(1) Background If placenta percreta (PP) is suspected, one should take into account ultrasound and MRI data, which allow one to assess not only the depth of invasion of the placenta into the myometrium, but also the degree of involvement of the blood vessels of the uteroplacental region and the pelvis, the formation of adhesions and collaterals between organs as well; (2) Methods: The patient with suspected PP was examined by ultrasound and Magnetic Resonance Imaging (MRI) examination. Histological study was performed on paraffin sections (hematoxylin & eosin, Mallory staining); cytotrophoblast was detected with antibodies to cytokeratin-8; (3) Results MRI and ultrasound examinations showed placental invasion extending beyond the serous lining of the uterus involving the posterior wall of the bladder. Elective abdominal delivery was performed at 37 weeks. Surgical excision of the uterine wall with invaded villi and involved fibrous bladder wall were performed. Histological study revealed invasive cytotrophoblast cells in the uterine wall located up to adventitia of the uterine subserosal vessels only. Thinning of the uterine wall up to the serous membrane was detected; (4) Conclusions: Placental villi and trophoblast extended beyond the uterus is not histology equivalent to placenta percreta. To diagnose PP instrumental visualization methods should be used.

Bacteria’s ability to withstand the detrimental effects of antimicrobials may take the form of resistance or tolerance with the minimum inhibitory concentration (MIC), the mutant prevention concentration (MPC), and the mutant selection window as salient concepts. Isolates exposed for 30 days to different concentrations of selected antibiotics, biocides, and heavy metals, singly and in combination, were additionally exposed to very high (15 × MIC) concentrations of ampicillin., and their tolerance was calculated the time to kill 99.9% of the isolate population (MDK99.9). These values were increased by 30 to 50% in test isolates compared to the untreated control. BAC 10-exposed isolates had the highest tolerance increase, and the tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes using diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the amplification of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting for persisters that could evolve into resistant isolates.

Introduction Prostate Cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various US counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan Meier method was performed for 5 racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. Results 279,000 PCa records were extracted, 5-year PCa-specific survival was 94%. Overall, living in counties with worst poverty/income quintile and highest proportions of foreign-born/language-isolated increased PCa mortality by 23% each. No association was observed with county-level High-School education, while Bachelor’s-level education decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. Discussion Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanics. The inclusion of Healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival, through performing biopsy and or/surgery. County-level education plays an important role in PCa decision-making as it might elucidate discussions of other non-invasive management options. Conclusion Findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritizing. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.

The main channel for disseminating information is now the Internet. Users have different expectations for the calibre of websites regarding the posted and presented content. The WEB site's quality is influenced by up to 120 factors, each represented by two to fifteen attributes. A major challenge is quantifying the features and evaluating the quality of a website based on the feature counts. One of the aspects that determines a website's quality is its completeness, which focuses on the existence of all the objects and their connections with one another. It isn’t easy to build an expert model based on feature counts to evaluate website quality, so this paper has focused on that challenge. Both a methodology for calculating a website's quality and a parser-based approach for measuring feature counts are offered. We provide a multi-layer perceptron model that is an expert model for forecasting website quality from the "Completeness" perspective. The accuracy of the predictions is 98%, whilst the accuracy of the nearest model is 87%.

Extension of a derivation on a universally reversible JC-algebra A⊆B(H)_{sa} to the C*-algebra [A] generated by A in B(H) was studied by Upmier [20, Theorem 2.5]. In this article we study the extension of a Jordan derivation on a universally JC-algebra A to its universal enveloping real and complex C*-algebras R and U, respectively. Also, we establish the relationship between local derivations (resp., 2-local derivations, weak local derivations, weak-2-local derivations) of a universally JC-algebra A and the corresponding maps on its universal enveloping real and complex C*-algebras R and A, respectively.

The nonlocality (superdiffusion) of turbulence is expressed in the empiric Richardson t3 scaling law for the mean square of the mutual separation of a pair of particles in a fluid or gaseous medium. The development of the theory of nonlocality of various processes in physics and other sciences based on the concept of Lévy flights resulted in the idea of Shlesinger and colleagues about the possibility of describing the nonlocality of turbulence using a linear integro-differential equation with a slowly falling kernel. The close approach developed by us made it possible to establish the closeness of the superdiffusion parameter of plasma density fluctuations moving across a strong magnetic field in a tokamak to the Richardson law. In this paper, we show the possibility of a universal description of the characteristics of nonlocality of transfer in a stochastic medium (including turbulence of gases and fluids) using the Biberman-Holstein approach to the transfer of excitation of a medium by photons, generalized to take into account the finiteness of the velocity of excitation carriers. This approach enables us to propose a scaling that generalizes Richardson's t3 scaling law to the combined regime of Lévy flights and Lévy walks.

