In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

We attempted to establish an objective method to accurately evaluate the motility of bull sperm and examined the effects of media for sperm suspensions and frame rates on data of computer-assisted sperm motility analysis (CASA). Sperm incubated in Brackett and Oliphant medium (BO) more clearly showed hyperactivation-like motility than those in synthetic oviductal fluid. Sperm images captured at 150 frames per second (fps) showed a trajectory that was closer to the real pathway than those at other frame rates (30, 50, and 75 fps). We then examined the characteristics of sex-sorted and non-sorted semen using a cluster analysis followed by a discriminant analysis of sperm motility in BO at 150 fps. The results indicated that sex-sorted semen contained sperm with hyperactivation-like motility as the main subpopulation immediately after thawing and this subpopulation decreased after 2-h incubation. The main subpopulation in non-sorted semen had progressive motility that was maintained during incubation. In conclusion, usage of BO for sperm suspensions and capturing sperm motility at 150 fps by CASA were appropriate for evaluating bovine sperm motility. A discriminant analysis using data from a cluster analysis of motile sperm has the ability to accurately describe differences in the structures of sperm motility subpopulations.

Red mud is a hazardous waste of alumina industry that contains high amounts of iron, aluminum, titanium and REEs. One of the promising methods for the extraction of iron from red mud is car-bothermic reduction with the addition of sodium salts. This research focuses on the process of hy-drochloric high-pressure acid leaching using 10–20% HCl of two samples of non-magnetic tailings obtained by 60-minute carbothermic roasting of red mud at 1300 °C and the mixture of 84.6 wt. % of red mud and 15.4 wt. % Na2SO4 at 1150 °C, respectively, with subsequent magnetic separation of metallic iron. An influence of temperature, leaching duration, solid-to-liquid-ratio and acid con-centration on dissolution behavior of Al, Ti, Mg, Ca, Si, Fe, Na, La, Ce, Pr, Nd, Sc, Zr were studied. Based on the investigation of the obtained residues, mechanism of passing of valuable elements into the solution was proposed. It has shown that 90% Al, 91% Sc and above 80% of other REEs can be dissolved under optimal conditions; Ti can be extracted into the solution or the residue depending on the leaching temperature and acid concentration. Based on the research results, novel flowsheets for red mud treatment were developed.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

There are currently around 78 Nuclear Power Plants (NPP) in the world based on Boiling Water Reactors (BWR). The current parameter to assess BWR instability issues is the linear Decay Ratio (DR). However, it is well known that BWRs are complex non-linear dynamical systems that may even exhibit chaotic dynamics that normally preclude the use of the DR when the BWR is working at a specific operating point during instability. In this work a novel methodology based on an adaptive Shannon Entropy estimator and on Noise Assisted Empirical Mode Decomposition variants is presented. This methodology was developed for real-time implementation of a stability monitor. This methodology was applied to a set of signals stemming from several NPPs reactors (Ringhals-Sweden, Forsmark-Sweden and Laguna Verde-Mexico) under commercial operating conditions, that experienced instabilities events, each one of a different nature

The maritime industry contributes to over 80% of global trade and ranks as the sixth-largest emitter of greenhouse gases. The International Maritime Organization has taken strides to reduce these emissions, while the European Union spearheads efforts to establish sustainable maritime transport. However, meeting decarbonisation targets poses significant challenges, with the potential implications of adopting an EU Emission Trading System (ETS) on shipping allowances, particularly at specific borders. If not managed effectively, this could result in diversifying regular container shipping routes away from EU ports, potentially leading to increased shipping emissions and disrupting the logistics trade and security chain. These challenges are exacerbated by the International Maritime Organization's lack of a carbon fee on bunkering, which creates an imbalance. The ETS Directive has fostered unfair competition between EU and non-EU ports due to discrepancies in applying emission unit allowances. It is imperative to implement preventive measures to contain and prevent the shift of operations from EU ports to nearby ports, ensure equitable treatment of EU transhipment ports and their competitors, and thwart carbon leakage. Additionally, the recent Houthis attacks on the Red Sea have significantly impacted shipping costs on the Cape of Good Hope route to Europe, necessitating increased allowances to and from Europe.

Barrett’s esophagus (BE) is a known precursor to Esophageal Adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered an acceptable alternative to esophagogastroduodenoscopy (EGD). This study presents analytical validation of EsoGuard® (EG), a two gene DNA methylation biomarker assay, in esophageal cell samples collected with the 510(k)-cleared, swallowable EsoCheck® (EC) device. EG is a Next Generation Sequencing (NGS) assay that evaluates methylated Vimentin (VIM) and Cyclin A1 (CCNA1) genes, clinically validated biomarkers for detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for analytical validation of molecular assays. Comparison to Sanger sequencing showed EG was 100% accurate at all 31 CpG sites evaluated by the assay. Analytical sensitivity, specificity and accuracy of the assay was 89%, 100% and 96% respectively. Intra- and inter-assay precision was 100%. Limit of detection (LOD) was 1 in 400 methylated cells and reference range was 84%. In summary, EsoGuard is a robust DNA methylation test to detect BE with high accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device.

Dissemination of resistant pathogens via food supply chains is a notable public health danger from farm to fork. The proposed work analysed the distribution of E. coli among various sources of animal-based food supply chain. Overall, 500 samples were heaped up from livestock, poultry sectors, environment, fisheries, and dairy. Standard microbiological procedures were used to isolate and identify E. coli. Further, isolates were confirmed by using MALDI-TOF and virulence associated genes (VAGs). The phenotypic resistance pattern of the isolates was determined by molecular identification of antibiotic resistance genes (ARGs) through PCR using specific primers. Shiga toxin producing E. coli (STEC) were subjected to PCR based O typing using specific primers against different O types. Overall results revealed that 154 (30.5%) samples were confirmed as E. coli, in which77 (50%) isolates were MDR E. coli. Among these, total 52 (67.53%) isolates showed array of VAGs in which 21 (40.38%) were confirmed as STEC based on stx1 and stx2. Furthermore, 12/52 (23.07%) isolates were detected as Non-O157 STEC co-harboring mcr-1 and blaNMD-1. Overall, O26 STEC was found to be the most prevalent among different non-O157 types. Herein, results proposed that detection of such STEC MDR E. coli causing serious public health consequences in developing countries.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

This paper provides the first-time ever analytic modelling for Pointwise Stationary Fluid Flow Approximation(PSFFA) model of the non-stationary

Suppose for n∈ ℕ, set A⊆ℝⁿ and function f∶A→ℝⁿ. If set A, using the Hausdorff outer measure, is measurable in the sense of Carathèodory; we want to find an extension of the expected value, w.r.t the Hausdorff measure, that's unique, finite and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. The issue is current extensions of the expected value are finite for all functions in only a shy subset of ℝᴬ. The reason this issue wasn't resolved is mathematicians have not thought of the problem, focusing on application rather than generalization. Despite the lack of potential use, we'll attempt to solve the problem by defining a choice function---this shall choose a unique set of equivalent sequences of sets (Fₖ***) , where the set-theoretic limit of Fₖ*** is the graph of f; the measure Hʰ is the ℎ-Hausdorff measure, such for each k∈ℕ, 0 < Hʰ(Fₖ***) < +∞; and (fₖ*) is a sequence of functions where {(x,fₖ*(x))∶x∈ dom(Fₖ***)}=Fₖ***. Thus, the extended expected value of or E**[f,Fₖ***] is: ∀(ε>0)∃(N∈ℕ)∀(k∈N)(k≥N⇒1/Hʰ(dom(Fₖ***))∫dom(Fₖ*** )fₖ* dHʰ - E**[f,Fₖ***]<ε ) which should be unique, finite, and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. Note we guessed the choice function using computer programming but we don’t use mathematical proofs due to the lack of expertise in the subject matter. Despite this, the biggest use of this research is the extension of the expected value is finite for "almost all" functions: this is easier to use in application when finding the "average" of functions covering an infinite expanse of space.

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Multiple sources influence air quality and regional climate in complicated atmospheric emission situations like urban agglomerations. To resolve pollution plumes and source influences in polluted areas, a comprehensive chemical fingerprinting of sources utilizing non-methane hydrocarbons (NMHCs) and the identification of acceptable tracer molecules and emission ratios is required, in contrast to pristine locations, where reliance on a single or a few chemical tracers is frequently sufficient. We have characterized the prevalence of NMHCs fingerprints in the urban areas and quantified the correlation of windspeed with the concentration of these pollutants. eNose sensors and Air quality management stations provide the data to identify the emission sources of such pollutants. Based on our analysis, the average NMHC concentration in 2021 has been recorded 0.424 ppm at point 1 AQMS whereas at point 2 AQMS it was 0.256 ppm. Such outcomes could be attributed to the proximity of emissions sources, the direction and speed of the wind, or both. Moreover, traffic can be a major contributor to pollution levels in any urban area. More research based on a larger dataset is required before definitive conclusions can be drawn, and viable solutions can be proposed.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth about particular real phenomena.

