The opportunistic pathogen Pseudomonas aeruginosa is responsible for numerous chronic infections and has a case fatality rate of 50%. All P. aeruginosa strains express β–lactamase, an enzyme capable of inactivating β–lactam antibiotics, including penicillins. However, β–lactams are still considered desirable therapeutics by physicians due to their low toxicity. The short-term goal of this study was to create an optimal model for ampC expression in P. aeruginosa and determine the selecting antibiotic to be used during mutagenesis. In the long term, this study aims to renew effectiveness of β–lactams by identifying potential allosteric binding sites on β–lactamase for the development of novel β–lactamase inhibitors. To create a system for ampC expression, the chromosomal P. aeruginosa ampC gene encoding for β–lactamase was cloned into Escherichia coli, then conjugated into P. aeruginosa ∆ampC. β– lactamase assays on recombinant E. coli and P. aeruginosa detected much higher production of β–lactamase in pMMB67HE, which was confirmed with antibiotic susceptibility testing (AST) to numerous β-lactams. From AST, carbenicillin was chosen as the antibiotic to select functional β–lactamase production during mutagenesis. Future work includes conducting mutagenesis on ampC to identify allosteric binding sites on the β–lactamase enzyme that may enable the discovery of new β–lactamase inhibitors. This work allows for the development of novel β–lactamase inhibitors that could renew the utility of β–lactams and drastically reduce morbidity and mortality from chronic Pseudomonas infections.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to its inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The previous COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances when vaccination is not accessible or in individuals with compromised immune systems, drugs can give additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds including anti-viral. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Epigenetic modifications in the genome can affect gene expression without altering DNA sequence. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses have recruited cellular epi transcriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we are exploring the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing modulation processes and anti-viral effects on DNA and RNA viruses, and addressing future research objectives in this rapidly emerging field.

Hydrogel wound dressings hold great potential in eliminating bacteria and accelerating the healing process. However, it remains a challenge to fabricate hydrogel wound dressings that simultaneously exhibit excellent mechanical and photothermal antibacterial properties. Here we report the development of polydopamine-functionalized graphene oxide/calcium alginate/Polypyrrole cotton fabric-reinforced hydrogels (abbreviated as rGO@PDA/CA/PPy FHs) for tackling bacterial infections. The mechanical properties of hydrogels were greatly enhanced by cotton fabric reinforcement and an interpenetrating structure, while excellent broad-spectrum photothermal antibacterial properties based on the photothermal effect were obtained by incorporating PPy and rGO@PDA. Results indicated that rGO@PDA/CA/PPy FHs exhibited superior tensile strength in both the warp (289±62.1N) and weft directions (142±23.0N) similar to cotton fabric. By incorporating PPy and rGO@PDA, the swelling ratio was significantly decreased from 673.5% to 236.6%, while photothermal conversion performance was significantly enhanced with a temperature elevated to 45.0 ℃. Due to the synergistic photothermal properties of rGO@PDA and PPy, rGO@PDA/CA/PPy FHs exhibited excellent bacteria-eliminating efficiency for S. aureus (0.57%) and E. coli (3.58%) after exposure to NIR for 20 min. We believe that the design of fabric-reinforced hydrogels could serve as a guideline for developing hydrogel wound dressings with improved mechanical properties and broad-spectrum photothermal antibacterial properties for infected wound treatment.

The evolution of the H5 highly pathogenic avian influenza (HPAI) viruses has led to the emergence of distinct groups with genetically similar clusters of hemagglutinin (HA) sequences. In this study, a consensus H5 HA sequence was cloned into the baculovirus expression system. The HA protein was expressed in baculovirus-infected insect cells and utilized as the antigen for the production of an oil emulsion-based H5 avian influenza vaccine (rBacH5Con5Mut). 21-day old SPF chickens were immunized with this vaccine and then challenged at 21 days post-vaccination (dpv) with clade 2.3.2.1, clade 2.3.4.4 and clade 7.2 of H5 HPAI virus, respectively. The chicken sera of vaccinated chickens exhibited high hemagglutination inhibition (HI) titers against the rBacH5 vaccine antigen, while lower HI titers were observed against the different challenge virus H5 hemagglutinins. Furthermore, the rBacH5Con5Mut vaccine provided 100% protection from mortality and clinical signs. Virus isolation results showed that oropharyngeal and cloacal shedding was prevented in 100% of the vaccinated chickens when challenged with clade 2.3.2.1 and clade 2.3.4.4 H5 viruses. When the rBacH5Con5Mut vaccine candidate was administrated at one day of age, 100% protection was demonstrated against challenge of clade 2.3.4.4 virus at 3 weeks of age, indicating the potential of this vaccine for hatchery vaccination. Overall, the rBacH5Con5Mut vaccine candidate with a consensus HA antigen and a single dose can protect chickens against different clades of H5 HPAI viruses throughout the rearing period of broiler chickens without a boost, thus fulfilling the criteria for an efficacious broad-spectrum H5 avian influenza vaccine.

The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 minutes. The study showed efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was affected significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation was increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 hour using a 1.0 ppm AZT solution containing 3 ml of H2O2. The experimental data obtained was well-fitted to zero-order reaction kinetics. The results of this study were found to be superior when compared with those reported in the literature, with photocatalysis using nanomaterials and photolysis using irradiation and H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater. To this point, such a study has not been reported specifically for AZT photodegradation.

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC >32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Bisphenol A diglycidyl ether (BADGE) is widely existed in the inner coating of canned foods. It migrates into food and generate various derivatives in the process of storage, such as Bisphenol A (2, 3-dihydroxypropyl) glycidyl ether (BADGE·H2O), Bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl) and Bisphenol A (3-chloro-2-hydroxypropyl) (2, 3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H2O), which have negative effects on human health. A gold nanoparticle-based immu-nochromatographic assay for simultaneous detection of BADGE and its derivatives was developed by using a broad-spectrum polyclonal antibody, and the detection can be finished in 15 min. The visuali-zation of results was processed by Adobe Photoshop CC software to achieve quantitative analysis and the detection limit (IC15) is 0.97ng/mL. The recoveries of BADGE and its derivatives at various spiking levels in canned food samples ranged from 79.86% to 93.81%. The detection results of the proposed immu-nochromatographic assay were also validated by HPLC analysis, and got good consistency (R2=0.9580).

The current recommendation to avoid non-steroidal anti-inflammatory drugs (NSAIDs) in management of dengue virus disease is, as it was adopted earlier in COVID-19, scientifically considered of very low to low certainty. In this perspective I argue, for the first time globally, basing on real-life practice that NSAIDs might be lifesaving in early management of dengue virus disease as I originally argued and proved rightful in COVID-19. Moreover, I also argue that the Egyptian immune-modulatory Kelleni’s protocol, including nitazoxanide as an integral component, can be safely and effectively used to early manage COVID-19, human metapneumovirus, dengue virus disease, Zika virus separate or co-infections similar to what has already been experienced and published with separate or conjoined infections with SARS CoV-2, influenza, RSV and Norwalk viruses without the need of prior serological or molecular investigations to determine the causative agent.

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs to treat EV71 infections. In this study, we conducted an antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be relieved greatly by exposing virus-infected cells to extracellular low-pH culture media. Together, we have identified an FDA-approved antidepressant with the new indication for the broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. In the present work, two magnetic nanocomposites, based on Graphene Oxide (GO) and Multiwall Carbon Nanotubes (MWCNTs) were studied. The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of Iron Magnetic Nanoparticles (MNPs) was carried out in the presence of MWCNTs and GO using the Co-precipitation method. The second phase consisted of the adsorption of photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase was the encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, in order to obtain the magnetic nanocomposites: VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the PTT/PDT effect. This research describes the optical, morphological, magnetic and photophysical characterizations of nanocomposites and their application as antimicrobial agents. It was evaluated the antimicrobial effect of magnetics nanocomposites based on the Photodynamic/Photothermal (PDT/PTT) effect; for this purpose, doses of 65 mW cm-2 at 630 nm of light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite was able to eliminate colonies of E. coli and S. aureus, while VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to eliminate the three types of microorganisms; consequently, the latter is considered a broad-spectrum of antimicrobial agent in PDT and PTT.

Rare Earth Elements (REE), also known as Lanthanides (Ln3+), are a group of 17 elements showing peculiar physical and chemical properties. Unlike technological applications, very little is known about the physiological role and toxicity of Ln3+ on biological systems, in particular on microorganisms (e.g., bacteria), which represent the most abundant domains on our planet. Up to now, very limited studies have been conducted due to Ln3+ precipitation with some anions commonly present in the culture media. Therefore, the development of a minimal medium is essential to allow the study of Ln3+-microbial interactions, limiting considerably the precipitation as insoluble salts. In this regard, a new minimal culture medium capable of solubilizing large amounts of Ln3+, and allowing the growth of different microbial taxa, was successfully developed. Assays have shown that the medium is capable of solubilizing Ln3+ up to 100 times more than other common culture media and allowed the growth of 63 bacteria and 5 fungi. The kinetic growth of one yeast and one gram-positive bacterium has been defined, proving to support superior growth and biomass compared to other commonly used minimal media. Moreover, the sensitivity and uptake/absorption of a Bacillus stratosphericus strain was tested, highlighting its capability to tolerate concentrations up to 10 mM of either Cerium, Gadolinium or Lanthanum and accumulate different quantities of the three.

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7,196 participants, comprising 6,775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines, and believing in the virus's artificial origins (81%). Primary determinants of hesitancy included perceptions that the vaccine poses greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake.

