324v1, 2023]}. It also answers a question asked by Prof. Philip B. Stark to the author.

A unified electro-gravity (UEG) theory, which has been successfully used for modeling an elementary particle, is applied in this paper to model gravitation in spiral galaxies. The new UEG model would explain the "flat rotation curves'' commonly observed in the spiral galaxies, without need for any hypothetical dark matter. The UEG theory is implemented in a somewhat different manner for a spiral galaxy, as compared to the simple application of the UEG theory to an elementary particle. This is because the spiral galaxy, unlike the elementary particle, is not spherically symmetric. The UEG constant $\gamma$, required in the new model to support the galaxies' flat rotation speeds, is estimated using measured data from a galaxy survey, as well as for a selected galaxy for illustration. The estimates are compared with the $\gamma$ derived from the UEG model of an elementary particle. The UEG model for the galaxy is shown to explain the empirical Tully-Fisher Relationship (TFR), is consistent with the Modified Newtonian Dynamics (MOND), and is also independently supported by measured trends of galaxy thickness with surface brightness and rotation speed. The UEG theory may similarly be extended to emulate the hypothetical dark matter in galaxy clusters as well as in cosmology.

Let $\{f_j\}_{j=1}^n$ and $\{g_k\}_{k=1}^m$ be Parseval p-frames for a finite dimensional Banach space $\mathcal{X}$. Then we show that \begin{align}\label{UE} \log (nm)\geq S_f (x)+S_g (x)\geq -p \log \left(\displaystyle\sup_{y \in \mathcal{X}_f\cap \mathcal{X}_g, \|y\|=1}\left(\max_{1\leq j\leq n, 1\leq k\leq m}|f_j(y)g_k(y)|\right)\right), \quad \forall x \in \mathcal{X}_f\cap \mathcal{X}_g, \end{align} where \begin{align*} &\mathcal{X}_f\coloneqq \{z\in \mathcal{X}: f_j(z)\neq 0, 1\leq j \leq n\}, \quad \mathcal{X}_g\coloneqq \{w\in \mathcal{X}: g_k(w)\neq 0, 1\leq k \leq m\},\\ &S_f (x)\coloneqq -\sum_{j=1}^{n}\left|f_j\left(\frac{x}{\|x\|}\right)\right|^p\log \left|f_j\left(\frac{x}{\|x\|}\right)\right|^p, \quad S_g (x)\coloneqq -\sum_{k=1}^{m}\left|g_k\left(\frac{x}{\|x\|}\right)\right|^p\log \left|g_k\left(\frac{x}{\|x\|}\right)\right|^p, \quad \forall x \in \mathcal{X}_g. \end{align*} We call Inequality (1) as \textbf{Functional Deutsch Uncertainty Principle}. For Hilbert spaces, we show that Inequality (1) reduces to the uncertainty principle obtained by Deutsch \textit{[Phys. Rev. Lett., 1983]}. We also derive a dual of Inequality (1).

Let $(\{f_j\}_{j=1}^n, \{\tau_j\}_{j=1}^n)$ and $(\{g_k\}_{k=1}^n, \{\omega_k\}_{k=1}^n)$ be two p-orthonormal bases for a finite dimensional Banach space $\mathcal{X}$. If $ x \in \mathcal{X}\setminus\{0\}$ is such that $\theta_fx$ is $\varepsilon$-supported on $M\subseteq \{1,\dots, n\}$ w.r.t. p-norm and $\theta_gx$ is $\delta$-supported on $N\subseteq \{1,\dots, n\}$ w.r.t. p-norm, then we show that \begin{align}\label{ME} &o(M)^\frac{1}{p}o(N)^\frac{1}{q}\geq \frac{1}{\displaystyle \max_{1\leq j,k\leq n}|f_j(\omega_k) |}\max \{1-\varepsilon-\delta, 0\},\\ &o(M)^\frac{1}{q}o(N)^\frac{1}{p}\geq \frac{1}{\displaystyle \max_{1\leq j,k\leq n}|g_k(\tau_j) |}\max \{1-\varepsilon-\delta, 0\},\label{ME2} \end{align} where \begin{align*} \theta_f: \mathcal{X} \ni x \mapsto (f_j(x) )_{j=1}^n \in \ell^p([n]); \quad \theta_g: \mathcal{X} \ni x \mapsto (g_k(x) )_{k=1}^n \in \ell^p([n]) \end{align*} and $q$ is the conjugate index of $p$. We call Inequalities (\ref{ME}) and (\ref{ME2}) as \textbf{Functional Donoho-Stark Approximate Support Uncertainty Principle}. Inequalities (\ref{ME}) and (\ref{ME2}) improve the finite approximate support uncertainty principle obtained by Donoho and Stark \textit{[SIAM J. Appl. Math., 1989]}.

Let $(\{f_j\}_{j=1}^n, \{\tau_j\}_{j=1}^n)$ and $(\{g_k\}_{k=1}^n, \{\omega_k\}_{k=1}^n)$ be two p-orthonormal bases for a finite dimensional Banach space $\mathcal{X}$. Let $M,N\subseteq \{1, \dots, n\}$ be such that \begin{align*} o(M)^\frac{1}{q}o(N)^\frac{1}{p}< \frac{1}{\displaystyle \max_{1\leq j,k\leq n}|g_k(\tau_j) |}, \end{align*} where $q$ is the conjugate index of $p$. Then for all $x \in \mathcal{X}$, we show that \begin{align}\label{FGJU} (1) \quad \quad \quad \quad \|x\|\leq \left(1+\frac{1}{1-o(M)^\frac{1}{q}o(N)^\frac{1}{p}\displaystyle\max_{1\leq j,k\leq n}|g_k(\tau_j)|}\right)\left[\left(\sum_{j\in M^c}|f_j(x)|^p\right)^\frac{1}{p}+\left(\sum_{k\in N^c}|g_k(x) |^p\right)^\frac{1}{p}\right]. \end{align} We call Inequality (1) as \textbf{Functional Ghobber-Jaming Uncertainty Principle}. Inequality (1) improves the uncertainty principle obtained by Ghobber and Jaming \textit{[Linear Algebra Appl., 2011]}.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time type-DED is common, and stabilization of the tear film is the first goal of treatment. Treatment of DED begins with eye drops. Until now, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side effects (cataracts, increased intraocular pressure). This review evaluates the new generation of DED therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on these considerations, it is proposed that the optimal treatment for DED in Asia is the initial application of mucin secretion enhancing eye drops (long-acting diquafosol) and oral supplements, and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

In the literature, frames generated by unitary representations of groups (known as group-frames) are studied only for Hilbert spaces. We make first study of frames for Banach spaces generated by isometric invertible representations of discrete groups on Banach spaces. These frames are characterized using left regular, right regular, Gram-matrices and group-matrices on classical sequence spaces. A sufficiently large collection of functional-vector pairs using the double commutant of the representation is identified which generate group-frames for Banach spaces. Subsequently, we study Schauder frames generated by time-frequency shift operators on finite dimensional Banach spaces. We derive Moyal formula, fundamental identity of Gabor analysis, Wexler-Raz criterion and Ron-Shen duality in functional form.

