Physical symptoms are defined as symptoms for which adequate examination does not reveal a sufficient underlying root cause, e.g., pain and fatigue. The extant literature of the neurobiological underpinnings of physical symptoms has been largely inconsistent and primarily consists of (clinical) case-control studies with relatively small samples sizes. Therefore, we studied the association of brain morphology with physical symptoms in pre-adolescents from two independent and population-based cohorts. This study included 2,683 individuals from the Generation R Study (51% girls, 10.1 ± 0.6 years old) and 10,567 pre-adolescents from the ABCD Study (48% girls, 9.9 ± 0.6 years old). High- resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Physical symptoms were evaluated using the somatic complaints syndrome scale from the parent-reported school-age version of the Child Behavior Checklist. Linear regression models were fitted for global brain metrics (i.e., cortical and subcortical grey matter volume and total white matter volume) as well as surface-based vertex-wise measures (surface area and cortical thickness). Analyses were initially conducted separately in each cohort and later meta-analysed. No associations were observed in either cohort separately. In the combined vertex-wise meta-analysis of both cohorts; the right hemisphere surface area, most notably the rostral middle frontal gyrus, superior frontal gyrus and anterior cingulate cortex, were related to physical symptoms after correcting for multiple comparisons (cluster area = 1,882 mm2). The present study, which is the most representative and well-powered to date, suggests that surface area, but not other measures of brain morphology, are modestly related to physical symptoms in pre- adolescents. While these effects are subtle, future longitudinal research is warranted to elucidate whether such associations indicate a cause or a consequence of the physical symptoms.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

We have investigated the antiferromagnetic phase transition in the frustrated and multiferroic hexagonal manganites $h$-(Y$_{0.98}$ Eu$_{0.02}$)MnO$_3$ (YEMO) and $h$-YMnO$_3$ (YMO). Elastic neutron scattering has been used to study in detail the phase transition in YMO and YEMO in zero pressure and in YMO at a hydrostatic pressure of 1.5~GPa. In zero pressure, we find the critical temperature $T_{\rm N} = 72.11(5)$~K and 71.3(1)~K and the critical exponent $\beta = 0.206(3)$ and 0.22(2), for YEMO and YMO, respectively. This is in agreement with earlier work by Roessli {\em et al.}. In applied hydrostatic pressure of 1.5~GPa, the ordering temperature increases to $T_{\rm N} = 75.2(5)$~K, in agreement with earlier reports, while $\beta$ is unchanged. Inelastic neutron scattering was used to determine the anisotropy spin wave gap at the phase transition, expected from spin wave theory to close with a critical exponent $\beta'$ identical to the one of the order parameter, $\beta' = \beta$. Our results indicate that the gap in YEMO indeed closes at $T_{\rm N}=72.4(3)$~K with $\beta' = 0.24(2)$, while the in-pressure gap in YMO closes at 75.2(5)~K with an exponent of $\beta' =0.19(3)$. In addition, the low-temperature anisotropy gap was found to have a slightly higher absolute value under pressure. The consistent values obtained for $\beta$ in the two systems support the likelihood of a new universality class for triangular, frustrated antiferromagnets.

In this paper, we introduce two discrete degenerate random variables, namely the degenerate binomial and degenerate Poisson random variables. We deduce the expectations of the degenerate binomial random variables. We compute the generating function of the moments of the degenerate Poisson random variables, which leads us to define the new type degenerate Bell polynomials, and hence obtain explicit expressions for the moments of those random variables in terms of such polynomials. We also get the variances of the degenerate Poisson random variables. Finally, we illustrate two examples of the degenerate Poisson random variables.

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.

The impact of riparian wetlands on the cycling, retention and export of nutrients from land to water varies according to local environmental conditions and is poorly resolved in catchment management approaches. To determine the role a specific wetland might play in a catchment mitigation strategy, an alternative approach is needed to the high frequency and spatially detailed monitoring programme that would otherwise be needed. Here, we present a new approach using a combination of novel and well-established geochemical, geophysical and isotope ratio approaches. This was developed and tested against a 2-year high-resolution sampling programme in a lowland permeable wetland in the Lambourn catchment, UK. The monitoring programme identified multiple pathways and water sources feeding into the wetland, generating large spatial and temporal variations in nutrient cycling, retention and export behaviours within the wetland. This complexity of contributing source areas and biogeochemical functions within the wetland were effectively identified using the new toolkit approach. We propose that this technique could be used to determine the likely net source/sink function of riparian wetlands prior to their incorporation into any catchment management plan, with relatively low resource implications when compared to a full high frequency nutrient speciation and isotope geochemistry-based monitoring approach.

Dysfunction of the WW domain-containing adaptor with coiled-coil, WAC, gene underlies a rare autosomal dominant disorder, DeSanto-Shinawi syndrome (DESSH). DESSH is associated with facial dysmorphia, hypotonia, and cognitive alterations, including attention deficit hyperactivity disorder and autism. How the WAC protein localizes and functions in neural cells is critical to understanding its role during development. To understand the genotype-phenotype role of WAC, we developed a knowledgebase of WAC expression, evolution, human genomics, and structural/motif analysis combined with human protein domain deletions to assess how conserved domains guide cellular distribution. Then assessed in a cell type implicated in DESSH, cortical GABAergic neurons. WAC contains conserved charged amino acids, phosphorylation signals, and enriched nuclear motifs, suggesting a role in cellular signaling and gene transcription. Human DESSH variants are found within these regions. We also discovered and tested a nuclear localaization domain that impacts the cellular distribution of the protein. These data provide new insights into the potential roles of this critical developmental gene, establishing a platform to assess further translational studies, including the screening of missense genetic variants in WAC. Moreover, these studies are essential for understanding the role of human WAC variants in more diverse neurological phenotypes, including autism spectrum disorder.

To address the issue of reduced orbit estimation accuracy resulting from discrepancies between in-orbit measured geomagnetic field values and IGRF model values in autonomous orbit estimation of microsatellites based on geomagnetic field measurements, this study introduces an adaptive cubature H-infinity filtering algorithm. Firstly, it presents the low-altitude orbital dynamics model and geomagnetic field measurement model for microsatellites. Subsequently, within the adaptive cubature H-infinity filtering algorithm, a spherical simplex rule and a second-order Gaussian-Legendre quadrature criterion are employed to compute the spherical surface integral and radial integral. Additionally, a spherical simplex-radial quadrature rule is proposed to enhance the approximation accuracy of nonlinear Gaussian weighted integrals. Furthermore, by integrating extended H-infinity filtering based on game theory with the cubature quadrature rule, an inverse proportional relationship between constraint level and filtering innovation is established. This allows for adaptive adjustment of the constraint level to enhance robustness against model errors. Finally, through semi-physical simulation experiments, it is demonstrated that compared with traditional algorithms, the proposed algorithm improves autonomous orbit estimation position accuracy of microsatellites by 7.49%, while also enhancing velocity accuracy by 3.1%, thus validating its effectiveness.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

Autogenous demineralized dentin matrix (ADDM), derived from human extracted tooth, is commonly used as a bone-graft substitute to reconstruct alveolar defects when placing dental implants. The purpose of this retrospective study is to examine efficacy of ADDM in terms of surgical complications and marginal bone resorption by analyzing the medical records and radiographs of patients who received ADDM graft from 2008 to 2011 in our institute. Occurrence of complications, marginal bone loss around implants were investigated with regard to the type of defect, location of bone grafting, and types of bone graft techniques. ADDM-based bone grafting was performed on 221 sites in 82 patients and 208 implants were placed afterwards: The percentage of complications after bone grafting was 15.84%, and the implant survival rate was 95.19%. All complications were resolved with conventional treatment except for the 10 cases of osseointegration failure. The average marginal bone loss was 0.31 mm at the last examination after the average follow-up period of 7.2 years. Within the limitation of this study, the results of long-term follow-up are consistent with the short-term results of relevant studies. ADDM can produce promising clinical outcomes when used for alveolar ridge augmentation around implants.

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.

Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomization (MR). Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566), and rMDD (cases=17,451; controls=62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g. cIVW), highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR_cIVW 0.90 per SD increase; 95% CI 0.85- 0.95; p=0.0003); erythrocyte copper (OR_cIVW 0.97; 95% CI 0.95- 0.99; p=0.0004); and 25(OH) vitamin D (OR_cIVW 0.81; 0.66- 0.99; p=0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR_cIVW 1.03; 95% CI 1.02-1.05; p=0.0003) and rMDD (OR_cIVW 1.08; 95% CI 1.00-1.08; p=0.06), and serum magnesium on rMDD (OR_cIVW 1.21; 1.01- 1.44; p=0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates, and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Over the past decades, overweight and obesity has become a global epidemic and the leading threat for death. To prevent the serious risk, an overweight or obese individual must apply a long-term weight-management strategy to control food intake and physical activities, which is however, not easy. Recently, with the advances of information technology, more and more people can use wearable devices and smartphones to obtain physical activity information, while they can also access various health-related information from Internet online social networks (OSNs). Nevertheless, there is a lack of an integrated approach that can combine these two methods in an efficient way. In this paper, we address this issue and propose a novel mobile-social framework for health recognition and recommendation, namely, H-Rec². The main ideas of H-Rec² include (1) to recognize the individual's health status using smartphone as a general platform, and (2) to recommend physical activity and food intake based on personal health information, life science principles, and health-related information obtained from OSNs. To demonstrate the potentials of the H-Rec² framework, we develop a prototype that consists of four important components: (1) an activity recognition module that senses physical activity using accelerometer, (2) a health status modeling module that applies a novel algorithm to generate personalized health status index, (3) a restaurant information collection module that collects relevant information from OSN, and (4) a restaurant recommendation module that provides personalized and context-aware recommendation. To evaluate the prototype, we conduct both objective and subjective experiments, which confirm the performance and effectiveness of the proposed system.

Tubulin superfamily (TSF) proteins are widespread and known for multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. Functions of the lesser-known archaeal TSF proteins are beginning to be identified, and show surprising diversity, including homologs of tubulin and FtsZ, and a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we defined sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identified CetZ groups and diversity amongst archaea, and identified potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. At least three subfamilies of orthologous CetZ proteins were identified in the archaeal class Halobacteria, including CetZ1 and CetZ2 and a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another and to cell shape and motility phenotypes across diverse Halobacteria. Amongst other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales affiliated strongly with Halobacteria CetZs, suggesting they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting a potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods included nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. The findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis and motility.

In applied mathematics, statistics, operation research, physics, and engineering mathematics, confluent representations of hypergeometric functions in one and two variables are known to exist, and their occurrence in a variety of applications is also well recognised. In this article, we intend to present a new derivation of the extended Watson summation theorem for the Kim et al. given series 4F3. We assessed four attractive integrals involving generalized hypergeometric function as an application. With a few particular cases, this note will come to an end. In the results given above, symmetry appears on its own.

In this paper, inspired by recent articles of G. Anatriello and G. Vincenzi (see \cite{Ana}), and G. Cerda-Morales (see \cite{Cer1,Cer2}), we will introduce the third-order $\overline{h}$-Jacobsthal and third-order $\overline{h}$-Jacobsthal--Lucas sequences and their associated quaternions. The new results that we have obtained extend most of those obtained in \cite{Cer2}.

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

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

The past years saw the rise of genomic biobanks and mega-scale meta-analysis of genomic data that promise to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limit the global understanding of disease risk and intervention efficacy, but also inhibit viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared, and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable, computable, operate without access to raw data due to privacy concerns. But they must be comparable, both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of commonly used genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks, locally and internationally, increase the accuracy of association analyses, and inform developmental efforts.

To obtain an accurate and reproducible experimental results in microbial fuel cell (MFC), it is important to know ‘anode maturation biofilm’ to produce a stable and maximum performance. For this purpose, four single chamber MFCs were tested in this study. The linear sweep voltammetry (LSV) polarization tests illustrated that maximum power densities of three MFCs became stable after 9 weeks. Although there were variations afterwards, such variations were negligible. Average maximum power densities from the 9th to the 17th week were 2,990 mW/m2 (MFC-4), 2,983 mW/m2 (MFC-2), 2,368 mW/m2 (MFC-3) and 837 mW/m2 (MFC-1). Polarization resistance shows that MFC-1 had much larger anode resistance (36.6-85.4 Ω) than the other MFCs (1.7-11.6 Ω). Anodic cyclic voltammetry (CV) shows that current production increased over time and MFC-1 had much smaller current production (24.4 mA) than the other MFCs (31.0-34.9 mA) at 17th week. The increased current production indicates anode biofilm became more mature over time, but overall cell performance did not increased accordingly. Possibly due to the bad inoculation, MFC-1 showed the lowest performance. However, its performance was restored to the initial performance and anode resistance was reduced by 47% at 17th week. This study shows that the optimum anode maturation time is 9 weeks and that bioanode performance is a key factor for MFC performance. This study also shows than LSV polarization and CV tests are accurate and non-destructive measurement methods for diagnosing anode performance.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Understanding swash zone dynamics is of crucial importance for coastal management as the swash motion, consisting of the uprush of the wave on the beach face and the subsequent downrush, is responsible for driving changes the beach morphology trough sediment exchanges between the sub-aerial and sub-aqueous beach. Improved understanding of the probabilistic characteristics of these motions has the potential to allow coastal engineers to develop improved sediment transport models which, in turn, can be further developed into coastal management tools. In this paper, novel descriptors of swash motions are obtained by combining field data and statistical modelling. Our results indicate that the probability distribution function (PDF) of shoreline height (p(ζ)) and trough-to-peak swash heights (p(ρ)) measured at a high energy, sandy beach were both inherently multimodal. Based on the observed multimodality of these PDFs, Gaussian Mixtures are shown to be the best method to statistically model them. Further, our results show that both offshore and surf zone dynamics are responsible for driving swash zone dynamics, which indicates unsaturated swash. The novel methods and results developed in this paper, both data collection and analysis, could aid coastal managers to develop improved swash zone models in the future.

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.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

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

Source water quality is a key determinant of drinking water quality. The recast European Union 2020/2184 drinking water directive (DWD) introduced the obligation for comprehensive risk assessment in drinking water supplies, including the water source and incorporated new elements of natural origin in the list of parameters to be monitored. The current study is the first comprehensive assessment of 15 natural elements (B, Ba, Be, Ca, Co, K, Li, Mg, Mo, Na, Se, Sr, Ti, U and V) in 1155 (82%) Hungarian drinking water sources, including surface water, bank filtered and groundwater sources. Parameters posing a risk to health (Se, V and U) were typically below the lower limit of quantification (LOQ), but higher concentrations (max. 7.0, 17 and 41 µg/L, respectively) may occur in confined locations, the latter exceeding the DWD parametric value in one water supply. Li in a small geographical area, Mg and Ca in the majority of the water supplies reached the concentration range assumed to be protective to health. Water sources were grouped in 6 clusters based on their element distribution, some of them also showing clear geographical patterns. Water types were not differentiated, with the exception of karstic waters (dominated by Ca and Mg). None of the investigated parameters are expected to be a source of public health concern.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

Research rarely explores LGBTQ+ youth bullying in the context of culture-specific outcomes (e.g., LGBTQ+ identity development) and what can mitigate the impact of peer stressors. This study used a concurrent mixed methods design to explore how experiences of peer victimization predicted LGBTQ+ youth’s identity development (i.e., stigma sensitivity, concealment motivation, and difficult process) and whether social support and outness served as protective, moderating factors. The mixed-methods approach provides a culture-specific context via qualitative inquiry to inform whether the quantitative findings align with how youth qualitatively discuss their experience of bullying, negative outcomes, and social support. Our sample consisted of 349 LGBTQ+ youth 14-17 years old who completed a survey (quantitative sample), and a subset of 39 LGBTQ+ youth who completed a semi-structured interview (qualitative sample). Our quantitative findings indicated that greater overall peer victimization was positively related to LGBIS-revised subscales of stigma sensitivity, concealment motivation, and difficult process, where both outness and social support moderated such relations. Qualitatively, victimized youth also reported stigma sensitivity and concealment motivation, while also endorsing how being out and having a support system played a role in their experience of being victimized. These qualitative findings align with our quantitative findings that classmate support mitigated the effects of peer victimization on difficulty of coming out. Implications for practitioners and researchers are provided.