A power factor correction (PFC) rectifier is compulsory for any electronic circuitry connected to the electrical grid. The majority of PFCs that are utilized are based on a step-up converter that supplies high DC voltage at its output terminal. Electric vehicle battery voltage varies from a few hundred to almost a thousand volts. Thus, an additional conversion step is obligatory when designing an all-brand universal charger. This paper presents a new type of front-end versatile step up / down three voltage level PFC. The rectifier can operate in continuous conduction mode or discontinuous conduction mode. First, the rectifier’s principle of operation is described, and then an innovative rectifier is analyzed for continuous and discontinuous conduction modes. Finally, the proposed theory is experimentally validated in a multiplier-less dual loop mode at discontinuous conduction modes. It was shown that although there is no multiplier use in the control circuitry, the power factor is near unity. It was revealed that the rectifier could swing the output voltage from 50 V to 900 V while the input voltage was 230 Vrms. The innovative topology suits any standard PFC rectifier, three-level voltage supplement, and dual-stage low-voltage power supply.

Metallo-β-lactamases (MBLs) are a group of Zn(II)-dependent enzymes that pose a major threat to global health. They are linked to an increasing number of multi-drug resistant bacterial pathogens, but no clinically useful inhibitor is yet available. Since β-lactam antibiotics, which are inactivated by MBLs, constitute ~65% of all antibiotics used to treat infections, the search for clinically relevant MBL inhibitors is urgent. Here, derivatives of a 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile (1a) were synthesised and their inhibitory effects assessed against representatives of each of the three subgroups of MBLs (B1, B2, B3). Several compounds are potent inhibitors of each MBL tested, making them excellent candidates for the development of broad-spectrum drug leads. In particular, compound 5f is highly potent across the MBL subfamilies, with Ki values in the low µM range. Furthermore, this compound also dis-plays synergy in combination with antibiotics such as penicillin G, cefuroxime or meropenem. This molecule thus represents one of the most promising compounds developed yet to combat MBLs.

Fire detection from satellite sensors relies on an accurate estimation of the unperturbed state of a target pixel, from which an anomaly can be isolated. Methods for estimating the radiation budget of a pixel without fire depend upon training data derived from the location's recent history of brightness temperature variation over the diurnal cycle, which can be vulnerable to cloud contamination and the effects of weather. This study proposes a new method that utilises the common solar budget found at a given latitude in conjunction with an area's local solar time to aggregate a broad-area training dataset, which can be used to model the expected diurnal temperature cycle of a location. This training data is then used in a temperature fitting process with the measured brightness temperatures in a pixel, and compared to pixel-derived training data and contextual methods of background temperature determination. Results of this study show similar accuracy between clear-sky medium wave infrared upwelling radiation and the diurnal temperature cycle estimation compared to previous methods, with demonstrable improvements in processing time and training data availability. This method can be used in conjunction with brightness temperature thresholds to provide a baseline for upwelling radiation, from which positive thermal anomalies such as fire can be isolated.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimal host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteosome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of Enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR and biophysical techniques. The present structural data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong. The most notable variation is the orientation of the phenylmethyl ester of GC-376 with the S4 subsite of the proteases. This is linked to the flexibility of the protein structure around the region of the catalytic triad shown by our NMR data. Other structural variations include distinct ligand interactions in subsites S1 and S2, influenced by the presence of Glu71 in CVB3 3CPro. Despite these differences, the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

Broad bean paste (BBP) is a traditional fermented soy food, and its high salt content not only prolongs the fermentation time but also threatens human health. In this study, three BBP-meju with different salt concentrations were prepared, and the effects of varying salinity on the fermentation process were comprehensively compared. The results showed that salt-reduced fermentation contributed to the accumulation of amino acid nitrogen, reducing sugars, free amino acids, and organic acids. Alcohols, esters, aldehydes, and acids were the main volatile flavor compounds in BBP-meju, and the highest total volatile flavor compounds were found in medium-salt meju. Bacillus, Staphylococcus, Aspergillus, and Mortierella were the dominant microbial communities during fermentation, and there were also three opportunistic pathogens, Enterobacter, Pantoea, and Brevundimonas, respectively. According to Spearman correlation analysis, Wickerhamomyces, Bacillus, Staphylococcus, and Mortierella all showed highly significant positive correlations with ≥3 key flavor compounds, which may be the core functional flora. Furthermore, the dominant microbial genera worked synergistically to promote the formation of high-quality flavor compounds and inhibit the production of off-flavors during salt-reduced fermentation. This study provides a theoretical reference for the quality and safety control of low-salt fermented soy foods.

ntroduction: Respiratory tract Infections are the greatest cause of death worldwide. Since its outbreak in 2019, the coronavirus pandemic (COVID-19) has been a challenge to humans in terms of treatment and prevention of this respiratory viral infection. The re-emergence of respiratory viral infections like influenza, pose a serious hazard to global public health because they occur seasonally. Creating broad-spectrum antiviral compounds for rapid action in the case of an outbreak crisis, as well as bioweapon defences, is critical. Human galectin-3 is found in high concentrations in activated T lymphocytes, epithelial and endothelial cells, and fibroblasts. ProLectin -I and ProLectin -M are both galectin antagonists. Blocking viral entry with a complex polysaccharide component "ProLectin-M" has downstream effects on viral reproduction enabling it to be used as a therapeutic tool and a safe alternative to conventional anti-viral medicines. Methods: In total, 3 cell based assays have been conducted to evaluate antiviral efficacy of ProLectin–I and ProLectin-M against SARS-CoV-2 virus, Influenza-A (H1N1), and human respiratory syncytial virus (hRSV) strain A2. ProLectin-M and ProLectin-I were evaluated for their anti-viral potency using SARS-CoV2 virus strain by viral RNA Extraction and qRT-PCR assays. The plaque assays were carried out to determine the antiviral activity of the test products (ProLectin-I and ProLectin-M) against ‘Influenza-A (H1N1)-A/PR/8/34 (TC adapted)’ and ‘Human respiratory syncytial virus (hRSV) strain A2’ in a cell based in vitro setting. As eference standard, "Oseltamivir Phosphate" and "Remdesivir" were used to determine antiviral activity of test products against H1N1 and hRSV strains respectively.Results: The IC_{50 of} ProLectin-M and ProLectin-I against SARS-CoV-2 virus was found to be 6248 ng/ml (6.2µg/ml) and 4207 ng/ml (4.2μg/ml) respectively. The CC₅₀ value was similar in both the test products i.e. >100 µg/ml. Against Influenza A (H1N1) strain, ProLectin-M exhibited 95 % reduction in the viral load at the test concentration of 21.8 µg/mL with an IC₅₀ value of 5.4 µg/mL whereas, ProLectin-I did not show any cytotoxicity till 250 µg/mL concentration. Against 'human respiratory syncytial virus (hRSV) strain A2, ProLectin-M exhibited 65 % reduction in the viral load at the test concentration of 43.75 µg/mL with an IC₅₀ value of 27.41 µg/mL whereas, ProLectin- I did not show any cytotoxicity till 250 µg/mL concentration. Conclusion: Both ProLectin-I and ProLectin-M have been reported to exhibit broad-spectrum antiviral activity in ‘in-vitro’ setting. ProLectin-M reducing influenza-A virus by 95% and hRSC strain A2 by 65%. To better understand broad spectrum antiviral activity of ProLectin-I and ProLectin-M, further pre-clinical research is warranted.

Hereditary cardiomyopathies (CMPs), including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Dilated Cardiomyopathy (DCM), and Hypertrophic Cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in Next-Generation Sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated to CMPs. Nowadays, a set of core genes is included in diagnostic panels for ARVC, DCM, HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines, provides a thorough overview of the genetic landscape of minor genes in CMPs and offers insights for future research and translation to clinical practice. Given the increasing knowledge on these less-understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

Placenta accreta spectrum (PAS) disorders are characterized by abnormal trophoblastic invasion into the myometrium, leading to significant maternal health risks. PAS includes placenta accreta (invasion &lt;50% of the myometrium), increta (invasion &gt;50%), and percreta (invasion through the entire myometrium). The condition is most associated with previous cesarean deliveries, and its incidence increases with the number of cesareans. Other risk factors include advanced maternal age, multiparity, and various uterine surgeries. The increasing global cesarean rates heighten the importance of early PAS diagnosis and management. The study reviewed molecular mechanisms driving PAS, focusing on signaling pathways, genetic expression, biomarkers, and non-coding RNAs involved in trophoblastic invasion. It explored genetic expression and key regulatory processes such as apoptosis, cell proliferation, invasion, and inflammation. The manuscript was compiled from recent scientific literature (2014 – 2024) from the Scopus, PubMed, Google Scholar, and Web of Science databases. Placenta Acreta Spectrum; acreta; increta; percreta; trophoblast invasion; miRNAs, lncRNAs; genetic expression; biomarkers; signaling pathways were the employed keywords to compile relevant literature. The PAS is an important obstetric health problem that challenges maternal health risks associated with abnormal trophoblastic invasion that relies on abnormal placentation, uterine scarring, and impaired decidualization. Identifying new biomarkers like AFP, sFlt-1, β-hCG, PlGF, and PAPP-A aids early detection and management. Understanding genetic expression and non-coding RNAs is crucial for unraveling PAS complexities. Besides, aberrant signaling pathways like Notch, PI3K/Akt, STAT3, and TGF-β offer potential therapeutic targets to modulate trophoblastic invasion. This review underscores the need for interdisciplinary care, early diagnosis, and ongoing research into PAS biomarkers and molecular mechanisms to improve prognosis and quality of life for affected women.