Let $(\{f_j\}_{j=1}^n, \{\tau_j\}_{j=1}^n)$ and $(\{g_k\}_{k=1}^m, \{\omega_k\}_{k=1}^m)$ be p-Schauder frames for a finite dimensional Banach space $\mathcal{X}$. Then for every $x \in \mathcal{X}\setminus\{0\}$, we show that \begin{align}\label{UE} \|\theta_f x\|_0^\frac{1}{p}\|\theta_g x\|_0^\frac{1}{q} \geq \frac{1}{\displaystyle\max_{1\leq j\leq n, 1\leq k\leq m}|f_j(\omega_k)|}\quad \text{and} \quad \|\theta_g x\|_0^\frac{1}{p}\|\theta_f x\|_0^\frac{1}{q}\geq \frac{1}{\displaystyle\max_{1\leq j\leq n, 1\leq k\leq m}|g_k(\tau_j)|}. \end{align} where \begin{align*} \theta_f: \mathcal{X} \ni x \mapsto (f_j(x) )_{j=1}^n \in \ell^p([n]); \quad \theta_g: \mathcal{X} \ni x \mapsto (g_k(x) )_{k=1}^m \in \ell^p([m]) \end{align*} and $q$ is the conjugate index of $p$. We call Inequality (\ref{UE}) as \textbf{Functional Donoho-Stark-Elad-Bruckstein-Ricaud-Torr\'{e}sani Uncertainty Principle}. Inequality (\ref{UE}) improves Ricaud-Torr\'{e}sani uncertainty principle \textit{[IEEE Trans. Inform. Theory, 2013]}. In particular, it improves Elad-Bruckstein uncertainty principle \textit{[IEEE Trans. Inform. Theory, 2002]} and Donoho-Stark uncertainty principle \textit{[SIAM J. Appl. Math., 1989]}.

Cutaneous T cell lymphomas (CTCLs) are caused by malignant clonal proliferation of skin-tropic T cells. Most patients have an indolent disease course managed with skin-directed therapies, while some entities, or in advanced stages of disease, have aggressive progression and poor survival. To efficiently treat CTCL consistent entity markers are needed to prevent the delay in diagnosis and to provide disease specific treatment to patients. Recently, the introduction of high throughput parallel sequencing methods resulted in identification of numerous genetic and ep-igenetic alterations affecting the transcriptome of CTCL cells. In this review, most relevant genes, including TOX, CADM1, PLS3, DNM3, CXCL13, PD-1, BCL11B and TMEM244 are reported that are specifically expressed in CTCL. Upon verification their specificity and sensitivity in larger studies, their altered expression will be able to be recognized as novel biomarkers, that can im-prove the early diagnosis of CTCL.

We solve the And\^{o} dilation problem for linear maps on vector space asked by Krishna and Johnson in \textit{[Oper. Matrices, 2022]}. More precisely, we show that any commuting linear maps on vector space can be dilated to commuting injective linear maps.

Scientific, technical and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure and other product- and process-related attributes are comparable within the limits of testing then a biosimilar candidate would have safe safety and efficacy as its reference products. The current model of animal and human testing becomes redundant since all of these studies have much lower sensitivity and reproducibility in confirming biosimilarity. The recent AI-based protein structure prediction model has confirmed that the 3D structure can be predicted from the amino acid sequence, reducing the need for structural analysis; however, the new test methods based on MS are millions of times more sensitive and accurate. While the regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, removing clinical pharmacology profiling brings a dramatic paradigm shift, reducing development costs without compromising safety and efficacy. Also shared is a list of 160+ products ready to enter as biosimilars. Major actions from regulatory agencies and developers are required to make this paradigm shift.

Saturated lights appear brighter than white lights of the same luminance. This phenomenon is known as the Helmholtz-Kohlrausch (H-K) effect and can be estimated by modeling achromatic luminance and saturation to total brightness. These models have been shown to differ between women and men and are more variable in women. The variation in brightness models among women may be due to hormonal changes across the menstrual cycle. To test this, total brightness and achromatic luminance were measured across blue, green, yellow-green, yellow, and red hues. These data were measured along with salivary hormone levels for nine cycling women at points representing the menstrual, peri-ovulation, and luteal phases. These data were also collected for seven oral contraceptive (OC) users. There were no main effects of OC use nor menstrual cycle phase on B/L ratios, but ratios were higher for the red stimulus in cycling women than OC users. Red B/L ratios were also higher for cycling women than OC users during the luteal phase. Estrogen, progesterone, and their interaction predicted 18% of the variation in brightness for cycling women. These models could not be fit for OC users, and estrogen only accounted for 5% of brightness variance with progesterone terms omitted. These findings and potential mechanisms are discussed in the context of previous results.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

We suggest that despite McLuhan’s claim not to have a theory of communication that in fact the body of his work does indeed constitute a theory of media and their effects which I have called his General Theory of Media (GToM) that also includes his Laws of Media (LoM). Both McLuhan’s GToM and his LoM are described. A comparison is made of three notions of law: i. McLuhan’s notion of law as used in his Laws of Media; ii. the notions of the Law in the legal sense and iii. the notion of law as formulated in scientific laws. McLuhan’s understanding of media is used to analyze some of the negative effects of social media suggesting that laws need to be formulated to prevent the misuse of social media that are antithetical to democracy and the invasion of the privacy of the individual users of these apps. McLuhan’s Laws of Media are then used to provide insights into the nature of scientific laws, the Law in the legal sense and his own Laws of Media.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

In this note we introduce the notion of polynions and discuss their mathematical relevance. We note that the well-known mathematical structures like quaternions, octonions and sedenions etc. are special cases of polynions.

Novel Coronavirus infection mediated pandemic started in China in December 2019 and is still killing 1000s of people throughout the world. The second most populous country, India too is fighting against this infectious disease. The country is taking effective measures to curb the pandemic by exerting extensive campaigning on sanitation and strict social distancing measures to quell the explosion of the infection rate. The future of the COVID-19 infections in India still remain unpredictable, so precautionary methods need to be continued until the growth rate of new cases drop below one.

A comprehensive heuristic analysis of the Pollard's Rho Method (PRM) is given. The analysis is based on ultimate periods and tails distribution of sequences. If $n$ is the composite number to be factored, then an improved version of PRM is developed which has an expected run time of $O(\sqrt[8]{n}\ln n)$ on a multi-core architecture which utilized a clever way of evaluating polynomials.

Sustainable development (SD) is essential to reduce and mitigate climate change impacts, environmental deterioration and to increase social sustainability. SD is therefore highly relevant for the engineering profession and is today found integrated with the higher education of specific engineering programs. This paper investigated the knowledge of SD for students entering the master’s program in Sustainable Building Information Management (BIM) by comparing levels of knowledge at the start and end of the first course Sustainability, Analyses and Simulations. The level of knowledge of SD was analyzed by classifying students’ conceptions of sustainability using SOLO taxonomy and the spectrum of liminality and the threshold concept. Students written responses to the question “What do you know about sustainability?” and written group project reports were used for analyzing levels of knowledge of SD. Levels of knowledge of SD was classified as pre (pre-liminal or pre-structural); uni-structural, multi-structural, relational and post-stages (extended abstract or post-liminal). In total, 68% of the students entering the master’s program in 2017 and 88% in 2018 showed a pre-structural, uni-structural and multi-structural SD knowledge. In general, few students entering the program showed relational and post-stages of SD knowledge, 32% and 12% of the students in 2017 and 2018, respectively. The students at the post-stage were able to express themselves more individually and creatively compared to previous levels in that they could connect the dimensions of SD to the context of SD of buildings, but also argue why SD of buildings was important and they could also suggest actions or tools for improved SD that engineers should use. Only one group of five (in 2017) showed a post-stage level of knowledge in the group project report. It is likely that the student’s general approach to the work with the reports was to mainly cope with the course requirements which is a sign of surface approach to learning. It, therefore, seems reasonable that future developments of the course should ensure that the students use the scientific literature in their group project reports to make it easier for them to understand the relationship between software use and the connection to green buildings certificate systems and SD of buildings. By making it mandatory to include scientific literature in the reports the students will be encouraged to read and think critically, and deeper, and to put the practical implementation of the software analysis results into a scientific context of SD and BIM.