Hepatitis B virus (HBV) is a major global health challenge. Emerging evidence suggests that poor knowledge and stigma are impacting HBV control efforts in sub-Saharan Africa (SSA), however their role is not well understood. We conducted a cross-sectional study of adults aged ≥ 18 years in a community and pharmacy setting in Freetown, Sierra Leone. A structured questionnaire was used to assess knowledge, stigmatizing attitudes, and health-seeking behaviors regarding HBV. Logistic regression was used to identify predictors of HBV knowledge and related stigma. A total of 306 adult participants were enrolled (50.7% male, 7.5% HBV positive and 11.7% vaccinated). Overall, 52.2% had comprehensive HBV knowledge and 49.3% expressed a stigmatizing attitude towards people with HBV. Notwithstanding, 72.2% stated they would receive the HBV vaccine if offered, 80.4% would take anti-HBV medication and 78.8% would be willing to attend clinic regularly. Comprehensive HBV knowledge was associated with HBV positive status (aOR 4.41; p = 0.029) and being vaccinated against HBV (aOR 3.30; p = 0.034). HBV-related stigma was associated with secondary or higher level of education (aOR 2.36; p < 0.001), good HBV knowledge (aOR 2.05; p = 0.006) and pharmacy setting (aOR 1.74, p = 0.037). These findings suggest that education and stigma reduction may benefit HBV elimination efforts in SSA.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Multiresistant pathogens pose a serious threat to human health. The genus candida is one class of human pathogenic yeasts responsible for infections affecting healthy and immunocompromised patients. In this context, plant essential oils emerged as a future natural alternative to control the diseases caused by these pathogens. Here, it highlighted antimicrobial activity and the mechanisms of action of the essential oil extracted from Croton pluriglandulosus Carn.-Torres & Riina (CpEO) leaves on human pathogenic microorganisms in planktonic and biofilm lifestyles. In addition, for the first time, the oil composition was revealed by GC-MS analysis and the toxicity to human red blood cells (HRBC). Twenty-six chemical compounds were identified in EOCp, Elemicin, Bicyclogermacrene, caryophyllene, brevifolin and 2,4,6-trimethoxy-styrene. Through hemolytic assay, it was shown that CpEO has no toxicity to human RBCs. At the concentration of 50 μg mL-1, CpEO did not show great antibacterial potential. However, promising data were found for C. krusei and C. parapsilosis inhibiting by 89.3% and 80.7% of planktonic cell growth and 83.5% and 77.9% the biofilm formation, respectively. Furthermore, the mechanisms of action CpEO were elucidated by fluorescence. Scanning electron microscopy revealed damage to the cell membrane and pore formation, ROS overproduction, and Induction of apoptosis in candida cells. Our results reinforce the potential of CpEO as an effective alternative molecule of pharmaceutical interest.

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via Stereolithography (SLA) of features at the micro-scale. Using a custom benchmark part, deviations in feature dimensions (micro-pores diameters and depths) were detected and measured by confocal microscopy. Samples characterization and experimental observations allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and to the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on pores diameters were up to -46%. A compensation method of the nominal laser spot diameter (85m) was defined and implemented resulting in relevant improvements in dimensional accuracy of 9.8% and 11.3% on full-open pores diameter and depth, respectively. Further investigation was performed on a customized test part to adjust the calibration procedure. The measurements revealed that the estimate of the laser beam spot size is 968m. Measurements on micro-pores having different sizes revealed that a constant compensation parameter (i.e., C=85, 96, 120m) is not fully effective at the micro-scale, where average errors still remain at -24%, -18.8%, and -16% for compensations equals to 85, 96 and 120m, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the micro-feature size C= f (D). Results show a sharp improvement in dimensional accuracy on micro-pore fabrication, with errors consistently below +8.2%. The proposed compensation method can be extended for the fabrication of any micro-features without restrictions on the specific technology implementation. Concerning the inaccuracy introduced by the laser path, experimentation with a customized part allowed the optimization of the part orientation to reduce the errors and their differences along the X and Y machine axes.

1) Landsat operational land imager (OLI) data and consequent laboratory measurements were used to predict Chlorophyll-a (Chl-a) concentration and the trophic states for an inland lake within the East Kolkata Wetland, India; 2) The most suitable band ratio was identified by performing Pearson correlation analysis between Chl-a concentrations and possible OLI band and band ratios from the study points; 3) The results showed highest correlation coefficient from the band ratio OLI5/OLI4 with an R value of 0.85. The prediction model was then developed by applying regression analysis between the band ratio OLI5/OLI4 and Chl-a concentration of the study points. The reflectance ratios of the validation points were given as input on the prediction model and the model output was considered as predicted Chl-a values of the validation points to check the efficiency of the prediction model. The regression model between laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points revealed a high correlation with an R² value of 0.78. Trophic State Index (TSI) of the lake was also calculated from laboratory-derived Chl-a value and model-fitted Chl-a value of the validation points. The study presented a high correlation of TSI determined from predicted data with TSI from laboratory reference data (R = 0.88). The TSI values of the lake ranged from 65 to 75 which indicate that the lake is appeared to be eutrophic to hypereutrophic conditions. 4) This empirical study showed that Landsat 8 OLI imagery can be effectively applied to estimate Chl-a levels and trophic states for inland lakes.

The present study explored the expression of CD62L and CD44 by bovine peripheral blood mononuclear cells (PBMCs) and WC1.1+ γδ T cells under Staphylococcus aureus cell culture stimu-lation. In this study, peripheral blood cells were isolated from ten dairy cows and cocultured with S. aureus. Afterward, the γδ T cell subpopulation and the expression of CD44, CD62L and prolif-erative (Ki67+) cells were evaluated by flow cytometry. Our results showed that the percentages of proliferative PBMCs and WC1.1+ γδ T cells were higher when stimulated with S. aureus. The percentage of CD44+ cells increased in S. aureus-stimulated cultured PMBCs and WC1.1+ γδ T cells, as did the CD44 geometric mean fluorescence intensity (GMFI). The rate of CD62L cells did not differ among groups for either PBMCs or WC1.1+ γδ T cells. A higher GMFI of CD62L in prolif-erative PBMCs than nonproliferative PBMCs upon stimulation with S. aureus was detected, whereas no impact on the GMFI of CD62L was observed in WC1.1+ cells. In summary, our study identified that S. aureus was associated with high expression of CD44 in overall PBMCs and WC1.1+ γδ T cells, and they could generate memory WC1.1+ γδ T cells, preferably central memory cells.

