Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

The extended finite element method (XFEM) is now widely used in crack simulations and the direction of propagation of the XFEM crack in SS-304 has been quite interesting. This paper discusses the direction,θ(+ve in anti-clockwise direction), of the XFEM crack (under mode-I) propagation based on the von Mises stress-field around the crack-tip for static loading under the light water reactors (LWRs) conditions. The Mises core region from the crack-tip is chosen for β=〖90〗^o, the angle between the load and the initial crack. Experimental data for LWRs’environment is obtained and the simulations have been carried out applying three different static loads and results for the direction of the crack are calculated by measuring the stress-field around the crack-tip. It has been found that the direction of the XFEM varies inversely as the stress-field around the crack tip is increased. The computational results have been compared with the numerical results based on the minimum strain energy density criterion[S-criterion].

Feature selection is one of the main data preprocessing steps in machine learning. Its goal is to reduce the number of features by removing extra and noisy features. Feature selection methods must consider the accuracy of classification algorithms while performing feature reduction on a dataset. Meta-heuristic algorithms are the most successful and promising methods for solving this issue. The symbiotic organisms search algorithm is one of the successful meta-heuristic algorithms which is inspired by the interaction of organisms in the nature called Parasitism Commensalism Mutualism. In this paper, three engulfing binary methods based on the symbiotic organisms search algorithm are presented for solving the feature selection problem. In the first and second methods, several S-shaped and V-shaped transfer functions are used for binarizing the symbiotic organisms search algorithm, respectively. These methods are called BSOSS and BSOSV. In the third method, two new operators called BMP and BCP are presented for binarizing the symbiotic organisms search algorithm. This method is called EBSOS. The third approach presents an advanced binary version of the coexistence search algorithm with two new operators, BMP and BCP, to solve the feature selection problem, named EBSOS. The proposed methods are run on 18 standard UCI datasets and compared to base and important meta-heuristic algorithms. The test results show that the EBSOS method has the best performance among the three proposed approaches for binarization of the coexistence search algorithm. Finally, the proposed EBSOS approach was compared to other meta-heuristic methods including the genetic algorithm, binary bat algorithm, binary particle swarm algorithm, binary flower pollination algorithm, binary grey wolf algorithm, binary dragonfly algorithm, and binary chaotic crow search algorithm. The results of different experiments showed that the proposed EBSOS approach has better performance compared to other methods in terms of feature count and accuracy criteria. Furthermore, the proposed EBSOS approach was practically evaluated on spam email detection in particular. The results of this experiment also verified the performance of the proposed EBSOS approach. In addition, the proposed EBSOS approach is particularly combined with the classifiers including SVM, KNN, NB and MLP to evaluate this method performance in the detection of spam emails. The obtained results showed that the proposed EBSOS approach has significantly improved the accuracy and speed of all the classifiers in spam email detection.

Macromolecules with well-defined structures in terms of molar mass and monomer sequence became interesting building blocks for modern materials. The precision of the macromolecular structure makes fine-tuning of the properties of resulting materials possible. Conjugated macromolecules exhibit excellent optoelectronic properties that make them exceptional candidates for sensors construction. The importance of chain length and monomer sequence is particularly important in conjugated systems. The sequence lengths, monomer sequence and structural modification often influence the energy bang gap between HOMO and LUMO orbitals of the molecules that reflect in their properties. Moreover, the supramolecular aggregation that is often observed in oligo-conjugated systems is usually strongly affected by even minor structural changes that are used for sensor designs. This review summarizes the examples of well-defined conjugated macromolecules based on oligo(arylene ethynylene)s skeleton used for sensor applications. The sensing mechanisms and importance of uniformity of structure are discussed.

Local binary pattern is one of the visual descriptors and can be used as a powerful feature extractor for texture classification. In this paper, a novel representation for face recognition is proposed, called it Bilateral Line Local Binary Patterns (BL-LBP). This scheme is an extension of Line Local Binary Patterns descriptors in the statistical learning subspace. The present bilateral descriptors are fused with an ensemble learning of calibrated SVM models. The performance of this scheme is evaluated using 5 standard face databases. It is found that it is robust against illumination variation, diverse facial expressions and head pose variations and its recognition accuracy reaches 98 percent, running on a mobile device with a processing speed of 63 ms per face. Results suggest that our proposed method can be very useful for the vision systems that have limited resources where the computational cost is critical.

Binary switches, which are the primitive units of all digital computing and information processing hardware, are usually benchmarked on the basis of their ‘energy-delay product’ which is the product of the energy dissipated in completing the switching action and the time it takes to complete that action. The lower the energy-delay product, the better the switch (supposedly). This approach ignores the fact that lower energy dissipation and faster switching usually come at the cost of poorer reliability (i. e. higher switching error rate) and hence the energy-delay product alone cannot be a good metric for benchmarking switches. Here, we show the trade-off between energy dissipation, energy-delay product and error-probability, for both an electronic switch (a metal oxide semiconductor field effect transistor) and a magnetic switch (a magnetic tunnel junction switched with spin transfer torque). As expected, reducing energy dissipation and/or energy-delay-product generally results in increased switching error probability and reduced reliability.

In this paper, we proposed a novel saddle type FinFET (S-FinFET) to effectively solve problems occurring under the capacitor node of dynamic random-access memory (DRAM) cell and showed how its structure was superior to conventional S-FinFETs in terms of short channel effect (SCE), subthreshold slope (SS), and gate-induced drain leakage (GIDL). The proposed FinFET exhibited 4 times lower Ioff than modified S-FinFET called RFinFET with more improved DIBL characteristics while minimizing Ion reduction compared to RFinFET. Our results also confirmed that the proposed device showed improved DIBL and Ioff characteristics as gate channel length decreased.

The search for novel brewing strains from non-brewing environments represents an emerging trend to increase genetic and phenotypic diversities in brewing yeast culture collections. Another valuable tool is hybridization, where beneficial traits of individual strains are combined in a single organism. This has been used successfully to create de novo hybrids from parental brewing strains by mimicking natural Saccharomyces cerevisiae ale x Saccharomyces eubayanus lager yeast hybrids. Here, we integrated both these approaches to create synthetic hybrids for lager fermentation using parental strains from niches other than beer. Using a phenotype-centered strategy, S. cerevisiae sourdough strains and the S. eubayanus x Saccharomyces uvarum strain NBRC1948 (also referred to as Saccharomyces bayanus) were chosen for their brewing aptitudes. We demonstrated that, in contrast to S. cerevisiae x S. uvarum crosses, hybridization yield was positively affected by time of exposure to starvation, but not by staggered mating. In laboratory-scale fermentation trials at 20°C, one triple S. cerevisiae x S. eubayanus x S. uvarum hybrid showed a heterotic phenotype compared with the parents. In 2L wort fermentation trials at 12°C, this hybrid inherited the ability to consume efficiently maltotriose from NBRC1948 and, like the sourdough S. cerevisiae parent, produced appreciable levels of the positive aroma compounds 3-methylbutyl acetate (banana/pear), ethyl acetate (general fruit aroma) and ethyl hexanoate (green apple, aniseed, and cherry aroma). Based on these evidences, the phenotype-centered approach appears promising for design of de novo lager beer hybrids and may help to diversify aroma profiles in lager beers.