Infiltration based stormwater best management practices bring considerable economic, social and ecological benefits. Controlling stormwater quantity and quality are primarily important to prevent urban flooding and minimizing loads of pollutants to the receiving waters. However, there have been growing concerns about how the traditional design approach contributes to the failure of infiltration based BMP’s that have caused flooding, ponding, prolonged movement of surface water, and frequent clogging, etc. Many of these problems were due to the fact that the current design approaches of stormwater BMP’s only focus on surface hydrology and give little or no attention to the underline subsoil permeability rate and other constraints during the design and sizing process. As a result, we are exhibiting many newly constructed infiltration based BMP’s are failing to function well. This paper presents and demonstrates a new paradigm shift in designing infiltration-based stormwater BMP’s by combining subsurface hydrology and undelaying native soil constraints to establish acceptable criteria for sizing infiltration based BMPs.

Beginning in 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on a myriad of host cell proteins and processes. The major breakthrough finding from these recent endeavors was the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

The climate crisis is developing to a life-changing event on a global level. Health promotion with the aim to increase the health status of individuals, independent from the present health status has been developed on scientific basis at least for the last eight decades and follows. There are some basic principles, which are prerequisites for both, health promotion and climate protection. Those principles include (1) sustainability, (2) orientation on determinants, and (3) requirement of in-dividual as well as community approaches. People are generally aiming to protect their lifestyle habits (e.g. traveling, consumer habits) and personal properties (e.g. car, house) by easy solution with as little effort as possible, and this can affect both, health and climate. To reduce the emission of greenhouse gases and to protect our environment, changes towards a sustainable lifestyle have to be embed into everybody’s mind. Examples for domains, that need to be addressed in health promotion as well as in climate protection include education/ knowledge/ (health) literacy, physical activity, nutrition and dietary habits, mental health, and social capital. If health promo-tion fails to tackle those domains, this will continue to drive climate crisis. And climate change, in turn, will affect health. On the other hand, developing and promoting health resources in the domains mentioned could again help to mitigate the health-damaging effects of climate change.

Novel 4-(diphenylphosphoryl)-1-phenylbutane-1,3-dione was synthesized by the reaction of diketone enamine with diphenylchloro phosphine followed by oxidation and hydrolysis of the enamine phosphine formed. Tautomeric transformation of the diketone moiety of phosphine oxide was investigated by ¹H NMR. Three out of five possible tautomers were observed in the 4-(diphenylphosphoryl)-1-phenylbutane-1,3-dione solution. The major tautomer was the form with a diketone fragment.

In the fast-paced internet world that we live in today, internet technologies and tools that enable us to connect online are rapidly changing and improving. To adapt to the changing environment, many game developers are changing their business models to adjust to this online environment by developing games that are centred around online gaming. As such, the internet demands of consumers such as gamers are increasing because of the need for quality internet connection for optimal gameplay. There are too many factors that can affect online gameplay. Moreover, not all gamers are equipped with the network knowledge and skills to diagnose and troubleshoot any internet issues that may arise during their gameplay session. The main contribution of this research was to gather insights from Malaysian broadband internet consumers, mainly from gamers and general users regarding their opinions of their ISP service experience in gaming, general use and service quality. A 1-click solution is presented as a smart autonomous network monitoring tool that can autonomously monitor, diagnose, and troubleshoot network problems with minimal input from the user. This research was conducted using a mixed-mode research methodology where the participants were asked to fill up a questionnaire regarding the user experience of their Internet Service Provider (ISP), and their perception of the 1 click-automated networking tool for their personal use. It is shown that there is a market demand for a 1 click-automated networking tool as gamers and general users both agree that such a tool would be beneficial to them by improving the internet quality of a network.

The cellular model we teach and have theorized assumes that the cell is the basic unit of multicellular living beings. This fundamental element has been the subject of many theories concerning its properties and the exchanges that exist with its environment. In this article, we demonstrate that certain functional aspects, in particular the electrical aspects related to diffusion, have not been correctly assumed or that certain initial conditions have been purely ignored and are in contradiction with physics, chemistry and thermodynamics.

This study investigated the effects of a ten-visit individual coordinative locomotor training (CLT) program, including both a hands-on and a hands-off approach, on static and dynamic trunk stability in healthy adults with sedentary occupations. During the ten-visit program, the performance of eight subjects was monitored using a modified one-leg stance test in the sprinter and skater position, the Y-balance test, and the scapula and ischial tuberosity control test in the four-legged position. The data were analyzed using parametric and nonparametric statistics at an overall level of significance α=0.05. In the one-leg stance test, all subjects achieved a maximum value of 60 s on all ten visits. The improvement over time in the Y-balance test results was statistically significant for all directions (p<0.001). In addition, a statistically significant improvement in the Y-balance test composite score was observed between the first and the last visit (p=0.015-0.041). Subject-specific patterns were observed in the results of the Y-balance test. Significant improvements were observed over time in the four-legged position test score (p=0.008-0.010). Overall, the CLT program led to a significant improvement in trunk stability and leg extension in the anterior and posterolateral directions, as well as a reduction in instability as determined by the composite score of the Y-balance test.

Despite the best efforts in air-purification, airborne infectious diseases do and will continue to spread due to continuous emission of bioaerosols by the host/infected person. To tackle the rapid spread of airborne infectious diseases, a shift in focus from air-purification to bioaerosol disinfection/ decontamination is urgently needed. In this work, we studied a cold plasma ionizer (CPI) and electrostatic precipitator (ESP)-coupled CPI (CPI-ESP) for disinfection and cleaning of bioaerosols. Using porcine respiratory coronavirus (PRCV) and E. coli in a testing chamber, we demonstrated that CPI coupled with ESP is an effective technology for inactivating aerosolized microorganisms and microorganisms spread on surfaces. In addition, we have demonstrated the efficiency of a CPI-ESP coupled device for disinfection of naturally occurring airborne microbials in a few indoor settings (i.e., an living room, a discussion room, a schoolroom and an office) to determine the treatment duration- and human activity-dependent efficacy. To understand the disinfection mechanism, we conduced fluorescence microscopy study to reveal different degree of bacteria cell membrane damage under CPI treatment.