This research emphasizes a meta-heuristic Modified Ant Lion Optimizer (MALO) optimization approach for simultaneous utilization of DSTATCOM devices and distributed Photovoltaic (PV) sources with network reconfiguration in a radial power distribution scheme. In a radial power distribution network with network reconfiguration majority of the research is based on Constant Power model analysis. However, it is noticed that load models have a substantial impact on the distributed PV sources and the D-STATCOM device's optimal size and position. The effect of the Constant Power (CP) and Polynomial (ZIP) with load growth load models for the simultaneous insertion of distributed PV sources and DSTATCOM devices with network reconfiguration examined in this research work for power system planning. The penetration levels of distributed PV sources considered for the investigation are 25%, 50%, 75%, and 100%. The principal objective of this research is to reduce network total power losses, enhance the voltage magnitude profile at all buses, and reduce the overall operating cost while adhering to equality and inequality constraints. The proposed algorithm verified on 118-node test systems. The investigation is carried out for planning network upgradation to a High Voltage Distribution System(HVDS) on 317 nodes in the rural Bangalore Electricity Supply Company Limited(BESCOM) radial distribution scheme. Simulated results obtained by this method are validated with the BAT algorithm and available techniques in the literature.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Data augmentation techniques recently gained more adoption in speech processing, including speech emotion recognition. Although more data tends to be more effective, there may be a trade-off in which more data will not provide a better model. This paper reports experiments on investigating the effects of data augmentation in speech emotion recognition. The investigation aims at finding the most useful type of data augmentation and the number of data augmentations for speech emotion recognition. The experiments are conducted on the Japanese Twitter-based emotional speech corpus. The results show that for speaker-independent data, two data augmentations with glottal source extraction and silence removal exhibited the best performance among others, even with more data augmentation techniques. For the text-independent data (including speaker and text-independent), more data augmentations tend to improve speech emotion recognition performances. The results highlight the trade-off between the number of data augmentation and the performance of speech emotion recognition showing the necessity to choose a proper data augmentation technique for a specific application.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to in-healable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. Initially, a descriptive statistical treatment of PM10 concentrations took place. Furthermore, the AirQ2.2.3 software developed by the WHO was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, during the examined period PM10 concentrations present a significant decreasing trend. Also, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70% of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.

Biocomposite membranes based on polylactic acid (PLA) and cellulose nanocrystals (CNCs) were developed using a scientific approach. Dicumyl peroxide (DCP) was used as a polymerization ini-tiator, while tin octoate (Sn(Oct)2) and triphenylphosphane (P(C6H5)3) were used as catalysts. A torque rheometer was used to mix the components of the biocomposite, and thin films was prepared by solvent casting. Fourier transform infrared (FTIR) spectroscopy confirmed the coupling between the PLA and CNCs. Field emission scanning electron microscopy (FESEM) showed that the CNCs were well-dispersed in the PLA matrix with an unimodal particle size distribution and a maximum particle size of around 200 nm. Thermogravimetric analysis (TGA) and differential scanning calo-rimetry (DSC) analysis demonstrated good thermal stability and improved biodegradability of the biocomposite membrane compared to pure PLA. Mechanical characterization showed a Young's modulus of 1.65 GPa, which is comparable to that of other composite materials, and a maximum tensile strength of 20.31 MPa, which is higher than that of pure PLA. These results suggest that the developed biocomposite membrane has potential applications in water filtration, food packaging, and biomedical devices.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

A selection of 36 commercial probiotic fermented dairy products from UK and Europe markets were evaluated for the numbers, types and viability of Lactobacillus strains against the stated information on their packages. A comparative study was carried out on selectivity of MRS-Clindamycin, MRS-Sorbitol and MRS-IM Maltose, to select the right medium for enumeration of probiotic Lactobacillus. Based on selectivity of medium for recovery of the targeted lactobacilli and also simplicity of preparation, MRS-Clindamycin was chosen as the best medium for enumeration of probiotic Lactobacillus in fermented milks. The results of enumeration of lactobacilli showed that 22 out of a total 36 tested products contained more than 106 colony forming units/g at the end of their shelf- life, which comply with the recommended minimum therapeutic level for probiotics. Rep-PCR using primer GTG-5 was applied for initial discrimination of isolated strains, and isolates, which presented different band profile, were placed in different groups. The isolated Lactobacillus spp. were identified mainly as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus paracasei by analysis of partial sequences of the 16S ribosomal RNA and rpoA genes. In conclusion, it is unknown to recommend the adequate number of probiotic bacteria to be consumed to ensure the beneficial properties.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

We assessed true bugs among above-groundand and soil inhabitants of four different biocoenosis of pine forests representing the intra-zone areas of flora and fauna of the Kazakh upland. 15 species of three families were listed for the Central Kazakhstan region for the first time. Species Eremocoris podagricus was not registered for the territory of Kazakhstan earlier. Fifteen species (50 %) were true above-ground inhabitants or ones living on grasses, whereas other species use soil surface and ground litter as temporary habitats. Drymus brunneus and Eremocoris fenestratus play a key role in the structure and function of the true bugs assemblages in the in biotopes studied. The ecological success of typically forest and boreal inhabitants in biotopes of arid region is explained by relict nature of forests and ancient connections with the taiga zone of Western Siberia and mountain forests of the Urals and Altai. The results of a comparative analysis of the similarities and differences of the dominant and ecological structures of Heteroptera complexes of aboriginal studied forests and derived type of forest are presented.

This work introduces a novel numerical method designed to address three-dimensional unsteady free surface flows incorporating integral viscoelastic constitutive equations, specifically, the K-BKZ-PSM (Kaye–Bernstein, Kearsley, Zapas - Papanastasiou, Scriven, Macosko) model. The new proposed methodology employs a second-order finite difference approach along with the deformation fields method to solve the integral constitutive equation, and the marker-particle method (known as \emph{Marker-and-Cell}) to accurately capture the evolution of the fluid's free surface. The newly developed numerical method has proven its effectiveness in handling complex fluid flow scenarios, including confined flows and extrudate swell simulations of Boger fluids. Furthermore, a new semi-analytical solution for velocity and stress fields is derived, considering fully developed flows of a K-BKZ-PSM fluid in a pipe.