This article introduces a novel payload structure, which has been experimentally proven to have smaller impact force while the carried internal electronics remains intact. The study describes in details how materials and geometric structures were chosen based on information analysis. It is clarified how possible geometric structures and materials can be chosen to yield optimal efficiency. Finite element method simulations were carried out to investigate the mechanical properties of several geometric structures, which has led to the dodecahedron form. For the frame, Polylactic Acid were chosen as an optimal material. A low air pressure test for parts of the structure, and also the whole structure were carried out with successful results. Drop tests, with force measuring sensors and high speed videos, were carried out for measuring and comparing the maximal impact force of classical payloads and the novel one. Laboratory and real life tests demonstrated that the developed new structure is safer and it is applicable.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

As the demand of heating and air conditioning is increasing day by day due to getting a comfortable life, for that reason, the market for heat pump and air conditioning systems or both, is seeing a steady increase in low global warming potential. All researchers on heat pump and air conditioning systems are searching for environmentally friendly refrigerants. However, a significant number of contemporary refrigerants (HCFCs) have the potential to cause global warming and ozone depletion, such as those found in heat pump air conditioning systems. Using more environmentally friendly refrigerants, including hydrocarbon and blend refrigerant mixtures, is one way to lower GWP and Ozone depletion potential. This study examines the performance of several alternative refrigerants, including R32, R134A, R410A, R22, and R290. In order to examine the performance of R290, theoretical and simulation results are compared on various refrigerants while taking into account a number of performance parameters, including the refrigerant energy efficiency ratio, mass flow rate, coefficient of performance, cooling capacity, and compressor work for one ton of refrigeration (1TR) air conditioners. One player with a very low GWP is R290. However, the only drawback is that it can catch fire and is hazardous to use in split-type commercial heat pump air conditioning applications. The environmental and thermo physical properties of HC-290 are significantly better than those of other materials, according to theoretical and simulation studies utilizing Cool Pack software, hence it is a viable replacement.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild type (WT) and knock out (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. Tail suspension test (TST) was performed in TRPA1 WT and KO animals. C-FOS immunohistochemistry was carried out on TRPA1 WT animals. DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on Trpa1 KO mice. DMTS administration induced neuronal activation in stress-related brain areas such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy in stress-related disorders.

In this paper a full state feedback control of a double inverted pendulum on a cart (DIPC) are designed and compared. Modeling is based on Euler-Lagrange equations derived by specifying a Lagrangian, difference between kinetic and potential energy of the DIPC system. A full state feedback control with H infinity and H 2 is addressed. Two approaches are tested: open loop impulse response and a double inverted pendulum on a cart with full state feedback H infinity and H 2 controllers. Simulations reveal superior performance of the double inverted pendulum on a cart with full state feedback H infinity controller.

This paper presents a particular tunneling method or new Austrian tunneling method (NATM) which plays an important role in reducing the subsidence of the Earth surface and the damage to the structures in urban areas. It has a wide range of applications in shallow tunneling projects all over the world. In this study, numerical modeling of third-line Metro tunnel in Tehran is under discussion which is designed and stabilized by NATM. The foregoing tunnel is excavated manually with a one-meter advancing step. In this project, the constructors used a lattice girder and sprayed concrete with 31 cm thickness as the initial lining. A suitable numerical software for this modeling is Plaxis 3D tunnel, which allows performing high-resolution finite element modeling (FEM) of the studied object. The performance of this method is investigated and compared with other NATM methods. As a result of numerical modeling, we give a value of 30.01 mm earth subsidence in the most damaged area of the settlement, in comparing with that of earth surface monitoring, which confirmed it with a dramatically low difference. Moreover, this tunnel was drilled and excavated with various methods, among which the less settlement has obtained by the proposed method. The results are promising to continue the tunneling with this method to expand the subway line in the city.

The current report contributes to the understanding of the stereoselectivity of the chiral dirhodium(II) carboxylate catalysts derived from N-protected amino acid ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

Geopolymers, made from aluminosilicate raw materials, offer significant environmental advantages over conventional concrete (CC) mixes. This study explores the compressive strength, setting time, and durability of geopolymer concrete (GPC) cylinders, some of which include an additional ordinary portland cement (OPC) mix. Consistent material composition and testing methods are emphasized to achieve reliable results. MATLAB was utilized to develop and assess a neural network model predicting the compressive strength of GPC based on key variables. The model was validated using 16 experimental samples and 1047 samples from various studies. The performance plot displayed the Mean Squared Error (MSE) over iterations, identifying the best training performance at epoch 658 with an MSE of 5.3408. The Error Histogram highlighted distribution errors between predicted and actual compressive strength values, with the highest range from -1.015 to 0.3587, meaning that the predicted values were mostly within a small margin of error from the actual values. This narrow error range indicates that the ANN model has high accuracy in its predictions, as most errors are small and clustered around zero, demonstrating reliable performance in estimating compressive strength. Regression analysis showed varying correlation coefficients (training set R=0.98373, test set R=0.88164, and whole set R=0.96982), indicating adequate predictive accuracy. The results demonstrate that properly trained neural networks can effectively predict the compressive strength of GPC, highlighting its potential as a sustainable construction material.

Using the h-index to assess individual researchers is not only unethical and unfair but also inaccurate and misleading. This index fails to offer a reliable measure of a researcher's impact based on their citation scores. Beyond statistical and conceptual considerations, authorship practices, especially in the case of multi-authored publications, give rise to significant problems that often go unnoticed. While some modifications of the h-index have been proposed to mitigate these weaknesses, the fundamental deficiencies persist. Most of these flaws have been effectively addressed by the c-score, a composite citation index. The c-score excludes self-citations, normalizes the number of citations by considering the number of authors in each paper, and takes into account first, single, and last authorship. This approach provides a more realistic measure of the impact of each individual researcher based on raw citations.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal “core” population plus a tenuous energetic “halo” population. At first, such a feature was empirically fitted with the Kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the Kappa distribution as reflecting the non-extensive nature of the space plasma. From the viewpoint of microscopic plasma theory, the formation of non-thermal electron velocity distribution function can be interpreted in terms of the plasma being in a state of turbulent quasi equilibrium. Such a finding brings forth the possible existence of a profound inter-relationship between the non-extensive statistical state and the turbulent quasi-equilibrium state. The present paper further develops the idea of solar wind electrons being in the turbulent equilibrium, but unlike the previous model, which involves the electrostatic turbulence near the plasma oscillation frequency (i.e., Langmuir turbulence), the present paper considers the impact of transverse electromagnetic turbulence, particularly, the turbulence in the whistler-mode frequency range. It is found that the coupling of spontaneously-emitted thermal fluctuations and the background turbulence leads to the formation of non-thermal electron velocity distribution function of the type observed in the solar wind during quiet times. This demonstrates that the whistler-range turbulence represents an alternative mechanism for producing the Kappa-like non-thermal distribution, especially close to the Sun and in the near-Earth space environment.

The human voice has the potential to serve as a valuable biomarker for the early detection, diagnosis, and monitoring of pediatric conditions. This scoping review synthesizes the current knowledge on the application of Artificial Intelligence (AI) in analyzing pediatric voice as a biomarker for health. The included studies featured voice recordings from pediatric populations aged 0-17 years, utilized feature extraction methods, and analyzed pathological biomarkers using AI models. Data from 62 studies were extracted, encompassing study and participant characteristics, recording sources, feature extraction methods, and AI models. The review showed a global representation of pediatric voice studies, with a focus on developmental, respiratory, speech, and language conditions. The most frequently studied conditions were Autism Spectrum Disorder, intellectual disabilities, asphyxia, and asthma. Mel-Frequency Cepstral Coefficients were the most utilized feature extraction method, while Support Vector Machines were the predominant AI model. The analysis of pediatric voice using AI demonstrates promise as a non-invasive, cost-effective biomarker for a broad spectrum of pediatric conditions. However, further research and development are crucial to enhance the accuracy and applicability of these tools in clinical settings.