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases. Methods: Cross-sectional descriptive study with 501 individuals aged 35 to 75 years recruited from five health centers by random sampling stratified by age and sex (55.90±14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor^® device and carotid intima-media thickness using Sonosite Micromax^® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X^® accelerometer. Results: The mean VAI value was 61.23±12.86; (Men 63.47±13.75 and women 59.04±11.54; p<0.001). HVA was found in 18.9% (men 19.9% and women 17.8%). In the multiple regression analysis after adjusting for possible confounding factors, the mean VAI value showed a positive association with alcohol use (β=0.020) and sedentary hours per week (β=0.109), and a negative association with hours of activity per week (β=-0.102) and with the number of healthy lifestyles (β=-0.640). In the logistic regression analysis after adjusting for possible confounding factors, and compared to those classified as non-HVA, subjects classified as HVA were more likely to show adherence to MD (OR = 0.571), perform more than 26 hours per week of physical activity (OR = 1.735), spend less than 142 hours per week being sedentary (OR = 1.696), and have more than two healthy lifestyles (OR = 1.877). Conclusion: The results of this study suggest that the more time spent doing physical activity and the less time spent sitting, the lower the vascular aging index and the greater likelihood of being classified in the group of subjects showing HVA.

Background: many studies, on for example taste-visual dissonance, have shown that the influence of the visual cortex on taste sensation is enormous. The aim of the presented work is to investigate, using fNIRS, whether a taste stimulus, in this case the taste of bitter, also causes stimulation of the visual cortex in fNIR study. Methods: 51 participants (204 examinations, 9 996 records) were examined with fNIRS, which collects signals from whole left hemisphere. Differences between the maximum and minimum changes in oxyHb concentrations (ΔoxyHb) for the areas of the brain cortex considered responsible for recording visual and gustatory signals were analyzed. Protocol I, II, III and IV – activation with distillate water, coffee with lower concentration, reference (no stimulation) and coffee with higher concentration respectively, were used. Results: We recorded high signals for teste activation on channels covered gustatory cortex, which confirms the correctness of the choice of research method. What seems important, and somewhat surprising, is the fact that we also received high signals for the channels 45-49, which cover the visual cortex. The statistical analysis does not show any statistical differences between the protocols I, II and IV (different taste activation – water, coffee A and coffee B) for specific channels. As a results of the analysis of the correlation between the subjective bitterness assessment solutions, and the signal ΔoxyHb height, it was observed that statically important correlation, although weak, occurs only for 14 and gustatory channels, only for coffee with a higher concentration. Additionally we recorded the only statistically significant difference between women and men for protocol I (water), where the ΔoxyHb signal was twice as high for women. Conclusions: In conclusion, we can clearly state that the senses of sight and taste work closely together. Moreover, this cooperation is not one-sided - not only the visual activation affects the perception of taste, but interestingly, the taste stimulus can generate a hemodynamic response - activity in the visual cortex.

Unquestionably the rapidly changing climate and, therefore, alterations in the associated bioclimate, constitute an alarming reality with implications in daily practice and natural capital management. In this research the present and projected bioclimate evolution over the phytogeographical regions of Greece is displayed. For this purpose, ultrahigh-resolution computation results on the spatial distribution of the Emberger index’s Q2 classes of bioclimatic characterisation are analysed and illustrated for the first time. The assessments are performed over the reference period (1970–2000) and two future time frames (2021–2040; 2041–2060) under the RCP4.5 and RCP8.5 emission scenarios. By 2060 and under the extreme RCP8.5, intense xerothermic trends are demonstrated owing to the resulting significant spatial evolution mainly of the Arid-Hot, Semi-Arid-Very Hot, Semi-Arid-Hot and Semi-Arid-Temperate Q2 classes, respectively, over the phytogeographical regions of Kiklades (up to 29% occupation), Kriti and Karpathos (up to 30%), West Aegean Islands (up to 26%), North East (up to 56%)–North Central (up to 31%). The RCP8.5 long-term period exhibits the strongest impacts over approximately the right half of the Greek territory the bioclimate of which appears as more dry-thermal in the future.

This study tests the utilization of Bluetooth noise-canceling headphones in improving the quality of eye exams in patients with hearing loss. University of Texas Medical Branch patients above 55 years of age were screened for hearing loss using SoundCheck audiometry. All 29 subjects (18 red-zone and 11 yellow-zone) answered pre-recorded Amsler grid and patient education questions that solicited precise responses. As controls, subjects were randomly administered half of the questions via headphones and half via a smartphone at normal speech volume (60 decibels). Points were awarded for responses demonstrating comprehension, and a post-exam survey was collected. Collectively, the mean score was 1.79 with headphones versus 0.96 with control on the Amsler grid segment and 1.90 with headphones versus 0.97 with control on education questions (p=0.001). Between the red and yellow zone hearing loss patients, the red-zone group answered significantly better in both Amsler (1.78 versus 0.50; p=0.0003) and education questions (1.88 versus 0.44; p&lt;0.0001) with headphones. The yellow zone group answered better with headphones overall but failed to reach significance. Post-exam survey indicated that 28 of 29 patients (97%) preferred the headphones during ophthalmic exams. Patients with severe hearing loss demonstrated better comprehension with the noise-canceling headphones; thus these devices show great promise in improving effective, compassionate communication between providers and hearing-loss patients.

The decomposition of straw is a dynamic process, which is reflected in the decomposing microbial consortia, however, this process is poorly understood. Here we performed an experiment on the gradual colonization of oat straw by the soil microbial community. The results showed that soil respiration and bacterial diversity were negatively correlated – while the first decreased, the latter increased. In accordance with the dynamics of diversity and respiration, succession was divided into early, middle, and late decomposition phases. Analysis of 16S rRNA and ITS2 amplicon sequencing data revealed three jointly changing groups of phylotypes, corresponding with distinguished phases of decomposition. The presence of cellulolytic members of Proteobacteria, Bacteroidota, Firmicutes, and Actinobacteriota for bacteria and Ascomycota for fungi had been detected since the early phase, but most of the initial phylotypes were gone by the end of the phase. The second phase marked the functional core with a constant set of other phylotypes from these phyla, persisting in the community. Full metagenome sequencing of the microbial community from the end of the middle phase confirmed that major members of this consortium had GH genes, connected to cellulose and chitin degradation. The appearance of non-cellulolytic members from Bdellovibrio, Myxococcota, Chloroflexi, and Crenarchaeota characterized the last phase of the mature community.

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker which can be detected in urine, an easily collected sample. This review discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next-generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

The atomic structures of Zn and Na borophosphate glasses were studied by X-ray and neutron diffraction. Peaks assigned to the B−O, P−O, and O−O distances confirm that only BO4 units co-exist with the PO4 tetrahedra. The Zn−O and Na−O coordination numbers are found to be a little larger than four. The narrowest peaks of the Zn−O first-neighbor distances exist for the glasses along a line connecting the Zn(PO3)2 and BPO4 compositions (50 mol% P2O5) which is explained by networks of ZnO4, BO4, and PO4 tetrahedra with twofold coordinated oxygens. Calculated amounts of the available oxygen support this interpretation. Broadened peaks occur for glasses with lower P2O5 contents, consistent with the presence of threefold coordinated oxygens. The two distinct P−O peak components of the Zn and Na borophosphate glasses differ in their relative abundances which is interpreted by Na+ cations that coordinate oxygens in some P−O−B bridges, something not seen for the Zn2+ ions.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