The Qiushuwan Cu-Mo deposit, located in the East Qinling molybdenum belt, which is a major mining site recognized for its enormous reserves of medium-sized molybdenum. In order to enhance our comprehension and ascertain supplementary mineral resources, it is critical to conduct an in-depth investigation of both the deep and peripheral regions. The primary goal of this study is to investigate the Qiushuwan Copper Molybdenum Mine, which is located in Zhenping County, Henan Province. The spread spectrum-induced polarization (SSIP) method is utilized as a means of conducting mining exploratory analysis. Significant findings have been obtained through the collection of SSIP data, geological analysis, and electrical parameter study of rock and ore samples along profile-80. By conducting a meticulous examination of the SSIP data at suitable frequencies, two prominent conductive ore bodies, specifically C2 and C4, have been successfully discovered. C2 exhibits a correlation with granite porphyry and molybdenum veins, while C4 is linked to a skarn deposit that contains a concentration of copper ore. The spatial differences in conductivity within the research area have been precisely characterized using resistivity models obtained from the SSIP data. The precision and dependability of our conclusions have been confirmed through the integration of borehole data and the matching of geological sections with inversion models. The recovered core samples show a diverse range of minerals, containing both valuable ores and minerals that have undergone alteration. Pyrite constantly appears with molybdenite in the majority of samples. The aforementioned results provide a strong foundation for future exploration initiatives and sustainable resource exploitation, enabling informed decision-making in the effective use and administration of natural resources. This study adds to the existing body of knowledge on the Qiushuwan Cu-Mo deposit and improves exploration methods in the region by utilizing the SSIP approach. The findings are a useful asset for geologists, mining experts, and stakeholders, offering essential knowledge for future exploration and sustainable utilization of resources.

This study investigates Autism Spectrum Disorders (ASD) in Greece, focusing on estimating prevalence and identifying regional disparities in children aged 4 to 7 years. Utilizing a quantitative, descriptive, and exploratory methodology, the research employed a structured questionnaire to gather extensive maternal and child health data. The sample consisted of 517 mothers of children diagnosed with ASD from all over Greece contributing to a nuanced understanding of ASD predictors. The study aims to elucidate the role of prenatal factors in the likelihood of an ASD diagnosis and their impact on the subsequent functionality of children with ASD. The study identified significant predictors of lower functionality in children with ASD, including higher maternal age, delayed ASD diagnosis, lower family income, and higher birth order. Prenatal health issues, such as vaginal bleeding and infections, also influenced functional outcomes. Notably, a family history of neurological or psychiatric conditions appeared protective. The regression model demonstrated robust predictive power, underscoring the complexity of genetic, environmental, and socioeconomic factors in ASD development. The findings advocate for early diagnosis and intervention, systematic screening, and addressing socioeconomic disparities to improve functional outcomes. The results support evidence-based service development and policy adjustments to enhance early identification, intervention, and rehabilitation for children with ASD. Establishing standardized case-recording procedures and an ASD register at national and regional levels is recommended for systematic monitoring and resource evaluation.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

The radio spectrum is a scarce and extremely valuable resource that demands careful real-time monitoring and dynamic resource allocation. Dynamic spectrum access (DSA) is a new paradigm for managing the radio spectrum, which requires AI/ML driven algorithms for optimum performance under rapidly changing channel conditions and possible cyber-attacks in the electromagnetic domain. Fast sensing across multiple directions using array processors, with subsequent AI/ML based algorithms for sensing and perception of the waveforms that are measured from the environment is critical for providing decision support in DSA. As part of directional and wideband spectrum perception, the ability to finely channelize wideband inputs using efficient Fourier analysis is much needed. However, a fine-grain fast Fourier transform (FFT) across a large number of directions is computationally intensive and leads to high chip area and power consumption. We address this issue by exploiting recently proposed approximate discrete Fourier transforms (ADFT) which has its own sparse factorization for real-time implementation at low complexity and power consumption. The ADFT is used to create a wideband multi-beam RF digital beamformer and temporal spectrum-based attention unit which monitors 32~discrete directions across 32~sub-bands in real-time using a multiplierless algorithm having low computational complexity. The output of this spectral attention unit is applied as a decision variable to an intelligent receiver that adapts its center frequency and frequency resolution via FFT channelizers that are custom-built for real-time monitoring at high resolution. This two-step process allows the fine-gain FFT to be applied only to directions and bands of interest as determined by the ADFT based low-complexity 2D spacetime attention unit. The fine-grain FFT provides a spectral signature that can find future use cases in neural network engines for achieving modulation recognition, IoT device identification, and RFI identification. Beamforming and spectral channelization algorithms, digital computer architecture, and early prototypes using a 32-element fully digital multichannel receiver and field programmable gate array (FPGA)-based high-speed software defined radio (SDR) is provided.

In the scientific community, it is difficult to find a consensus on defining BIM. Just as the acronym BIM is developed in different ways, it is also understood in different ways. Depending on its understanding, different definitions emerge. It is defined differently by organizations and standards, still differently by academics. Many years of academic discourse on the subject have failed to produce a solution. Despite the fact that the acronym BIM has already done its work for the construction industry, it still stirs up excitement. There is still no clear definition, as the view of BIM varies from one perspective to another. This article attempts to sort out the definitions cited so far by important organizations and key academics. The review was based on deep literature study has attempted to be inclusive and consistent. The question still remains open: do we need a single, correct definition of BIM? The aim of the article is to try to answer this question, open up a renewed discussion and come to a satisfactory consensus. BIM can be identified with an activity, product or system. The article breaks down the definitions of BIM, identifies six key attributes of BIM, presents the evolution of the understanding of BIM and proposes new definitions in a narrow and broad approach.

This paper describes some of the challenges that need to be addressed in order to develop collaborative spectrum sharing systems. The importance of these challenges stems from the assumption that rules for spectrum sharing can change after the deployment of radio networks and the whole system must be able to adapt to them. To address such a requirement, we used a policy-based approach in which transmissions are controlled by a policy interpreter system, and the policies can be modified during system operation. Our primary goal was to develop a prototype of such a system. In this paper, we outline the implementation of policy interpretation, automatic generation of transmission opportunities in case a request for transmission is denied by the policy reasoner, and the generation of rendezvous channels for the synchronization of otherwise asynchronously running software defined radios.

Due to the rapid development of unmanned aerial vehicles (UAVs) communication technology, UAVs are gradually competing with primary users (PUs) for spectrum resources. Cognitive radio (CR) is a promising solution to meet the needs. Cooperative spectrum sensing (CSS) is considered as an effective method to detect the PU signal and identify available spectrum resources for UAVs in a cognitive UAV network (CUAVN). However, the cooperative mode among multiple UAVs may incur a high overhead, resulting in performance degradation. Therefore, we introduce a differential sequential 1 (DS1), which incorporates a differential mechanism and leverages the sequential idea based on the classical voting rule to enhance cooperative performance and efficiency. In view of this, we formulate three scenarios to characterize the PU activity and introduce a multi-slot cooperative mode within a single UAV to realize cooperative gain. Further, only the information change about the PU status is sequentially calculated in DS1, and combined with a sequential idea, the efficiency of the voting rule is greatly improved. Moreover, the application of support vector machines (SVM) in dynamic selection enables the selection of the most suitable voting rule based on diverse sensing parameters. This dynamic selection process ensures optimal performance and efficiency by adapting the voting rule to the specific characteristics of the given scenario. Finally, simulation results demonstrate that the superiority of our proposal with respect to the detection performance, sample size and the energy efficiency is evident, which proves the high performance of the proposed policy.

Successful geophysical exploration works in Gucheng-Yaxi area located in Gaochun District, Jiangsu province, China, have been limited partly due to complex geological condition of the area and high artificial noise in data acquired using electrical and electromagnetic methods. In this work, we deployed the new anti-interference spread spectrum induced polarization method (SSIP) and audio magnetotellurics (AMT) method to detect a copper-polymetallic deposit in the area. Two-dimensional (2D) inversion results at Gucheng-Yaxi Area revealed a high chargeability anomalous zone on SSIP profile that coincided with a zone of moderate resistivity located between two resistor bodies on AMT profile. A follow up 1200 meters drill hole was established at this high chargeability-moderate resistivity zone which encountered polymetallic (copper, lead, zinc, gold and silver) mineralization at the depth ≥ 400 m. Drill hole data analysis showed that mineralization occurs interspaced in marble rock mass at varies depth. Furthermore, several low resistivity-weak chargeability sections were revealed and inferred attributed to Cretaceous sediments and faults. These faults are thought to have played critical role in the polymetallic mineralization genesis. In summary, this work demonstrated the successful of application of SSIP and AMT at detecting a metallic deposit in an area with high artificial noise. Hence the geophysical prospection potential of Gucheng-Yaxi area is great.

Circulating tumor DNA (ctDNA) in fluids has gained attention because ctDNA seems to identify tumor-specific abnormalities, which could be used for diagnosis, follow-up of treatment, and prognosis: the so-called liquid biopsy. Liquid biopsy is a minimally invasive approach and presents the sum of ctDNA from primary and secondary tumor sites. It has been possible not only to quantify the amount of ctDNA but also to identify (epi)genetic changes. Specific mutations in genes have been identified in the plasma of patients with several types of cancer, which highlights ctDNA as a possible cancer biomarker. However, achieving detectable concentrations of ctDNA in body fluids is not an easy task. ctDNA fragments present a short half-life, and there are no cut-off values to discriminate high and low ctDNA concentrations. Here, we discuss the use of ctDNA as a cancer biomarker, the main methodologies, the inherent difficulties, and the clinical predictive value of ctDNA.

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

To make wind power more competitive, it is necessary to reduce turbine downtime and reduce costs associated with wind turbine Operation and Maintenance (O&amp;M). Incorporating machine learning in developing condition-based predictive maintenance methodologies for wind turbines can enhance their efficiency and reliability. This paper presents a monitoring method that utilizes Base Density for the Support Vector Machine (BDSVM) and the evolutionary Fourier spectra of vibrations. This method allows smart monitoring of the function evolution of the turbine. A complex optimal function (FO) for 5-degree order has been developed that will be the boundary function of the BDSVM to timely determine the magnitude, frequency, and place of the failure occurring in wind turbine drive.