In this article, we introduce a relatively new concept of multi-valued (θ;R)-contractions and utilize the same to prove some xed point results for a new class of multi-valued mappings in metric spaces endowed with an amorphous binary relation. Illustrative examples are also provided to exhibit the utility of our results proved herein. Finally, we utilize some of our results to investigate the existence and uniqueness of a positive solution for the integral equation of Volterra type.

We have proposed a simple algorithm to retrieve the total ozone column and snow properties (spectral albedo and effective light absorption path) using the high spatial resolution single – view MSI/S-2 measurements over Antarctica.

The following is the Collatz Conjecture: Suppose we begin with a positive number, multiply it by 3 and add 1 if it is odd, and divide it by 2 if it is even. Then continue doing this as long as you can. Will it matter where you start, whether you end up at the number 1? The Collatz conjecture has been studied for around 85 years. We transform the Collatz function from decimal to binary, then use the binary string's character to prove the Collatz conjecture. In addition, we use mathematics to give another interpretation to chaos, which is the ultimately periodic positive integer sequence.

The -blocker (S)-practolol ((S)-N-(4-(2-hydroxy (isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the -blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)- 3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol was also produced in 53% yield, with 99% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. The yield of all four chlorohydrins increased by use of catalytic amounts of base. The reason for this was found to be less formation of the dimeric by-products compared to use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previous reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB) from SyncoZymes Co, Shanghai, China. Optical rotations confirmed the absolute configuration of the enantiopure drugs.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

According to Swiss-American Doctor of Sciences and Agricultural Engineer Jean-Pierre Jost, "plants communicate with each other by the quality of light emitted by their leaves or by means of stress hormones and other volatile chemicals. They also make use of cocktails of chemicals, pheromones, shape and colors to attract pollinators whereas other signals repel unwanted organisms. Insects are able to decode such messages and respond accordingly. Plants are apparently also communicating by sounds and electric signals." (1) How do plants do these things? Of course, it's easy to imagine it's all purely mechanical. But at the risk of sounding like a mysticism fanatic, I wonder if plants' activities are part of a spectrum of consciousness that pervades the entire universe. This spectrum would result from everything in the universe having the BITS or BInary digiTS of electronics as their ultimate composition. As explained in this hypothesis, something I call vector-tensor-scalar geometry is essential to my hypothesis. VTS geometry produces the particles of chemicals and pheromones, and refers to communication via electric signals when it speaks of electromagnetic-gravitational interaction. There's another consequence if everything in the universe is ultimately composed of electronic BITS and the cosmos is a spectrum of consciousness/artificial intelligence. It's impossible for an absence of consciousness to exist, either after death or before conception.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

The Landauer principle asserts that “the information is physical”. In its strict meaning Landauer's principle states that there is a minimum possible amount of energy required to erase one bit of information, known as the Landauer bound W=kBTln2 where T is the temperature of a thermal reservoir used in the process and kB is Boltzmann’s constant. Modern computers use the binary system in which a number expressed in the base-2 numeral system. We demonstrate that the Landauer principle remains valid for the physical computing device based on the ternary and more generally N-based logic. The energy necessary for erasure of one bit of information (the Landauer bound) W=kBTln2 remains untouched for the computing devices exploiting a many-valued logic.

In this manuscript we use an exactly solvable stochastic binary model for regulation of gene expression to analyse the dynamics of response to a treatment aiming to modulate the number of transcripts of RKIP gene. We demonstrate the usefulness of our method simulating three treatment scenarios aiming to reestablish RKIP gene expression dynamics towards pre-cancerous state: i. to increase the promoter’s ON state duration; ii. to increase the mRNAs’ synthesis rate; iii. to increase both rates. We show that the pre-treatment kinetic rates of ON and OFF promoter switching speeds and mRNA synthesis and degradation will affect the heterogeneity and time for treatment response. Hence, we present a strategy for reducing drug dosage by simultaneously targeting multiple kinetic rates. That enables a reduction of treatment response time and heterogeneity which in principle diminishes the chances of emergence of resistance to treatment. This approach may be useful for inferring kinetic constants related to expression of antimetastatic genes or oncogenes and on the design of multi-drug therapeutic strategies targeting master regulatory genes.

A two-fold integrated research study was conducted; firstly, to understand effects of copper (Cu) and zinc (Zn) on the growth and oxidative stress in Nile tilapia, Oreochromis niloticus; secondly, to study the beneficial effects of the duckweed Lemna minor L. as a heavy metal remover from wastewater. Experiments were conducted in mesocosms with and without duckweed. Tilapia fingerlings were exposed to Cu (0.004 and 0.02 mg/L) and Zn (0.5 and 1.5 mg/L) and fish fed for four weeks. We evaluated the fish growth performance, the hepatic DNA structure using comet assay, the expression of antioxidative genes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx and glutathione-S-transferase, GST) and GPx and GST enzymatic activity. The results showed that Zn exhibited more pronounced toxic effects than Cu. Low dose of Cu did not influence the growth whereas higher doses of Cu and Zn significantly reduced the growth rate of tilapia compared to control, but addition of duckweed prevented weight loss. Further, in the presence of a high dose of Cu and Zn, DNA damage decreased, antioxidant gene expressions and enzymatic activities increased. In conclusion, results suggest that duckweed and Nile tilapia can be suitable candidates in metal remediation wastewater assessment programs.

Work from the last years indicate that the extracellular matrix (ECM) plays a direct role in vari-ous cellular processes including proliferation, migration and differentiation. Besides homeostat-ic processes, its regulatory function in inflammation becomes more and more evident. In in-flammation like inflammatory bowel disease, the ECM composition is constantly remodeled which can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we will provide an over-view of relevant diagnostic methods focusing on ECM changes.

Polarization in online social networks has gathered a significant amount of attention in the research community and in the public sphere due to stark disagreements with millions of participants in topics surrounding politics, climate, the economy and other areas where an agreement is required. There are multiple approaches to investigating the scenarios in which polarization occurs and given that polarization is not a new phenomenon but that its virality may be supported by the low cost and latency messaging offered by online social media platforms; an investigation into the intrinsic dynamics of online opinion evolution is presented for complete networks. Extending a model which utilizes the Binary Voter Model (BVM) to examine the effect of the degree of freedom for selecting contacts based upon homophily, simulations show that different opinions are reinforced for a period of time when users have a greater range of choice for association. The facility of discussion threads and groups formed upon common views further delays the rate in which a consensus can form between all members of the network. This can temporarily incubate members from interacting with those who can present an alternative opinion where a voter model would then proceed to produce a homogeneous opinion based upon pairwise interactions.

Mass plays a strange multiple role in classical physics. This results in a difference between gravity and all other forces - a difference that stood at the beginning of Einstein's development of his general theory of relativity. The equivalence principle (EP) deals with homogenious gravitational fields, which, in fact, don‘t exist in nature. There is only an approximation for this field in Einstein-Lift possible for local situations. Nevertheless this EP can be true, because in classical formal binary logic there can be formulated a true conclusion from a wrong premise or assumption.