This article has been studied the synthesis of a new derivative of the known alkaloid cytisine contained in the seeds of plants of Cytisus laburnum L. and Thermopsis lanceolata R.Br., both of the Lugiminosae family. The new compound has been obtained from two biologically active compounds such as isoxazole and cytisine. It has been demonstrated that the reaction led to the single-stage method under very mild conditions to obtain some 4-[(3,5-dimethyl-1,2-oxazole-4-yl)sulfonyl]amides. This class of compounds is promising to obtain the new biologically active compounds. This article has examined in detail a structure with using the 1H and 13C NMR and two-dimensional NMR spectroscopy of COSY (1H-1H), HMQC (1H-13C) and NMVS (1H-13C). As a result, the homo- and heteronuclear spin-spin couplings should be established. The X-ray diffraction analysis has determined the spatial structure of a new derivative based on cytisine alkaloid. Thus, its hemorheological activity has been studied.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The wide-ranging effects of healthful vs. damaging consequences of UV irradiation on key physiologic parameters are reviewed in this paper. The effects are largely dependent on the wavelengths encountered, the absolute intensity and duration of the exposure, the tissues exposed, and whether the UV effects were delivered via in vivo or as an extracorporeal exposure in vitro typically performed with freshly obtained heparinized aliquots of whole blood. While damaging effects of high UV intensity may include irreversible irradiation damage to key cellular and molecular components, controlled low dosages of UV irradiation delivered via a conventional biophotonic apparatus at specific, controlled wavelengths can deliver beneficial effects on blood oxygenation, tissue repair, immune responses, glycemia, and glycated hemoglobin (HbA1c) concentrations. HbA1c is an important diagnostic marker for the effectiveness of diabetes management. Studies reviewed demonstrate increases in blood oxygenation and corresponding decreases in HbA1c concentrations following nominal biophotonic treatment and indicate that the application of this therapy extends beyond its more commonly applied applications in the treatment and control of infectious illnesses.

There is a long standing ‘two times problem’ in that a satisfactory reconciliation between the time of physics and that of psychology has not been realized. A partial solution to the past/present/future phenomenon has been successfully given by the Hartle information gathering and processing system (IGUS) view. That model IGUS robot is enhanced here for the entire ‘two times problem’ to deal with not only the temporal experiences of the flow of time but also those of manifest time. A dualistic robot is proposed which has a veridical system of temporal experiences that are compatible with various spacetime cosmologies. It also has an illusory system of corresponding temporal experiences. This dualistic IGUS robot was made possible by discovering temporal experience within the brain that correspond to those of physics. The dualistic theory suggests that the veridical system, as a result of evolution, begets the illusory system to enhance behavioral adaptation. Thus, there is just one fundamental physical time which the brain does, indeed, possess and then enhances with illusory counterparts. Therefore, there should no longer be a need to reify illusory temporal experiences as modern spacetime cosmologies tend to do. Physical time already resides within human time.

Non-suicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss management of older adults and transplant-ineligible patients who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

Norepinephrine plays an important role in modulating memory consolidation and evocation through its beta-adrenergic receptors (Adrβ: β1, β2 and β3), which are expressed in the hippocampus (HC) and amygdala (AMY). Here we hypothesized that multisensory stimulation would reverse the memory impairment caused by the inactivation of the Adrβ3 with consequent inhibition of sustained glial-mediated inflammation and glutamatergic depuration. To test this, 21- and 86-day-old Adrβ3KO mice and respective controls underwent to (i) gustative and olfactive stimuli of positive and negative valence associated with (ii) intellectual challenges to reach the food in addition to (iii) objects in hidden places (iv) foraging for 8 weeks followed by (v) analysis of GFAP, Iba-1 and EAAT2 protein expression in the HC and AMY. While this protocol restored the memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsens the memory of Adrβ3KO mice. Although no significant expression of GFAP and Iba1 were observed in HC of young and old mice, Adrβ3KO increased EAAT2 expression HC of old mice, while MS didn’t change EAAT2 in young mice but enhanced it expression in older. Relative to AMY of old mice Adrβ3KO increased GFAP expression compared whit WT mice and MS sustained the GFAP expression and increased the EAAT2 expression compared with WT group. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied right after weaning Adrβ3KO animals, also show that the changes in GFAP, Iba1 and EAAT2 expression levels in young and old mice indicate a functional significance in the process of learning and memory and that the control of neuroinflammation in limbic areas mediates this response. They also reinforce the idea that disruption of noradrenergic signaling could be involved in the cognitive impairment observed later in life.

The objective of this study was to detail the monomer composition of resin-based dental materials sold in the market in 2023 and to evaluate the proportion of BPA derivatives in relation with their applications. A search on manufacturers’ websites was performed to reference resin-based dental materials currently on the market. Their monomer composition was determined from material safety data sheets and completed with a search on PubMed database. Among the 543 material compositions exploitable, 382 (70.3%) contained BPA derivatives. Among them, 56.2% contained BisGMA, 28% BisEMA, the most frequently reported. A total of 59 monomers of which 6 BPA-derivatives were found. 309 materials (56.9%) contained UDMA and 292 (53.8%) TEGDMA. Less than one third of materials identified contained no BPA derivatives. These proportions vary a lot depending on their applications with materials dedicated to dental care of young populations containing the highest proportions of BPA-derivatives monomers. The long-term effects on human health of the different monomers identified including BPA-derivatives monomers is a source of concern. For children and pregnant or lactating women arises the question to take a precautionary principle and avoid the use of resin-based dental materials likely to release BPA by opting for alternative materials.