For decades SrTiO3 is in the focus of research with seemingly never-ending new insights regarding its ground state properties, its application potentials, its surface and interface properties, the superconducting state, the twin boundaries and domain functionalities, etc. Here, we focus on the already well-investigated lattice dynamics of STO and show that four different temperature regimes can be identified which dominate the elastic properties, the thermal conductivity and the birefringence. These regimes are the low-temperature quantum fluctuation dominated one, followed by an intermediate regime, the region of the structural phase transition at ~105 K and its vicinity, and at high temperatures a regime characterized by precursor and saturation effects. They can all be elucidated by lattice dynamical aspects. The relevant temperature dependences of the soft modes are discussed and their relationship to lattice polarizability is emphasized.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Background and Aim. Since virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, post-hepatitis C virus (HCV) infection would be a cause for liver cirrhosis that would progress to HCC. Cytotoxic T cells (Tc) are known to be involved in post-HCV complications and HCC pathogenesis. The inhibitory checkpoint Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) is expressed on Tc. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression post-HCV and moreover, to evaluate LAIR-1 expression as a non-invasive biomarker for HCC progression in the context of liver cirrhosis post-HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. We studied LAIR-1 expression on Tc related to the progression of liver cirrhosis in a case-controlled study enrolled 64 patients with post-HCV G4-HCC and 37 patients with post-HCV G4-liver cirrhosis. Methods: LAIR-1 expression was analyzed by flow cytometry. Results: LAIR-1 expression on Tc and the percentage of Tc positive for LAIR-1 (LAIR-1+Tc %) were significantly higher in the post-HCV G4-HCC group compared to the post-HCV G4-liver cirrhosis

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

Ethylene is an essential plant hormone critical in various physiological processes. These processes include seed germination, leaf senescence, fruit ripening, and the plant's response to environmental stressors. Ethylene biosynthesis is tightly regulated by two key enzymes, namely 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). Initially, the prevailing hypothesis suggested that ACS is the limiting factor in the ethylene biosynthesis pathway. Nevertheless, accumulating evidence from various studies has demonstrated that ACO, under specific circumstances, acts as the rate-limiting enzyme in ethylene production. Under normal developmental processes, ACS and ACO collaborate to maintain balanced ethylene production, ensuring proper plant growth and physiology. However, under abiotic stress conditions, such as drought, salinity, extreme temperatures, or pathogen attack, the regulation of ethylene biosynthesis becomes critical for plants’ survival. This review highlights the structural characteristics, examines the transcriptional, post-transcriptional, and post-translational regulation of ACS and ACO, and their role under abiotic stress conditions. Reviews on the role of ethylene signaling in abiotic stress adaptation are available. However, a review that delineates the role of ACS and ACO in abiotic stress acclimation is not available.

Significant efforts are being made across academia and industry to better characterize lithium-ion battery cells as reliance on the technology for applications ranging from green energy storage to electric mobility increases. The measurement of short-term and long-term volume expansion in lithium-ion battery cells is relevant for several reasons. For instance, it provides information about the quality and homogeneity of battery cells during charge and discharge cycles, as well as aging over it’s lifetime. The expansion measurements are useful for the evaluation of new materials and the improvement of end-of-line quality tests during cell production. These measurements may also indicate the safety of battery cells by aiding in predicting state of charge and state of health over the lifetime of the cell. Expansion measurements can also assess inhomogeneities on the electrodes and defects such as gas accumulation and lithium plating. In this review, we first establish the known mechanisms through which short term and long term volume expansion in lithium-ion battery cells occurs. We then explore the current state-of-the-art for both contact and non-contact measurements of volume expansion. This review compiles existing literature to outline the various options available to researchers aiming to make ex situ volume expansion measurements by doing post mortem analyses on individual components and in operando measurements on entire battery cells. Finally, we discuss the different considerations when selecting an appropriate measurement technique. The selection of the optimal method for measuring battery cell expansion depends on the objective of the characterization, duration, required resolution, and repeatability of results. Costs and required space for the measurement equipment are also considered.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

Parts produced by laser or electron-beam powder bed fusion (PBF) additive manufacturing are prone to residual stresses, deformations, and other defects linked to non-uniform temperature distribution during the manufacturing process. Several researchers have highlighted the important role scan sequence plays in achieving uniform temperature distribution in PBF. However, scan sequence continues to be determined offline based on trial-and-error or heuristics, which are neither optimal nor generalizable. To address these weaknesses, we have articulated a vision for an intelligent online scan sequence optimization approach to achieve uniform temperature distribution, hence reduced residual stresses and deformations, in PBF using physics-based and data-driven thermal models. This paper proposes SmartScan, our first attempt towards achieving our vision using a simplified physics-based thermal model. The conduction and convection dynamics of a single layer of the PBF process are modeled using the finite difference method and radial basis functions. Using the model, the next best feature (e.g., stripe or island) that minimizes a thermal uniformity metric is found using control theory. Simulations and experiments involving laser marking of a stainless steel plate are used to demonstrate the effectiveness of SmartScan in comparison to existing heuristic scan sequences for stripe and island scan patterns. In experiments, SmartScan yields up to 43% improvement in average thermal uniformity and 47% reduction in deformations (i.e., warpage) compared to existing heuristic approaches. It is also shown to be robust, and computationally efficient enough for online implementation.

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

The method of doublet frequency distance (DFD-) maps was applied, here, for visualization of DNA sequence structures of yeast chromosomes. The colour scale “rainbow” of the Octave programming tool is well suited for such visualization. The DFD-maps are generated by comparison of the differences in the number of all base doublets in a shifting frame with all other positions of this frame in a regarded DNA sequence section. This procedure can be applied from DNA-sections of between a few hundred bases (bps) up to a complete chromosome with a million or more bps. An orthogonal DFD-map pattern dominates all chromosomes and its parts. It can be interpreted by a large number of successive mutation events during evolution. In contrast, diagonal patterns indicate duplications of sequence sections and multiple tandem repeats. These periodic structures are found in several chromosomes and are more or less regular or noised. The larger tandem repeat in the subtelomeric region of chromosome 12 presents a characteristic example of a nested multiple-repeat structure. Its pattern in the DFD-map illustrates obviously a temporal order of duplication and mutation events leading to a hierarchical sequence architecture.

Brushless Synchronous Machines (BSM) are replacing conventional synchronous machines with static excitation in generation facilities due to the absence of sparking and lower maintenance. However, this excitation system makes challenging measuring electric parameters in the rotor. This fact highly difficult the detection of ground faults, which are the most common type of electrical fault in electric machines. In this paper, a ground fault detection method for BSM is proposed. It is based on an inductive AC/DC rotating current sensor installed in the shaft. In case of a ground fault in the rotating parts of the BSM, a fault current will flow through the rotor’s sensor, inducing voltage in its stator. Analyzing the frequency components of the induced voltage the detection of a ground fault in the rotating elements is possible. The ground faults detection method proposed covers the whole rotor and discern between DC and AC sides. To corroborate the detection method, experimental tests have been performed using a prototype of this sensor connected to laboratory synchronous machines achieving satisfactory results.

Generalized Bayes is a Bayesian approach based on the learning rate parameter η. In this study, we examine the effect of parameter η on the estimation results considering joint type-I and type-II hybrid censored samples from k exponential populations. In addition to the learning rate parameter, we consider two loss functions, the Linex and general entropy loss functions in the Bayesian approach. Monte Carlo simulations are performed to compare the performances of the estimation results under losses and different values of η. An illustrative example is performed to study the effect of the learning rate parameter and the different losses with different parameters.