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

The rapid growth of network services, Internet of Things devices and online users on the Internet have led to an increase in the amount of data transmitted daily. As more and more information is stored and transmitted on the Internet, cybercriminals are trying to gain access to the information to achieve their goals, whether it is to sell it on the dark web or for other malicious intent. Through thorough literature study relating to the causes and issues that are brought from the security and privacy segment of wireless networks, it is observed that there are various factors that can cause the networks to be an insecure; especially factors that revolve around cybercriminals with their growing expertise and the lack of preparation and efforts to combat them by relevant bodies. The aim of this paper is to showcase major and frequent security as well as privacy issues in wireless networks along with specialized solutions that can assist the related organizations or the public to fathom how great of an impact these challenges can bring if every related stakeholder took a step in reducing them. Through this paper it is discovered that there are many ways these challenges can be mitigated, however, the lack of implementation of privacy and security solutions is still largely present due to the absence of practical application of these solutions by responsible parties in real world scenarios.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Glacial ripping is a newly recognized process sequence in which subglacial erosion is triggered by groundwater overpressure. Investigations in gneiss terrain in lowland Sweden indicate that ripping involves three stages of (i) hydraulic jacking, (ii) rock disruption under subglacial traction and (iii) glacial transport of rock blocks. Evidence for each stage includes, respectively, dilated fractures with sediment fills, disintegrated roches moutonnées and boulder spreads. Here we ask: can glacial ripping also occur in sedimentary rocks, and, if so, what are its effects? The case study area is in hard, thinly bedded, gently dipping Cambrian quartz-arenites at Loch Eriboll, NW Scotland. Field surveys reveal dilated, sediment filled, bedding-parallel fractures, open joints and brecciated zones, interpreted as markers for pervasive, shallow penetration of the quartz-arenite by water at over-pressure. Other features, including disintegrated rock surfaces, boulder spreads and monomict rubble tills, indicate glacial disruption and short distance subglacial transport. The field results, together with published cosmogenic isotope ages, indicate that glacial ripping operated with high impact close to the former ice margin at Loch Eriboll at 17.6-16.5 ka. Glacial ripping thus can operate effectively in bedded, hard sedimentary rocks and the accompanying brecciation is significant – if not dominant - in till formation. Candidate markers for glacial ripping are identified in other sedimentary terrains in former glaciated areas of the Northern Hemisphere.

A modular approach to the construction of electric machines, drive systems, power supply systems is a new direction of modern technology development. Especially, the modular approach is promising for electric vehicles due to such positive aspects as increased efficiency, fault tolerance, overall reliability, safety, enhanced control capabilities, etc. In this work, the modular approach is comprehensively applied to an EV powertrain system, which includes a dual three-phase (DTP) BLDC motor with two machine modules of an asymmetric configuration, two battery modules and a supercapacitor module (SCM). The proposed H–H configuration of modular EV powertrain system includes four voltage source inverters that combine the power modules with the open ends of the windings (OEW) of the module machine armature, and provide control of their operation. Based on the developed mode system of the OEW machine module operation for EV traction and braking, a general control algorithm for the proposed configuration of the modular EV powertrain system has been developed. It combines the control of the operating modes with the functions of maintaining the required SOC level of the SCM and equalizing the SOCs of the two battery modules. The conducted simulation and experimental studies confirmed the workability and effectiveness of the proposed solutions.

The evidential value of an mtDNA match between biological remains and its potential donor is determined by the random match probability of the haplotype. This probability is based on the haplotype’s population frequency estimate. Consequently, implementing a population study representative of the population relevant to the forensic case is vital to correctly evaluating the evidence. The emerging number of poaching cases and the limited availability of such data emphasizes the need for improved fallow deer mtDNA population databank for forensic purposes, including targeting the entire mitochondrial control region. By sequencing the whole mitochondrial control region in 138 animals from five populations in Hungary we found four different haplotypes, including one which has not yet been described. Our results, supplemented with data already available from previous research do not support the possibility of determining the population of origin, although some patterns of geographical separation can be distinguished. Estimates of molecular diversity indicate approximately similarly low mtDNA diversity (Hd=0.565 and π = 0.002), compared with data from other countries. The calculated random match probability of 0.547 shows a high probability of coincidence and, therefore, a limited capacity for exclusion. Consequently, it may be necessary to search for polymorphic sites on other mitochondrial gene sections or to sequence the entire mitogenome of fallow deer.

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterised by thrombosis and the presence of antiphospholipid antibodies (aPL): lupus anticoagulant and/or IgG/IgM anti-β2-glycoprotein I and anticardiolipin antibodies. APS carries significant morbidity for a relatively young patient population from recurrent thrombosis in any vascular bed (arterial, venous or microvascular), often despite current standard of care, which is anticoagulation with vitamin K antagonists (VKA). Platelets have established roles in thrombosis at any site, and platelet hyperreactivity is clearly demonstrated in the pathophysiology of APS. Together with excess thrombin generation, platelet activation and aggregation are the common end result of all the pathophysiological pathways leading to thrombosis in APS. However, antiplatelet therapies play little role in APS, reserved as a possible option of low dose aspirin in addition to VKA in arterial or refractory thrombosis. This review outlines the current evidence and mechanisms for excessive platelet activation in APS, how it plays a central role in APS-related thrombosis, what evidence for antiplatelets is available in clinical outcomes studies and potential future avenues to define how to target platelet hyperreactivity better with minimal impact on haemostasis.

The world is currently experiencing COVID-19, one of the worst pandemics that have happened in this century, affecting 10.7 million people worldwide. It has caused massive growth in the number of employees working from home. However, employees have minimal cybersecurity resources unlike organizations with security teams protecting them against attacks. Hence, cybersecurity plays an important role as users can be easily targeted by cybercriminals. This paper examines how cyberattacks have increased during this pandemic and shows how greatly they have affected health organizations, individuals and social networking applications. Results of the attacks include data breaches, false announcements and operations being disrupted. Attacks occurring during this pandemic and how they were handled are also critically discussed. The existing contributions do touch on related attacks but do not provide in-depth solutions regarding the issues. Even though there are many works and findings that were done previously, technology is ever evolving. Therefore, we need to be well versed with current and future issues and provide the latest mechanisms to prevent cybersecurity threats from occurring. On our share, we intend to present our findings on the challenges being faced by the population and its increasing threats as well as presenting unique solutions that can help organizations or related persons understand or spread awareness on the importance of cybersecurity. Through the research performed in this paper, it is found that there are many ways these issues can be alleviated. However, the issue is that there is significant lack of action and investment in terms of actual implementation and application of the available solutions.

This study explores the impact of multi-user interaction, group work, and simulations within virtual worlds on language learning and the development of intergroup empathy. Two distinct research projects were conducted, involving a total of 241 participants aged 19-45. The language learning study engaged 116 participants in diverse interactive experiences, while the intercultural study had 125 participants collaborating in multicultural groups and participating in perspective-taking simulations. Both studies employed qualitative data collection methods, including surveys, interviews, and observations. The findings suggest that the combination of networking strategies, collaborative learning, and simulations within virtual worlds contributes to improvements in learners' language proficiency, confidence, and empathy towards diverse social groups. Participants reported increased motivation and engagement, attributed to the immersive and interactive nature of the virtual environments. The studies highlight the importance of collaboration and reflection in facilitating language acquisition and intercultural understanding. Technical challenges were identified as potential barriers to implementation. The results demonstrate the potential of virtual worlds to enhance language education and foster empathy in diverse societies, offering valuable insights for educators and researchers. However, the findings may be limited by the specific contexts and sample sizes of the studies, warranting further research to explore the generalizability and long-term impact of virtual world interventions. not exaggerate the main conclusions.

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.

The human landscape transforming activity contributes to the global change of vegetation in different forms. Hunting is one of the most ancient human landscape-shaping activities. Feeders for hunting are particularly disruptive to vegetation. In the present study, we conducted a vegetation survey in these highly disturbed places. We are investigating the vegetation dynamics over several years in in the turkey oak–sessile oak zone, in two areas with different moisture and shade conditions (forest and clearing). One important background factor is changes in precipitation and temperature. The novelty of our present study lies in the fact that the observation takes place with continuous disturbance, where the human influence is very large. Our results confirm that the weed infestation be detectable at bait sites over a long period, and the interannual changes were typical in every year, according to the fact that in August, more weed species are usually present with a greater cover at the bait sites. The main meteorological factors played a role in the degree of weed infestation in each year. There was a higher proportion of vegetation regeneration in wetter years, while dry periods do not favor successional processes. With the drying of the climate, the disturbed areas are constantly losing their natural value, but wetter weather is not an automatic solution either. A more precise understanding of vulnerable systems and careful planning of treatment interventions is necessary.

Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.

This study explores the application of the Laban/Bartenieff Movement System (® LBMS), particularly its Effort component, to analyze the biomechanical dynamics of the golf swing. Focusing on the initiation of the downswing, this paper investigates how the instantaneous screw axis (ISA) with rotational and linear motions contributes to subsequent movements, such as the hip turn. We propose that the physical forces generated by the golf club, characterized by mass moment inertia, extend beyond the body's boundaries, such as through the hand grip. A skilled golfer’s ability to 'allow' these forces to influence body dynamics without opposing them is analyzed through the lens of LBMS's Free Flow Effort, suggesting an indulgent and expansive use of movement energy.

In this paper, the design and analysis of coupled tank water level control system is done using robust control theory. The main aim of this work is to improve level controlling mechanisms in industries and household areas. In this paper, H ∞ and μ –synthesis controllers are designed to improve the level control system. The coupled tank water level control system is designed using the proposed controller’s comparison and tested for tracking a reference level signals (step, sine wave and random) and simulation results have been analyzed successfully. Finally the comparative simulation results prove the effectiveness of the proposed coupled tank water level control system with H ∞ controller for improving the tracking mechanism performance of the system.

In this work, we introduce the class of h-MN-convex functions by generalizing the concept of MN-convexity and combining it with h-convexity. Namely, let M : [0, 1] → [a, b] be a Mean function given by M (t) = M (t; a, b); where by M (t; a, b) we mean one of the following functions: A_t (a, b) := (1 − t) a + tb, G_t (a, b) = a^1−tb^t and H_t (a, b) := $\frac{ab}{ta+\left(1-t\right)b}=\frac{1}{A_t\left(\frac{1}{a},\frac{1}{b}\right)}$ with the property that M (0; a, b) = a and M (1; a, b) = b. Let I, J be two intervals subset of (0, ∞) such that (0, 1) ⊆ J and [a, b] ⊆ I. Consider a non-negative function h : J → (0, ∞), a function f : I → (0, ∞) is said to be h-MN-convex (concave) if the inequality f (M (t; x, y)) ≤ (≥) N (h(t); f (x), f (y)), holds for all x, y ∈ I and t ∈ [0, 1]. In this way, nine classes of h-MN-convex functions are established, and therefore some analytic properties for each class of functions are explored and investigated. Characterizations of each type are given. Various Jensen’s type inequalities and their converses are proved.

Several stochastic H∞ filters for estimating the attitude of a rigid body from line-of-sight measurements and rate gyro readings are developed. The measurements are corrupted by white noise with unknown variances. Our approach consists of estimating the quaternion while attenuating the transmission gain from the unknown variances and initial errors to the current estimation error. The time-varying H∞ gains are computed through differential and algebraic linear matrix inequalities whose parameters are independent of the state. The case of a gyro drift is addressed, too. Extensive Monte Carlo simulations show that the proposed stochastic H∞ quaternion filters perform well for a wide range of noise variances. The actual attenuation, which improves with the noise level and is worst in the noise-free case, is better than the guaranteed attenuation by one order of magnitude. The proposed stochastic H∞ filter produces smaller biases than a standard quaternion Kalman filter and similar standard deviations at large noise levels. An essential advantage of this H∞ filter is that the gains are independent of the quaternion, which makes it insensitive to modeling errors. This desired feature is illustrated by comparing its performances against those of unmatched Kalman filters. When provided with too high or too low noise variances the Kalman filter is outperformed by the $H_\infty$ filter, which essentially delivers identical error magnitudes.

In this study, we propose an efficient field-free line (FFL) generator for mechanically driven FFL-magnetic particle imaging (MPI) applications. The novel FFL generator comprises pairs of Halbach arrays and bar magnets. The proposed design generates high-gradient FFLs with low-mass permanent magnets, realizing fine spatial resolutions in MPI. We investigate the generated magnetic field using simulations and experiments. Our results show that the FFL generator yields a high gradient of 4.76 T/m at a cylindrical field of view of 30 mm diameter and a 70 mm open bore. A spatial resolution of less than 3.5 mm was obtained in the mechanically driven FFL-MPI.

We present the design, fabrication, and response of a polymer-based Laterally Amplified Chemo-Mechanical (LACM) humidity sensor based on mechanical leveraging and parametric amplification. The device consists of a sense cantilever asymmetrically patterned with a polymer and flanked by two stationary electrodes on the sides. When exposed to a humidity change, the polymer swells after absorbing the analyte and causes the central cantilever to bend laterally towards one side, causing a change in the measured capacitance. The device features an intrinsic gain due to parametric amplification resulting in an enhanced signal-to-noise ratio (SNR). 11-fold magnification in sensor response was observed via voltage biasing of the side electrodes without the use of conventional electronic amplifiers. The sensor showed a repeatable and recoverable capacitance change of 11% when exposed to a change in relative humidity from 25-85%. The dynamic characterization of the device also revealed a response time ~1s and demonstrated a competitive response with respect to a commercially available reference chip.

This work explores the use of Kuhn verdazyl radicals as building blocks in multifunctional molecular materials in an exemplary study, focusing on the magnetic and the electron transfer (ET) characteristics, but also addressing the question whether chemical modification by cross-coupling is possible. The ET in solution is studied spectroscopically whereas solid state measurements afford information about the magnetic susceptibility or the conductivity of the given samples. The observed results are rationalized based on the chemical structures of the molecules, which have been obtained by X-ray crystallography. The crystallographically observed molecular structures as well as the interpretation based on the spectroscopic and physical measurements are backed up by DFT calculations. The measurements indicate that only weak, antiferromagnetic coupling is observed in Kuhn verdazyls owed to the low tendency to form face-to-face stacks, but also that steric reasons alone are not sufficient to explain this behavior. Furthermore, it is also demonstrated that ET reactions proceed rapidly in verdazyls/verdazylium redox couples and that Kuhn verdazyls are suited as donor molecules in ET reactions.

Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual’s own stool (autologous FMT) to mitigate risks of disease transmission from donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. Stool was collected prior to starting first-line therapy. Patients that progressed to HSCT were offered FMT via 3 x re-tention enemas before day +5 (HSCT = day 0). Feasibility was determined by recruitment rate, number and volume of enemas administered, and retention time. Longitudinally collected stool samples were also col-lected to explore the influence of auto-FMT using 16S rRNA gene sequencing. N=4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25(1-3) enemas (43.67(25-50)mL total, retained for an average of 60.78(10-145)minutes). No AEs, attributed to the FMT, were identified. Although minimum requirements were met for the volume and retention of auto-FMT, recruitment was significantly impacted by the logistical challenges of pre-therapy stool collection. This ultimately under-mined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

Introduction: Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Materials and methods: Fetal biometric data, and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Results: Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β=0.39, p

The Combined Elevation Test (CET) is a musculoskeletal screening technique (MST) replicates the streamline position in swimming and is commonly used in various sports. Although the CET is widely used, no normative data exist within an adolescent population. Therefore, the purpose of this study was to develop a normative data set for the CET within an adolescent population and to evaluate the influence various demographic and anthropometric variables. Data was collected for 416 participants aged between 8 and 18 years old. Age and arm span showed a significant correlation with CET scores (arm span r_s (105) = .478, p = .000, age r_s (416) = .238 p = .000). Regression analysis further quantified the influence of arm span and age on CET scores accounting for 23.1% and 5.3% of variability respectively. These results can be used as a reference point for clinicians and coaches who are using the CET within their assessment.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values < 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

Co-management is increasingly recognized as an effective approach of forest governance while recognizing local people's forest dependency and traditional rights. Moreover, co-management is expected to positively impact forest cover and ecosystem health. Bangladesh, facing a rapid decline in forest cover, has one of the lowest per capita forest areas worldwide. For quite a while, co-management practices have been used to improve forest cover and the livelihoods of forest-dependent people in Bangladesh. Several studies have assessed the efficacy of co-management in different protected areas in Bangladesh from livelihood, social, and cultural aspects. However, the overall changes in forest cover due to co-management from the very beginning of co-management initiatives in the country have been overlooked. We used remotely sensed Landsat images to assess the changes in forest cover and overall land use in five forest protected areas where co-management was piloted. Three major vegetation indices (NDVI, EVI, and MSAVI) were examined to ensure the study's robustness. This study aims to assess the scope and weaknesses of the current policy that incorporates co-management in the country's first five protected areas (SNP, LNP, RKWS, TWS, and CWS), which were brought under co-management in 2003, and compare the efficacy of the co-management relative to non-comanaged protected areas (RRF). The land cover analysis based on NDVI, MSAVI, and EVI values indicated dominant dense forest coverage (41–71%) across five protected areas. During the co-management period (2004–2015), there was a significant decrease in the dense forest proportion, with slopes ranging from -3.7 to -0.96. Similarly, the RRF showed a decreasing pattern, with the slope of the decreasing trendline ranging from -0.48 to -0.62 across the three indices. Agriculture and forest-agriculture mosaics showed a significant increase, with varying slopes among protected areas in both co-managed and non-comanaged sites. Pixel-to-pixel changes revealed dynamic shifts in vegetation indices, and Global Forest Watch data highlighted forest cover losses, notably in CWS (158.77 ha) and SNP (0.49 ha).