The effects of acidic electrolyzed water (AEW) on the microbiological and physicochemical properties of fresh-cut red cabbages were studied. The fresh-cut red cabbages and artificially inoculated red cabbages with Salmonella Typhimurium DT104 were washed with distilled water (DW) and different available chlorine concentration (ACC) of AEW for different times. AEW treatments significantly reduced the populations of native aerobic bacteria, molds and yeasts, and artificially inoculated S. Typhimurium DT104 compared to the DW treated and untreated red cabbage samples. The effectiveness of AEW treatments was greatly enhanced with increasing ACC and treatment times. S. Typhimurium DT104 were not detected in the washing water after the red cabbages treated by AEW. The surface color, pH, and total phenolic contents were did not significantly change when the red cabbages were washed with DW and 100 ppm AEW for 3 min. The anthocyanin contents and antioxidant activities of red cabbage were significantly reduced by 18.5% for cyanidin, 22.1% for pelargonidin, and 11.2% for DPPH radical scavenging activity, the impacts on the nutritional benefits of red cabbage were considered as limited and acceptable. The optimal process condition of AEW for washing red cabbage was 100 ppm for 3 min. In these conditions, most of the native microflora were inactivated, and artificial inoculated S. Typhimurium DT104 on the red cabbage were reduced by 40.2% (3.67 log CFU/g) and with minimal losses of nutrients and antioxidant activity, as well as no requirement of discontinuation treatment on the washing water.

Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3’-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and found to occur with the homologous domains of influenza B and C FluPols. Residues [1-72] of RPB4 were found critical in this interaction. Numerous punctual mutants generated at conserved positions between influenza A, B and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defect. These results suggest that FluPol interacts with several domains/subunits of Pol II, the CTD to bind Pol II initiating host transcription and a second on RPB4 to locate FluPol at the proximity of the 5’-end of nascent host mRNA.

The part of this article dealing with topological insulators and topological superconductors was first written about two years ago - the ideas in the part about the topological universe originated six years ago or more. It’s rather strange that I never put the two parts together in writing before. My belief in unification is unshakeable - I’ve been convinced for years that the universe must be composed of topology. Since Earth is part of the cosmos, entanglement means it must have topological materials. The reverse is also true: topological materials on Earth are well known to science - so in a unification, space and time inevitably possess topological composition. Topological materials (topological insulators, topological superconductors) can be less mystifying if they’re related to the paradigm-shifting deterministic view of quantum mechanics which is described in the universal topology (the “rubber-sheet geometry” of the cosmos): see my previous submission “Hypothesis of Quantum Gravity - Resulting from a Static, Topological Universe Resulting from the Positives and Negatives of the Steady State and Big Bang Theories" at https://www.preprints.org/manuscript/202105.0239/v1 (the first section of this present article is a quick summary of the relevant parts).

Background: Insecticide resistance in Anopheles gambiae s.l. is a major challenge for malaria vector control in Nigeria. Both target-site insensitivity and metabolic resistance have been im-plicated in resistance process, with the latter receiving little attention in Nigeria. Therefore, we investigated metabolic enzyme activities in Anopheles gambiae s.l populations resistant to Del-tamethrin and Diethyldichlorotriethylethane (DDT) in South-West Nigeria. Methods: Anopheles larvae were collected from Ibadan, Oyo and Badagry, Lagos. Adults were exposed to Deltamethrin and DDT using WHO method. Cohorts of populations were further exposed to Pyperonil Butoxide (PBO) and Deltamethrin. Insecticide-exposed and unexposed co-horts were examined for metabolic enzyme activities. Results were compared between exposed and unexposed samples ANOVA (P<0.05). Results: Mosquitoes were identified as An. gambiae (89%, Ibadan; 0%, Badagry) and An. coluzzii (11%, Ibadan; 100%, Badagry). The populations showed varied level of resistance to Deltamethrin (26%, Ibadan; 71%, Badagry) and DDT (2%, Ibadan; 44%, Badagry). Mortality to Deltamethrin in-creased from 26% to 64% (Ibadan) and 71% to 84% (Badagry) when populations were pre-exposed to PBO. Biochemical analysis revealed significant high levels (P<0.05) of cytochrome P450 and GST in exposed samples. Conclusions: Cytochrome P450 and GST are involved in Deltamethrin and DDT resistance in Anopheles gambiae s.l populations in South-West Nigeria.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

In 2011, by 1.3 mm wavelength VLBI radio wave observations of the SgrA*, Fish, V. L. et al showed that the emissions tightly related to the formation of a black hole shadow have a remarkably large time-varying feature within a region of less than 50 μas. The present paper suggests that the origin of the time variation in the observed emission is due to effects of the orbital motion of the existing super-massive black hole binary orbiting at SgrA* with a period of 2150±2.5 s. This suggestion is based on observations of decameter radio wave pulses from SgrA*. We show a good correlation between the time variation in the coherent flux density of the VLBI results and the time variation model of estimated emission intensities based on the periodic motion of the super-massive black hole binary by applying parameters deduced from the decameter radio wave pulse observation model (DRWP-Model). With further confirmation by Fourier analyses of the potential periodicity of the VLBI data that show the same periods of DRWP Model, we conclude that the time variation detected by the 1.3 mm wavelength radio wave VLBI is evidence of an existing super-massive black hole at Sgr A*.

Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected. In the 90s cases related to CFS, com-plaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis. As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a differ-ence in treatment and recovery. Low grade inflammatory conditions are related to Th2 predom-inance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests. In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.

Staphylococcus aureus is a major food-borne pathogen. The ability of S. aureus to produce biofilm is a significant virulence factor triggering its persistence in hostile environments. In this study, we screened a total of 420 different food samples and human hand swabs to detect S. aureus and to determine their biofilm formation ability. Samples analyzed were meat, milk, egg, fish, fast foods, and hand swabs. S. aureus were detected by culturing, staining, biochemical, and PCR. Biofilm formation ability was determined by Congo Red Agar (CRA) plate and Crystal Violet Microtiter Plate (CVMP) tests. The icaA, icaB, icaC, icaD, and bap genes involved in the synthesis of bio-film-forming intracellular adhesion compounds were detected by PCR. About 23.81% (100/420; 95% CI: 14.17-29.98%) samples harbored S. aureus as revealed by detection of the nuc gene. CRA plate revealed 20% of S. aureus isolates as strong biofilm producers, while 69% and 11% as in-termediate and non-biofilm producers, respectively. By the CVMP staining method, 20%, 77%, and 3% of the isolates were found strong, intermediate, and non-biofilm producers. Furthermore, 21% of S. aureus isolates carried at least one biofilm-forming gene, where icaA, icaB, icaC, icaD, and bap genes were detected in 15%, 20%, 7%, 20%, and 10% of the S. aureus isolates, respectively. Bivariate analysis showed high significant correlations (p<0.001) between any of the two adhesion genes of S. aureus isolates. To the best of our knowledge, this is the first study in Bangladesh describing the detection of biofilm-forming S. aureus from foods and hand swabs with molecular-based evidence. Our findings suggest that food samples should be deemed a potential reservoir of biofilm-forming S. aureus that indicates a potential public health significance.

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH towards different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g. sulfenylation, S-thiolation, nitrosylation and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

In this paper, inspired by Jleli and Samet [journal of inequalities and applications 38 (2014) 2 1–8] we introduce two new classes of auxiliary functions and utilize the same to define (q, y)R-weak 3 contractions. Utilizing (q, y)R-weak contractions, we prove some fixed point theorems in the setting 4 of relational metric spaces. We employ some examples to substantiate the utility of our newly proved 5 results. Finally, we apply one of our newly proved results to ensure the existence and uniqueness of 6 solution of a Volterra-type integral equation.