The main objective of this paper is to find a close link between the adaptive level of significance, presented here, and the sample size. We, statisticians, know of the inconsistency, or paradox, in the current classical tests of significance that are based on p-value statistics that is compared to the canonical significance levels (10%, 5% and 1%): "Raise the sample to reject the null hypothesis" is the recommendation of some ill-advised scientists! This paper will show that it is possible to eliminate this problem of significance tests. The Bayesian Lindley's paradox – "increase the sample to accept the hypothesis" – also disappears. Obviously, we present here only the beginning of a possible prominent research. The intention is to extend its use to more complex applications such as survival analysis, reliability tests and other areas. The main tools used here are the Bayes Factor and the extended Neyman-Pearson Lemma.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Background Legionella pneumophila is one of the causes of legionellosis. Water environments serve as the natural habitat and the main sources of Legionella pneumophila. Objectives The aims of this study was to understand the differences of Legionella pneumophila serogroups distribution in well water, tap water, ice cubes, hospital and hotel water in East Java-Indonesia. Methods a total of 60 water samples in east java-Indonesia; from well water (n=25), tap water (n=5), ice cubes (n=5), water from the hospital (n=16), and hotel water (n=9) were detected using polymerase chain reaction with mip gene spesific primers and then it was analyzed by phylogenetic tree. Results For the 60 water samples collected in East Java, 12% of the samples (7/60) were positively contaminated by L. pneumophila. In details, there was 8% of the well water samples (2/25), 2% of the tap water samples (1/5), 2% of the ice cubes samples (1/5), 0% of the hospital water samples (0/16) and 33.33% of the hotel water samples (3/9). The phylogenetic tree showed that Legionella pneumophila contaminating well water isolate 1 from Surabaya and tap water isolate from Sidoarjo was closer to L.pneumophila serogroup 2, 4, 6, 8, 10, 12, isolates from Brazil, China, Spain and Australia. L.pneumophila contaminating the ice cubes from Sidoarjo was closer to serogroup 1, 2, 4, 7, 8, 11, 13, 14, while the bacteria contaminating well water isolate 2 from Sidoarjo as well as water in hotel of Surabaya (hotel water isolate 1, 2 and 3) classified into their own group. Conclusion There is a difference in the distribution of L. pneumophila serogroups between well water, tap water, ice cubes, and hotels.

Burn-induced cardiac dysfunction is thought to involve mitochondrial dysfunction although the mechanisms responsible are unclear. In this study, we used our established model of in vivo burn injury to understand the genetic evidence of burn-induced mitochondrial metabolism confusion by describing cardiac mitochondrial metabolism-related gene expression after burn. Cardiac tissue was collected at 24 hours after burn injury. An O2K respirometer system was utilized to measure cardiac mitochondrial function. Oxidative phosphorylation complex activities were determined using enzyme activity assays. RT Profiler PCR array was used to identify differential regulation of genes involved in mitochondrial biogenesis and metabolism. Quantitative qPCR and Western Blotting were applied to validate differentially expressed genes. Burn-induced cardiac mitochondrial dysfunction was supported by the finding of decreased state 3 respiration and decreased mitochondrial electron transport chain activity in complex I, III, IV, and V following burn injury. Eighty-four mitochondrial metabolism-related gene profiles were measured. The mitochondrial gene profile showed that one third of genes related to mitochondrial energy and metabolism was differentially expressed. Of these 28 genes, 15 were more than 2-fold upregulated and 13 were more than 2-fold downregulated. All genes were validated using qPCR; 4 genes had a protein level which correlated with the observed change in gene expression. This study provides preliminary evidence that a large percentage of mitochondrial metabolism-related genes in cardiomyocytes were significantly affected by burn injury.

Staphylococcus aureus is a common pathogen in human. Methicillin resistant Staphylococcus aureus (MRSA) infection poses a big and perplexing difficulty in terms of therapy. The acquisition of the non-native gene PBP2a, which has a decreased tolerance for β-lactam antibiotics, frequently confers resistance. PBP2a has a less attraction for methicillin and it helps bacteria to continue peptidoglycan biosynthesis, and it is cell wall’s core component in bacteria. So, even in the presence of methicillin or any other antibiotic, bacteria develop resistance. Due to resistance-causing genes, S. aureus becomes MRSA. The main premise of the resistance mechanism is well understood. The current demand for novel antibiotics is legitimate in the face of therapeutic concerns posed by resistant micro-organisms. The emphasis of this review is on PBP2a scaffolds and the different screening approaches used to find PBP2a inhibitors. Penicillin, Cephalosporins, Pyrazole-Benzimidazole based derivatives, Oxadiazole containing derivatives, non-β-lactam allosteric inhibitors, 4-(3H)-Quinazolinones, Pyrrolylated chalcone, Bis-2-Oxoazetidinyl macrocycle (β-lactam antibiotics with 1, 3-Bridges), Macrocycle-embedded β-lactams as novel inhibitors, Pyridine-Coupled Pyrimidinones, novel Naphthalimide corbelled aminothiazoximes, non-covalent inhibitors, Investigational-β-lactam antibiotics Carbapenem, novel Benzoxazole derivatives, Pyrazolylpyridine analogues, and other miscellaneous classes of scaffolds for PBP2a are also represented as well as with their biological activity is discussed. The penicillin-binding protein is also discussed, which is the crucial target for the cell wall of MRSA. Various aspects of PBP2a, the cell wall of bacteria, peptidoglycans, different crystal structures of PBP2a, synthetic routes for PBP2a inhibitors, and future perspectives of MRSA inhibitors are also enumerated.

Eutrophication, a global concern, impacts water quality, ecosystems, and human health. It’s crucial to monitor algal blooms in freshwater reservoirs, as they indicate the trophic condition of a waterbody through Chlorophyll-a (Chla) concentration. Traditional monitoring methods, however, are expen-sive and time-consuming. Addressing this hindrance, we developed models using remotely sensed data from the Sentinel-2 satellite for large-scale coverage, including its bands and spectral indexes, to estimate the Chla concentration on 149 freshwater reservoirs in Ceará, Brazil. Several machine learning models were trained and tested, including k-nearest neighbours, random forests, extreme gradient boosting, the least absolute shrinkage, group method of data handling (GMDH), and sup-port vector machine models. A stepwise approach determined the best subset of input parameters. Using a 70/30 split for the training and testing datasets, the best-performing model was the GMDH, achieving an R2 of 0.91, MAPE of 102.34%, and RMSE of 20.38 g/L, which are values consistent with the ones found in the literature. Nevertheless, the predicted Chla concentration values were most sensitive to the red, green, and near infra-red bands.