This study explores the application of the Laban/Bartenieff Movement System (® LBMS), particularly its Effort component, to analyze the biomechanical dynamics of the golf swing. Focusing on the initiation of the downswing, this paper investigates how the instantaneous screw axis (ISA) with rotational and linear motions contributes to subsequent movements, such as the hip turn. We propose that the physical forces generated by the golf club, characterized by mass moment inertia, extend beyond the body's boundaries, such as through the hand grip. A skilled golfer’s ability to 'allow' these forces to influence body dynamics without opposing them is analyzed through the lens of LBMS's Free Flow Effort, suggesting an indulgent and expansive use of movement energy.

This paper presents an interpretable support vector machine (SVM) and its application to rehabilitation assessment. We introduce the concept of nearest boundary point to standardize the one-class SVM decision function and determine the shortest path for data from abnormal cases to become those from normal cases. This analytical approach is computationally simple and provides a unique solution. The nearest boundary point of abnormal data can also be used to analyze the cause of abnormal classification and indicate countermeasures for normalization. These properties render the proposed interpretable SVM valuable for medical assessment applications and other problems that require careful consideration of classification results for treatment. Simulation and application results demonstrate the feasibility and effectiveness of the proposed method.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

This paper aims to unify q-derivative/q-integral and h-derivative/h-integral in a single definition, this will be called q−h-derivative/q−h-integral. These notions are further extended on finite interval [a,b] in the form of left and right q−h-derivatives and q−h-integrals. Some inequalities are studied for q−h-integrals which are directly connected with well known results. In diverse fields of science and engineering the theory based on q-derivatives/q-integrals and h-derivatives/h-integrals can be unified by using the concept of q−h-derivative/q−h-integral.

As argued by ‘Declaration of Concrete Environment (2010)’ of Korea and ‘Declaration of Asian Concrete Environment (2011)’ of six Asian countries, concrete as a single material has lately shown extremely large impact on environmental issues such as climate change. Assessment of environmental impact from concrete material and production has considerable importance. Concrete is a major material used in the construction industry that emits a large amount of substances with environmental impacts during its life cycle. Accordingly, technologies for the reduction in and assessment of the environmental impact of concrete from the perspective of Life Cycle Assessment must be developed. At present, the studies in relation to greenhouse gas emission from concrete are being carried out globally as a countermeasure against climate change. In this study, a sustainable concrete mix design algorithm was designed using correlation analyses, and its carbon emission and cost reduction performances were assessed. Using correlation analyses, the concrete strength, w/b and s/a ratios, and CO₂ emissions were identified as major variables of concrete mix design that influenced other variables. Also, this study aims to evaluate the CO₂ emission reduction performance of the algorithm-deduced sustainable concrete mix design, and therefore, the CO₂ emissions of the sustainable concrete mix design are compared with those of the actual concrete mix design applied to the construction of the office building A in South Korea.

In this study, we define new classes of convexity called of h-Godunova-Levin and h-Godunova-Levin preinvexity, through which some new inequalities of Hermite-Hadamard type were established. These new classes are the generalisation of several known convexity including the s-convex, P-function, Godunova-Levin. Further, the properties of h-Godunova-Levin function were also discussed. Meanwhile, the applications of h-Godunova-Levin Preinvex function are given

In this work, several inequalities of Popoviciu type for h-MN-convex functions are proved, where M and N are denote to Arithmetic, Geometric and Harmonic means and h is a non-negative superadditive or subadditive function.

Polyethylene terephthalate (PET) pollution poses significant environmental consequences, and thus new degradation methods must be explored to mitigate this problem. We previously demonstrated that a consortium of three Pseudomonas and two Bacillus species can synergistically degrade PET in culture. The consortium more readily consumes Bis(2-Hydroxyethyl) terephthalate (BHET), a byproduct made in PET depolymerization, compared to PET, and can fully convert BHET into metabolically usable monomers terephthalic acid (TPA) and ethylene glycol (EG). Because of its crystalline structure, the main limitation of the biodegradation of post-consumer PET is the initial transesterification from PET to BHET, depicting the need for the transesterification step in the degradation process. Additionally, there have been numerous studies done on the depolymerization reaction of PET to BHET, yet few have tested the biocompatibility of that product with a bacterial consortium. In this report, a two-step process was implemented for sustainable PET biodegradation, where PET is first depolymerized to form BHET using an Orange Peel Ash (OPA) catalyzed glycolysis reaction, followed by complete degradation of the BHET glycolysis product by the bacterial consortium. Results show that OPA-catalyzed glycolysis reactions can fully depolymerize PET, with an average BHET yield of 92% (w/w) and that the reaction product is biocompatible with the bacterial consortium. After inoculation with the consortium, 19% degradation of the glycolysis product was observed in 2 weeks, for a total degradation percentage of 17% when taking both steps into account. Furthermore, the 10-week total BHET degradation rate was 35%, demonstrating that the glycolysis products are biocompatible with the consortium for longer periods of time, for a total two-step degradation rate of 33% over 10 weeks. While we predict complete degradation is achievable using this method, further experimentation with the consortium can allow for a circular recycling process, where TPA can be recovered from culture media and reused to create new materials.

Background: The use of technology in paediatrics is increasing, and new health technology will change the way in which paediatric care is delivered in the future. This review is part of the Royal College of Paediatrics and Child Health Paediatrics 2040 project, which is developing a credible vision for the future of paediatrics in the UK. Aims: To summarise the impact of health technology on the delivery of paediatric care over the last ten years. To learn from existing technology use and make recommendations for future implementation. Methods: A search strategy was developed and two databases (Cochrane Library and PubMed) were systematically searched in August 2019 for relevant publications in English. Searches were limited to papers published between January 2009 and August 2019 (with further rapid review of papers published between September 2019 and November 2020). We included papers that studied young people up to the age of 24 or on those providing care for this population. A thematic synthesis of the data from the included studies was undertaken using seven domains of paediatric care. Results: 128 studies were included, grouped by domain of care. Most included studies were defined as digital (n=55) or communication (n=37). Studies looked at the different types of health technology used within different domains of care, including secondary and tertiary care (n=39), public health and prevention (n=29), and community (n=20). Studies were assessed on delivery of care outcomes using positive, negative, mixed and no effect. The most common outcomes reported were adherence and satisfaction. Discussion: This review highlights the growing importance of technology in delivering paediatric care. Six themes emerged: the importance of clear guidelines, continuity of care, confidentiality and privacy, digital poverty, using a personalised approach, and using technology to supplement rather than replace. In future, technology development should involve the end user throughout the design process.