Blueberries are rich in a variety of functional substances and have high nutritional and health values, but they are not resistant to decline during fresh storage. Here, the effects of six Bacillus species on storage quality of, and antioxidant levels in, the southern highbush blueberry ‘O'Neal’ fruit were investigated. Bacillus treatments reduced the fruit decay rate, slowed fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. Bacillus altitudinis Y-14 had the best effect overall. Further, the effects of 1-methylcyclopropene (1-MCP), B. altitudinis Y-14, and 1-MCP+B. altitudinis Y-14 treatments on the storage quality and antioxidant of rabbiteye blueberry ‘Brightwell’ fruit were investigated, and each treatment effectively reduced the decay rate and weight loss of fruit. When stored for 25 days, the decay rate of the 1-MCP+B. altitudinis Y-14 group was only 8.33%, significantly lower than that of the control. The three treatments delayed the fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. The 1-MCP+B. altitudinis Y-14 treatment had the best effect. Thus, the combined 1-MCP and B. altitudinis Y-14 treatment may be an effective way to improve the storage quality and extend the storage period of blueberries.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy that involves the continuous administration of antiretroviral drugs to HIV-negative individuals wit a substantial risk of contracting an HIV infection. The use of PrEP has shown a reduction in the risk of HIV acquisition through sexual intercourse by up to 99%. Despite its effectiveness, PrEP uptake remains low among populations at high risk of HIV infection. This highlights the need for further research in stratetegies to enhance awareness and uptake of PrEP amongst these specific populations

Alkyl moieties—open chain or cyclic—are common in drug molecules and can be internal or terminal. The open-chain alkyls can be linear or branched; the cyclic alkyls may be substituted. Usually, the branches in open-chain alkyls and substituents in cycloalkyls influence both the pharmacokinetics and pharmacodynamics of a drug molecule. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some parent-drug equiactive hydroxy metabolites have been developed into metabolite ester prodrugs, while some of the parent-drug carboxy metabolites have been developed into metabolite drugs. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. Some subtexts found to manifest from the hydroxy and carboxy functionalization of alkyl moieties in drug molecules are presented and discussed. The review provides basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules; and (ii) whether the resulting metabolites will possess pharmacologic activity or be devoid of it.

Mushroom cultivation vastly improves the yield of mushrooms under optimized, controlled conditions, but may be susceptible to opportunistic colonization by pest species that can establish themselves, as well as the pathogens and pests they may transmit. Here we describe our investigation into the bacterial communities of adult Lycoriella ingenua (Diptera: Sciaridae) and Megaselia halterata (Diptera: Phoridae) collected from button mushroom (Agaricus bisporus) production houses in Pennsylvania. We collected adult flies and sequenced the hypervariable v4 region of the bacterial 16S rRNA using the Illumina MiSeq. The most abundant bacterial genus detected in both species was Wolbachia, but phylogenetic analysis revealed that the infections are from different clades. Future studies include the characterization of Wolbachia infections on fly behavior and biology, comparison of microbial diversity of fly species colonizing wild mushrooms, and other microbiota that may contribute to the success of certain pest fly species.

Structural and functional materials are subjected to harsh oxidizing environments that lead to a rapid decline in their surface chemical stability. At high-temperatures, the diffusion of atoms is erratic; thus, the reactive elements (REs) get a chance to migrate to the surface and look for oxygen-reactive sites. Their migration from the lattice sites creates vacancies in the matrix and thus weakens the bond, making the material prone to environmental degrading factors. Subsequently, the inward diffusion of oxygen, sulfur, nitrogen, or carbon may occupy these vacancies, resulting in undesired precipitation at the grain boundary, which is usually brittle. The solubility and dissociation of attacking species and corrosion products play the most critical role in corrosion in high-temperature water. To evade such situations, Ti, Al, and Cr are added in Ni/Fe-based alloys, forming a dense oxide layer on the surface that impedes further surface migration of ions. The stability of the alloys is then determined by the capability of these oxide layers to heal or reform during spalling/cracking. This review attempts to understand the migration of REs at the interfaces to prepare structural materials in any unexpected set of oxidizing service conditions. This review will also try to establish the interaction mechanism of REs novel/conventionally added in the alloys with the oxidizing elements in the environments to design better degradation-resistant high-temperature alloys.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

Ammonia synthesis is one of the most important chemical reactions. Due to thermodynamic restrictions and the reaction requirements of the current commercial iron catalysts, it is also one of the worst reactions for carbon dioxide emissions and energy usage. Ruthenium-based catalysts can substantially improve the environmental impact as they operate at lower pressures and temperatures. In this work, we provide a screening of more than 40 metals as possible promoter options based on a Ru/Pr2O3 catalyst. Cesium was the best alkali promoter and was held constant for the series of double-promoted catalysts. Ten formulations outperformed the Ru-Cs/PrOx benchmark, with barium being the best second promoter studied and the most cost-effective option. Designs of experiments were utilized to optimize both the pretreatment conditions and the promoter weight loadings of the doubly promoted catalyst. As a result, optimization led to more than a five-fold increase in activity compared to the unpromoted catalyst, therefore creating a possibility for low ruthenium ammonia synthesis catalysts to be used at scale. Further, we have explored the roles of promoters using kinetic analysis, XPS, and in situ infrared spectroscopy. Here, we have shown that the role of barium is to act as a hydrogen scavenger and donor, which may permit new active sites for the catalyst, and have demonstrated that the associative reaction mechanism is likely used for the unpromoted Ru/PrOx catalyst with hydrogenation of the triple bond of the dinitrogen occurring first before any dinitrogen bond breakage.

Existing implants used with Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and other joint reconstruction treatments, have displayed premature failures and frequent needs for revision surgery in recent years, particularly with young active patients who represent more than 55% of all joint reconstruction patients. Bone cement and stress shielding have been identified as the major reasons for premature joint failures. A breakdown of the cement may happen, and revision surgery may be needed because of the aseptic loosening. The significant mismatch of stiffness properties of patient trabecular bones and metallic implant materials in joint reconstruction surgery results in the stress shielding phenomenon. This could lead to significant bone resorption and increased risk of bone fracture and the aseptic loosening of implants. The present project introduces an approach for development of customized cellular structures to match the mechanical properties and architecture of human trabecular bone. It consists of four modules:1- characterization of geometry, microarchitecture, and stiffness properties of patient’s bones; 2- developing customized lattice structures tailored to mimic properties established in module 1; 3 - integration of developed lattice structure into full scale implant design and manufacturing; 4- implementation of the developed technology for use in implants that would overcome most of the issues related to aseptic loosening phenomenon. The present work aims at fulfilling the objectives of module 2 by exploring new designs of customized lattice structures and texture tailored to mimic closely patients’ bone anisotropic properties and that can incorporate an engineered biological press-fit fixation technique. The effects of various lattice design variables on mechanical performance of the structure are examined through systematic experimental plan using statistical design of experiments technique and analysis of variance method. All tested lattice designs were explored under realistic geometrical, biological, and manufacturing constraints. Of the four design factors examined in this study, strut thickness was found to have the highest percent contribution (41%) regarding the structure stiffness, followed by unit cell type, and cell size. Srut shape was found to have the lowest effect with only 11% contribution. The introduced solution offers lattice structure designs that can be adjusted to match bone stiffness distribution and promote bone ingrowth and hence eliminating the phenomenon of stress shielding while incorporating biological press-fit fixation technique.