In this study, our primary objective was to analyze the tradeoff between accuracy and complexity in machine learning models, with a specific focus on the impact of reducing complexity and entropy on the production of landslide susceptibility maps. We aimed to investigate how simplifying the model and reducing entropy can affect the capture of complex patterns in the susceptibility maps. To achieve this, we conducted a comprehensive evaluation of various machine-learning algorithms for classification tasks. We compared the performance of these algorithms in terms of accuracy and complexity, considering both "before" and "after" scenarios of dimensionality reduction using Principal Component Analysis (PCA). Our findings revealed that reducing complexity and lowering entropy can lead to an increase in model accuracy. However, we also observed that this reduction in complexity comes at the cost of losing important complex patterns in the produced landslide susceptibility maps. By simplifying the model and reducing entropy, certain intricate relationships and uncertain patterns may be overlooked, resulting in a loss of information and potentially compromising the accuracy of the susceptibility maps. The analysis encompassed a diverse range of machine learning algorithms, including Random Forest (RF), Extra Trees (EXT), XGboost, LightGBM, Catboost, Naive Bayes (NB), K-Nearest Neighbors (KNN), Gradient Boosting Machine (GBM), and Decision Trees (DT). Each algorithm was evaluated for its strengths and limitations, considering the tradeoff between accuracy and complexity. Before dimensionality reduction, the algorithms demonstrated promising results, with RF exhibiting excellent AUC/ROC scores and average accuracy. However, computational costs were noted as a potential drawback for RF, especially when dealing with large datasets. EXT showcased robust performance and good accuracy, while XGboost demonstrated its ability to handle complex relationships within large datasets, albeit requiring careful hyperparameter tuning. The efficiency and scalability of LightGBM made it a suitable choice for large datasets, although it displayed sensitivity to class imbalance. Catboost excelled in handling categorical features, but longer training times were observed for larger datasets. NB showcased simplicity and computational efficiency but assumed independence among features. KNN, known for its capability to capture local patterns and spatial relationships, was found to be sensitive to the choice of distance metric. GBM, while capturing complex relationships effectively, was prone to overfitting without proper regularization. DT, with its interpretability and ease of understanding, faced limitations in terms of overfitting and limited generalization. After dimensionality reduction, certain algorithms exhibited improvements in their AUC/ROC scores and average accuracy, including RF, EXT, XGboost, and LightGBM. However, for a few algorithms, such as NB and DT, a decrease in performance was observed. This study provides valuable insights into the performance characteristics, strengths, and limitations of various machine learning algorithms in classification tasks. Researchers and practitioners can utilize these findings to make informed decisions when selecting algorithms for their specific datasets and requirements. We also aim to identify the potential factors contributing to the high accuracy rates obtained from these ensembled algorithms and explore possible shortcomings of non-ensembled algorithms that may result in lower accuracy rates. By conducting a comprehensive analysis of these algorithms, we seek to provide valuable insights into the benefits and limitations of ensembled approaches for landslide susceptibility mapping. Our study sheds light on the challenges faced when balancing accuracy and complexity in machine learning models for landslide susceptibility mapping. It emphasizes the importance of carefully considering the level of complexity and entropy reduction in relation to the specific patterns and uncertainties present in the data. By providing insights into this tradeoff, our research aims to assist researchers and practitioners in making informed decisions regarding model complexity and entropy reduction, ultimately improving the quality and interpretability of landslide susceptibility maps.

Background: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Objectives: To investigate the efficacy of manual therapy (MT) program combined with Capacitive and Resistive Electric Transfer (TECAR) therapy in individuals with CNSLBP. Method: Sixty adults with CNSLBP were randomly equally divided into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet and the third group (Control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 hours with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), Pressure Pain Threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both in the second week as well as in the one-month follow-up (p < .001). Between-groups differences were also noticed between the two intervention groups in the second week (p < .05). Differences in the RMDQ score in the second week and on the one-month follow-up were detected between the intervention groups and the control group (p < .001), while differences between the two intervention groups were only detected in the one-month follow-up (p < .001). Regarding the PPT values, differences were found mainly between the MT + TECAR and the control group and between the MT + TECAR and the MT group (p < .05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant in the one-month follow-up (p < .05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region in both time points compared to the control group without, however, statistically significant differences between them (p> .05). Conclusion: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.

: Studies on the effects of non-nutritive sweeteners (NNSs) in pregnant women are scarce are conflicting. A major challenge is to accurately assess NNS intake, especially in countries where many foods and beverages have been reformulated with the progressive replacement of sugar by NNSs, due to the implementation of new nutrition labelling policies for preventing obesity. This study aimed to develop and valid a food frequency questionnaire (FFQ) to examine the intake of NNSs in pregnant women. This questionnaire was tested in 29 women in their eighth month of gestation, compared to a 3-day dietary records (3-DR). FFQ validity was assessed using Spearman´s correlation coefficient, Lin´s concordance correlation coefficient (CCC) and Bland-Altman plots. Spearman correlations between NNS FFQ and 3-DR ranged from 0.50 for acesulfame K to 0.83 for saccharin. The CCC ranged from 0.22 to 0.66. Bland-Altman plots showed an overestimation of saccharin, sucralose and steviol glycosides intake by the NNS FFQ, and an underestimation of acesulfame K and aspartame, compared to 3-DR. Overall, the most frequently consumed NNS was sucralose None of the participants exceeded the acceptable daily intake for any of the NNSs evaluated. The FFQ of NNSs appears to be a reasonably valid tool for assessing NNS consumption in pregnant women.

The present work is a numerical simulation of velocity and mixture fraction fields in a turbulent non-reaction Propane jet flow issuing into parallel co-flowing air, in isothermal condition which has been experimentally described here: http://www.sandia.gov/TNF/DataArch/ProJet.html. The objective is a better understanding of the flow structure and mixing process, a situation in which there is no chemical interaction and heat-transfer. The two-equation Realizable k-ε eddy viscosity turbulence model has been used to simulate the turbulent flow field on a 2D plane (i.e., on a 5-degree sector of the experimental domain), because Realizable k-ε more accurately predicts the spreading rate of both planar and round jets and presents the best proficiency in comparison with all versions of the k-ε models. Afterward, axial and radial profiles of mean velocities, turbulence energy, mean mixture fraction, the mixture fraction half radius (Lf), and the mass flux diagram have been numerically elicited for grid independent mesh (mesh B) and compared with corresponding experimental data to assess the numerical model. To obtain turbulence kinetic energy, k, due to lack of w' in the experimental data, the assumption of w'=v' seems to be valid. Simulations have demonstrated that mean mixture fraction (at radial profiles at locations x/D=0, 4, 15, 30 and 50) and its half radius, Lf, which characterizes jet width expanse, are prominently well-captured; Moreover, mean vertical velocity fields (in X-direction: Umean) have revealed less accuracy but still conspicuously well-captured. However, mean vertical velocity fields (in Y-direction: Vmean) have disclosed less resolution; Likewise, turbulence kinetic energy, k, have manifested moderate accuracy (between Umean and Vmean). It should be noticed that although numerical results for absolute pressure, p, have been obtained on aforementioned sections, there were no experimental data to compare with them. Thus, the corresponding numerical data has not been demonstrated in this study.

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

Dietary polyphenols exist in two forms; extractable polyphenols (EPP) or compounds solubilised by aqueous/organic solvents, and non-extractable polyphenols (NEPP) or compounds remain in the corresponding residues after the extraction. At present, most researchers focus on EEP fractions, while NEPP is neglected. Thus, this study aimed to release NEPP from the remaining powder residue of Barhi date palm kernels (BDPK) with acid hydrolysis. The related extraction conditions were determined and optimised using response surface methodology (RSM) for maximisation of NEPP with highest cytotoxic and antioxidant activities. The face-centred central composite design (FCCCD) was used to establish treatments based on three independent variables, namely; extraction temperature, time, and solvent/sample ratio. Under the optimal conditions, the experimental values for DPPH radical-scavenging capacity of NEPP (IC50=57.52µg/mL), and cytotoxicity of NEPP against A549 and HT29 cells were IC50=17.4 µg/mL and 31.4µg/mL, respectively. The experimental values were in agreement with those predicted by RSM models, confirming the suitability of the model employed and the success of RSM for optimisation of the extraction conditions for NEPP from BDPK. These results indicate that NEPP from industrial date fruit waste could be a promising candidate as natural antioxidants with significant antiproliferation effect against A549 and HT29 cancer cells in-vitro.