Knowledge of the spatio-temporal occurrence of avalanche activity is critical for avalanche forecasting and hazard mapping. We present a near-real time automatic avalanche monitoring system that outputs detected avalanche polygons within roughly 10 min after Sentinel- 1 SAR data download. Our avalanche detection algorithm has an average probability of detection of 67.2 % with a false alarm rate averaging 45.9, with maximum POD's over 85 % and minimum FAR's of 24.9 % compared to manual detection of avalanches. The high variability in performance stems from the dynamic nature of snow in the Sentinel-1 data. After tuning parameters of the detection algorithm, we processed five years of Sentinel-1 images acquired over a 150 x 100 km large area in Northern Norway, with the best setup. Compared to a dataset of field-observed avalanches, 77.3 % were manually detectable. Using these manual detections as benchmark, the avalanche detection algorithm achieved an accuracy of 79 % with high POD's in cases of medium to large wet snow avalanches. For the first time, we can present a dataset of spatiotemporal avalanche activity over several winters from a large region. This unique dataset allows for research into the relationship between avalanche activity and triggering meteorological factors, mapping of avalanche prone areas and near-real time avalanche activity monitoring to assist public avalanche forecasting. Currently, the Norwegian Avalanche Warning Service is using our processing system for pre-operational use in three regions in Norway.

Poor soil health is a critical problem in many urban landscapes. Degraded soil restricts plant growth and microorganism activity, limiting the ability of urban landscapes to perform much needed ecosystem services. Incorporation of approximately 33% compost by volume into degraded soil has been proven to improve soil health and structure over time while avoiding the financial and environmental costs of importing soil mixes from elsewhere. However, additions of high volumes of compost could potentially increase the risk of nutrient loss through leaching and runoff. The objective of our study was to consider the effects of different compost amendments on soil health, plant health and susceptibility to nutrient leaching in order to identify ranges of acceptable compost characteristics that could be used for soil remediation in the urban landscape. We conducted a bioassay with Phaseolus vulgaris (Bush Bean) to measure the effect of nine composts from different feedstocks on various plant health parameters. We collected leachate prior to planting to measure nutrient loss from each treatment. We found that all compost amendments improved soil health. Nutrient-rich, manure-based composts produced the greatest plant growth, but also leached high concentrations of nitrate and phosphorus. Some treatments provided sufficient nutrients for plant growth without excess nutrient loss. We concluded, when incorporating as much as 33% compost by volume into a landscape bed, the optimal compost will generally have a C:N ratio of 10-20, P-content <1.0% and a soluble salt content between 1.0 and 3.5 mmhos/cm. These recommendations should ensure optimal plant and soil health and minimize nutrient leaching.

Background: This study attempted to construct musculoskeletal JEM using KWCS data and use it to evaluate the burden of these disorders in Korean workers. Methods: This study was conducted using data from the second to the sixth KWCS, and a total of 210,500 people were included. The jobs of the subjects were reclassified based on the unit groups of the 7th Korean Standard Classification of Occupation (KSCO). The intensity of exposure to work-related risk factors for musculoskeletal disorders was classified into ‘high’, ‘moderate’, and ‘low’ for the body segments involving the ‘upper extremities and neck’, ‘lower back’, and ‘lower extremities’. Results: The time of exposure was longest in the standing posture and repetitive hand and arm movements. An analysis of the intensity of exposure by body segments revealed that the highest intensity of exposure was to the upper extremities. For the upper extremities and neck, and the lower back, there was a exposure-response relationship in the association between intensity of exposure and musculoskeletal symptoms. However, for the lower extremities, there was a exposure-response relationship only at high exposure. Conclusion: In this study, a JEM for work-related risk factors for musculoskeletal disorders was constructed for the first time in Korea. The intensity of exposure to musculoskeletal risk factors was estimated for each occupation. The JEM constructed in this study is expected to have high applicability for assessing the risk of musculoskeletal disorders for each job with respect to the upper extremities and neck, and lower back.

A lead zirconate titanate [PZT;Pb(Zr_0.52Ti_0.48)O₃] layer embedded infrared (IR) detector decorated with wavelength-selective plasmonic crystals has been investigated for high-performance non-dispersive infrared (NDIR) spectroscopy. A plasmonic IR detector with an enhanced IR absorption band has been designed based on numerical simulations, fabricated by conventional microfabrication techniques, and characterized with a broadly tunable quantum cascade laser. The enhanced responsivity of the plasmonic IR detector at specific wavelength band has improved the performance of NDIR spectroscopy and pushed the limit of detection (LOD) by an order of magnitude. In this paper, a 13 fold enhancement in the LOD of a methane gas sensing using NDIR spectroscopy is demonstrated with the plasmonic IR detector.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

This paper details the approach to the efficient design and optimization of reversible adder and multiplier utilizing Peres gates which is a three input, three output gate. Peres gates are recognized for their universality and energy efficient properties and present an intriguing option for constructing reversible circuits. Reversible logic are characterized by its ability to uniquely determine input states from output states. The design methodology involves a cascading arrangement of Peres gates each performing a reversible XOR operation on corresponding bits of the input numbers and the carry out from the preceding stage. The paper presents a detailed schematic representation, simulation results and analysis of the proposed designs of different adders and multipliers showcasing their potential for reversible applications. The integration of Peres gates in the adder and multiplier design signifies a step forward in the exploration of reversible logic circuits and their applications in contemporary computing paradigms. The overall hardware reduction is the main achievement of this research in terms of quantum cost.

Vessel co-option correlates with resistance against anti-angiogenic agents and chemotherapy in colorectal cancer liver metastasis (CRCLM). We previously identified higher intensity of neutrophils in the tumour microenvironment of vessel co-opting CRCLM lesions compared to their angiogenic counterparts. Herein, we demonstrated that over 50% of the neutrophils in vessel co-opting lesions are expressing pro-apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1). Our previous publications suggested upregulation of transforming growth factor-beta (TGFβ1) in the microenvironment of vessel co-option CRCLM. Therefore, we examined the effect of TGFβ1 on the expression of cleaved caspase-3 and PARP-1 in neutrophils in vitro. Significantly, we noticed the upregulation of pro-apoptotic markers upon exposure to TGFβ1. This finding might pave the way to determine the role of neutrophils in developing vessel co-option in CRCLM in the future.

The aim of this study was to analyze whether the respiratory variation in ECG standard lead II R-wave amplitude (ΔRDII) could be used to assess intravascular volume status following inferior vena cava (IVC) clamping. This clamping causes an acute decrease in cardiac output during liver transplantation (LT). We retrospectively compared ΔRDII and related variables before and after IVC clamping in 34 recipients. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to derive a cutoff value of ΔRDII for predicting pulse pressure variation (PPV). After IVC clamping, cardiac output significantly decreased while ΔRDII significantly increased (P = 0.002). The cutoff value of ΔRDII for predicting a PPV >13% was 16.9% (AUC: 0.685) with a sensitivity of 57.9% and specificity of 77.6% (95% confidence interval 0.561 – 0.793, P = 0.015). Frequency analysis of ECG also significantly increased in the respiratory frequency band (P = 0.016). Although significant changes in ΔRDII during vena cava clamping were found at norepinephrine doses < 0.1 μg/kg/min (P = 0.014), such changes were not significant at norepinephrine doses > 0.1 μg/kg/minP = 0.093). ΔRDII could be a noninvasive dynamic parameter in LT recipients presenting with hemodynamic fluctuation. Based on our data, we recommended cautious interpretation of ΔRDII may be requisite according to vasopressor administration status.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across >40 host species on 6 continents. Pathogen species with >5 articles were: Bursaphelenchus xylophilus, Candidatus Liberibacter asiaticus, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, Fusarium oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs, Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, Ca. Liberibacter asiaticus, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, Fusarium oxysporum f. sp. cubense Tropical Race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, 4 pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens – tomato brown rugose fruit virus and cucurbit chlorotic yellows virus – to be actively emerging in/spreading to new locations. Although three important pathogens – Ca. Liberibacter asiaticus, citrus tristeza virus and Fusarium oxysporum f. sp. cubense – were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

Modern automotive systems should must satisfy strict reliability requirements. Most of the real vehicle systems and safety-critical networks have complex interconnections. Sensitivities and probabilistic uncertainties of reliability of System with Complex Interconnections (SwCI) can be investigated by the Monte-Carlo Simulation (MCS). The paper focuses on sensitivities and parametrical uncertainties of SwCIs reliability. The proposed method can be used forimplemented in the investigation of uncertainties of SwCIs reliability – in other wordsi.e., for in the determination of critical system elements and to estimateion of the Required Number of Spare Parts (RNSP) of the system, which depends on the probability of allowable spare equipment shortage.