Trend patterns of melanoma skin in Serbia from 1999 to 2020 *Rancic K. Natasa 1,2, Tiodorovic B. Danica 1,4, Ilic V. Mirko 2, Biljana N. Kocic 1,2, Maksimovic S. Natasa 3, Ilija D. Kocic 4, Dusan P. Miljkovic 4, Otasevic A. Suzana 1,2 Introduction. Melanoma of the skin represents about 1% of all skin cancers and it causes nearly 80% of skin cancer deaths. Due to its increasing incidence, particularly in the most developed countries it represents a great challenge for primary prevention. Objective. To explore patterns and analyze incidence trends of melanoma in Central Serbia from 1999 to 2020. Materials and Methods. Descriptive study was done and data were obtained from the Population-based Cancer Registry of Serbia. The joinpoint regression analysis was done to assess the incidence trend of the melanoma skin: the annual percent change (APC) along with its 95% confidence interval (95% CI) was calculated. Results. A total number of 9952 new melanoma cases were registered melanoma (5204 in males and 4748 in females) during the observed period. Males represented 52.3% of all patients, with male to female ratio of incidence 2.09:1. A non significant increasing trend of incidence in males from 1999 to 2013 with APC of 2.53% (95%CI: from -18.2 to 21.9, p=1) and significantly increasing trend from 2013 to 2020 with the APC of 11.29 % (95%CI: from 1.4 to 5.8, p<0.001) was established. An incidence trend in females has stabilized in the whole studied period, with APC of 0.42% (95%CI: from -3.3 to 6.8, p=0.1). Melanoma of the skin was not common before the age of 30. Out of all cases and about of 76% new cases were diagnosed in persons ≥ 50 years of age. Conclusion. The incidence trend of new melanoma cases significantly increase in the whole population from 1999 to 2020. The significant increasing of incidence trend in males and stabilization of incidence trend in females was established. Males had significantlly higher incidence rates than femalesand over of 76% new melanoma cases were diagnosed in persons above 50 years of age.

Worldwide, depressive disorder is one of the leading determinants of disability-adjusted life years. Although the benefits associated with physical activity (PA), there is a lack of information related to depression, especially in countries like Czechia, where modern approaches to mental health care only recently emerged. The PA levels were associated with aspects of depression such as clinician-diagnosed history; different severities; continuous depression scores; and specific symptoms that characterize the depression. The multivariable-adjusted Poisson regression models were carried out on 2123 participants (45.3% men, median 48 years). Compared to subjects with insufficient PA, the moderate and high PA levels were inversely associated with clinician-diagnosed depression history (respectively, prevalence rate [PR]= 0.84; 95% CI 0.66-0.82 and PR=0.50; 95% CI 0.36-0.67); and with continuous depression scores (PR=0.85; 95% CI 0.75-0.97; and PR=0.79; 95%CI 0.70-0.90).; but only high PA showed association with depression categories (PR=0.75; 95%CI 0.60-0.95). Depressed mood and worthlessness were the symptoms associated with moderate and high PA. Tiredness, change in appetite, and problems with concentration only with high PA. Although only high PA was sufficient for people intending changes among depression categories, the moderate PA may be enough for slight changes in depressive symptoms, and a good strategy when starting.

The purpose of this study was to explore the role of moral distress on physician burnout during COVID-19. Physicians in the US were interviewed between February and March 2021; 479 responded to our survey. Results indicated that moral distress was a key mediator in explaining the relationship between perceived organizational support, medical specialization, emotional labor, and coping on burnout. There was no support for increased burnout among female physicians, and contracting COVID-19 likewise did not play a role in burnout. Our findings suggest that physician burnout can be mitigated by increasing perceived organizational support; likewise, physicians who engaged in deep emotional labor and problem-focused coping tended to fare better when it came to feelings of moral distress and subsequent burnout.

Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.

In-plane electro-optical switching (IPS) is a natural feature of a conventional planar aligned display cell based on deformed helix ferroelectric liquid crystal effect (DHFLC-effect) with sub-wavelength helix pitch if the tilt angle close to 40 degrees.

Radiological imaging is an essential component of a swallowing assessment. Artificial intelligence (AI), and especially deep learning (DL) models, have enhanced the efficiency and efficacy through which imaging is interpreted, and subsequently have important implications for swallow diagnostics and intervention planning. However, the application of AI for the interpretation of videofluoroscopic swallowing studies (VFSS) is still emerging. This review showcases recent literature in the use of AI to interpret VFSS and highlights clinical implications for speech pathologists (SPs). With a surge in AI research, there have been advances made in dysphagia assessment. Several studies have demonstrated successful implementation of DL algorithms to analyze VFSS. Notably, convolutional neural networks (CNNs) have been used to detect pertinent aspects of the swallowing process with high levels of precision. DL algorithms have the potential to streamline VFSS interpretation, improve efficiency and accuracy, and enable precise interpretation of instrumental dysphagia evaluation, which is especially advantageous when access to skilled clinicians is not ubiquitous. By enhancing precision, speed, and depth of VFSS interpretation, SPs can obtain a more comprehensive understanding of swallow physiology and deliver targeted and timely intervention that is tailored towards the individual. This has practical applications for both clinical practice and dysphagia research. As this research area grows and AI technologies progress, the application of DL in the field of VFSS interpretation is clinically beneficial and has the potential to transform dysphagia assessment and management. With broader validation and inter-disciplinary collaborations, AI-augmented VFSS interpretation is likely to transform swallow evaluation and ultimately improve outcomes for individuals with dysphagia.