QSO B0218+357 is a blazar located at a cosmological redshift of 0.944. The source is gravitationally lensed by a spiral galaxy located at the redshift of 0.68. Strong gravitational lensing splits the signals emitted by the source into two components separated by 10-12 days, as observed in radio and gamma-ray bands. In July 2014 a GeV flare was observed by Fermi-LAT, triggering follow-up observations with the MAGIC telescopes at energies above 100 GeV. The expected time delay between the components allowed us to plan broad band MWL observations before, during and after the trailing component of the emission. The MAGIC observations at the expected time of arrival of the trailing component resulted in the first detection of QSO B0218+357 in Very-High-Energy (VHE, >100 GeV) gamma rays. It is both the farthest known VHE object and one of only a few Flat Spectrum Radio Quasars detected in this energy range. We report here the observed multiwavelength spectral and temporal properties of the emission during the 2014 flare.

With the increasing demand for energy worldwide, researchers from different fields have been striving to improve the sustainability and proper utilization of energy resources. Passive radiative cooling, as a natural energy transport method, can achieve cooling without additional external energy input. This review provides a comprehensive examination of passive radiative cooling, including its fundamental theories and latest development. A particular emphasis is placed on the diverse range of fields where passive radiative cooling has been applied, notably including but not limited to construction and architecture. The current state of applications, potential challenges that may arise with wider adaption and promising research directions for each field are thoroughly discussed. This review underscores the universal applicability and feasibility of passive radiative cooling and contributes to its future development by identifying promising areas for further exploration.

Considering the spectrum shortage problem of IoT devices, we introduce a collaborative spectrum sensing (CSS) framework in this paper to identify available spectrum resources, so that IoT devices can access it and meanwhile avoid causing harmful interference to the normal communication of the primary user (PU). However, in the process of the PU’s signal detection in IoT devices, the issue about the stopping time and decision cost arises. To this end, we propose a distributed cognitive IoT model, which includes two IoT devices independently using sequential decision rules to detect the PU. On this basis, we define the stopping time and cost function for IoT devices, and formulate an average cost optimization problem in CSS. To solve this problem, we further regard the optimal stopping time problem as a finite horizon problem, and solve the threshold of the optimal decision rule by dynamic programming. At last, numerical simulation results demonstrate the correctness of our proposal in terms of the global false alarm and miss detection probability, and it always achieves minimal average cost under various cost of each observation taken and thresholds.

Observations of the X-ray binary system Her X-1 by the AstroSat Soft X-ray Telescope 1 (SXT) were carried out in 2020 through 2023 with the goals of measuring X-ray spectrum changes with the 35-day disk rotation phase and measuring eclipses at different 35-day phases. The four multi-day long observations were scheduled during: turn-on to Main High (MH) and MH rise; MH state; Short High (SH) state; and Low State (LS). 35-day phase was determined using monitoring observations with the Swift Burst Alert Telescope (BAT). Nine eclipses were observed at a range of 35-day phases, with at least one eclipse during each observation. Data with dips were separated from data without dips. The variation of X-ray spectral parameters vs. 35-day phase shows the following: eclipse parameters are nearly constant, showing that the scattering corona does not change with 35-day phase; dips show an increase in covering fraction but not column density compared to non-dip data; the 1 keV line normalization indicates an origin in a small region near the continuum emission region, likely the magnetospheric accretion flow from the inner disk onto the neutron star; and the change in blackbody normalization (area) shows that the emission region is much larger than the 1 keV emission region, and consistent with the inner edge of the accretion disk.

Automatic and blind parameter estimation based on the inherent features of wireless signals is a major research area due to the fact that these techniques lead to the simplification of receivers, especially in terms of coarse synchronization, more importantly reduce down the signaling load at the control channels. Thus, in the literature many techniques are proposed to estimate a vast set of parameters including modulation types and orders, data and chip rates, phase and frequency offsets and so on. In this paper, a cyclostationary feature detection based method is proposed to estimate the carrier numbers and carrier spacing of carrier-aggregated direct sequence spread spectrum cellular signals blindly. The particular chip rate of the signal is also estimated through the process jointly. In the paper, after the proposed method is formulated, the measurement setup which is developed to collect the data for the validation of the proposed method is introduced. The measurement results are post-processed for performance analysis purposes. To that end, the method is investigated in terms of SNR values, different channel conditions, and measurement durations. Furthermore, the performance of the proposed method is compared with that of energy detection. Measurement results indicate superior performance of the proposed method under significant wireless channel impairments and in low-SNR regions.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

This study presents a comprehensive investigation into the spectrum and determinants of child abuse and neglect in Nkpor-Uno, a community in Anambra State, Nigeria. Through a descriptive surveys design, the study explores various forms of abuse and neglect experienced by children, as well as the underlying factors contributing to these phenomena. The population for the study consisted of 1000 parents/ caregivers who are residents of Nkpor-uno. The sample for the study consisted of 100 respondents, purposive sampling techniques was used for the study. The questionnaire was a self-designed structured questionnaire. Data collected were analyzed using frequency, mean and standard deviation. Findings reveal alarming prevalence rates of child maltreatment, including physical, emotional, sexual abuse, and neglect. Socioeconomic factors such as poverty, parental substance abuse, family dynamics, and inadequate sex education emerged as significant contributors to child maltreatment. The study underscores the urgent need for targeted interventions and support systems to address the root causes of abuse and neglect and safeguard the well-being and development of children in Nkpor-Uno. By raising awareness, enhancing access to resources, and promoting positive parenting practices, we can strive towards building a safer and healthier environment for children, ensuring they are protected from harm and given the opportunity to thrive.

Aiming at solving difficulties related to aero-engine classification and identification, the infrared spectra of aero-engine hot jets are measured by telemetry Fourier transform infrared spectrometer, and a six types aero-engine hot jet spectrum data set is generated. The spectrum data set were randomly sampled at a ratio of 8:1:1 to generate training set, validation set and prediction set. In this paper, a Peak Finding Siamese Convolutional Neural Network (PF-SCNN) is designed to match and classify spectrum data. In the first place, the matching pairs of training set and validation set are made independently with the labels of positive and negative samples creating. The spectrum feature extraction and distance similarity calculation are carried out by the Siamese convolutional neural network (SCNN). When entering the prediction phase, the prediction set and training set are integrated to predict in the trained model. The prediction set labels are ultimately determined by matching them with the training set labels having the highest similarities to ensure accurate predictions. To improve the operation efficiency of the SCNN, a peak finding method is introduced to extract the spectrum peaks. Peak positions of high frequency are counted, while the peak data are extracted. The peak data are used to take the place of the original data for training and prediction. The performance measures are defined as Accuracy, Precision, Recall, Confusion matrix and F1-score, and the prediction accuracy was up to 99%. The experimental results indicate that the proposed PF-SCNN is suitable for our spectral dataset and can complete the task of infrared spectrum classification of aero-engine hot jets.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

(1) Background: Parents of children with autism spectrum disorders often experience psychological distress, which can affect the quality of childcare they provide. It is crucial to screen for psychiatric symptoms among these parents. The Core Symptom Index (CSI) is a widely used tool for assessing general symptoms such as depression, anxiety, and somatic symptoms, with demonstrated validity and reliability across various populations. However, there is limited research on the validity and reliability of the CSI in the general Chinese population. This study aimed to investigate the psychometric properties of the Chinese version of the CSI among parents of children with autism spectrum disorders using Confirmatory Factor Analysis (CFA). (2) Methods: A total of 794 Chinese parents raising children with autism participated in this study. All completed the CSI, along with the social inhibition subscale of the Interpersonal Problems Inventory and the Couple Satisfaction Index. Factorial validity was assessed using CFA to determine how well the bifactor three-factor model fits the data. Various structural models were compared using model fit indices. Convergent and discriminant validity were examined by exploring correlations with the social inhibition subscale and the Couple Satisfaction Index. Invariance testing of the CSI was conducted across multiple groups based on gender, age, and education using CFA. The reliability of the CSI was evaluated using McDonald’s omega coefficients. (3) Results: The bifactor model emerged as the best-fitting model for the data, suggesting that the total score of the CSI adequately represents overall psychiatric symptoms. The CSI exhibited significant correlations with the social inhibition subscale (r = 0.41, p &lt; 0.01) and smaller correlation coefficients with the Couple Satisfaction Index (r = -0.16, p &lt; 0.05), indicating both convergent and discriminant validity. Invariant tests supported scalar invariance levels based on gender and age but only partial invariance for education. The Chinese version of the CSI demonstrated high consistency, with McDonald's omega coefficients ranging between 0.86 and 0.95. (4) Conclusions: The bifactor model of the Chinese version of the CSI is validated, making it a suitable tool for measuring depression, anxiety, and somatization symptoms among parents of children with autism spectrum disorders. Further research on other Chinese populations is encouraged.