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

Efficient alternatives in energy production and consumption are constantly investigated by increasingly strict policies. In this way, the pollutant emissions that contribute to the greenhouse effect reduce and sustainability of the electricity sector increase. With more than a third of the world's energy consumption, buildings have great potential to contribute these sustainability goals. Additionally, with growing incentives in the Distributed Generation (DG) and Electric Vehicle (EV) industry, it is believed that Smart Buildings (SBs) can be a key in the field of residential energy sustainability in the future. In this work, an energy management system in SBs are developed to reduce the power demanded of a residential building. In order to balance the demand and power provided by the grid, microgrids such as Battery Energy Storage System (BESS), EVs and Photovoltaic Generation panels (PV) are used. Here, a Mixed Binary Linear Programming formulation (MBLP) is proposed to optimize the charge and discharge scheduling of EVs and also BESS. In order to show the efficiency of the model, a case study involving three scenarios and an economic analysis is considered. The results point a 65% reduction in peak load consumption supplied by grid and a 28.4% reduction in electricity consumption costs.

The biofilm is a conglomerate of cells surrounded by an extracellular matrix, which contributes to the persistence of infections. The difficulty in removing the biofilm drives the research for new therapeutic options. In this work, the effect of terpenes (-)-trans-Caryophyllene, (S)-cis-Verbenol, (S)-(-)-Limonene, (R)-(+)-Limonene, and linalool was evaluated, individually and in combinations on bacterial growth, by assay with resazurin; the formation of biofilm, by assay with violet crystal; and the expression of associated genes, by real-time PCR, in two clinical isolates of S. aureus, ST30-t019 and ST5-t311, responsible for more than 90% of pediatric infections by this pathogen in Paraguay. All combinations of terpenes can inhibit biofilm formation in more than 50% without affecting bacterial growth. The most effective combination was (-)-trans-Caryophyllene and linalool at a 500 μg/mL concentration for each, with an inhibition percentage of 88%. This combination decreased the expression levels of the sdrD, spa, agr, and hld genes associated with the initial cell adhesion stage and quorum sensing. At the same time, it increased the expression levels of the cap5B and cap5C genes related to the production of capsular polysaccharides. The combinations of compounds tested are promising alternatives to inhibit biofilm formation in S. aureus.

We investigate the effect of geopolitical risk on the returns of the Information Technology, Communication Services, and Consumer Staples sector firms within the S&P 500 index. We use the event study methodology and perform more than 17,000 regressions to provide empirical evidence at the sector level that geopolitical risk leads to different responses across these 3 sectors. The response of the Information Technology sector is negative for all event windows under study, except the one spanning 10 days prior to the geopolitical event and 10 days after. The Communication Services sector has positive returns as a result of geopolitical events for all event windows, except the one from the geopolitical event date and 5 days after. The Consumer Staples sector shows a negative impact on geopolitical risk for all event windows except the one from the geopolitical event date and 5 days after, demonstrating a negative correlation to the Communication Services sector.

Imaginary dimensions in physics require an imaginary set of base Planck units and some negative parameter $c_n$ corresponding to the speed of light in vacuum $c$. The second, negative fine-structure constant $\alpha_2^{-1} \approx -140.178$ present in Fresnel coefficients for the normal incidence of electromagnetic radiation on monolayer graphene leads to the imaginary Planck units. Furthermore, it sets $c_n \approx -3.06 \times 10^8~\text{[m/s]}$. It follows that electric charges are the same in real and imaginary dimensions. Neutron stars and white dwarfs, objects emitting perfect black-body radiation, need energy exceeding their mass-energy equivalence ratios. Complex energies are defined in terms of real and imaginary Planck units. Their imaginary parts, inaccessible for direct observation, store the excess of these energies. It follows that black holes are fundamentally uncharged, charged micro neutron stars and white dwarfs with masses lower than $5.7275 \times 10^{-10}~[\text{kg}]$ are unphysical, and the radii of white dwarfs' cores are limited to $R_{\text{WD}} < 6.7933~G M_{\text{WD}}/c^2$. It is conjectured that the maximum atomic number $Z=238$. A black-body object is in the equilibrium of complex energies of masses, charges, and wavelengths if its radius $R_\text{eq} \approx 2.7665~G M_{\text{BBO}}/c^2$, which corrects the value of the photon sphere radius $R_{\text{ps}}=3G M/c^2$, taking into account the value(s) of the fine-structure constant(s), which is otherwise neglected in general relativity.

INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.

The Kwee van Woerden (KvW) method for the determination of eclipse minimum times has been a staple in eclipsing binary research for decades, due its simplicity and independence of external input parameters. However, its estimates of the timing error have been known to be of low reliability. During the analysis of very precise photometry of CM Draconis eclipses from TESS space mission data, KvW’s original equation for the timing error estimate produced numerical errors, which evidenced a fundamental problem in this equation. This contribution introduces an improved way to calculate the timing error with the KvW method. A code that implements this improved method, together with several further updates over the original method is presented as well. An example application on the CM Draconis light curves from TESS is given, where we show that its timing error estimates of about 1 second are in excellent agreement with error estimates obtained by other means.

The two main strategies used in this study are the binary representation and the decomposition of a natural number into many compound functions of odd function and even function. The Collatz conjecture regarding odd even numbers in number theory can be examined and discussed using them in this way: The sequence created by the finite iterations of the Collatz function becomes the ultimately periodic sequence if any natural number is the beginning value, proving the conjecture that has been held for 85 years.

In this paper, we present the results of the research concerning extraction of informative gene expression profiles from high-dimensional array of gene expressions considering the state of patients' health using clustering method, ensemble of binary classifiers and fuzzy inference system. Applying of the proposed stepwise procedure can allow us to extract the most informative genes taking into account both the subtypes of disease or state of the patient's health for further reconstruction of gene regulatory networks based on the allocated genes and following simulation of the reconstructed models. We used the publicly available gene expressions data as the experimental ones which were obtained using DNA microarray experiments and contained two types of patients' gene expression profiles: the patients with lung cancer tumor and healthy patients. The stepwise procedure of the data processing assumes the following steps: in beginning, we reduce the number of genes by removing non-informative genes in terms of statistical criteria and Shannon entropy; then, we perform the stepwise hierarchical clustering of gene expression profiles at hierarchical levels from 1 to 10 using SOTA clustering algorithm with correlation distance metric. The quality of the obtained clustering was evaluated using complex clustering quality criterion which is considered both the gene expression profiles distribution relative to center of the clusters were these gene expression profiles are allocated and the centers of the clusters distribution. The result of this stage execution was selection of the optimal cluster at each of the hierarchical levels which corresponded to minimum value of the quality criterion. At the next step, we have implemented classification procedure of the examined objects using four well known binary classifiers: logistic regression, support-vector machine, decision trees and random forest classifier. The effectiveness of the appropriate technique was evaluated based on the use of ROC analysis using criteria included as the components the errors of both the first and the second kinds. The final decision concerning extraction of the most informative subset of gene expression profiles was taken based on the use of fuzzy inference system, the inputs of which are the results of the appropriate single classifiers operation and output is the final solution concerning state of the patient's health. To our mind, the implementation of the proposed stepwise procedure of the informative gene expression profiles extraction create the conditions for increasing effectiveness of the further procedure of gene regulatory networks reconstruction and the following simulation of the reconstructed models considering the subtypes of the disease and/or state of the patient’s health.