Background: Evaluation of nutrition programs is essential to guarantee the effectiveness of community-based management of acute malnutrition (CMAM). Methods: The Rainbow Project Supplementary Feeding Programs (SFPs) in Zambia were evaluated between years 2015-17, following implementation of new recommendations based on previous evaluations (years 2012-14). Outcomes of the program were compared with International Standards and with those of 2012-14. Cox proportional risk regression analysis was performed to identify predictors of mortality and defaulting. Results: Data for 900 under age 5 years malnourished children (48.8% male; mean age 19.7months ±9.9) were analyzed. Rainbow 2015-17 program outcomes met International Standards, for general malnutrition or stratified moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). When comparing with 2012-14 outcomes, better performance was noted: mortality rates were reduced by half (5.6% vs 3.1%, p = 0.01; for SAM: 12.4% vs 6.7%, p = 0.006), with significant improvement in average weight gain and mean length of stay (p<0.001), and increased awareness of HIV status (+30%; p < 0.001). HIV infection (5.5; 1.9–15.9), WAZ < −3 at baseline (4.6; 1.3–16.1) and kwashiorkor (3.5; 1.2–9.5) remained the major predictors of mortality. Conclusion: The effectiveness of the Rainbow SFPs for child malnutrition treatment and prevention in Zambia has significantly improved after evaluation and implementation activities, with impressive outcomes which resulted in a 50% reduction in mortality.

Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.

This study was conducted to evaluate the yield and quality parameters of milk from 60 indigenous South African goats of different genotypes namely Nguni, Boer and Non- descript reared under a free ranging system. Milk yield and quality parameters (milk fat, protein, lactose, solid non-fat and minerals) from Nguni (10), Boer (10) and Non-descript (10) goats was measured and analysed per week at each stage of lactation. Result showed that, Nguni goats produced (1.2±0.09, 1.3±0.11 and 1.2±0.07 litres per day) more milk (P ˂ 0.05) at early, mid and late stages of lactation than Boer (0.6±0.10, 1.0±0.17 and 0.6±0.09 litres per day) and Non-descript (0.3±0.10, 0.3±0.12 and 0.3±0.09 litres per day) goats, respectively. The mean value of milk fat, protein and lactose content from Nguni goat was (3.98, 3.54 and 5.31); Boer goat (2.9, 3.59 and 5.04) and Non-descript goat (4.05, 3.39 and 5.02), respectively. There was significant effect (P ˂ 0.05) of genotypes on milk fat, milk magnesium and sodium contents of Nguni, Boer and Non-descript goats. It could be concluded that, Nguni goat produced more milk than Boer and Non-descript goats, but the Non-descript goat had higher mean percentage of milk fat compared to Nguni and Boer goats.

In the era of mounting water scarcity, particularly in arid regions, the agricultural sector is striving to optimize the water resource management practices. Treated wastewater (TWW) has emerged as a viable alternative to freshwater for irrigation, offering a sustainable solution to water conservation. However, ensuring the safety and quality of TWW is paramount to safeguard for both crop health and environmental integrity. Electrical conductivity (EC), a critical factor in assessing TWW suitability for irrigation, can significantly impact crop yields and soil health since it is directly linked to the concentration of dissolved salts and ions. Therefore, this study delves into the development of advanced predictive models for EC assessment by employing supervised machine learning (ML) techniques like the Support Vector Regression (SVR), Adaptive Network-based Fuzzy Inference System (ANFIS), and Multiple Linear Regression (MLR). The TWW samples collected from Al-Qatif area, Saudi Arabia were assessed in the lab through a sensor-based real-time monitoring system integrated with Internet of Things (IoT) network and a multiprobe device. The key water quality parameters assessed involved, temperature (T), pH, Oxidation Reduction Potential (ORP), Resistivity (RES), Total Dissolved Solids (TDS), Salinity and Turbidity which served as the foundation for these models, given their profound influence on and their anticipated impact on EC levels. Following feature selection, two distinct model combinations were identified for the SVR, ANFIS and MLR models. Furthermore, to evaluate prediction performance, four statistical criteria, including coefficient of determination (R²), correlation coefficient (R), mean square error (MSE), and root mean square error (RMSE), were employed. Overall, the comparative performance results proved that ANFIS-M2 indicated the strongest predictive capability with the R² value of 0.99572 and 0.75145 and the RMSE values of 0.00965 and 0.01134, respectively in both calibration and verification stages.

In this work, we introduce a new concepts for $\alpha$-type $F$-Suzuki contraction and $\alpha$-type $F$-weak-Suzuki contraction in the context of $b$-metric spaces. Compared to the $\alpha$-type $F$-contraction and $F$-Suzuki contraction mappings, these contractions are essentially weaker. For these type of contraction mappings, sufficient conditions are established for the fixed point's existence and uniqueness in $b$-metric spaces. As a result, the findings encompass several generalizations. To show the usability of our obtained results, we provide a supportive example and an application to a non-linear differential equation with fractional order.

The autosomal recessive disorder Ataxia-Telangiectasia is caused by dysfunction of the stress response protein ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumor risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies the cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits by bone-marrow transplantation, and reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated ATM depletion to trigger upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently neuropeptide machinery, e.g. Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM localized only to cytoplasm, similar to brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient / oxidative stress, not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation.

Many studies link changes in avian phenology in Europe to the North Atlantic Oscillation (NAO), as a proxy of conditions at western Europe. But effects of climate variation in other regions of Eu-rope on phenology of short-distance migrants with wide non-breeding grounds remain unclear. We determined the combined influence of large-scale climate indices, NAO, the Mediterranean Oscillation Index (MOI), and the Scandinavian Pattern (SCAND), during the preceding year on spring migration timing of European Wren at the southern Baltic coast during 1982–2021. We modelled the effects of these climate variables on the entire passage and subsequent percentiles of Wren’s passage at Bukowo-Kopań and Hel ringing stations. The start and median of migration shifted earlier at Hel, but the end of passage shifted later at both stations over 1982–2021. In the effect, the duration of passage at Hel extended by 7.6 days. Early passage at Hel was related with high MOI1 in spring and in preceding autumn. Spring passage at Bukowo-Kopań was late after high NAO in the previous breeding season, and high winter and spring NAO. At both stations late spring passage occurred after high SCAND in previous summer. Early beginning or median of passage at our stations followed high local temperatures. We conclude that phenology of Wren’s spring migration at the Baltic coast was shaped by conditions that different populations encounter at wintering quarters in western Europe, where NAO operates, and in the south-eastern Europe, where the MOI1 operates, in combination with conditions in Scandinavia during previous breed-ing season. We showed that climate variability in different parts of the migrants’ range has com-bined carry-over effects on in migrant’s phenology in Europe.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

COVID-19 pandemic has caused a large-scale havoc in almost every country across the globe, putting major challenges for the healthcare system in many parts of the world. Several of the laboratories are running in the race with undying efforts for developing potential vaccine, drugs or therapeutics to treat or prevent the infection. However, with the limited time window and high rate of infection, the task is very big for humanity to find a cure. With hundreds of genomic data of SARS-CoV-2 virus isolates from humans are being submitted almost every day, it is coming into knowledge that virus is mutating, slower in countries with sporadic cases, but higher in countries experiencing large outbreak. These types of mutations in virus may bring challenges in vaccine or therapeutic development for use in each and every country, as each hotspot region may have their own pattern of mutations in virus with ongoing outbreak. In our current study, we retrieved non-synonymous mutation data of around 12,225 SARS-CoV-2 virus samples isolated from humans globally, and discovered all mutations that are collectively happening in antibody epitope regions of the virus country-wise. We found a few numbers of epitope regions in SARS-CoV-2 that are highly conserved collectively in all variants and may be used for epitope-based vaccine development for whole world. We also found epitope regions that are conserved collectively in SARS-CoV-2 variants country-wise and can be used for customized epitope-based vaccine development in each different country.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

This paper identifies a criterion for choosing the largest set of rejected hypotheses in high-dimensional data analysis where Multiple Hypothesis testing is used in exploratory research to identify significant associations among many variables. The method neither requires predetermined thresholds for level of significance, nor uses presumed thresholds for false discovery rate. The upper limit for number of rejected hypotheses is determined by finding maximum difference between expected true hypotheses and false hypotheses among all possible sets of rejected hypotheses. Methods of choosing a reasonable number of rejected hypotheses and application to non-parametric analysis of ordinal survey data are presented.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

We investigate the structural correlation of non-covalent crown ether/H+/L-tryptophan (CR/TrpH+) host-guest complexes in the solution phase with those in the gas phase generated through electrospray ionization/mass spectrometry (ESI/MS) techniques. We perform quantum chemical calculations to determine their structures, relative Gibbs free energies, and infrared spectra. We compare the calculated infrared (IR) spectra with the IR multiphoton dissociation (IRMPD) spectra observed for the 18-Crown-6/TrpH+ complex by Polfer and co-workers [J. Phys. Chem. A 2013, 117, 1181−1188] for assigning the IR bands. We observe that the carboxyl group remains ‘naked’, lacking hydrogen bonding with the CR unit in the gas phase, and that this most stable conformer originates from the corresponding lowest Gibbs free energy structure in solution. Based on these findings, we propose that gas phase host-guest complexes directly correlate with those in solution, reinforcing the possibility of obtaining invaluable information about host-guest-solvent interactions in solution from the structure of the host-guest pair in the gas phase.