This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase of multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide, encouraging scientific community to discover and develop new antimicrobial strategies. In the present work, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against antibiotic-resistant strains of H. pylori. Most of these novel antimicrobials exhibited minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, additive effect in combination with metronidazole and clarithromycin, as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggested that in vivo inhibition of HsrA triggered lethal global disturbances in H. pylori physiology, including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

Background: Atopic dermatitis (AD), a common dermatological condition, is often associated with significant economic and social burdens. Despite extensive studies globally, there is a gap in understanding the comprehensive impact of this condition in Romania. Objectives:This study evaluated the economic burden and quality of life impact of AD in Romania, considering both direct and indirect costs. Materials & Methods: A mixed methods cost of illness study was conducted from April to October 2023. A patient survey, expert reviews, and national health data analysis were used to assess direct medical costs (treatments, medical services), direct non-medical costs (transportation, accommodation), and indirect costs (productivity losses). Quality of life was evaluated using the EuroQol EQ-5D-5L instrument. Results: In 2022, the total cost of atopic dermatitis in Romania was 32.983.498 EUR for adults and 31.573.968 EUR for children. Adult costs included 24.534.603 EUR in direct and 8.429.884 EUR in indirect medical costs, with an average annual cost per patient of 447 EUR. Pediatric costs involved 15.026.781 EUR in direct and 16.516.410 EUR in indirect costs, averaging 290 EUR per patient annually. Conclusion: Care expenditure with AD management in Romania is substantially lower than in other countries, posing a significant economic burden, primarily driven by indirect costs. This study provides a foundation for future policy interventions and highlights the need for targeted management strategies for AD.

Ion current rectification (ICR) is the ratio of ion current by forward bias to by backward bias and is a critical indicator of diode performance. In previous studies, many attempts have been continued to improve the performance of this ICR, but there is the intrinsic problem for geometric changes that induce ionic rectification due to their fabrication problem. Additionally, the high ICR could be achieved in the narrow salt concentration range only. Here, we propose a multi-layered bipolar ionic diode based on an asymmetric nanochannel network membrane (NCNM), which is realized by soft lithography and self-assembly of homogenous-sized nanoparticles. Owing to the freely changeable geometry based on soft lithography, the ICR performance can be explored according to the variation of microchannel shape. Interestingly, very stable ICR performance can be achieved using the multi-layered 3D configuration for the bipolar diode in a broad range of salt concentrations (0.1mM ~ 100 mM). This demonstrates the promising potential of multi-layered NCNM for applications in highly concentrated electrolytes, such as biosensors, desalination, or energy harvesting.

Purpose Prospective life cycle assessment (pLCA) is a key method for providing environmental decision support for future technologies. The specific technology under study is often modeled by the practitioner (the so-called foreground system), whereas data for supply chains are sourced from life cycle inventory databases (the so-called background system). Within pLCA, it is paramount to consider possible future developments for both foreground and background systems to avoid a temporal mismatch between the specific technology under study and the wider economy, which could lead to incorrect conclusions. Therefore, and given the importance of future-oriented environmental decision support, efforts to develop prospective life cycle inventory (pLCI) databases have recently increased. However, there is still much to be improved to realize the widespread use of these databases and to have a stronger real-world effect on how future technology is designed. Methods This paper summarizes recent developments and structures the information chain behind pLCI databases. We then discuss conditions for the broad application of pLCI databases, and we propose priorities and ways forward to overcome existing challenges to foster the use of pLCI databases. Results The conditions are scientific integrity, usefulness to LCA practitioners, accessibility, usability, interpretability, and a continuous improvement process in which core stakeholders coordinate efforts to streamline the generation, sharing, and use of pLCI databases. Conclusions Priority should be given to installing a continuous process to improve the coverage and consistency of pLCI databases, to improve related guidance and documentation, and to remove practical barriers relating to the access and usability of pLCI databases in LCA software.

Introduction: Lipoyl transferase 2 is involved in biosynthesis of the lipoate. Lipoate is the cofactor for the glycine cleavage system and four dehydrogenase enzymes. Biallelic variants in LIPT2 causing severe neonatal encephalopathy was first described in 2017. Methods: Clinical data was collected by retrospective chart review after obtaining consent from parents. The pathogenicity of these variants was further delineated using a yeast model. The YEp352-LIPT2 plasmid was used as a template to generate the two patient variants using QuickChange Lightning Site-Directed Mutagenesis Kit. Results: Patient was a 15-month-old female who presented at 1 month with dystonia, developmental delay and feeding difficulties. MR Brain showed cortical malformations including colpocephaly, polymicrogyria and heterotopia. Patient had elevations in lactate (6.1 mmol/L) and glycine. Exome sequencing showed 2 variants of uncertain significance in trans in the LIPT2 gene: c.346 G>T and c.418C>T. Patient was started on lipoic acid, thiamine and COQ10. Yeast complementation experiments indicate that both patient mutation variants result in diminished function versions of the LIPT2 protein. Conclusion: We report the fourth case of LIPT2-related disorder. Proband shared significant overlap with previous patients, however had a distinct movement disorder and brain malformations which have not been previously described. Unlike most neurometabolic disorders where dystonia develops later after metabolic stroke in basal ganglia, LIPT2- related disorder seems unique due to early onset of dystonia due to energy deficit in the developing brain. Lipoic acid supplementation has not led to significant clinical improvement. Analyses in yeast indicate that novel variants are deleterious but have retained some functionality.

We propose a theory of ASD as a condition of comorbid cognitive impairments that corrupt the learning, encoding, and manipulation of episodic and semantic memories. We consider (i) episodic and semantic memory functions of the entorhinal-hippocampal complex, (ii) constraints on the transfer and encoding of these memory components into neocortical areas, and (iii) the demands of cognitively manipulating memories in distributed computations being necessary for goal oriented interactions. In ASD, learning and cognitive challenges manifest in diverse ways but especially in high-complexity model predictive control tasks with latent variables. ASD impairments in social interactions represent a prototypical example. Social interactions are at the high end of complexity and require processes (i)–(iii) to work in a concerted fashion due to the need for the learning and estimation of many, sometimes latent, parameters, including emotions, intention, physical and mental capabilities as well as the predictive modeling of these parameters for decision making and timed-action series. We put forth the idea that autism is a result of an arbitrary combination of otherwise not prominent corruptions in processes (i)–(iii). Together, these corruptions may severely impair intelligence and slow down learning, especially in high complexity learning tasks. Over time, slow learning may spare the spontaneous learning-by-doing method - namely, repetitive behavioral patterns, whereas behavioral failures related to complex tasks can restrict interest in such task, thus inducing a fear of novelty; conversely, the fear of novelty restricts interest and can slow learning down. We embed our thoughts into a predictive autoencoding, goal-oriented model of a deterministic world. We compare this model to others, such as the noisy brain model, the Bayesian prior theory, the mirror neuron theory and the weak central coherence theory. We argue that the predictive autoencoder model of the deterministic world harmonizes with these other models and embraces them in a straightforward way.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven a promising method for fast SOM content estimation. However, soil physical properties significantly affect the sensitivity of satellite hyperspectral imaging to SOM, leading to poor generalization ability of the estimation model. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on the spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root mean squared height, RMSH), and soil bulk weight (SBW), a soil spectral correction strategy was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPD) exceeding 1.4 in almost all bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, root mean square error (RMSE) of 5.74 g/kg, and RPD of 1.68. The prediction accuracy, R2, RMSE, and RPD of the model after migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction strategy based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. The performance comparison highlighted the advantages of considering soil physical properties in regional-scale SOM prediction.

Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

The Model-View-Controller (MVC) architecture, a cornerstone of modern software engineering, offers a robust framework for developing dynamic user interfaces. This paper conducts a broad analysis of MVC’s deployment across various sectors, emphasizing its critical role in technological advancement and market integration. By examining implementation strategies in web development, mobile applications, and enterprise solutions, the study illustrates how MVC enhances application manageability, promotes efficient code reuse, and facilitates parallel development. The paper explores the adoption of MVC principles within major technologies such as Java, .NET, and JavaScript frameworks, underlining its widespread acceptance. Additionally, the analysis covers the preferential use of MVC frameworks within diverse market sectors including technology enterprises, educational institutions, e-commerce, and financial services, which leverage MVC for superior data management and user experience. Emerging trends such as the shift towards the Model-View-ViewModel (MVVM) architecture and the integration of MVC with artificial intelligence and machine learning technologies are also discussed. This comprehensive review not only reaffirms MVC’s enduring relevance but also its adaptive evolution in response to emerging technological demands and market needs.

The concept of “hyperferritinemic syndrome” defines a complex pathophysiological and clinical entity, characterized by a systemic hyperinflammatory state, generally associated with elevated levels of proinflammatory cytokines (hypercytokinemia) and high serum levels of ferritin (hyperferritinemia), traditionally recognized as an iron-binding plasma protein involved in the storage of iron in a biologically available form for different physiological cellular processes. Recent studies have shown that ferritin has other important functions as well, operating both as a proinflammatory mediator and as a immunosupressive agent, its elevated levels in the serum being detected in various conditions associated with inflammatory states, such as infectious diseases, autoimmune and autoinflammatory disorders and, in some cases, in malignancies. Catastrophic antiphospholipid syndrome (cAPS), systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) and acquired forms of hemophagocytic lymphohistiocytosis (HLH), which includes macrophage activation syndrome (MAS), have been associated with hyperinflammatory states and dramatic elevations of serum ferritin, generating hyperferritinemic syndromes. Severe forms of coronavirus disease-2019 (COVID-19), in which MAS may frequently develop, has also been linked to the development of a hyperferritinemic syndrome. This review offers several insights into the physiological and pathophysiological roles of ferritin in several (hyper-)inflammatory diseases, but also into the causal entities, the underlying pathophysiological mechanisms, clinical manifestations and diagnostic features of somewhat obscure, yet potentially fatal pathological conditions, reunited under the concept of hyperferritinemic syndromes.