Genomics involving tens of thousands of genes is a complex system determining phenotype. An interesting and vital issue is that how to integrate highly sparse genetic genomics data with a mass of minor effects into prediction model for improving prediction power. We find that deep learning method can work well to extract features by transforming highly sparse dichotomous data to lower dimensional continuous data in a non-linear way. This idea may provide benefits in risk prediction based on genome-wide data associated e.g. integrating most of the information in the genotype data. Hence, we developed a multi-stage strategy to extract information from highly sparse binary genotype data and applied it for risk prediction. Specifically, we first reduced the number of biomarkers via a univariable regression model to a moderate size. Then a trainable auto-encoder was used to extract compact representations from the reduced data. Next, we performed a LASSO problem process over a grid of tuning parameter values to select the optimal combination of extracted features. Finally, we applied such feature combination to two prognostic models, and evaluated predictive effect of the models. The results of simulation studies and real data applying indicated that these highly compressed transformation features could better improve predictive performance and did not easily lead to over-fitting.

This paper reports an experimental investigation on compression after low-velocity impact response for two lay-up configurations of symmetric CFRP laminated composite specimens obtained by reversing their angle-ply orientation, namely [0/-45/45/90]s versus [90/45/-45/0]s, the impact velocity of the projectile up to the BVID level being subsequently considered. To this aim, a modified Compression-After-Impact (CAI) test device is proposed that involves clamping the specimen's upper and lower edges between two adjustable wide and flat anti-buckling plates through a removable bolt-nut assembly. Such a solution relies on the fact that the specimen's active length is shortened, reducing the risk of global buckling. Besides, the bolts carry part of the load with minor localized bearing damage, provided that the metallic plates act as washers by supporting the bolt-bearing region laterally, thus avoiding crashing failures at the specimens’ loaded edges. With these settings, roughly the same percent decrease in the average values of maximum compression load (i.e., 22%) was recorded for both lay-up configurations impacted up to their BVID threshold, whereas in terms of compressive stiffness behavior, a reduction of 17 % was found for [0/-45/45/90]s specimens compared to 6 % obtained for [90/45/-45/0]s specimens.

This prospective study provides data on long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison to two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. Concentration of antibodies against SARS-CoV-2 spike protein in plasma 5-7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after first vaccine dose was 86% after ChAd compared to 35% and 39% after BNT and m1273, respectively (p &lt; 0.0001), and after second vaccine dose highest (89%) in the m1273/m1273 group (p &lt; 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

In this article, the new Hermite–Hadamard type inequalities are studied via generalized s-convexity on fractal sets. These inequalities derived on fractal sets are shown to be the generalized s-convexity on fractal sets. We proved that the absolute values of the first and second derivatives for the new inequalities are the generalization of s-convexity on fractal sets.

In this paper, a multi-mode waveguide-based optical resonator is proposed for an integrated optical refractive index sensor. Conventional optical resonators have been studied for single-mode waveguide-based resonators to enhance the performance, but mass production is limited owing to the high fabrication costs of nano-scale structures. To overcome this problem, we designed an S-bend resonator based on a micro-scale multi-mode waveguide. In general, multi-mode waveguides cannot be utilized as optical resonators, because of a performance degradation resulting from modal dispersion and an output transmission with multi-peaks. Therefore, we exploited the mode discrimination phenomenon using the bending loss, and the resulting S-bend resonator yielded an output transmission without multi-peaks. This phenomenon is utilized to remove higher-order modes efficiently using the difference in the effective refractive index between the higher-order and fundamental modes. As a result, the resonator achieved a Q-factor and sensitivity of 2.3x10³ and 52 nm/RIU, respectively, using the variational finite-difference time-domain method. These results show that the multi-mode waveguide-based S-bend resonator with a wide line width can be utilized as a refractive index sensor.

The Sidi Bou Othmane (SBO) pegmatite district is in the Central Jebilet massif, Occidental Meseta domain, Morocco. The SBO district is hosted essentially in a volcano-sedimentary series composed of the Late-Devonian Sarhlef shales. Pegmatite bodies crop out as dykes, which are oriented from N-S to E-W and are generally variably deformed with ductile and/or brittle structures with ante, syn- or post kinematic criteria. Petrographic observations of pegmatite dykes show that feldspars (i.e., albite, microcline) are the most abundant mineral phases, followed by quartz, micas, with tourmaline and accessory mineral as garnet, and zircon and secondary minerals as clinochlore, sericite, and illite. The geochemical study indicates that, according to the major pegmatite elements dykes of SBO have mainly a S-type granitic composition and are peraluminous granite with calc-alkalic affinity. The study of trace elements pointed out that SBO pegmatite formed under post-orogenic syn-collision context during the Variscan orogeny, by the partial melting of argilliferous sediment and can be ascribed to the muscovite-bearing pegmatite; moreover, they have a good potential on ceramic and contain minerals, such as feldspar, recently assessed as Critical raw materials by European Union.

From the merge of arts and crafts towards a practice for mass production of desirability, consumption and product development in a capitalist economy of scale, design has lost its natural ability of problem comprehension and tension alleviation. The modern world needs the creativity, flexibility, and responsiveness embedded into design practices, mostly when a behavioural change, either individual or organizational, is intended. Still, the informality nature of the field is creating a gap between the study, research, and industrial design practice. Here it is presented the Biology of Creativity Model (BoC) which is a design-by-analogy method that promotes an empowered design practice through analysis of mostly biology reference texts for enhanced creativity and innovation performance in a diverse array of contexts.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

Increased data acquisition by uncalibrated, heterogeneous digital sensor systems such as smartphones present new challenges. Binary metrics are proposed for the quantification of cyber-physical signal characteristics and features, and a standardized constant-Q variation of the Gabor atom is developed for use with wavelet transforms. Two different continuous wavelet transform (CWT) reconstruction formulas are presented and tested under different signal to noise ratio (SNR) conditions. A sparse superposition of Nth order Gabor atoms worked well against a synthetic blast transient using the wavelet entropy and an entropy-like parametrization of the SNR as the CWT coefficient-weighting functions. The proposed methods should be well suited for sparse feature extraction and dictionary-based machine learning across multiple sensor modalities.

The following article presents an analysis of the determinants of diabetes using a dataset containing the surveys of 2000 patients from the Frankfurt Hospital in Germany. The data were analyzed using the following models, namely: Tobit, Probit, Logit, Multinomial Logit, OLS, WLS with heteroskedasticity. The results show that the presence of diabetes is positively associated with "Pregnancies", "Glucose", "BMI", "Diabetes Pedigree Function", "Age" and negatively associated with "Blood Pressure". A cluster analysis is realized using the fuzzy c-Means algorithm optimized with the Elbow method and three clusters were found. Finally a confrontation among eight different machine learning algorithms is realized to select the best performing algorithm to predict the probability of patients to develop diabetes.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer.Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME).Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed.Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Various techniques to tackle the black hole information paradox have been proposed. A new way out to tackle the paradox is via the use of pseudo-density operator. This approach has successfully dealt the problem with a two-qubit entangle system for a single black hole. In this paper, we present the interaction with a binary black hole system by using an arrangement of the three-qubit system of Greenberger–Horne–Zeilinger (GHZ) state. We show that our results are in excellent agreement with the theoretical value. We have also studied the interaction between the two black holes by considering the correlation between the qubits in the binary black hole system. The results depict a complete agreement with the proposed model. In addition to the verification, we also propose how modern detection of gravitational waves can be used on our optical setup as an input source, thus bridging the gap with the gravitational wave’s observational resources in terms of studying black hole properties with respect to quantum information and entanglement.