Evidence regarding the role of oral antibiotics (oA) alone or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8,359 colorectal resections gathered over a 32-month period in 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1,013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA), and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSIs) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs 6 (2.5%) events; OR 3.77; 95%CI 1.22-11.67; p = .021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

While many studies have described the association between cognitive decline and eating habits, little attention has been paid to its association with cheese intake. In this cross-sectional study of 1,035 community-dwelling women aged ≥ 65, we investigated the association between intake/type of cheese and cognitive function. The anthropometry, functional ability, and the frequency of food intake, including cheese, were assessed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a score of 20–26 was defined as mild cognitive decline (MCD). We found that MMSE score was significantly different between the presence of cheese intake (cheese intake: 28.3±1.9; non-cheese intake: 27.8±2.2) and between the type of cheese consumed (Camembert cheese: 28.7±1.3; others: 28.3±1.9). After adjusting for confounders, multiple logistic regression revealed four significant independent variables for MCD: Camembert cheese intake (odds ratio [OR] = 0.448, 95% confidence interval [CI] = 0.214–0.936), age (OR = 1.114, 95% CI = 1.059–1.171), usual walking speed (OR = 0.2620, 95% CI = 0.109–0.621), and repetitive saliva swallowing test scores (OR = 0.865, 95% CI = 0.750–0.995). Our results, while based on cross-sectional data from Japanese community-dwelling older women, demonstrated that Camembert cheese intake is significantly associated with MCD.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

The ecotoxic effect of glyphosate, a commonly used Parthenium control herbicide, was evaluated in laboratory on biological and fitness attributes of Zygogramma bicolorata. Bioassay of glyphosate was carried within a minimum range of field recommended dose. Indirect exposure experiment reveals that glyphosate caused maximum mortality of 3^rd larval instars, extends the development stages of larvae, pre pupation and pupation. Significant negative effect was observed on sex ratio, fecundity, egg viability and on other fitness attributes. The study demonstrated the non-compatibility of glyphosate and unsafe with Zygogramma bicolorata. The study concludes that owing to acute toxicity of glyphosate at recommended field dose may be used in combination with Z. bicolorata for successful control of Parthenium weed, but needs to be evaluated under natural field conditions.

Electroencephalography (EEG) is essential for tracking brain activity and identifying seizure effects. However, epileptic behaviour can only be detected after a specialist has carefully analysed all EEG recordings along with a proper history of the patient. A skilled physician is required for the right epilepsy diagnosis and therapy. But most of the time, patients visit the clinician in the interictal stage with no proper history documented. Therefore, it was essential to the automatic prediction of stages of seizure. K nearest neighbours (KNN) and random forest (RF) models using raw EEG signals, preictal, ictal, postictal, and interictal stages were identified in this study. The possibility of these characteristics is explored by examining how well time-domain signals work in the prediction of epileptic stages using intracranial EEG datasets from Freiburg Hospital (FH), Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT), and Temple University Hospital (TUHEEG). To test the viability of this approach, two different types of simulations were carried out on three binary classifications (interictal vs. preictal, interictal vs. ictal, preictal vs. postictal, and interictal vs. postictal), and one four-class problem (interictal vs. preictal vs. ictal vs. postictal) was performed for each model. The average accuracy when using time-domain signals in the FH database was 90.5% and 75.0%; CHB-MIT was 92.87% and 75.9%; and TUHEEG was 94.46% and 76.8%, respectively, for the KNN and RF models.

Background: Heart failure (HF) with preserved ejection fraction (pEF) has lacked effective 23 treatments for reducing mortality. However, previous studies have found an association between 24 statin use and decreased mortality in patients with HFpEF. The aim of this study was to analyze 25 whether statin therapy is associated with a reduction in mortality in these patients and whether the 26 effect differs according to presence or absence of ischemic heart disease (IHD). Methods: We ana- 27 lyzed data from the National Registry of Heart Failure, a prospective study including patients ad- 28 mitted for HF in Internal Medicine units nationwide. Patients with HFpEF were classified according 29 to the use of statins and differences between two groups were analyzed. A multivariate analysis 30 was performed using Cox regression to assess factors independently related to mortality. Results: 31 2788 patients with HFpEF were included, 63% of them were women with a mean age of 80.1(±7.8) 32 years. The statin-treated group (40.2%) was younger, with better functional status, and had a more 33 common diagnosis of vascular disease and lower frequency of atrial fibrillation. The most frequent 34 etiology of HF in both groups was the hypertensive one. Nevertheless, ischemic HF was more com- 35 mon in those who received statins (24.8% vs. 9.6%; p<0.001). Multivariate analysis showed lower 36 mortality at 1-year follow-up in statin-treated patients (OR:0.74; 95%CI:0.61-0.89; p=0.002). This as- 37 sociation was observed in patients without IHD (p<0.001), but not in those with IHD (p=0.11). Con- 38 clusion: Statins are associated with a decrease in total mortality in patients with HFpEF. This benefit 39 occurs mainly in those without IHD.

The paper presents the results of a study of the concept of address fiber Bragg structures in the problem of vibration control. The mathematical model of measuring transformation is presented; the experimental study of a vibration diagnostics system based on Address Fiber Bragg Gratings is carried out; the quantitative and qualitative comparative assessment with electronic accelerometers is made; the gain by an order of magnitude in some parameters is shown.

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

Semiconductor nanowhiskers, in particular, nanostructured whiskers based on zero-dimensional (0D) C70 fullerene, are being actively discussed due to the great potential of their application in modern electronics. For the first time, we proposed and implemented a method for the synthesis of nanostructured C70 fullerene whiskers based on the self-organization of C70 molecules during thermal evaporation of C70 droplets on the substrate surface. We found that the onset of the synthesis of C70 nanowhiskers upon evaporation of drops of a C70 solution in toluene on the substrate surface depends on the substrate temperature. We have provided experimental evidence that an increase in both the C70 concentration in the initial drop and the substrate temperature leads to an increase in the geometric dimensions of C70 nanowhiskers. The obtained results provide useful vision on the role of solute concentration and substrate temperature in the synthesis of one-dimensional materials.

Ribavirin and its analogues exhibit an in vitro antiproliferative effect in cancer cells. In this work we studied the biological activities of a number of oxymethyl derivatives of ribavirin’s aglycon – 1,2,4-triazole-3-carboxamide. Oxymethyl derivatives of 1,2,4-triazole-3-carboxamide with substitu-tions at the fifth or first position of the triazole ring, were synthesized and their antiproliferative and antimicrobial effects were assessed. For both series the presence of an antiproliferative effect was inves-tigated and in the case of 1-oxymethyl derivatives was shown an antimicrobial potential against a Gram-positive bacteria Micrococcus luteus and Gram-negative bacterium Pseudomonas aeruginosa. The obtained results showed that the n-decyloxymethyl derivatives induced leukemia cell death at low mi-cromolar concentrations. We confirmed that n-decyloxymethyl derivatives of ribavirin inhibited cell cy-cle progression and induced accumulation of leukemia cells in subG1-phase. The molecular docking results suggest that oxymethyl derivatives may act by inhibiting translation initiation due to interfering with eIF4E assembly. The outcome results relived that active derivatives (1- or 5-n-decyloxymethyl-1,2,4-triazole-3-carboxamides) can be considered as a lead compound for anti-cancer treatments.