In this study, a modular multi-step photometric microflow injection analysis (micro-FIA) system for the automatic determination of Cu(II) in a bioreactor has been developed. The system incorporates diverse 3D-printed modules, including a platform formed by a mixer module to mix Cu(II) with hydroxylamine which reduces Cu(II) to Cu(I) linked to a diluter module via a Tesla valve, a chelation mixer module, a disperser module, and a detector module provided by a LED light source at λ= 455 nm and a light dependence resistor (LDR) as a light intensity detector. The system measures the color intensity resulting from the chelation between Cu(I) and neocuproine. The micro-FIA system has demonstrated good capability for automatic and continuous Cu(II) determination, in a wide range of Cu concentrations from 34 to 2000 mg L-1. The device exhibits a good repeatability (coefficient of variation below 2% across the concentration range), good reproducibility, and has an accuracy of around 100% between 600 to 1900 mg·L-1. Real samples were analyzed using both the micro-FIA system and an atomic absorption spectroscopy method, revealing no statistically significant differences. Additionally, a Tesla valve located before the detector substituted a 3-way solenoid valve, eliminating the need for moving parts.

The measurement range of a conventional current sensor is narrow because it is used with signals relative to the rated values of the measurement range from a voltage-type device. Consequently, multiple current sensors must be used in accordance with the measurement range. To address this problem, this paper proposes a new current sensor with a clamp-shaped part for low current measurement and a simple straight structure for high current measurement. The output signals of the proposed current sensor are amplified with a Hall element using the magnetic force of a rectangular air gap inside the clamp. To verify the characteristics of the proposed current sensor, a current was applied to an external load, and the value determined by the current sensor noted. Then, electromagnetic field analysis was performed through current sensor modeling and the results obtained compared to the actual sensor results. The proposed sensor had a 1% linearity in the output signals and exhibited dynamic characteristics over a wide current range.

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease manifesting as hypotonia, autism and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants, Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means was not capable of increasing the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a psychiatric condition in which susceptible alleles along with epigenetic memories contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (licensed) bands. Therefore, in this paper, we present a SDR based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe two use cases for the proposed framework.

Introduction. Autism Spectrum Disorder (ASD) includes different manifestations of an individual’s level of functioning. It is characterised by qualitative alterations in reciprocal social interaction and social communication, and the presence of repetitive behaviours and restricted interests. Based on two dimensions, three levels are differentiated: social communication, restricted interests, and repetitive behaviour. Aim. To gain knowledge of the application and usefulness of BRIEF‐P in the evaluation of Executive Functions (EFs) in people with ASD. Method. Out of a total of 161,773 potentially eligible published articles from different databases. 13 appropriate articles were revised and 4 articles were selected. Studies that were included evaluated samples involving individuals with ASD aged 2 to 8 years, and were published in English or Spanish during the period of 2012‐2022. Results. The executive profile obtained from the application of BRIEF‐P in individuals with ASD was analysed. Conclusion. Results confirm deficits in flexibility, although they are not conclusive. This may be due to aspects related to methodology, whereby the studies (i) include very large and heterogeneous age groups, (ii) do not discriminate based on the level of competence, and (iii) use instruments for evaluating Executive Functions that are not validated or adapted to people with ASD. Another reason is due to the lack of consensus in the very operational definition of the Executive Functions construct, with the studies focusing mainly on the cold dimension while ignoring the hot dimension.

Malaria, leishmaniasis, and African trypanosomiasis are protozoan diseases that constitute a major global health problem, especially in developing countries; however the development of drug resistance coupled with the toxicity of current treatments have hindered their management. The implication of certain enzymes (dihydrofolate reductase, DHFR) or proteins (potassium channels) in the pathogenesis of these protozoan diseases is undeniable. In this study, a series of three DHFR inhibitors (6-5 fused heterocyclic derivatives X, Y and Z) and one K+ channel blocker (E4031) were screened for their inhibitory effect on Leishmania donovani, Plasmodium falciparum, and Trypanosoma brucei. Resazurin assay was used to assess antitrypanosomal and antileishmanial activities of test compounds, whereas the antimalarial activity was appraised through SYBR Green I test. Moreover, cytotoxicity of test compounds was evaluated on Vero, Raw 264.7 and HepG-2 cells using the resazurin-based test, whilst their pharmacokinetic properties were predicted using the online tool pkCSM. As a result, compound Y revealed a selective (selectivity index range: 2.69 - &gt;61.4; Vero, Raw 264.7 and HepG-2 cells) and broad-spectrum antiprotozoal activity against L. donovani promastigotes (IC50: 12.4 µM) and amastigotes (IC50: 4.28 µM), P. falciparum (IC50: 0.028 µM), and T. brucei brucei (IC50: 0.81 µM). In addition, compound X inhibited the growth P. falciparum (IC50: 0.0052 µM) and T. brucei brucei (IC50: 6.49 µM). In silico screening of the active antiprotozoal compounds revealed positive drug-likeness scores as none of Lipinski's rule of five’s criteria was violated by these compounds. However, in-depth pharmacokinetic and mechanistic studies are warranted to support discovery of novel antiprotozoal agents against malaria, leishmaniasis, and African trypanosomiasis by repurposing K+ channel blocker and DHFR inhibitors.

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

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

In this case series, we examine the impact of the Titan-iR Pro® deep spectrum biotherapeutic device on brain function in healthy individuals. Here we present 15 participants, aged 26-68 years, who enrolled in this open-label study, designed to assess the effect of a single 15-minute course of deep spectrum biotherapy on brain function. Although symptom-free upon enrollment, participants had diverse medical histories with some displaying early signs of cognitive decline. As part of the evaluation, all participants engaged in electroencephalogram (EEG) recording sessions that focused on assessing event-related potential (ERP) evaluations, including audio P300 amplitudes and latencies (speeds), neurocognitive testing, and physical reaction times. Following the Titan-iR Pro intervention an improvement in EEG-based cognitive markers was observed. These results underscore the importance of further investigation into the potential of advanced and deep spectrum photobiomodulation in the prevention and treatment of cognitive decline and other neurological disorders.

We propose an electrocardiogram (ECG) signal-based algorithm to estimate the respiratory rate is a significant informative indicator of physiological state of a patient. The consecutive ECG signals reflect the information about the respiration because inhalation and exhalation make transthoracic impedance vary. The proposed algorithm extracts the respiration-related signal by finding out the commonality between the frequency and amplitude features in the ECG pulse train. The respiration rate can be calculated from the principle components after the procedure of the singular spectrum analysis. We achieved 1.7569 breaths per min of root-mean-squared error and 1.7517 of standard deviation with a 32-seconds signal window of the Capnobase dataset, which gives notable improvement compared with the conventional Autoregressive model based estimation methods.

We analyzed the plant-litter-soil continuum to investigate the carbon and nitrogen distribution and ecological stoichiometry of an evergreen broad-leaved forest at Dagangshan Mountain, Jiangxi. The results showed that the average C and N contents and C:N ratios in the leaves and fine roots among 6 different tree species were 401.87g/kg, 21.41g/kg, 19.27 and 348.64g/kg, 15.73g/kg, 23.97, respectively; the average C and N contents and C:N ratios were 323.06 g/kg, 12.76 g/kg, 25.58 respectively in leaf litter, and 16.40 g/kg, 1.09 g/kg, 16.27 respectively for soil. In contrast with the C content, the total N content of the fine roots and litter had a high coefficient of variation and a high spatial heterogeneity. We ranked the six different representative tree species according to total C and N content in leaves and fine roots. The results for each species were generally consistent with each other, showing a positive correlation relationship between total C and N content in the leaves and roots. Among them, S. discolor (Champ. ex Benth.) Muell. plants displayed high carbon and nitrogen storage capacities, and on the other hand, C. fargesii Franch., C. myrsinifolia (Blume) Oersted, A. fortunei (Hemsl.) Makino, and V. fordii (Hemsl.) Airy Shaw showed a high nitrogen transfer rate. Total soil N and C decreased with depth. Soil organic carbon (SOC), soil resistant organic carbon (ROC), total N, alkali nitrogen, NH4+-N and NO3--N contents were all also negative correlated with soil depth, but the contents of the NH4+-N and NO3--N did not change significantly; The spatial distribution of soil NO3--N was significantly heterogeneous. At 0-10 cm soil depth, SOC was positively correlated with alkaline nitrogen, and at 10-20 cm soil depth, SOC was significantly positively correlated with total N. In general, when soil carbon was abundant, nitrogen supply capacity was also high.

The Evolutionary history and domestication of Camels are largely unexplored because of the lack of well dated early archaeological records. However, limited records suggest that domestication of Camels likely happened in the late second millennium BCE. Over the time, camels have helped human for their basic needs like meat, milk, wool, dung to long routes transportation. This multifaceted animal has helped the mankind to connect through continents and in trade majorly through the Silk route. In India, both dromedary and Bactrian camels are found and their habitat is entirely different from each other, dromedaries inhabit in hot deserts and Bactrians are found mostly in cold places (Nubra Valley, Ladakh). Fewer studies on Indian dromedaries have been conducted but no such studies are done on Bactrian camels. It is needed to study the genetics of Bactrian camels to find out their genetic affinity and evolutionary history with other Bactrians found in different parts of the world. Furthermore, parallel studies on humans and Bactrian camel are required to understand the co-evolution and migration pattern of humans during their dispersal in different time periods.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

The rapidly increasing adoption of high-resolution accurate-mass methods in analytical laboratories has fueled demand for instruments that combine high performance and reliability with small size and greater ease-of-use. This paper presents the major design principles that are driving the evolution of the hybrid quadrupole-Orbitrap instrument architecture to enable a greater range of applications and users. These principles may be summarized as follows: better usage of physical space and better access for service by means of size reduction of pumping and ion optics; expanded use of technologies from electronics in ion-optical design; flexibility in performance via modularity of design of the hardware and software components; and, harmonization of interfaces with other instruments to facilitate sharing and transferability of analytical workflows. The design of a novel family of hybrid mass spectrometers is described in detail, and performance evaluation is carried out on a wide variety of samples for its three representatives: the Orbitrap Exploris 120, Orbitrap Exploris 240 and Orbitrap Exploris 480 mass spectrometers.The new instrument family is shown to offer compelling potential not only for high-end proteomics and biopharmaceutical applications, but also for screening, trace, targeted and clinical analysis by liquid chromatography/mass spectrometry methods.