From the hospital wastewater, a novel bacteriophage was isolated and characterized. According to characterization properties, this bacteriophage belongs to the Siphoviridae family, the maximum bacteriophage titer was recorded at 37°C and a pH of 7.2, had a 44,789 bp linear double-strand DNA genome, and within the genome sequence, there are 61 genes, all of which are encoded into proteins. Although this bacteriophage does not have any virulence factors or antimicrobial resistance genes and had specific lytic activity against some antimicrobial resistance S. aureus clinical isolates.

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

Axial resolution is one of the most important characteristics of a microscope. In all microscopes, a high axial resolution is desired in order to discriminate information efficiently along the longitudinal direction. However, when studying thick samples that do not contain laterally overlapping information, a low axial resolution is desirable as information from multiple planes can be recorded simultaneously from a single camera shot instead of plane-by-plane mechanical refocusing. In this study, we increased the focal depth of an infrared microscope non-invasively by introducing a binary axicon fabricated on barium fluoride substrate close to the sample. Preliminary results of imaging thick and sparse silk fibers showed an improved focal depth with a slight decrease in lateral resolution and increase in background noise.

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p&lt;0.0001 and 5% vs 11%, p&lt;0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p&lt;0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

The present work reports on the calculated electronic and magnetic structure of the binary Co-Ga system at high Co content. β-CoGa adopts a simple cubic CsCl type structure. Well-ordered CoGa does not exhibit collective magnetism but is a paramagnetic, metallic compound. Neither Co nor Ga deficiency induces magnetic order, however, ferromagnetism is observed for Co-Ga anti-site disorder. The magnetic moment per cell increases up to about 1.2 μB in the completely disordered body centered cubic structure. With increasing Co content, Co1+xGa1−x maintains the CsCl type structure and becomes ferromagnetic. Most important, a discontinuity of the magnetic order with composition is observed at about 10% excess Co, where a change from a low magnetic moment state to a high moment state is observed. This is accompanied by a change in the electronic structure and transport properties. The discontinuity is forced by the increasing exchange splitting related to the localized moment of the additional Co atoms that replace Ga. Subsequently, the magnetic moment increases continuously up to 2.5 μB for x=0.6. For x≳0.6, the structure changes to face centered cubic with random site occupation and the magnetic moment further increases. Above the magnetic discontinuity, the Curie temperature increases linearly with the Co content from the onset of ferromagnetism, until it reaches its maximum in pure Co.

In the article, we are trying to find a general law that describes the physical properties of a complex compound through the same physical properties of compound elements. For metal alloys operated under extreme conditions - neutron and proton irradiations and thermal heating, the mechanical properties of these alloys and their elements have been studied. It turned out that the ultimate tensile strength of tantalum alloys used in the design of space reactors can be expressed in terms of the weighted sum of the ultimate tensile strengths of its elements in the range of neutron doses: (0 - 0.96) displacement per atom (dpa) for Ta–10W alloy and (1.4 - 1.7) dpa for T–111 alloy with a neutron energy of more than 0.1 MeV. For tungsten binary alloys used in the design of fusion reactors, the Vickers hardness can also be expressed in terms of the weighted sum of the Vickers hardnesses of the alloy elements in the range of proton irradiation doses: (0 - 0.05) dpa for W-1%Re alloy, (0.05 - 0.2) dpa for W-3%Re alloy and (0.05 - 1) dpa for W-1%Ta with a proton energy of 1 MeV.

Magnetic and morphological properties of equiatomic B2-ordered FeRh thin films irradiated with single high-intensity ultrashort laser pulses are investigated. The goal is to elucidate the effect of femtosecond laser ablation on the magnetic properties of FeRh. We employed Scanning Magneto-Optical Kerr Effect (S-MOKE) microscopy to examine the magnetic phase after laser processing, providing high spatial resolution and sensitivity. Our results revealed the appearance of a magneto-optical signal from the bottom of ablation craters, suggesting a transition from antiferromagnetic to ferromagnetic behavior. Fluence-resolved measurements clearly demonstrate that the ablation threshold coincides with the threshold of the antiferromagnet-to-ferromagnet phase transition. The existence of such magnetic phase transition was independently confirmed by temperature-dependent S-MOKE measurements using a CW laser as a localized heat source. Whereas the initial FeRh film displayed a reversible antiferromagnet-ferromagnet phase transition, the laser-ablated structures exhibited irreversible changes in their magnetic properties. This comprehensive analysis revealed the strong correlation between the femtosecond laser ablation process and the magnetic phase transformation in FeRh thin films.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Sorghum grain processing can improve the nutritional content by promoting dietary properties that contribute to food security and economic development. The quality, nutritional content, and processing properties of sorghum bicolor grain can greatly affected by the inbred line races and variance in pericarp colour.The current study assessed the influence of the Husking Fraction Time Units (HFTU) process, which employed set time units per second (S), on the variation in the nutritional profile of fifty-one inbred line sorghum varieties based on distinct pericarp colours. When the assessment of the nutritional profile was involved: dry matter, total protein besides, namely mineral (P, K, S, Ca, Mg, Na, Fe, Zn, and Mn). The variety groups showed a significance value of (P < 0.05), indicating the study hypothesis's truth.The results demonstrated substantial impacts implied by the Husking Fraction Time Unit (HFTU) technique. This occurrence was noted when the dry matter percentage was increased in the husked products, specifically the endosperm (grits) and bran. The protein percentage redistributed by 19.2% compared to the whole grain and bran content. In comparison, the ratio of N/S was 14:1 in the S. bicolor and 12:1 in the kafirin in the bran part. Moreover, a strong correlation was observed among the examined minerals of S.bicolor and kafirin, such as the correlation between Ca: P, K: Na, and Fe: Zn attributed 80 (S) time unit, with correlation coefficients of R = 0.784 and R = 0.586, R= 517, R= 0.884, R= 0.745, and R = 0.893, respectively. At the same time, the 80 (S) time unit showed a significant effect on the colour property profile.The study results could benefit breeders and nutrition specialists in developing genotypes and processing sorghum grains, promoting research, and aiding several industrial sectors owing to the grain's adaptability and nutritional properties.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

In this paper, I introduce a new concept of representing numbers in base ; in other words, I have found new series for any number similar to series that could be written according to the collatz sequence which is called zi(n) in this article. These series need to end with 1. Then, we use two sets of rules to make a diagram which then proves the existence of such series for any number.In this diagram, by branching numbers into different branches in accordance to the modularity of 4 and continuing branching to the point that their numbers have enough common terms in their collatz series, we could reduce zi(n) to zi(k) so that k<n in any branch by Rule Number One. This diagram shows that zi(n) exists for every number, in other words, this proves the theorem (A) or zi-existence theorem. The proof of zi-existence theorem leads to a proof of the collatz conjecture because the collatz series could be written as a linear combination of such series that all of them end with 1, so the collatz series for any number ends with 1.