Infectious bronchitis virus (IBV) is a highly variable RNA virus that affects chickens worldwide. Due to its inherited tendency to suffer point mutations and recombination events during viral replication, emergent IBV strains have been linked to nephropathogenic and reproductive disease that are more severe than the typical respiratory disease, leading, in some cases, to mortality, severe production losses, and/or unsuccessful vaccination. QX and DMV/1639 strains are examples of the above-mentioned IBV evolutionary pathway and clinical outcome. In this study, our purpose was to systematically compare whole genomes of QX and DMV strains looking at each IBV gene individually. Phylogenetic analyses and amino acid site searches were performed in datasets obtained from GenBank accounting for all IBV genes and using our own relevant sequences as a basis. The QX dataset studied is more genetically diverse than the DMV dataset, partially due to the greater epidemiological diversity within the five QX strains used as a basis compared to the four DMV strains from our study. Historically, QX strains have emerged and spread earlier than DMV strains in Europe and Asia. Consequently, there are more QX sequences deposited in GenBank than DMV strains, assisting in the identification of a larger pool of QX strains. It is likely that a similar evolutionary pattern will be observed among DMV strains as they develop and spread in North America.

Aquaculture production is under pressure to increase its production to meet the growing demand for food from a growing population. In the Philippines, aquaculture has experienced the shift from milkfish to prawn with its attractive marketable price. Its intensification has led to negative and positive impacts making its collapse inevitable in the mid-1990s and raised a range of environmental and socioeconomic problems. This paper reviewed the environmental impacts, challenges, and disease outbreaks that overtook the industry using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We examined gaps and changes required to revitalize the industry to properly take-off. It considers and gives details on the impacts of shrimp culture on the environment e.g. shrimp farm management, marine pollution, disease outbreaks, climate change impacts, and socioeconomic impacts. Moreover, the presence of viral diseases such as White Spot Syndrome Virus (WSSV), Monodon Baculovirus (MBV), Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV), Hepatopancreatic Parvovirus (HPV), and Yellow Head Virus (YHV), have caused socioeconomic impacts with approximate losses of 40,080 mt in 1997 to 51,000 mt in 2014 in the shrimp industry. Recommended strategies were considered to improve the environmental management of shrimp aquaculture, including disease management, and priorities that were highlighted for future research. This management relates to adopting good aquaculture practices on shrimp culture, proper environmental monitoring and sustainable practices at the farm level.

The review concerns the chemical structures of all the triterpene glycosides from the most valuable commercially harvesting North Atlantic sea cucumber Cucumaria frondosa and their biological activities. The isolation and structural elucidation of 17 specific triterpene glycosides are described along with isolation and identification of two known glycosides. Antitumor, immunomodulatory, antithrombotic and anti-Alzheimer disease activities are also described. Frondoside A, the major component of the glycosidic fraction seems to be very perspective leader-compound for creation of useful medicinal preparations.

Novel segmented tick-borne RNA viruses belonging to the group of Jingmenviruses (JMVs) are widespread across Africa, Asia, Europe, and America. In this work, we obtained whole-genome sequences of two Kindia tick virus (KITV) isolates and performed modeling and functional annotation of the secondary structure of 5’ and 3’ UTRs from JMV and KITV viruses. UTRs of various KITV segments are characterized by: (1) polyadenylated 3’ UTRs; (2) 5’ DAR and 3’ DAR motifs; (3) a highly conserved 5’-CACAG-3’ pentanucleotide; (4) a La protein binding site; (5) multiple UAG sites providing interactions with the MSI1 protein; (6) three homologous sequences in the 5’ UTR and 3’ UTR of segment 2; (7) the segment 2 3’ UTR of a KITV/2017/1 isolate comprises two consecutive 40 nucleotide repeats forming a Y-3 structure; (8) a 35-nucleotide deletion in the second repeat of the segment 2 3’ UTR of KITV/2018/1 and KITV/2018/2 isolates, leading to a modification of the Y-3 structure; (9) two pseudoknots in the segment 2 3’ UTR; (10) the 5’ UTR and 3’ UTR are represented by patterns of conserved motifs; (11) the 5’-CAAGUG-3’ sequence occurs in early UTR hairpins. Thus, we identified regulatory elements in the UTRs of KITV, which are characteristic of orthoflaviviruses. This suggests their functional significance for the replication of JMVs and the evolutionary similarity between orthoflaviviruses and segmented flavi-like viruses.

(1) Background: This report examines the unique demands of off-road triathlon (XT) by presenting physiological, field, and race data from a national champion off-road triathlete using several years of laboratory and field data to detail training and race intensity. (2) Methods: Laboratory and field data were collected when the athlete was at near peak fitness and included oxygen consumption (VO2), heart rate (HR), power output (W), and blood lactate (BLC) during cycling and running, while HR, cycling W, and running metrics were obtained from training and race data files over a period of seven years. Intensity was described using % HR max zones (Z) 1 &lt; 75%, 2 = 75 - 87%, and Zone 3 &gt; 87%, and W. An ordinary least squares analysis was used to model differences between event types. (3) Results: Weather conditions were not different across events. XT events had twice the elevation change (p&lt;0.01) and two-three times greater W’ (p&lt; 0.001) than road triathlon (ROAD), but similar HR intensity profiles (max, avg, and zones); both events are predominately performed at &gt; Z2 or higher intensity. Championship XT events were longer (p&lt;0.01) , with higher kJ expenditure (p&lt;0.001). OLS modelling suggested three variables were strongly related (R2 = 0.84; p &lt; 0.0001) to cycling performance: event type (XT vs ROAD), total meters climbed, and total bike duration. Championship XT runs were slower than either regional (p&lt;0.05) or ROAD (p&lt;0.01) runs, but HR intensity profiles similar. OLS modelling indicates that slower running is linked to either greater total bike kJ expenditure (R2 = 0.57; p&lt;0.001), or total meters gained (R2 = 0.52; p&lt;0.001). Race simulation data support these findings but failed to produce meaningful differences in running. Conclusions: XT race demands are unique and mirror MTB and trail running demands. XT athletes must be mindful of developing anaerobic fitness, technical ability, and aerobic fitness, all of which contribute to off-road cycling economy. It is unclear whether XT cycling affects subsequent running performance different from ROAD cycling.