Frost heave, which is the volumetric expansion of frozen soil, has great ecological significance, since it creates water storage spaces in soils at the beginning of the growing season in cold temperate forests. To understand the characteristics of frost heave in seasonally frozen soil and the factors that impact its extent, we investigated the frost heave rates of forest soil from different depths and with different soil moisture contents, using both lab-based simulation and in situ measurement in a broadleaved Korean pine forest in the Changbai Mountains (northeastern China). We found that frost heave was mainly affected by soil moisture content, soil type, and gravitational pressure. Frost heave rate increased linearly with soil moisture content, and for each 100% increase in soil moisture content, the frost heave rate increased by 41.6% (loam, upper layer), 17.2% (albic soil, middle layer), and 4.6% (loess, lower layer). Under the same soil moisture content, the frost heave rate of loam was highest, whereas that of loess was lowest, and the frost heave of the uppermost 15 cm, which is the biologically enriched layer, accounted for ~55% of the frost heave. As a result, we determined the empirical relationship between frost heave and freezing depth, which is important for interpreting the effects of frost heave on increases in the storage space of forest soils and for calculating changes in soil porosity.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

This paper brings to fruition recently found \cite{migdal2023exact} exact reduction of decaying turbulence in the Navier-Stokes equation in $3 + 1$ dimensions to a Number Theory problem of finding the statistical limit of the Euler ensemble. We reformulate the Euler ensemble as a Markov chain and show the equivalence of this formulation to the \textbf{quantum} statistical theory of $N$ fermions on a ring, with an external field related to the random fractions of $\pi$. We find the solution of this system in the turbulent limit $N\to \infty, \nu \to 0$ in terms of a complex trajectory (instanton) providing a saddle point to the path integral over the density of these fermions. This results in an analytic formula for the observable correlation function of vorticity in wavevector space. This is a full solution of decaying turbulence from the first principle without approximations or fitted parameters. The energy spectrum decays as $k^{-\frac{7}{2}}$. We compute resulting integrals in \Mathematica{} and present effective index $n(t) = -t\partial_t \log E $ for the energy decay as a function of time Fig.\ref{fig::NPlot}. The asymptotic value of the effective index in energy decay $n(\infty) = \frac{5}{4}$, but the universal function $n(t)$ is neither constant nor linear.

Generally, when cognitive radio users are in Underlay mode, through the analysis of the electromagnetic spectrum in time, frequency, space, and field of multiple dimensional data accounts for judging the inherent correlation of the radio spectrum used/idle state, this is the realization of cognitive radio users (secondary users, SUs) efficient access to the foundation of the limited spectrum resources. Therefore, how to efficiently use of spectrum status of each SU implementation of reception multidimensional combination forecasting is the core of this paper addressing the problem. In this paper, we propose a deep-learning hybrid model called TensorGCN-LSTM based on the tensor data structure. The model treats SUs deployed at different spatial locations under the same frequency and the spectrum status of SUs themselves under different frequencies in the task area as nodes and constructs two types of graph structures. Graph convolutional operations are used to sequentially extract corresponding spatial-domain and frequency-domain features from the two types of graph structures. Then, the long short-term memory (LSTM) model is used to fuse the spatial, frequency, and temporal features of the cognitive radio environment data. Finally, the prediction task of the spectrum distribution situation is accomplished through fully connected layers. Specifically, the model constructs a tensor graph based on the spatial similarity of SUs' locations and the frequency correlation between different frequency signals received by SUs, which describes the electromagnetic wave's dependency relationship in spatial and frequency domains. LSTM is used to capture the electromagnetic wave's dependency relationship in the temporal domain. To evaluate the effectiveness of the model, we conducted ablation experiments on LSTM, GCN, GC-LSTM, and TensorGCN-LSTM models using simulated data. The experimental results show that our model achieved better prediction performance in RMSE, and the correlation coefficient R2 of 0.8753 also confirmed the feasibility of the model.

Abstract: As the massive deployment of the heterogeneous IoT devices in the coexisting environment such as smart homes，Traditional channel-based spectrum sharing algorithms such as CSMA has great limitations to further optimize spectrum utilization. Therefore, exploring more efficient spectrum sensing algorithm becomes hot topic these years. This paper proposes Subcarrier-Sniffer, which utilizes Channel State Information (CSI) to sense the subcarrier-level detailed status of the spectrum. In order to evaluate the performance of Subcarrier-Sniffer, we implemented Subcarrier-Sniffer by USRP B200min, and the experimental results show that when the distance between Subcarrier-Sniffer and the monitored devices is not great than 7 m, the accuracy of subcarrier-level spectrum sensing could achieve 100% in our settings.

The widespread proliferation of sensor nodes in the era of Internet of Things (IoT) coupled with increasing usage of wireless spectrums especially the ISM band makes it difficult to deploy real-life IoT. Currently, the cognitive radio technology enables sensor nodes communicate with each other through the licensed spectrum bands as well as the free ISM bands. Cognitive radio networks (CRSNs) are considered as a promising solution to the problem of spectrum under utilization and artificial radio spectrum scarcity. The paradigm of dynamic spectrum access allows secondary users (SUs) to utilize wireless spectrum resources which belong to primary users (PUs) with minimal interference to PUs. Due to the dynamic spectrum availability and quality, routing for SUs in multi-hop CRSNs is a challenge. In this paper, we introduce novel routing metrics that estimate both the future spectrum availability and the average transmission time with the consideration of both the global statistical spectrum usage and local instant spectrum resources. In our novel routing metrics, one retransmission is allowed and considered to reduce the probability of rerouting upon PU's arrival. Then, we propose two routing algorithms for multi-hop CRSNs. Finally, we conduct simulations, whose results show that our proposed algorithms lead to a significant performance improvement over the reference algorithm.

We have presented a controllable and human-readable polynomial neural network (CR-PNN) that is the first human-readable neural network. One can imagine its influence on system identification. Subsequently, we developed a relation spectrum in a medical application, which is likely to stand alongside the Fourier spectrum. However, the system analysis methodology is incomplete in contrast to signal processing methodology. Here, we presented the system filters for the first time. In this paper, we used the simulation system to verify the availability of the system analysis methodology. The system analysis methodology showed great properties in system identification and filter. The contribution of this paper is the system analysis methodology: transform method (CR-PNN), relation spectrum, and system filter design.

It is always a difficult task to assign the peaks recorded from vibrational spectrum. Herein we explored a new pathway of density functional theory (DFT) simulation to present three kinds of spectra of ice XIV and can be referenced as inelastic neutron scattering (INS), IR, and Raman experimental spectrum. The INS spectrum is proportional to phonon density of states (PDOS) while the photon scattering signals reflect the normal vibration frequencies near the Brillouin zone (BZ) center. Based on good agreements with experimental data, we identified the relative frequency and made scientific assignments by normal vibration modes analysis. The debating two hydrogen bond (H-bond) peaks among ice phases from INS have been discussed and the dynamic process of H-bond vibrations were found to be classified into two basic modes. we deduce that two H-bond modes are a general rule among ice family and more works are ongoing to investigate this subject.

The redshifted 21 cm line signal is a powerful probe of the cosmic dawn and the epoch of reionisation. The global spectrum can potentially be detected with a single antenna and spectrometer. However, this measurement requires an extremely accurate calibration of the instrument to facilitate the separation of the 21 cm signal from the much brighter foregrounds and possible variations in the instrument response. Understanding how the measurement errors propagate in a realistic instrument system and affect system calibration is the focus of this work. We simulate a 21 cm global spectrum observation based on the noise wave calibration scheme. We focus on how measurement errors in reflection coefficients affect the noise temperature, and how typical errors impact on the recovery of the 21 cm signal, especially in the frequency domain. Results show that for our example set up, a typical VNA measurement error in the magnitude of the reflection coefficients of the antenna, receiver, open cable which are 0.001, 0.001, 0.002 (linear) respectively would result in a 200 mK deviation on the detected signal, and a typical measurement error of 0.48∘, 0.78∘, 0.15∘ in the respective phases would cause a 40 mK deviation. The VNA measurement error can greatly affect the result of a 21 cm global spectrum experiment using this calibration technique, and such a feature could be mistaken for or be combined with the 21 cm signal.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by persistent deficits in social interaction and communication, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Brain neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid (VPA) or acetaminophen (APAP) or ingestion of propionic acid (PPA) can increase the risk of ASD. Recently, epigenetic influences on ASD have been brought to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here we specifically focus on the molecular influence of the above-mentioned drugs on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. It is concluded that a better understanding of these phenomena can lead to more effective interventions in ASD.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition, characterized by persistent deficits in communication/social interaction and restricted and repetitive patterns of behavior, interests or activities. It is usually identified in childhood, despite late diagnoses in cases of greater functionality. Havighurst proposes a set of fundamental tasks throughout the life cycle, whose achievement is probably compromised in the ASD, even though it lacks scientific evidence. This study innovates, as it is based on Havighurst's theoretical model for understanding the development process of three adults and one young person, diagnosed with ASD level I, at different life stages. Through the methodology of life histories, interviews were subject to content analysis. Results pointed out the early detection and interventions importance, minimizing adversities, above all by those who had late diagnoses. Self-perceived success, not expected, was found in some development tasks (e.g. conscience and morality development). Also were noticed expected limitations related to ASD (e.g. difficulties in relationships with peers and in the labor market inclusion). Probably, in cases of greater severity and less functionality/autonomy, there would be greater failure in development tasks. It is crucial to improve research on this developmental model and on the factors that delay the diagnosis, including cases of different levels of severity.