Abstract: Background: Non-invasive acquistion of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r=0.64) and PCS (r=0.55) (p<0.01), as well as MAPIBP/DBPIBP for PES (r=0.6/0.55) and PCS (r=0.5/0.45) (p<0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease(0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

To explore the impact of parenting styles on the perception of campus non-physical bullying, 492 students in upper elementary school grades were surveyed by using the Delaware Bullying Victimization Scale, the Negative Coping Style Scale, the Negative Affect Scale, and the Egna Minnen Beträffende Uppfostran Questionnaire. The questionnaire survey was conducted in the fifth and sixth grades of eight primary schools in Zhejiang province. The results showed that cyberbullying was not significantly related to an anxious parenting style, but negative affect experiences, negative coping styles, negative family parenting styles, and the perception of campus non-physical bullying were all positively correlated with each other (p < 0.05). The refusal parenting style was shown to be an important factor that affected students’ perception of campus non-physical bullying; it was observed to directly affect students’ perception of campus non-physical bullying and indirectly affect students’ perception of campus non-physical bullying by influencing negative affect experiences and negative coping styles. In conclusion, negative affect experiences and negative coping styles had a chain-like mediating effect between the refusal parenting style and students’ perception of campus verbal bullying. Moreover, negative affect experiences had a partial mediating effect between the refusal parenting style and students’ perceptions of campus cyberbullying, relationship bullying, and non-physical bullying total scores. Implications and suggestions based on these results are also discussed.

Cadmium telluride (CdTe), a metallic dichalcogenide material, has been utilized as an absorber layer for thin film-based solar cells with appropriate configurations, and the SCAPS-1D structures program has been used to evaluate the results. In both known and developing thin film photovoltaic systems, a CdS thin film buffer layer has been frequently employed as a traditional n-type heterojunction partner. In this study, numerical simulation was used to find a suitable non-toxic material for the buffer layer instead of CdS, among various types of buffer layers (ZnSe, ZnO, ZnS, and In2S3), and carrier concentrations for the absorber layer (NA) and buffer layer (ND) were varied to determine the optimal simulation parameters. carrier concentrations (NA from 2 x 1012 cm-3 to 2 x 1017 cm-3 and ND from 1 x 1016 cm-3 to 1 x 1022 ??−3) have been differed. The results showed that the CdS as buffer layer based CdTe absorber layer solar cell has the highest efficiency (?%) of 17.43%. Furthermore, high conversion efficiencies of 17.42% and 16.27% have been found for ZnSe and ZnO based buffer layers, respectively. As a result, ZnO and ZnSe are potential candidates for replacing the CdS buffer layer in thin-film solar cells. Here, the absorber (CdTe) and buffer (ZnSe) layers were chosen to improve the efficiency by finding the optimal density of the carrier concentration (acceptor and donor). The simulation findings above provide helpful recommendations for fabricating high-efficiency metal oxide-based solar cells in the lab.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Background: This study explores the impact of a gluten-free diet (GFD) on regional gastrointestinal (GI) transit times in individuals with celiac disease (CD) and non-celiac gluten sensitivity (NGCS). While a GFD is established for managing CD and wheat allergy, its effects on NGCS remain controversial due to inconclusive evidence. Methods: Utilizing a wireless motility and pH capsule (WMC) to assess regional and whole gut transit, newly diagnosed CD (n=12) and NGCS (n=12) patients underwent baseline evaluations, including measurements of gastric, small bowel, and colonic transit times. Results: At baseline conditions, individuals diagnosed with CD exhibited prolonged colonic and intestinal transit times when compared to those with NGCS (p&lt;0.05). Following a 4-week GFD, CD patients experienced significant reductions in both intestinal and colonic transit times, along with enhanced small intestine contractility. NGCS individuals showed improvements in intestinal transit time and contractility with a GFD, although the colon exhibited no discernible effect. The GFD did not significantly impact intragastric, intestinal, or colonic pH. Conclusions: This study, employing WMC for the first time, provides novel insights into the positive effects of a GFD on intestinal and colonic transit, as well as contractility, in CD patients, and to a lesser extent, in those with NGCS.

Knowing the reasons for mobility choices, how users evaluate the characteristics of public transport and how satisfied they are with the travel experience is essential to promote the use of LTP (Local Public Transport), especially in rural or suburban areas where the use of private car is often prevalent. The present study aimed to investigate the mobility experience and the reasons for use and non-use of the LPT in a suburban area by the people travelling to a large Hospital Centre in a Province of the North-east of Italy. An anonymous questionnaire was completed by people from different categories travelling to the hospital (students, employees, clients), user and non-users of the LPT. The results showed that insufficient hourly coverage and accessibility of the service are the primary reasons for opting not to use LPT and together with reliability and comfort, these factors contribute to user satisfaction with their travel experience. Perceived sustainability of LPT contributes to overall travel satisfaction. However perceived sustainability alone does not appear to influence the choice of LPT if the service lacks adequate accessibility and does not meet the needs of travelers in terms of hourly coverage

Background: Spinal pain is highly prevalent and in Spain it produces a very high economic cost and the scientific evidence supporting treatments shows low to moderate evidence for exercise. Therefore, the aim of this study was to assess the effectiveness of a therapeutic group exercise protocol in reducing pain intensity and disability in patients with spinal pain in primary health care setting. Methods: A total sample of 149 patients who suffered from chronic non-specific spinal pain. Patients received a therapeutic exercise protocol, including exercises of auto-mobilization of the neck and lumbar regions, as well as core stabilization exercises. Pain intensity and disability were evaluated before and after the therapeutic exercise protocol. Results: Statistically significant differences (P&lt;0.05) were shown for pain intensity and disability of patients with neck and low back pain with an effect size from moderate to large. Conclusions: A therapeutic exercise protocol may provide beneficial effects on disability and pain intensity in patients with chronic non-specific spinal pain, including neck and low back pain conditions. Clinicians should consider the use of self-administered exercise protocols, demonstrate great effectiveness, and be less costly.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

This paper is in response to a critique of the author’s earlier papers on the matter of a non-local communication system by Ghirardi. The setup has merit for not apparently falling for the usual pitfalls of putative communication schemes, as espoused by the No-communication theorem (NCT) - that of non-factorisability. The enquiry occurred from the investigation of two interferometer based communication systems: one two-photon entanglement, the other single-photon path entanglement. Both systems have two parties: a sender (“Alice”) who transmits or absorbs her particle and a receiver (“Bob”) who has an interferometer, which can discern a pure or mixed state, ahead of his detector. Ghirardi used the density matrix and found that the system wasn’t factorisable; this was seen as a fulfilment of the NCT. We revisit the analysis and say quite simply that Ghirardi is mistaken. The system is rendered factorisable by a Schmidt decomposition and entanglement swapping to “which path information” of the interferometer; also one must consider the joint evolution before taking the partial trace. Ghirardi’s misuse, by the inapplicability of the NCT in this situation, renders this general prohibitive bar incomplete or entirely wrong.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.

To clarify whether changes in biological features of breast tumor cells and intra-tumor immunity after neoadjuvant chemotherapy (NAC) may correlate with pathological responses and prognosis in breast cancer patients treated with NAC, we investigated various biomarkers using both pre- and post-NAC tumor samples. The study subjects were 24 primary breast cancer patients, who were treated with NAC at the Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital between 2010 and 2011. All of them had a non-pathological complete response (pCR) to NAC and their pre- and post-NAC tumor samples were available for biomarker assays. Ki67 labeling index, apoptosis, factors related to cancer stem cells and epithelial-mesenchymal transition, tumor infiltrating lymphocytes (TILs), and expression levels of CD-8, CD-4, FoxP3, PD-L1, and PD-1 were studied using the paired samples. Biological characteristics of residual tumors such as nuclear grade (NG) and vascular invasion (v) were also investigated. The median age was 53 years-old and 14 patients had stage III tumors, while 10 had stage II tumors. A higher expression level of CD8, CD4, or PD-1 in pre-NAC samples and of CD8, CD4 or PD-L1 in post-NAC samples was significantly correlated with a better pathological response to NAC. Positivity of ZEB1, vimentin, and v or NG 3 in post-NAC samples was significantly correlated with either worse disease-free survival (DFS) or worse overall survival (OS) by univariate analyses. Multivariate analyses for DFS and OS revealed that positivity for v and vimentin expression in residual tumors were independent prognostic factors in this study. These findings indicate that activated intra-tumor immune microenvironments may play significant roles in pathological responses to NAC, and that the up-regulation of vimentin and v-positivity in residual tumors may be pivotal prognostic factors in non-pCR cases to NAC.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

Except for a few species, the outer shape of vertebrates normally is characterized by bilateral symmetry. The inner organs, on the other hand, normally are arranged in bilaterally asymmetric patterns, which are of special importance for the normal function of the cardiovascular system of lung-breathing vertebrates. Deviations from the normal organ asymmetry can occur in the form of mirror imagery of the normal arrangement (situs inversus), or in the form of arrangements that have the tendency for development of bilateral symmetry, either in a pattern of bilateral left-sideness (left isomerism) or bilateral right-sidedness (right isomerism). The latter two forms of visceral situs anomalies are called “heterotaxy syndromes”. During the past 30 years, remarkable progress has been made in uncovering of the genetic etiology of heterotaxy syndromes. However, the pathogenetic mechanisms causing the spectrum of cardiovascular defects found in these syndromes remain poorly understood. In the present report, a spontaneous case of left cardiac isomerism found in a HH-stage 23 chick embryo is described. The observations made in this case suggest that hearts with left cardiac isomerism may have the tendency for development of a non-compaction cardiomyopathy caused by defective development of the proepicardium.