In this paper, we propose an imagined speech-based brain wave pattern recognition using deep learning. Multiple features were extracted concurrently from eight-channel Electroencephalography (EEG) signals. To obtain classifiable EEG data with fewer number of sensors, we placed the EEG sensors on carefully selected spots on the scalp. To decrease the dimensions and complexity of the EEG dataset and to avoid overfitting during the deep learning algorithm, we utilized the wavelet scattering transformation. A low-cost 8-channel EEG headset was used with MATLAB 2023a to acquire the EEG data. The Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) was used to decode the identified EEG signals into four audio commands: Up, Down, Left, and Right. Wavelet scattering transformation was applied to extract the most stable features by passing the EEG dataset through a series of filtration processes. Filtration has been implemented for each individual command in the EEG datasets. The proposed imagined speech-based brain wave pattern recognition approach achieved a 92.50% overall classification accuracy. This accuracy is promising for designing a trustworthy imagined speech-based Brain-Computer Interface (BCI) future real-time systems. For better evaluation of the classification performance, other metrics were considered, and we obtained 92.74%, 92.50% and 92.62% for precision, recall, and F1-score, respectively.

Increasing concerns on animal welfare in commercial pig industry include aggression between pigs as it affects their health and growth. Early detection of aggressive behaviors is essential for optimizing their living environment. A major challenge for detection is that these behaviors are observed occasionally in normal conditions. Under this circumstance, a limited amount of aggressive behavior data will lead to class imbalance issue, making it difficult to develop an effective classification model for the detection of aggressive behaviors. To overcome this problem, we approach the aggressive behavior detection problem as a case of anomaly detection rather than classification and propose a model based on anomaly detection, which can better handle unbalanced class distribution and effectively detect the infrequent, aggressive episodes of pigs. The model consists of a convolutional neural network (CNN) and a variational long short-term memory (LSTM) autoencoder. Additionally, we adopted a training method similar to weakly supervised anomaly detection and included a few aggressive behavior data in the training set for prior learning. To effectively utilize the aggressive behavior data, we created Reconstruction Loss Inversion, a novel objective function, to train the autoencoder-based model to increase the reconstruction error of aggressive behaviors by inverting the loss function. Our anomaly detection approach significantly outperforms traditional classification-based methods, effectively identifying aggressive behaviors in a natural farming environment. This method offers a robust solution for detecting aggressive animal behaviors and contributes to improving their welfare.

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer) and SH-SY5Y (neuroblastoma) as well as human embryonal lung fibroblast MRC-5 served as reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. These results suggest that ovarian cancer might be considered as a prioritized target of treatment with 36.

On the H-type group G⊂Rm×Rn, we study the existence of solutions for the Brezis-Nirenberg problem

Most Acinetobacter baumannii strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of H-NS in the regulation of expression of genes related to natural competency and the ability to uptake foreign DNA. The expression levels of the natural transformation-related genes pilA, pilT, pilQ, comEA, comEC, comF, and drpA were significantly increased in a Δhns derivative of Acinetobacter baumannii A118. Complementation of the mutant with a recombinant plasmid harboring hns restored expression levels of six of these genes (pilT remained expressed at high levels) to those of the wild-type strain. The transformation frequency of the A. baumannii A118 Δhns strain was significantly higher than that of the wild-type. Similar, albeit not identical, effects occurred when hns was deleted from the hypervirulent A. baumannii AB5075 strain. Reduction of gene expression in a few cases was not as pronounced as to reach wild-type levels, and expression of comEA was enhanced further. In conclusion, the expression of all seven transformation-related genes was enhanced after deleting hns in A. baumannii A118 and AB5075, and these modifications are accompanied by an increase in the cells’ transformability. The results demonstrate a role of H-NS in A. baumannii’s natural competence.

This study reports rapid hydrolysis, acylation, and lipolysis with lipase B from Candida antarctica (CalB) and nanofructosome encapsulated CalB (CalB@NF) enzymes immobilized on silica-coated magnetic nanoparticles (Si-MNPs). Enzymatic hydrolysis was confirmed for conversion to p-nitrophenol (p-NP, λex=400 nm) from p-nitrophenyl butyrate (p-NPB, λex=270 nm), and various catalytic parameters such as Km, Vmax, and Kcat were calculated from Michaelis-Menten and Lineweaver-Burk plot. Efficiency of enzymatic hydrolysis was in the order of CalB > Si-MNPs@CalB > CalB@NF > Si-MNPs@CalB@NF, and reusability was much better with the enzyme immobilized on Si-MNPs than with the native enzyme. Enzymatic acylation was confirmed by the formation of benzyl benzoate (λex=229 nm) from benzoic anhydride (λex=240 nm), and efficiency exceeded 99% in all samples. Finally, enzymatic lipolysis was confirmed by the decomposition of olive oil to fatty acid such as oleic acid (λex=230 nm) using thin-layer chromatography (TLC), column chromatography, and proton nuclear magnetic resonance (1H -NMR). The lipases immobilized on Si-MNPs have the advantage of good thermal stability and reusability and are thus applicable to a wide range of industries.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

The utilization of Artificial Intelligence (AI) in biotechnology is widespread, addressing challenges such as elucidating disease pathophysiology and novel therapeutic approaches. AI plays a critical role in tasks such as drug manufacturing, chemical analysis, RNA and DNA sequencing, and enzyme studies by automating processes and expediting data collection and analysis. AI has particularly transformed the analysis of omics data for researchers, providing tools to handle complex and multifaceted datasets effectively. Through AI, integrative analysis of multi-omics data can be conducted in efficient ways. This article discusses the application of multi-omics and AI technologies in studying various diseases related to infection (COVID-19), mutation (cancer), and senescence (alopecia) to understand their pathophysiology. The applications of AI were performed as the aspect of the diagnosis, prognosis, and treatment for each disease. We introduce AI-driven analysis of pathophysiology can overcome traditional limitations in pathology, with diverse features showing potential in defining the causes of diseases, and potentially enhancing primary omics data in the distinguish the subtype of diseases. In this context, integrated approaches using multi-omics data and AI technology could provide fresh biological insights by comprehending the molecular mechanism of diseases and is instrumental in advancing precision medicine. We anticipate that the rapidly advancing AI-based multi-omics data analysis will significantly contribute to promoting healthy longevity.

Weight-bearing computed tomography (WBCT) enables acquisition of three dimensional bony structure images in a physiological weight-bearing position, which is fundamental in under-standing the pathologic lesions and deformities of the ankle joint. Over the past decade, re-searchers focused on validating and developing WBCT measurements, which has significantly enhanced our knowledge of common foot and ankle disease. Consequently, understanding the application of WBCT in clinical practice is becoming more important to produce improved out-comes in the treatment of disease around the ankle joint. This review will describe an overview of what is currently being evaluated in the foot and ankle surgery using WBCT and where the course of research will be heading in the future.

Retiring coal power plants can reduce air pollution and health damages. However, the spatial distribution of those impacts remains unclear due to complex power system adjustments and pollution chemistry and transport. Focusing on coal retirements in Pennsylvania (PA), we analyze six counterfactual scenarios for 2019 that differ in retirement targets (e.g., reducing 50% of coal-based installed capacity vs. generation) and priorities (e.g., closing plants with higher cost, closer to Environmental Justice Areas, or with higher CO₂ emissions). Using a power system model of the PJM Interconnection, we find that coal retirements in PA shift power generation across PA and the Rest of PJM region leading to scenario-varying changes in the plant-level release of several air pollutants. Due to air pollution chemistry and transport and socio-demographics, these changes in turn give rise to a reduction of 10 to 182 PM_2.5-attributable deaths in PJM across the six scenarios, with most reductions occurring in PA. Scenarios that reduce more coal power generation yield greater aggregate health benefits due to air quality improvements in PA and adjacent downwind regions. In addition, vulnerable populations—in both PA and Rest of PJM—benefit most in scenarios that prioritize plant closures in PA near Environmental Justice Areas. These results demonstrate the importance of considering cross-regional linkages and socio-demographics in designing equitable retirement strategies.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients’ colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cutoff values for these three markers. The high APRIL/TNFSH13 expression group showed a significantly higher rate of metastatic lesions than the low expression group, whereas the high MMP-3 expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low expression group. The five-year disease-free survival of the high MMP-3 expression group was significantly shorter than that of the low expression group (65.1% vs. 90.2%, p=0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.