The etiology of autism spectrum disorder (ASD) has not yet been completely elucidated. Through time, multiple attempts have been made to uncover the causes of ASD. Different theories have been proposed, such as that it is caused by “Gods Wrath,” alternations in the gut–brain axis with an emphasis on gut dysbiosis, post vaccine complications, and genetic or even autoimmune causes. In this review we present data covering over 170 000 participants at age ranging from 2 to 14 years focusing on human cell changes rather than using animal models found in previous studies. The male/female ratio was 4:1. Data collection occurred in many countries covering ethnically diversified subjects. Moreover, we aim to show how the progress in genetic techniques influence the explanation found in medical White Papers based on the human genetic samples we have observed from our studies

Neural networks require a large quantity of training spectra and detector responses in order to learn to solve the inverse problem of neutron spectrum unfolding. In addition, due to the under-determined nature of unfolding, non-physical spectra which would not be encountered in usage should not be included in the training set. While physically realistic training spectra are commonly determined experimentally or generated through Monte Carlo simulation, this can become prohibitively expensive when considering the quantity of spectra needed to effectively train an unfolding network. In this paper, we present three algorithms for the generation of large quantities of realistic and physically motivated neutron energy spectra. Using an IAEA compendium of 251 spectra, we compare the unfolding performance of neural networks trained on spectra from these algorithms, when unfolding real-world spectra, to two baselines. We also investigate general methods for evaluating the performance of and optimizing feature engineering algorithms.

The main goal of the paper is to compare the effects of the wave spectrum, computed using the Discrete Interaction Approximation (DIA) and the Webb–Resio–Tracy (WRT) methods, on statistical wave properties such as skewness and kurtosis. The statistical properties are obtained by integrating the three-dimensional free-surface Euler equations with a high-order spectral method combined with a phenomenological filter to account for the energy dissipation due to breaking waves. In addition, we investigate the minimum spatial domain size required to obtain meaningful statistical wave properties. The numerical simulations are performed over a physical domain of size 4.13 km × 4.13 km. The results indicate that statistical properties must be computed over an area of at least 4 km2. The results also suggest that selecting a more computationally expensive WRT method does not affect the statistical values to a great extent. The most noticeable effect is due to the energy dissipation filter that is applied. It is concluded that selecting the WRT or the DIA algorithm for computing the wave spectrum needed for the numerical simulations does not lead to major differences in the statistical wave properties. However, more accurate energy dissipation mechanisms due to wave breaking are needed.

The arguments on the origin and evolution of the evergreen broad-leaved forest in eastern Asia, especially in the evolutionary process, exist generally, even contrary in some cases. The origin and evolution of the flora of eastern Asia, the formation time of Asian monsoon, and the implications from phylogenetic and molecular biogeographic studies in some important taxa, as well as in palaeobotanical evidences, are debatable. Most researches from different disciplines suggested that the monsoon in Miocene is a key to diversification of eastern Asian flora and its evergreen broad-leaved forest. The common view is that the evergreen broad-leaved forest of East Asia is closely related to the monsoon intensity and developments, which are caused by the uplift of Himalaya-Tibet, during or after the mid-Miocene. The analysis on the floristic elements show that the present subtropical evergreen broad-leaved forest in eastern Asia could have an early or ancient tropical origin and a tropical Asian affinity, but their species are dominated by the Chinese endemic or eastern Asian distribution, many of which are the tropical sister ones. The time of Himalayan uplift and intensity of monsoon climate is believed the key for the formation of the evergreen broad-leaved forest in eastern Asia. Combined existing palaeobotanical findings, the uplift of Himalayas and the formation of monsoon climate, as well as floristic elements of the subtropical evergreen broad-leaved forest, we believe that it was evolved from a Asian tropical rain forest after mid-Miocene in southeastern region of eastern Asia, while the ancient subtropical evergreen broad-leaved forests in southwestern region continuously evolved into the present subtropical ones.

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder, is increasingly diagnosed and significantly affects communication, behavior, and social interaction. The current diagnostic framework, guided by the DSM-5, has limitations that may lead to clinical gaps due to overlapping symptoms of ASD and other disorders. This study proposes a comprehensive approach to enhance ASD diagnosis through clinical stratification based on comorbidities. We applied precision medicine techniques to identify and categorize ASD into ten clinical profiles. Our findings contribute to a more profound understanding of ASD, including its varied clinical manifestations and comorbidities, and facilitate the development of personalized therapeutic strategies.

A new method for multi-shot reconstruction of high-energy photon distributions in the context of studying the interaction between a beam and a plasma in plasma wakefield acceleration (PWFA) experiments is presented. The study investigates the effects of beam perturbations on betatron radiation and analyzes how these perturbations can lead to hosing, a transverse instability that can degrade the quality of the beam. The potential of betatron radiation spectroscopy as a non-invasive diagnostic technique for PWFA experiments is also emphasized.

Purpose: Pitch plays an important role in auditory perception of music and language. This study provides a systematic review with meta-analysis to investigate whether individuals with autism spectrum disorder (ASD) have enhanced pitch processing ability and identify the potential factors associated with processing differences between ASD and neurotypicals. Method: We conducted a systematic search through six major electronic databases focusing on the studies that used nonspeech stimuli to provide a qualitative and quantitative assessment across existing studies on pitch perception in autism. We identified potential participant- and methodology-related moderators and conducted meta-regression analyses using mixed-effects models. Results: On the basis of 22 studies with a total of 464 participants with ASD, we obtained a small-to-medium positive effect size (0.26) in support of enhanced pitch perception in ASD.Moreover, the mean age and non-verbal IQ of participants were found to significantly moderate the between-studies heterogeneity. Conclusion: Our study provides the first meta-analysis on auditory pitch perception in ASD and demonstrates the existence of different developmental trajectories between individuals with ASD and neurotypicals. Non-verbal ability can be a significant contributor to the lower-level/ local processing bias in ASD. We highlight the need for further investigation of pitch perception in ASD under challenging listening conditions. Future neurophysiological and brain imaging research studies with a longitudinal design are also needed to better understand the nature of the atypical processing in ASD to obtain new insights into the underlying neural mechanisms and to help guide auditory-based interventions for improving language and social functioning.

Autism Spectrum Disorders (ASD) are neurodevelopmental disturbances affecting social skills, whose incidence worldwide is dramatically increasing. Together with the rise of ASD prevalence, several immune conditions are following the same trend, including Atopic Dermatitis (AD), with a possible clinical relationship with ASD. To date, their pathogenesis is still unknown, but several studies highlighted the relevance of gene-environment interactions to the onset of both disorders. Among potential contributing factors, microRNAs (miRNAs), small molecules capable of controlling gene expression and targeting mRNA transcripts, might represent one of the major circulating link, unraveling the connections between neurodevelopmental and immune conditions. We conducted a systematic literature review, under the PRISMA guidelines, trying to define the panel of common miRNAs involved in both ASD and AD. The review retrieved articles published until December 13, 2018, in PubMed, ScienceDirect, PsycARTICLES and Google Scholar. We found a handful works dealing with miRNAs in ASD and AD, with the most overlapping dysregulated miRNAs being miR-146 and miR-155. Two possible compounds are abnormally regulated in both ASD and AD subjects, possibly cross-contributing to the interactions between the two disorders, setting the basis to investigate more precisely the possible link between ASD and AD from another, not just clinical, perspective.

Vaccine antigens must present the correct conformation of viral fusion glycoproteins to elicit effective immune responses. Virus-like particles (VLPs) serve as promising vaccine platforms because they mimic the membrane-embedded conformations of fusion glycoproteins on native viruses. Here, we employed SARS-CoV-2 VLPs (SMEN) presenting ancestral, Beta, or Omicron spikes to identify the variant that elicits potent and cross-protective immune responses in the highly sensitive K18-hACE2 mouse model. A combined intranasal and intramuscular administration regimen of the SMEN vaccine generated effective immune responses and was predominantly mediated by antibodies with minor contributions from T cells. Immunization with SMEN presenting an ancestral spike resulted in 100, 75, or 0% protection against ancestral, Delta or Beta VOC-induced mortality, respectively, whereas SMEN presenting the most divergent Omicron spike provided only limited protection (50%, 0%, and 25%) against ancestral, Delta, and Beta variants, respectively. By contrast, SMEN with a Beta spike offered 100% protection against the variants used in this study. Thus, the Beta variant not only overcame the immunity produced by other variants, but also elicited diverse and effective immune response. Our findings suggest that leveraging the Beta variant spike protein can enhance SARS-CoV-2 immunity, potentially leading to a more comprehensive vaccine against emerging variants.

Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

Recent years have witnessed a breakthrough in identification of a trimer-of-hairpins motif within viral envelopes that triggers a broad range of virus-host fusion. Identifying a domain capable of controlling virus-host fusion remains a challenge due to sequence diversity, heavy glycan shielding and multiple conformations. Here, we report that HR2, a prevalent heptad repeat sequence comprising an alpha-helical coil anchored in viral membranes, is an accessible site to triterpenes, a class of widely distributed natural products. Triterpenes and their derivatives inhibit the entry of Ebola, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes, upon activation by ultraviolet light, capture the viral envelope via crosslinking the HR2 coil. Profiling the Ebola HR2 sequence using amino acid substitution, surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) spectroscopy disclosed six constitutive residues that are accessible to triterpenoids, leading to wrapping of the hydrophobic helix by triterpenoids and blocking of the HR1-HR2 interaction, which is critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses. Our findings might translate into a shared mechanism that host utilize natural product triterpenoids to antagonize membrane fusion of respective viruses, complementing the current repertoire of antiviral agents.