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database γ-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

This paper provides a new discovery that adds to the contemporary theory of modelling of non-stationary queues, by capturing analytically the behavior of the root parameter, for the G1/M/1 PSFFA model of non-stationary Ek/M/1 queue. Additionally, it has been also revealed that the resulting root parameter reduces to the PSFFA model of non-stationary queue. Potential applications of PSFFA to Computer engineering are provided. Some challenging open problems are addressed combined with closing remarks and future research directions.

Abstract: Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components in NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background of NSCLC is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin. We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the effect of transcription factor (TF) LRF, a known epigenetic silencer, was examined on the epigenome modulation. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060-109,747,960 mouse chromosomal region to micro-RNA upregulated species. Fur-thermore, the novel epigenetic miR-148b-3p/PVT1/ZBTB7A axis was identified, which differentiates lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes. The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease and patient-tailored treatments.

Abstract Introduction: Antimicrobial resistance (AMR) is a recognised public health threat today globally. Though many active and passive stewardship strategies are employed to counter AMR clinically, educating school going children on AMR could be a futuristic cost-effective measure to minimize AMR development. We hypothesised NICE’s e-bug module to class VII school students on AMR determinants. Methodology: A prospective non-randomized intervention study on 327 students belonging to 9 schools of class VII around Manipal town, Udupi district, Karnataka state, India were included for the study. 10 questions on AMR determinants extracted from NICE’s e-bug program were quizzed in written as pre-test followed by an education intervention on the same questions followed by a post-test to end the session. Descriptive statistics to estimate epidemiological characteristics, Wilcoxon Signed Ranks and Kruskal-Wallis tests were applied to analyse statistical significance of pre/post-test performance scores for the 10 questions and between schools respectively Results: Students had inadequate knowledge on 7 AMR determinants (antimicrobial indication, its course, hand hygiene, fermentation, spread of infection, microbial multiplication and characteristics of microbe) when analysed for post-test performance (p<0.05). Comparison of post-test performance of 9 participating schools revealed statistical significance (p<0.05) for 3 questions (definition on antimicrobial, cover while cough/sneezing and microbial characteristics) Conclusion: Although students exhibited sub-optimal knowledge on few AMR determinants, they showed keenness to learn exhibited by their performance. Our findings and previous similar studies from Europe are suggestive of early pedagogic interventions on AMR through inclusion of such education modules in the curriculum could be potential tool for AMR prevention for future generations.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

A cuprous oxide (Cu₂O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50-200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum were carried out. Neither ascorbic acid nor uric acid even at a relatively high concentration level of 100mg/dL in serum interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer based glucose sensor. Chronoamperometry (CA) and single potential amperometric voltammetry were used to verify the measurements obtained by differential pulse voltammetry (DPV), and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. Cuprous oxide (Cu₂O) thin layer based sensor showed the best sensitivity for glucose detection among the sensors evaluated.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Monitoring the quality of stored bulk grain is generally done using temperature cables hung from silo roofs. Little investigation has been done into the effects of number of sensors and their placement in terms of reliability of the monitoring system with regard to making stored grain quality management decisions. A previously developed 3D finite element simulation model was verified and used to investigate these aspects. In the first study, a silo was loaded with about 228.6 Mg (9000 bushels) of maize and six temperature cables were placed in the grain mass. The maize was aerated continuously for a period of two weeks, and the cable sensor temperatures were compared to the predicted temperatures which were in close agreement with the observed readings. The standard error of prediction ranged from 2.0 to 3.7°C. In the second study, 15 and 30 sensors were placed at manufacturer recommended depths and horizontal locations in the grain mass of three silo sizes (i.e., 11x11, 14.6x14.6 and 14.6x18.3 m diameter by eave height). The average grain temperatures predicted by the 15 and 30 sensors over a one-year simulation period were compared to the average grain temperatures predicted for the entire grain mass (1968, 3052, and 3204 mesh nodes). The number of sensors needed to monitor stored grain temperatures reliably in the three silo sizes investigated heavily depended on whether the aeration control strategy achieved a sufficiently low temperature by the time the aeration fans were turned off and sealed ahead of the non-aerated storage period. Fifteen or 30 sensors were sufficient to monitor grain temperatures during the aeration cooling period but for the two larger silo sizes more than 30 sensors would be needed during the storage period. As silo size increased, and surface-to-volume ratio decreased, grain temperatures remained lower during the storage period. Results support the best management practice recommendation of leaving cooled grain cold and not warming it up in the spring ahead of storage into the summer.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

An efficacious treatment of H. pylori infection is cornerstone for the global control of the diseases caused by this bacterium. Continuous epidemiologic surveillance of susceptibility of H. pylori to the antibiotics recommended for its eradication is highly recommended. This study aimed to determine the antimicrobial susceptibility pattern of 651 isolates from five different collections isolated between 1996 to 2008 in México City. The susceptibility profile of H. pylori isolates was determined by the E-test strips for each antibiotic (amoxicillin, clarithromycin, metronidazole, and tetracycline). Antimicrobial susceptibility testing showed a very high proportion of H pylori strains susceptible to amoxicillin, clarithromycin, and tetracycline (94.5%, 95%, and 99.5 %, respectively). In contrast, a high proportion (95%) of isolates was resistant to metronidazole. Notably, the proportion of susceptible/resistant strains to the 4 antibiotics over 5 consecutive time periods remained stable over time. Despite a wide use of amoxicillin and clarithromycin in the general population, the H pylori high susceptibility to these 2 antibiotics has been preserved during more than a decade. The high prevalence of resistance to metronidazole in H. pylori strains in our population compromises its use in the empirical treatment of H. pylori infection.

The diel variations of viruses (< 0.2 μm), picoplankton (0.2—2 μm; heterotrophic bacteria, Syn-echococcus spp., Prochlorococcus spp. and picoeukaryotes) and nanoplankton (2—20 μm; hetero-trophic nanoflagellates and pigmented nanoflagellates) were investigated for 2 days with about 4 hours of temporal sampling in spring 2024 in coastal surface waters of the subtropical western Pacific. A period of wind change associated with rain and increased turbulence, disrupted diel patterns of the overall microbial communities during the second cycle. The abundance of bacteria did not follow a consistent diel pattern, while viral abundance positively correlated with bacterial abundance. Synechococcus spp. and Prochlorococcus spp. grew during the light period and with peak abundance at night, exhibited marked diel variability, however, opposite patterns were observed in picoeukaryotes. According to Synechococcus spp. and Prochlorococcus spp. diel changes, nano-flagellate grazing could control their abundances and may explain temporally varying picocyanobacteria abundances. As we observed in the culture experiments, the results showed a significant increase in picoeukaryotic abundance from noon to nighttime, and a decrease in bacterial abundance during nighttime, to show the prey-predator cycle. Our study suggests picoeukaryotes could serve as bacteria predators by being mixotrophs. Future studies aiming to understand the interactions between prokaryotes and picoeukaryotes within marine microbial communities should take these differences into account.

The Hyper-Torus Universe Model (HTUM) proposes a novel framework to unify quantum mechanics, cosmology, and consciousness. This paper introduces HTUM's core concept: a higher-dimensional hyper-torus encompassing all possible states of existence. HTUM suggests that the universe functions as a quantum system where all outcomes are inherently connected, with consciousness playing a significant role in actualizing reality. The model introduces several key innovations, including the universe's 4-dimensional toroidal structure (4DTS), providing a new geometric interpretation of spacetime. HTUM presents dark matter and dark energy as nonlinear probabilistic phenomena within this toroidal framework, offering a unique perspective on their nature and interactions. The model proposes a mechanism for wave function collapse through universal self-observation, bridging quantum mechanics and gravity. It introduces a Topological Vacuum Energy Modulator (TVEM) function, offering a potential resolution to the cosmological constant problem. Furthermore, HTUM integrates consciousness as a fundamental aspect of the universe, influencing quantum state actualization and potentially resolving the hard problem of consciousness. The model explores the implications of a timeless singularity and the emergence of time as a product of causal relationships within the toroidal structure. This framework addresses critical challenges in modern physics, including the nature of quantum entanglement, the origin and fate of the universe, and the relationship between mind and matter. The paper discusses the mathematical formulation of HTUM, its implications for quantum mechanics and cosmology, and its potential to bridge the gap between science and philosophy. We present detailed predictions for the cosmic microwave background (CMB) power spectrum, gravitational wave signatures, and large-scale structure formation, demonstrating how HTUM differs from the standard ΛCDM model. Our analysis reveals distinctive oscillatory patterns in the relative difference between HTUM and ΛCDM predictions, with deviations reaching up to ±20% at certain scales. The paper also explores the unification of fundamental forces within the HTUM framework, proposing novel approaches to particle physics and quantum field theory. It introduces the concept of unified mathematical operations, suggesting a more holistic approach to mathematical thinking that aligns with the model's interconnected view of the universe. Additional testable predictions and proposed experimental approaches are discussed, including advanced space-based tests and laboratory experiments probing quantum gravity effects. These specific, quantifiable predictions offer multiple avenues for empirical validation, highlighting HTUM's potential to be distinguished from ΛCDM and other alternative cosmological models. HTUM represents a significant new perspective in our understanding of the universe, inviting further research and exploration into the nature of reality, consciousness, and the fundamental structure of the cosmos. By providing a comprehensive framework that unifies various aspects of physics, cosmology, and consciousness studies, HTUM offers a promising path toward a more complete understanding of our universe.