The present study aimed to evaluate the psychometric properties of the Greek version of the Jefferson Scale of Empathy—Student version (JSE-S) and its association with potential predictors among Greek-speaking undergraduate medical students. This study adopted a cross-sectional, comparative–descriptive research design. The study was conducted during October and November 2023. Cronbach’s α for the JSE-S was 0.846. Cronbach’s α values for the factors “perspective taking”, “compassionate care”, and “standing in the patient’s shoes” were 0.800, 0.715, and 0.748, respectively. The intraclass correlation coefficient for the JSE-S score in the test–retest study was 0.827 (95% CI = 0.647 to 0.915, p-value &lt; 0.001), indicating a high level of reliability. The participants showed moderate empathy levels. Females scored higher than males on the Greek version of the JSE-S (108.8 vs. 102.8, p-value &lt; 0.001). Moreover, students enrolled in the fourth academic year showed higher empathy mean scores than those enrolled in the first year (108.6 vs. 103.6, p-value = 0.012). Statistically significant empathy differences by specialty preferences or faith in God/supreme power were not found. The present study provided satisfactory evidence that the Greek JSE-S is a psychometrically sound measurement instrument. Empathy differences by gender were found in line with prior literature.

With the aim to develop novel scaffolds for sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt) protected mercapto acids, followed by removal of the acid labile S-Mmt group. This method allowed the efficient synthesis of the title compounds in high yield and purity, which were further used in the development a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with preformed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nanosized characteristics of the initial liposomes and allowed sustained release of calcein (which was used as a chromophore), providing evidence for the efficient synthesis of a novel drug release scaffold consisted of nanoliposome building blocks.

Sepsis is a serious and life-threatening medical emergency associated with dysregulated host immune responses to infection. Like cerebral vascular or acute cardiovascular incidents, sepsis is considered a time-dependent condition having severe and long-term consequences on human health. Apart from organ support, prompt administration of appropriate antimicrobial therapy is crucial to limit the burden of complications related to sepsis in ICU patients. The management of septic patients requires comprehensive and multi-disciplinary strategies for an adequate diagnosis. Most of the ICU population receives empirical antibiotic therapy without having a confirmed diagnosis. The misuse of antibiotics in intensive care units may increase the possibility of developing multidrug resistance along with considerable ecological side effects. The first doses of empirical anti-microbial therapy are slightly higher, regardless of the presence or absence of organ dysfunction, which may upregulate the production of circulating pro-and-anti-inflammatory mediators, having negative effects on the general well-being of the patients. This notion supports the introduction of individualized antimicrobial approaches based on local patterns of resistance to ensure the appropriate dosage of empirical therapy, as well as to limit the emergence of multidrug resistance in advanced-care patients. The adequacy and treatment duration must be viewed at regular intervals for effective de-escalation, and novel diagnostic approaches must be introduced to improve the quality of care in the ICU population.

As humans age, aberrancies in several signaling pathways occur. In the aging population, some patients display abnormal bone morphogenetic protein (BMP) signaling. This can lead to osteoporosis (OP), a debilitating bone disorder caused by an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery as it is crucial for bone formation. However, complications have been reported with rhBMP-2 and primary osteoblasts isolated from OP patients are unresponsive to BMP-2. While patient samples are available, previous medical history may alter results. Therefore, C57BL/6 mice, an aging model that displays aberrant BMP-signaling, can be utilized to investigate OP and aging. We show that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month mice similar to previous data. We show that a conjugation between BMP-2 and Quantum Dots (QDot®s) effectively binds to BMPRIa and can investigate BMP-2 activity. After incubating BMSCs with methyl-β-cyclodextrin (MβCD), BMP-signaling is restored in 15-month mice as shown by western blotting and the von Kossa assay. MβCD may be used to rescue BMPRIa and the BMP-signaling pathway can be utilized by future therapeutics to treat OP.

After three years of the onset of the pandemic, there is scarce evidence about how COVID-19 disease affect the female reproductive system, and consequently, the menstrual cycle. Since the common causes of secondary amenorrhea are considered as exclusion criteria in the studies about menstrual changes following SARS-CoV-2 infection, the prevalence of this event and the influencing factors in formerly menstruating women remains unknown. A retrospective observational cross-sectional study was conducted on Spanish adult women (N= 17,512), using an online survey; a subpopulation of SARS-CoV-2-infected-formerly menstruating women was included in the present analysis (n= 72). Collected data included general characteristics, medical history, and specific information about COVID-19 disease. 38.9% of the respondents experienced menstrual-related disturbances after suffering from the COVID-19 disease, unexpected vaginal bleeding being the most common (20.8%). Other alterations related with the length – “shorter” by 12.5% − and the flow − “heavier than usual” 30.3% − of the menstrual bleeding were reported. The binary logistic regression showed that being a perimenopausal woman (AOR 4.608, CI 95%, 1.018 – 20.856, p = 0.047) and having heavy menstrual bleeding (AOR 4.857, CI 95%, 1.239 – 19.031, p=0.023) are influential factors. This evidence could help health professionals to provide scientifically up-to-date information to their patients, empowering them to actively manage their reproductive health, especially in those societies where menstrual health is still a taboo.

Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current an-tibiotics are no longer functioning, severe infections are becoming practically untreatable. Con-sequently, the discovering of new classes of effective antimicrobial agents with novel modes of action is becoming increasingly urgent. The bioactivity of Cannabis sativa, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocan-nabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ8 and Δ9-tetrahydrocannabinols (Δ8-THC and Δ9-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5–8 µg/mL), including methicillin-resistant Staphylococcus aureus (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolones and tetracycline-resistant strains. Particularly, the not psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate that mature, and to rapidly exterminate MRSA persiters cells. On this scenario, CBG, as well as other minor not psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by Cannabis plants. Here, after an extensive overture on cannabinoids including their reported an-timicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details.

Photocatalytic degradation plays a crucial role in wastewater treatment, and the key to achieving high efficiency is to develop photocatalytic systems that possess excellent light absorption, carrier separation efficiency, and surface-active sites. Among various photocatalytic systems, S-type heterojunctions have shown remarkable potential for efficient degradation. This work delves into construction of S-type heterojunctions of ternary indium metal sulfide and bismuth ferrite nanofibers with introduction of sulfur vacancy defects and morphology modifications to enhance the photocatalytic degradation performance. Through the impregnation method, BiFeO₃/Zn₂S₄ heterojunction materials were synthesized and optimized30% BiFeO₃/Zn₂S₄ heterojunction exhibited superior photocatalytic performance with higher sulfur vacancy concentration than Zn₂S₄. The in-situ XPS results demonstrate that the electrons between Zn₂S₄ and BFO are transferred via S-Scheme, and after modification, Zn₂S₄ has a more favorable surface morphology for electron transport, and its flower-like structure interacts with the nanofibers of BFO, which has a further enhancement of the reaction efficiency for degrading pollutants. This exceptional material demonstrated a remarkable 99% degradation of Evans blue within 45 min and a significant 68% degradation of ciprofloxacin within 90 min. This work provides a feasible idea for developing photocatalysts to deal with the problem of polluted water resources under practical conditions.

Purpose – The paper aims to view how researchers have operationalized social impact assessment for construction projects over the last ten years. Design/methodology/approach – A systematic review was used to investigate case studies in the Social Life-Cycle Assessment (S-LCA) to analyze the application of the methodology. A qualitative study of 19 articles published between 2012 and 2022 was used to collect content on multiple categories impeding S-LCA through case studies in the construction industry. Findings – Our results showed the existence of limitations on the qualitative and quantitative aspects in measuring the social indicators. They were associated with the scoring method and the lack of data in some articles. Social implications – From this review, we understood that S-LCA has flaws in terms of the quality of the measurement, scoring method, and the lack of social data. Lack of social data means social impacts are being neglected and not assessed properly since there are several challenges pointed out throughout literature Originality/value – The originality of this research is that it focuses on case studies in the construction industry. It studies the operationalization of the S-LCA in this specific industry showing the different characteristics and challenges in the last 10 years.