We analyzed the interaction of two acceptor materials, reduced graphene oxide (RGO) and [6,6]-phenyl-C6-butyric acid methyl ester (PCBM), and poly(3-hexylthiphene) (P3HT), as well as the dependence of its photophysical properties with the temperature in the range 90 to 300 K. The nanocomposite of the films was analyzed by optical absorption ultraviolet-visible (UV-Vis) and photoluminescence (PL) and emission ellipsometry (EE) in a function of sample temperature. The surface morphology was studied by atomic force microscopy (AFM). We noted that onset levels (Eonset) of the nanocomposite of P3HT and RGO is smaller than the others. The PL spectra showed the presence of anomalies in the emission intensities in the nanocomposite of P3HT and PCBM. It was also possible to determine the electron-phonon coupling by calculating the Huang-Hys parameters and its dependence with the sample’s temperature. Through EE it was possible to analyze the degree of polarization and the anisotropy. We observed a high degree of polarized emission of the P3HT films which varies subtly according to the temperature. For nanocomposites with RGO the polarization degree in the emission decreases and the roughness on the surface increases. As a result, the RGO improves the energy transfer between adjacent polymer chains at the cost of greater surface roughness. Then, the greater energy transfer may favor applications of this type nanocomposite in OPVC's with enhancement in energy conversion efficiency.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no proinflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.

We reported previously that poly (3-hydroxybutyrate) (PHB) oligomer is an effective antimicrobial agent against gram-positive bacteria, gram-negative bacteria, fungi and multi-drug resistant bacteria. In this work, it was further found that polyethylene glycol (PEG) can promote the antimicrobial effect of PHB oligomer synergistically. Three hypothetic mechanisms were proposed, that is, generation of new antimicrobial components, degradation of PHB macromolecules and dissolution/dispersion of PHB oligomer by PEG. With a series of systematic experiments and characterizations of HPLC-MS, it was deducted that dissolution/dispersion of PHB oligomer dominated the synergistic antimicrobial effect between PHB oligomer and PEG. This work demonstrates a way for promoting antimicrobial effect of PHB oligomer and other antimicrobial agents through improving hydrophilicity.

The role that aquatic aerosols might play in inter-ecosystem exchange in freshwater riparian environments has largely been understudied. In these environments, where freshwater streams are used both as drinking water and for treated waste disposal, water features like waterfalls, downed trees, and increased streamflow can serve as bioaerosol producers. Such water features could have an important role in the bacterial colonization of surrounding surfaces, including the riparian phyllosphere. In this study, we explore the influence of a freshwater stream’s bacterial community composition and micropollution on riparian maple leaves exposed to bioaerosols produced from the stream. Using culture-based and non-culture-based techniques, we compared phylloplane microbial communities in riparian zones, adjacent non-riparian forested zones, and the surface waters of the stream. In this system, riparian zone maple leaf surfaces had higher bacterial counts than non-riparian zone trees. Using metagenomic profiling of the 16S rRNA gene, we found that, while microbial communities on leaves in both riparian zone and forested sites were diverse, riparian zone bacterial communities were significantly more diverse. In addition, we found that riparian leaf bacterial communities shared more amplicon sequence variants (ASVs) with stream bacterial communities than forest leaves, indicating that the riparian zone phyllosphere is likely influenced by bioaerosols produced from water surfaces.

The integration of bacteriophages, a particular class of viruses that specifically infect bacteria and archaea, in biosensors for the monitoring of pathogens in foods and beverages is highly desirable. To this end, an increasing focus has been set on the exploration of covalent and physical methods for the immobilization of phages on solid surfaces. This work investigates the electrostatic assembly of tailed phages, specifically anti-Listeria monocytogenes P100 phages, on an ultrathin self-assembled monolayer (SAM) of 11-amino-1-undecanethiol (AUT). The cationic properties of AUT may allow for the electrostatic capture of P100 in a capsid-down fashion, thus, exposing the specific receptor-binding proteins on their tails to the corresponding pathogens in analytical samples. The physical properties of immobilized phages have been studied using AFM, SEM, and electrochemical techniques, providing insight into the orientation of the phages and revealing that the pH plays a remarkable role in the morphology and charge transfer behavior of the adsorbed films. Overall, this research portrays SAMs of amino-akylthiols as a valid platform for the oriented immobilization of bacteriophages on surfaces for electroanalytical purposes.

Water resource is considered as a significant factor in development of regional environment and society. Water consumption prediction can provide important decision basis for the regional water supply scheduling optimisations. According to the periodicity and randomness nature of the daily water consumption data, a Markov modified autoregressive moving average (ARIMA) model is proposed in this study. The proposed model, combined with the Markov chain, can correct the prediction error, reduce the continuous superposition of prediction error, and improve the prediction accuracy of future daily water consumption data. The daily water consumption data of different monitoring points are used to verify the effectiveness of the model, and the future water consumption is predicted, in the study area. The results show that the proposed algorithm can effectively reduce the prediction error compared to the ARIMA.

Determining halal product of fermented foods and bevearages becomes important for muslim consumers due to religious codification of halal. In order to help on site analysis, an alcohol biosensor was under development. The biosensor was constructed using bacteria producing alcohol oxidase (AOX). Bacteria from apple juice was isolated in advance to obtain pure bacteria. The bacteria was cultured in two solid media. Bacteria on the Acetobacter media had a resistance in a solution containing alcohol with a higher concentration. Acetobacter was cultured on solid and liquid media for measuring at various ethanol concentrations (0.01%-3%) with different absorbance value. Bacteria with absorbance value 0.500 had the highest oxidation current peak. Later, it was used as bioreceptor for measuring ethanol by cyclic voltammetry method. The linearity of measurement later was compared with spectrophotometric measurement. By using cyclic voltammetry the linearity had higher R² value than spectrophotometric method. However, it only had stability for two days, there fore it needs more improvement for lasting its lifetime. Basically, electrochemical method has potency for further being improved fur as an alternative method of ethanol on-site measurement.

Chiroptera includes of over 1,400 bat species with at least 35 of these present in Italy. Due to their role as lyssavirus reservoirs, in Italy, dead bats and oral swabs are routinely submitted to the laboratory network of the Istituti Zooprofilattici Sperimentali within in the framework of the rabies national passive and active surveillance programme. Carcasses and biological samples collected from January to December 2021 in Latium and Tuscany Regions were further screened for the presence of Coronaviruses (CoVs) and Herpesviruses, using pan-family virus PCR tests and relative PCR products were Sanger sequenced. Subsequent to the viral investigations, genetic bat species was also carried out. Viral characterization detected AlphaCoVs in Miniopterus schreibersii and Beta- and Gamma-Herpesviruses in Tadarida Teniotis.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Green synthesis offers a superior alternative to traditional methods for producing metal and metal oxide nanoparticles. This approach is not only benign and safe but also cost-effective, scalable, and straightforward, operating under ambient conditions. Notable metals and metal oxide nanoparticles, such as manganese oxides, iron oxides, silver, and gold, have been produced using various bio-reductants derived from plant extracts. These biological agents not only expedite the reduction process but also stabilize the nanoparticles, serving dual roles as reducing and capping agents. This review presents the green synthesis of nanoparticles (NPs) obtained from biogenic wastes and plant extracts. The green-synthesized nanostructured MnO2 are evaluated as a potential photocatalyst for water treatment and as an electrode material in lithium-ion batteries and supercapacitors. The green-derived iron oxide nanoparticles are examined as promising antioxidant, anti-inflammatory, and anti-diabetic agents. Additionally, this review discusses the green synthesis of precious metal nanoparticles, specifically silver (Ag NPs) and gold (Au NPs), highlighting their potential medical applications in areas like antiviral treatments and cancer therapy.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.