With the continuous advancement of digital transformation, digital payments are playing an increasingly important role in the financial industry. This study aims to utilize machine learning models to predict and analyze digital payment behavior. Initially, the background and significance of digital payments in the financial sector are introduced. Subsequently, the current status and trends of traditional digital payment distribution are reviewed, alongside related work on digital payment behavior prediction. Methodologically, principles and applications of machine learning models such as logistic regression, decision trees, and random forests are elaborated, along with experimental design and data preprocessing methods. The experimental results and discussion section illustrates the performance of each model in digital payment prediction and explores their impact on credit decisions. This exploration equips financial institutions with more effective user behavior analysis and risk management tools, thereby fostering future development and application of digital payment technologies.

The purpose of this narrative review is to provide an overview of the latest literature on bariatric and metabolic surgery for diabetes mellitus type II and obesity (diabesity) and to discuss its implications for future research and clinical practice.

Plant activators have emerged as promising alternatives to conventional pesticides for crop disease manage-ment due to their unique mode of action. By priming the plant's innate immune system, these compounds can induce systemic acquired resistance against a broad spectrum of pathogens without directly inhibiting their proliferation. Key advantages of plant activators include prolonged defense activity, lower effective dosages, and negligible risk of developing pathogen resistance. Among the various defensive pathways tar-geted, the salicylic acid (SA) signaling cascade has been extensively explored, leading to the successful devel-opment of commercial activators like benzothiadiazole for widespread application in crop protection. While the action sites of many SA-targeting activators have been preliminarily mapped to different steps along the pathway, a comprehensive understanding of their precise mechanisms remains elusive. This review provides a historical perspective on plant activator development and outlines diverse screening strategies employed across multiple levels, from whole-plant bioassays to molecular and transgenic approaches. We expound on the intricate components, biological relevance, and regulatory circuits governing the SA pathway, while criti-cally examining the structural features, bioactivities, and proposed modes of action of classical activators such as benzothiadiazole derivatives, salicylic acid analogs, and other small molecules. Insights from field trials as-sessing their practical applicability are also discussed. Furthermore, we highlight the current status, challenges, and future prospects in the realm of SA-targeting activator development globally, with a focus on recent en-deavors in China. Collectively, this comprehensive review aims to synthesize existing knowledge and provide a roadmap for future research toward developing more potent and mechanistically understood plant activa-tors that fortify crop immunity against disease.

In recent years, urbanization and industrialization have significantly increased the levels of outdoor noise pollution, affecting the quality of life in residential areas. In Uzbekistan, rapid development in urban centers has led to heightened concerns about the impact of noise on residents' health and well-being. Noise pollution can result from various sources, including traffic, construction, and industrial activities, causing disturbances and potential health issues such as stress, sleep disorders, and cardiovascular problems. Addressing this issue is crucial for creating a healthier living environment. This article explores effective strategies for mitigating the impact of outdoor noise on residential buildings in Uzbekistan.

At the end of the dry season in early March to early April each year, extensive agricultural biomass waste burnings occur throughout insular mainland Southeast Asia. During this biomass burnings period, smoke aerosols blanket the whole regions and were transported and dispersed by predominant westerly and south westerly winds to southern China, Taiwan and as far southern Japan and the Philippines. The extensive and intense burnings coincided with some wildfires in the forests due to high temperature making the region one of the global hot spots of biomass fires. In this study, we focus on the effect of pollutants emitted from biomass burnings in March 2019 at the height of the burnings period to the exposed population and their health impact. The Weather Research Forecast- Chemistry (WRF-Chem) model was used to predict the PM2.5 concentration over the simulating domain and health impacts are then assessed on the exposed population in the four countries of Southeast Asia, namely Thailand, Laos, Cambodia and Vietnam. Using the health impact based on log-linear concentration response function and Integrated Exposure Response (IER), the results show that at the peak period of the burnings from 13 to 20 March 2019, Thailand experienced the highest impact, with an estimated 2170 premature deaths. Laos, Vietnam, and Cambodia followed, with estimated mortalities of 277, 565, and 314 deaths respectively. However, when considering the impact per head of population, Laos exhibited the highest impact, followed by Thailand, Cambodia, and Vietnam. The results highlight the significant health impact and associated economic cost of agricultural waste burnings in Southeast Asia at the end of the dry season. And hence policy makers should take these into account to design measures to reduce the negative impact of widespread burnings on exposed population in the region.

The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer's disease. The potential of various compounds as AChE inhibitors has been investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks, statistical potentials, energy frustration, and volumetric cavity analyses. The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases.

Obstructive sleep apnea (OSA) often goes unrecognized despite common symptoms such as excessive daytime sleepiness, fatigue, and impaired quality of life (QoL). CPAP is the gold standard treatment for OSA, but optimal daily usage and time needed for observable effects remain unclear. This study aimed to investigate the short-term effects of CPAP on daytime sleepiness and QoL in patients with severe OSA. Medical records were collected from 87 patients with severe OSA who initiated CPAP therapy. Also, validated questionnaires were used before and after one month of CPAP to analyze QoL - the Calgary Sleep Apnea Quality of Life Index (SAQLI), the Cues to CPAP Use Questionnaire (CCUQ), and daytime sleepiness - the Epworth Sleepiness Scale (ESS). Multiple regression analysis was conducted to identify predictors of CPAP usage. Of the total participants aged 55.6±12.5, 77% were males, and 62% were CPAP adherent. Reductions in daytime sleepiness (ESS) were noted, as well as improvements in both overall QoL (SAQLI) and specifically in the domains of daily functioning, social interactions, emotional well-being, and symptom perception. Important cues for CPAP usage recognized by patients were physicians’ instructions and physicians’ worry regarding patients' condition. Furthermore, multiple regression revealed higher SAQLI scores and lower ESS scores as positive predictors of CPAP usage, along with lower AHI after one month of CPAP being associated with sufficient adherence.

The signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arose during the acute phase of COVID19 by an increased breakdown of haematocytes, to which the liver responds by reducing the production of plasma. In order to prevent a too large decrease in haematocrit. In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID. My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the intravenous administration of donor blood products, starting with albumin concentrate. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable. I suspect that we will find a haematocrit value at the high extreme of the reference range, and an albumin value at the low extreme of the reference range in most Long COVID patients before the start of the treatment, because the liver can not keep up with the recovery of the red bone marrow.

Substance abuse is a significant public health issue both globally and nationally. Substance abuse involves the detrimental or risky consumption of psychoactive substances, posing a significant global issue, particularly among the youth. In India, cannabis abuse is a major concern. Cannabis is consumed legally in many states as Bhang, also known as marijuana or weed, while Charas and Ganja are illegal under both international drug conventions and the Indian NDPS Act of 1985. The Cannabis users are at great risk of developing Cannabis use disorder which is a pattern of problematic cannabis use leading to clinically significant impairment or distress. It is the most widely used illegal substance worldwide, showing a high prevalence in India.

Conclusions: CGP do not substantially differ between initial tumor vs tumor recurrence and recurrent thymomas vs non-recurrent thymomas. Cell-cycle control genes alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

This paper presents a Cartesian model of sustainability by a novel integration of Circular Economy principles and ESG (Environmental, Social, and Governance) criteria to explicitly establish a clear path for closing the loops of negative social and environmental externalities. As global sustainability transformations accelerate, they bring both opportunities and inherent financial risks and social uncertainties. Historically, economic development has often been achieved at the expense of environmental balance. The contemporary challenge is to attain a dynamic equilibrium between natural and socio-economic systems. We introduce an integrated, multidisciplinary, and dynamic framework for studying and managing sustainability transitions. Our innovative 4-quadrant framework utilizes a Cartesian coordinate system to map the impacts of various business models on natural and socio-economic systems, spanning from linear open-loop to circular closed-loop ESG models. The framework is data-driven, employing normalized coordinates (-1 to 1) to facilitate empirical analysis and the establishment of temporal Key Performance Indicators. By integrating the Human Development Index within ecological limits, our model targets regenerative development that harmonizes human progress with planetary boundaries. This versatile and robust framework serves as a practical tool for businesses, households, organizations, and policymakers to navigate the complexities of sustainable development, promoting innovation and fostering a just transition towards regenerative practices. Our approach provides a comprehensive roadmap for achieving high human development within the planet's ecological limits, contributing significantly to the broader discourse on sustainability science and management.