Methyl Salicylate (MS), the principal constituent of Wintergreen oil (WO) was obtained from acetyl salicylic acid (ASA) by sequential transesterification-esterification reaction promoted by NbCl5for the first time. The reagents were added simultaneously, and the reaction process involved the transesterification and esterification reactions, which were accompanied by thin layer chromatography and gas chromatography. The conversion rate via GC was 100%, and the MS yield was 94%. A cytotoxicity of 50% and 64% for cultured S. aureus and metastatic melanoma cells, respectively, was observed for a concentration of 0.6 mg/mL, whereas no cytotoxicity for non-tumor cells was observed for this concentration, and it is considered to be the optimum concentration.

This study aimed to delineate the longitudinal antibody responses to the Pfizer- BioNTech COVID-19 vaccine (BNT162b2) within the Ugandan subset of the Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets. We enrolled 48 participants, collecting 320 specimens over 12 months after vaccination. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA concentrations (ng/ml) and optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, and the Wilcoxon test with Bonferroni correction. We showed a robust SIgG response within 14 days of the primary vaccine dose, consistent with global data. Remarkably, we observed no significant surge in S-IgG levels following the booster, contrasting trends other global populations. The S-IgM response was transient, and predominantly established thresholds, reflecting its typical early emergence and subsequent decline. S-IgA increased initially but declined six months post-vaccination, in line with the temporal dynamics of mucosal immunity. Eleven breakthrough infections occurred; however, all were asymptomatic, indicating a protective effect from the vaccination regardless of the participants' initial S-IgG serostatus. The Pfizer-BioNTech COVID-19 vaccine elicited strong S-IgG responses in the SSA demographic. However, antibody dynamics distinctly differed from global data highlight the significance of region-specific research and the necessity for customized vaccination strategies.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally, and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Methods: Using droplet digital polymerase chain reaction (ddPCR) we comprehensively analyzed and distinguished ccfDNA and ccf mtDNA in the serum and CSF of PD and control patients. Results: The quantitative analysis of serum ccf-DNA in PD patients demonstrated significant increase of ccf mtDNA and ccfDNA compared to healthy control patients and significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients compared to healthy controls. These decreases were not statistically significant, but were in agreement with previous data. In-terestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. Limitations: the small sample size of serum and CSF were the main limitations of this study. Conclusion: To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR and indicating the distribution of the copy number of ccf mtDNA, as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater than ccfDNA potential to lead the development of novel treatments for PD patients.

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

Intrusion detection is generally carried out by matching network traffic patterns with known attack patterns or by identifying abnormal network traffic patterns. One statistical methodological approach used in intrusion detection is Statistical Process Control (SPC) by constructing a control chart. Hotelling’s T2 control chart is a multivariate control chart commonly used to monitor the mean process. The performance of the T2 chart in monitoring mean shifts can be increased if a robust estimator is utilized. Based on previous research, T2 based on the Fast-MCD estimator has good performance in monitoring low to medium outlier contaminated data. Therefore, the MRCD estimator can be used to detect intrusion. On the other hand, this research focuses on developing a bootstrap-based robust Hotelling’s T2 charts with Fast-MCD and MRCD estimators for evaluating performance in detecting intrusion on intrusion detection datasets. Based application of UNSW-NB15, the proposed chart has better performance than the conventional T2 and Fast-MCD-based T2 despite the longer execution time.

The humoral response of the COVID-19 vaccine varies from person to person. It largely depends on prior SARS-CoV-2 infection, obtaining an adequate immune response, and leaving a trace of changing antibody concentration over time. We retrospectively analyzed five clinical cases from selected patients and employees of the oncology hospital. All mild COVID-19 convalescents received the BNT162b2-Comirnaty mRNA vaccine three or four times. The levels of SARS-CoV-2 IgM- and IgG-specific antibodies, as well as S-RBD antibodies, were analyzed for two years. The concentration of antibodies was assessed in the laboratory using the chemiluminescent immunoassay CLIA, MAGLUMI. Results: (1) Active autoimmune disease stabilized the level of IgG-specific antibodies after systemic mRNA vaccination for at least six months. (2) Post-vaccination IgG and S-RBD levels decreased when vaccination was performed within three months of onset. (3) The booster dose administered only increased the S-RBD antibody levels. Declining IgG-specific antibodies were observed. (4) The S-RBD IgG levels were not correlated with the SARS-CoV-2 IgG levels in the vaccinated convalescents. (5) Subsequent reinfection with SARS-CoV-2 after vaccination three times released a more significant specific antibody response. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive but not equivalent to a specific humoral response for SARS-CoV-2 IgG. We suggested that administering at least three doses of the mRNA vaccine should serve as the basis for immunization. The three-month interval may be the best alternative to an immunization schedule for non-immunocompromised people.

Background: Parkinson's disease (PD) is a global disease. However, there is a lack of research specifically focused on the AfrAbia population. Climate change, driven mainly by global warming, is linked to detrimental health impacts, including an increased frequency and intensity of heat waves. Neurological diseases, including neurodegenerative syndromes like Alzheimer's disease, Parkinson's disease, and motor neuron illnesses, have been increasingly seen and recorded in scientific literature. Although there is much literature demonstrating the growth in neurodegenerative disorders, the relationship between environmental variables such as global warming, air pollution, heavy metals, and pesticides and the higher occurrence of these illnesses is still unknown. Objective: The current article primarily aims to examine the relationship between climatic changes, air pollution, pesticides, heavy metals, and the occurrence of PD. Initially, we evaluate the influence of exposure to these variables on the cause or origin of Parkinson's disease. In addition, we will investigate how these variables disrupt processes such as excitotoxicity, oxidative stress, and neuroinflammation, all of which are strongly linked to Parkinson's disease (PD). Conclusions: This research presents a plausible rationale for the adverse effects of environmental influences on the brain, which are pivotal in the progression or onset of Parkinson's disease from an AfrAbian standpoint.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

The mechanistic influences of dopamine (DA) signaling and impact on motor function is nearly always interpreted from changes in nigrostriatal neuron terminals in striatum. This is a standard practice in studies of human Parkinson’s disease (PD) and aging, and related animal models of PD and aging-related parkinsonism. However, despite dozens of studies indicating an ambiguous relationship between changes in striatal DA signaling and motor phenotype, this perseverating focus on striatum continues. Although DA release in substantia nigra (SN) was first reported almost 50 years ago. assessment of nigral DA signaling changes in relation to motor function is rarely considered. Whereas DA signaling has been well-characterized in striatum at all 5 steps of neurotransmission (biosynthesis and turnover, storage, release, reuptake, and post-synaptic binding) in the nigrostriatal pathway, the depth of such interrogations in the SN, outside of cell counts, is sparse. However, there is sufficient evidence that these steps in DA neurotransmission in the SN are operational and regulated autonomously from striatum, and are present in human PD and aging, and related animal models. To complete our understanding of how nigrostriatal DA signaling affects motor function, it is past time to include interrogation of nigral DA signaling. This brief review highlights evidence that changes in nigral DA signaling at each step in DA neurotransmission are autonomous from those in striatum and changes in the SN alone can influence locomotor function. Accordingly, for full characterization of how nigrostriatal DA signaling affects locomotor activity, interrogation of DA signaling in SN is essential.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

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

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer. Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME). Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed. Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.