While there are millions of reptile images available online, they are not well organized and not easily findable, accessible, interoperable, or reproducible (FAIR). More importantly, they are not standardized and thus hardly comparable. Here we present a reference database of more than 14,000 standardized images of 1,045 reptile species (969 lizard and 76 snake species), that are based on preserved specimens in 20 different collections, including 533 type species of genera and type specimens of 72 species. All images were taken with standardized views, including dorsal and ventral body shots as well as dorsal, ventral, and lateral views of the heads and other body parts. Although only 11 out of the 20 collections are cross-referenced in Vertnet, some others are indexed in GBIF, and this fraction will certainly grow in the near future. The utility of this and similar image collections will further grow with additional material and further cross-referencing, e.g., to DNA sequence databases or citizen science projects. The images are searchable and freely available on Morphobank.org (Project 5121) and on Figshare.com.

This article raise a topic of critical examination of polypropylene, a key polymeric material, and its extensive application within the automotive industry, particularly focusing on the manufacturing of brake fluid reservoirs. The study aims to enhance the understanding of polypropylene's behavior under mechanical stresses through a series of laboratory destruction tests and numerical simulations, emphasizing the Finite Element Method (FEM). A novel aspect of this research is the introduction of the PEAK parameter, a groundbreaking approach designed to assess the material's resilience against varying states of strain, known as triaxiality. This parameter facilitates the identification of critical areas prone to crack initiation, thereby enabling the optimization of component design with a minimized safety margin, which is crucial for cost-effective production. The methodology involves conducting burst tests to locate crack initiation sites, followed by FEM simulations to determine the PEAK threshold value for the Sabic 83MF10 polypropylene material. The study successfully validates the predictive capability of the PEAK parameter, demonstrating a high correlation between simulated results and actual laboratory tests. This validation underscores the potential of the PEAK parameter as a predictive tool for enhancing the reliability and safety of polypropylene automotive components. The research presented in this article contributes significantly to the field of material science and engineering by providing a deeper insight into the mechanical behavior of polypropylene and introducing an effective tool for predicting crack initiation in automotive components. The findings hold promise for advancing the design and manufacturing processes in the automotive industry, with potential applications extending to other sectors.

The Ethnographic Museum in Dubrovnik holds an extensive textile collection that includes a range of dress and costume from Croatia and neighbouring countries. Until recently, the costumes were displayed on mannequins created by the academic artist Zvonimir Lončarić (1927–2004). His sculptures are expressive forms constructed from terracotta, fibreglass, wood, metal, acrylic paint and other materials selected for their visual appeal. Due to their importance, the museum considered the mannequins as protected artworks in the permanent exhibition, however, they had a harmful effect on the costumes displayed. In 2018, after completing a series of conservation-restoration projects within the collection, it was decided to replace the existing mounts with new, museum–quality mannequins. Two project–based learning workshops were organised, led by a team of textile conservators from the University of Dubrovnik and the Croatian Conservation Institute, in cooperation with the curator of the Ethnographic Museum. This case study highlights the challenges of exhibiting ethnographic costumes by discussing past presentation methods and how new solutions have been implemented conforming with the modern conservation-restoration profession. The new solutions consider ethics, decision–making processes, and the understanding of contemporary materials and methodology.

Laser Powder Bed Fusion (L-PBF)-based manufacturing is a growing area of research, with a particular focus on evaluating constraints in printed products. This research emphasises the importance of considering various factors—including mechanical properties and support structures—that influence the final product during the design phase. Specifically, the design of microchannel heat exchangers is highlighted, where all constraints are critical. This article will present a method for analysing channel pressure limitations and report findings about mechanical properties loss from examining tube porosity. This includes a summary of results and the establishment of an experimental device system.

Hyperspectral imaging data holds great potential for various stages of the mining life cycle in active and abandoned mines. The technology, however, has yet to achieve large-scale industrial implementation and acceptance. While hyperspectral satellite im-agery yields high spectral resolution, high signal-to-noise ratio (SNR), and global availability with breakthrough satellite sys-tems like EnMAP, EMIT, and PRISMA, limited spatial resolution poses challenges for mining sectors, which require decimeter- to centimeter-scale spatial resolution for applications such as reconciliation, ore/waste estimates, geotechnical assessments, and en-vironmental monitoring. Hyperspectral imaging from drones (Uncrewed Aerial Systems; UASs) offers high spatial resolution data relevant to the pit/ mine scale, with the capability for frequent, user-defined re-visit times. Collecting data in the visible to near and shortwave infrared (VNIR-SWIR) wavelength regions offers to detect different minerals and surface alteration patterns, potentially revealing crucial information for exploration, extraction, re-mining, waste remediation, and rehabilitation. In this paper, we review of applicable instrumentation, software components, and relevant studies deploying hyperspectral imaging in or appropriate to the mining sector, especially for hyperspectral VNIR-SWIR UASs. If directly applicable, draw on previous insights derived from airborne, satellite, and ground-based imaging systems. We also discuss common practices for UAS survey planning and sampling considerations for interpretation.

Complicated grief (CG) predicts decreased mental health over time. Furthermore, feeling connected to nature (CN) is positively associated with beneficial mental health outcomes, such as psychological wellbeing and perceived psychological resilience. Thus, we hypothesized that CN moderates the association between general grief or CG and negative mental health for bereaved people. Further, we hypothesized that one’s physical exposure to nature—that is, estimated time spent in nature and greenness (i.e., vegetation) surrounding one’s residential area—might moderate the association between general grief or CG and negative mental health for bereaved people. To test these hypotheses, we sampled 153 participants who experienced the death of a close other by COVID-19 infection. Participants reported CG, general grief, anxiety symptoms, depression symptoms, CN, estimated time spent in nature, and residential area postal code via a single online survey. We estimated greenness surrounding participants’ residential areas using their self-reported 5-digit U.S. postal code. Cross-sectional analyses indicated that, as predicted, CN attenuated the association between CG and depression, but only trended toward moderating the association between CG and anxiety and did not moderate the associations between general grief and depression or anxiety. Other variables related to the experience of nature—the estimated time an individual spends in nature and the greenness surrounding one’s residential area—did not moderate the association between general grief or CG and depression or anxiety. We thus conclude that a sense of feeling connected to nature—not simply spending more time in nature or being surrounded by nature—may serve an important role in the mental health status of people experiencing complicated grief, perhaps because CN replenishes general belonging when someone significant has passed away.

Background/Objectives: Encouraging results reported of Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). The present retrospective study reports the efficacy and safety of a high dose of neutrophile and red blood cell-depleted PRP to treat 212 patients with KOA. Methods: 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with 3 injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as a percentage of responders at 3,6, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain through VAS score and WOMAC score have also been recorded. Results: 4ml of PRP containing 4X109 platelets were obtained by single spin centrifugation and injected intra-articular into each patient with no pre-activation. The overall responder rate of patients responding to OMERACT-OARSI criteria at 3,6,12 months was 68.9%, 72,7% and 70,6%. There was a significant improvement in VAS and WOMAC scores at 3-, 6- and 12-month follow-up compared to the pre-treatment value (p&lt; 0.01). The lowest VAS score was observed at 6 months overall and in all three-grade KL groups. KL2 groups showed the best results regarding pain reduction and WOMAC score at 6 months (p&lt; 0.01). Conclusions: a high dose of neutrophil-depleted PRP is an effective treatment for KL1-3 KOA. It provides symptomatic relief, can potentially reduce disease progression, and has sustained effects for up to 12 months.

Both, in developed and developing countries, atmospheric pollution with particulate matter (PM) remains an important issue. Despite the health effects of poor air quality, studies on air pollution are often limited by the high costs of continuous monitoring and the need of extensive sampling. Furthermore, these particles are often enriched in potentially toxic trace elements and organics pollutants. This study evaluates both, the composition of atmospheric dust accumulated during a certain time-span on leaves of Hedera helix and Senecio cineraria, as well as the potential to use them as bio-monitors. The test plants were positioned nearby automatic air quality monitoring stations at four different sites with respectively high, moderate and low traffic intensity. Gravimetric deposition of PM10 and PM2.5 on leaves was consistent with data recorded by the monitoring stations and related to the weather conditions reported by Argentina´s National Meteorological service. To determine the presence of trace elements enriching the PM deposited on leaves, two analytical techniques were applied, XRF (not destructive) and ICP (destructive). The results indicated that only in the unpaved street location (site 2), PM10 and PM2.5 concentrations in the air exceeded WHO guidelines. However, several trace elements were found enriching PM deposited on leaves from all sites. Predominantly, increased concentrations of Cd, Cu, Ti, Mn, Zn and Fe were found, which were associated to construction, traffic and unpaved street sources. Furthermore, based on its high capability to sequester PM and trace elements Senecio cineraria can be take into consideration to be adopted as a bio-monitor or even for PM mitigation.

In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low molecular weight (≤ 1000 Da) collagen peptides, on skin aging and health. The trial was conducted in 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue) and corneometry (skin hydration) at baseline (T0), and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p &lt; 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low molecular weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin.

This paper presents the development of an analytical model of Microelectromechanical Systems (MEMS) internal vibrating ring gyroscope. The internal ring structure consists of eight semicircular beams that are attached to the externally placed anchors. The research work analyses the vibrating ring gyroscope inplane displacement behavior and the resulting elliptical vibrational modes. The elliptical vibrational modes appear as pairs with the same resonance frequency due to the symmetric structure of the design. The analysis commences by conceptualizing the ring as a geometric structure with a circular shape, possessing specific dimensions such as thickness, height, and radius. We construct a linear model that characterizes the vibrational dynamics of the internal vibrating ring. The analysis develops a comprehensive mathematical formulation for the radial and tangential displacements in local polar coordinates, considering the inextensional displacement of the ring structure. By utilizing the derived motion equations, we highlight the underlying relationships driving the vibrational characteristics of the MEMS vibrating ring gyroscope. These dynamic vibrational relationships are essential in enabling the vibrating ring gyroscope's future utilization in accurate navigation and motion sensing technologies.

This study aimed to develop a carbon yield model for a Makino bamboo plantation and addressed a monoculture Makino bamboo plantation in central Taiwan. We established a long-term trial to monitor the stand dynamic following thinning. A total of 16 plots were installed based on four thinning treatments, each sharing four plots. After thinning, data were collected from two investigations, resulting in 32 records. We calculated the number of culms (N), mean diameter at breast height (MDBH), and basal area (BA) for each record. An allometric function developed by previous research was used to predict aboveground biomass and to obtain aboveground carbon storage (AGCS). The model used the N, MDBH, and BA with various types (reciprocal and natural logarithm types) as independent variables to predict ln(AGCS) by the stepwise method. According to the Radj2 value, the best predictive models were: ln(ABCS) = -0.004 + 0.820 ln(MDBH) + 1.008 ln(BA), and ln(ABCS) = 7.550 - 0.820 ln(N) + 1.828 ln(BA). From these two models, we found the factors, either BA and MDBH or BA and N, can effectively predict AGCS. It indicated that stand density was critical in affecting AGCS, especially the variable BA.

Since the beginning of the internet era, there has been an explosion of growth in structured data (such as numbers, symbols, and labels) as well as unstructured data (including images, videos, and text). Efficient and accurate mixed query of these two types of data is a key technology to achieve high-quality information retrieval, and it is also a major challenge that needs to be solved urgently in the industry. In this study, we employ an advanced Transformer model that combines strategies and fine-tuning techniques for multi-task learning. Specifically, the model is first pre-trained on a large-scale, general-purpose dataset to learn different types of data representations and basic language comprehension skills. After that, we fine-tuned the parameters of the model to better suit these specific data processing tasks for specific application scenarios, such as image annotation, video content analysis, and structured data query. At the heart of the model is the self-attention mechanism, which allows the model to automatically emphasize the important parts and ignore irrelevant information when processing the input data. In addition, we have introduced task-specific adaptation layers that are designed to add additional processing power to the original Transformer architecture, such as a semantic analysis layer for unstructured text data and a relational extraction layer for structured data. This combination of general pre-training and task-specific fine-tuning allows the model to flexibly process and integrate information from different data sources, improving processing efficiency and accuracy. Experimental results show that the model performs well in a variety of data processing tasks, significantly improves the accuracy and efficiency of information retrieval, and verifies the strong potential and adaptability of large language models in processing mixed data types.

This study delves into the dynamics of 'Variations' and 'Claims' within construction projects, specifically under the FIDIC-Red Book 1999 framework. The study aims to identify, categorize, and devise mitigation strategies for key types of variations and claims aligning with the FIDIC conditions of contract. The research is drawing on inputs from construction industry professionals including contract administrators and project managers, focusing on the MENA region. This choice is driven by the region's extensive adoption of FIDIC standards and its rapidly growing construction sector. Data collection encompassed a questionnaire distributed to 80 industry experts predominantly through interviews that focused on countries like Saudi Arabia, UAE, Kuwait, and Egypt. These locations were chosen to reflect diverse construction practices and the involvement of international firms. Utilizing SPSS-V.25 for statistical analysis, the study uncovers the most prevalent and impactful causes of variations and claims, highlighting the critical need for managerial intervention. A key feature is the integration of scientometric analysis for a quantitative finding. A significant addition to the methodology is the implementation of a k-means clustering analysis. The survey had high internal consistency with a Cronbach's alpha of 0.97, and respondents reported frequent and significant claims like delayed drawings, ambiguous documents, and client changes. The results showed that effective claims management requires clear communication and balanced contracts, while poor design and contract documentation cause variations and claims. Spearman's correlation showed strong positive relationships between certain claim types and causes, emphasizing the importance of dealing with these factors to reduce claims. Most respondents said the survey could predict and reduce claims.

International cooperation and food diplomacy play a pivotal role in addressing global challenges to food security. This study explores the effectiveness of Indonesia's international partnerships and diplomatic strategies in bolstering its food security amidst global uncertainties. The research employs a mixed-methods approach, combining qualitative analysis of policy documents and interviews with key stakeholders, alongside quantitative data on food production and trade. Our findings indicate that Indonesia has benefited significantly from technical and financial assistance through collaboration with organizations such as FAO, ASEAN, and bilateral agreements with countries like Japan and China. These partnerships have facilitated the adoption of advanced agricultural technologies, improved infrastructure, and enhanced human resource capacities. However, challenges remain, including bureaucratic inefficiencies and dependency on food imports, which pose risks to sustainable food security. The study concludes that while international cooperation has provided critical support, Indonesia must further streamline its policy implementation processes and reduce its reliance on imports by fostering local production. Strengthening research and development collaborations and actively participating in global forums are also recommended to ensure long-term resilience and food sovereignty. This research provides valuable insights for policymakers and stakeholders aiming to develop effective strategies to navigate the complexities of global food diplomacy and cooperation.

Advanced persistent threat (APT) attacks are sophisticated and organized attacks commonly motivated by political, financial, and strategic objectives. In order to comprehend their tactics, techniques, and procedures (TTP) and indicators, APT reports are valuable sources. While blue teams typically rely on server logs, firewall rules and user authorizations managed in database tables, attackers have a graph-based mindset. In this work, we propose a framework for discovering and evaluating APTs using graph-based algorithms. Cyber threat intelligence (CTI) was extracted from 40,358 pages of APT reports and transformed into a graph. Centrality, community, and similarity analyses were executed on the graph. As a result, critical and influential APT groups and indicators of compromise (IoC) were discovered. Similar attacks and APT groups were revealed. Analysis results were interpreted to create new strategic CTI that can be utilized in future security operations.

With the widespread use of the Internet of Things, underwater control and monitoring systems for purposes such as ocean data sampling, natural disaster prevention, underwater surveillance, submarine exploration, and the like have become a popular and challenging topic in computers. So far, various topology control and routing solutions have been proposed for these networks. However, as technology expands and applications grow, so does the need for a stable underwater communication platform. On the other hand, underwater communication is associated with challenges such as node mobility, long propagation delays, low bandwidth, limited resources, and high error rates. In this research, for the first time, a topology control platform based on the RPL tree is modelled by applying its structural changes underwater. The proposed RPLUW methods in the case of RPLUWM fixed nodes are introduced to support the mobility of nodes underwater. Flexible objective functions, utilisation of decision-making systems, and application of control schedules in these methods have increased network life, reduced overhead, and increased node efficiency. The simulation results of the proposed method, in comparison with recent methods in this field, show an increase in network efficiency.

The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures, have contributed to the emergence of drug-resistant bacteria, which can spread at the human-animal-environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a "One Health" approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.

This study explores the potential of digital technologies for preserving cultural heritage through the case study of the Raya Gopura, an incomplete monument in Melukote, India. Employing a combination of terrestrial photogrammetry, drone-based photogrammetry and terrestrial laser scanning, the research team captured highly detailed 3D models of the structure. This non-destructive approach offers a comprehensive digital record for future research and preservation. Furthermore, for the conjecture for the Raya Gopura two possible purposes: an entrance to a planned fort or a gateway to the temple are perceived through the collective intelligence (CI) approach. These insights inform a conjectural architectural drawing of the potentially completed monument. The 3D models hold significant potential for various applications, including tourism, education, and architectural research, with the potential for immersive experiences through VR and AR technologies. The study demonstrated the effectiveness of digital tools in heritage preservation, not only safeguarding the Raya Gopura but also offering valuable in-sights for future research and public engagements.