Importance: The rapidly expanding 2019 novel coronavirus pandemic (COVID-19, caused by the SARS-CoV-2 virus) has challenged the medical community to an unprecedented degree. Physicians and healthcare workers are at added risk of exposure and infection during the course of the patient care. Due to the rapid spread of this disease through respiratory droplets, healthcare providers such as otolaryngologists-head & neck surgeons who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures are particularly at risk. Here we present a set of safety recommendations based on our review of literature and communications with physicians with first-hand knowledge of safety procedures during the 2019 COVID-19 pandemic.Observations: A high number of healthcare providers were infected during the first phase of the pandemic in Wuhan province. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for healthcare providers without jeopardizing the care of patients. We reviewed the most common procedures related to the examination and treatment of upper aerodigestive tract diseases. Each category was reviewed based on the potential risk imposed to healthcare workers. Specific recommendations were made, based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in COVID-19 patients. Conclusions and Relevance: Preserving highly skilled healthcare work force is a top priority for any community and healthcare system. Based on the experience of healthcare systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of healthcare providers could be significantly reduced, while providing high levels of care. The provided recommendations could be used as broad guidance for all healthcare workers who are involved with the care of COVID-19 patients.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC (Bruker), DD and E-test using MH- and ID-MH-agar plates with the reference BMD method using 100 carbapenem-resistant-A. baumannii isolates. Standard BMD was performed according to the EUCAST guidelines, DD and E-test were carried out using two commercial MH-agar plates (bioMérieux and Liofilchem) and an in-house ID-MH-agar plate, while ComASP and UMIC were performed according to the manufacturer’s guidelines. DD performed with the ID-MH-agar plates led to a higher categorical agreement (CA, 95.1%) with standard BMD and fewer categorization errors compared to the commercial MH-agar plates (CA bioMérieux 91.1%, Liofilchem 89.2%). E-test on ID-MH-agar plates exhibited a significantly higher essential agreement (EA, 75%) with standard BMD compared to the two MH-agar plates (EA bioMérieux 57%, Liofilchem 44%), and showed a higher performance in detecting high-level resistance than ComASP and UMIC (mean log2 difference with standard BMD for resistant isolates of 0.5, 2.83 and 2.08, respectively). In conclusion, DD and E-test on ID-MH-agar plates exhibit a higher diagnostic performance than on MH-agar plates and the commercial BMD methods. Therefore, we recommend using ID-MH-agar plates for cefiderocol susceptibility testing of A. baumannii.

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) chal-lenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. Methods: The general recommendations included working remote-ly when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were con-ducted using a virtual platform. Additionally, specific recommendations were given to each sec-tion to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. Results: These comprehen-sive COVID-19 related measures resulted in most staff expressing a consistent level of satisfaction in regards to personal safety, maintaining a safe work environment, continuing quality patient care and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appeciable increase in the number of tele-medicine e-visits. Conclusions: Survey results demonstrated substantial adaptability and resili-ence, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.

Information geometry (IG) is a fascinating combination of differential geometry and statistics where a Riemannian manifold's structure is applied to a statistical model. It may find numerous fascinating uses in the domains of theoretical neurology, machine learning, complexity, and (quantum) information theory, among others. (IG) aims to provide a differential-geometric perspective on statistical geodesic models' structure. In this case, IG, KD, and J-divergence (JD) are used to define the manifold of the Generalised Brownian Motion (GBM). Consequently, the geodesic equations (GEs) are devised, and GB information matrix exponential (IME) is presented. Moreover, for first time ever, the necessary and sufficient mathematical requirement that characterizes the developability of Generalized Brownian Motion(GBM) manifold is devised. Also, a novel sufficient and necessary conditions which characterizes the regions where the surface describing GBM is minimal is determined. Also, it is shown that GBM has a non-zero 0-Gaussian and Ricci curvatures. Consequently, this advances the establishment of a unified GBM- Relativistic Info-Geometric based analysis.

We study epidemic spreading in complex networks by a multiple random walker approach. Each walker performs an independent simple Markovian random walk on a complex undirected (ergodic) random graph where we focus on Barabási-Albert (BA), Erdös-Rényi (ER) and Watts-Strogatz (WS) types. Both, walkers and nodes can be either susceptible (S) or infected and infectious (I) representing their states of health. Susceptible nodes may be infected by visits of infected walkers, and susceptible walkers may be infected by visiting infected nodes. No direct transmission of the disease among walkers (or among nodes) is possible. This model mimics a large class of diseases such as Dengue and Malaria with transmission of the disease via vectors (mosquitos). Infected walkers may die during the time span of their infection introducing an additional compartment D of dead walkers. Infected nodes never die and always recover from their infection after a random finite time. This assumption is based on the observation that infectious vectors (mosquitos) are not ill and do not die from the infection. The infectious time spans of nodes and walkers, and the survival times of infected walkers, are represented by independent random variables. We derive stochastic evolution equations for the mean-field compartmental populations with mortality of walkers and delayed transitions among the compartments. From linear stability analysis, we derive the basic reproduction numbers R M , R 0 with and without mortality, respectively, and prove that R M < R 0 . For R M , R 0 > 1 the healthy state is unstable whereas for zero mortality a stable endemic equilibrium exists (independent of the initial conditions) which we obtained explicitly. We observe that the solutions of the random walk simulations in the considered networks agree well with the mean-field solutions for strongly connected graph topologies, whereas less well for weakly connected structures and for diseases with high mortality. Our model has applications beyond epidemic dynamics, for instance in the kinetics of chemical reactions, the propagation of contaminants, wood fires, among many others.

Due to the fact that abrasive media can deform flexibly in abrasive flow machining (AFM) making this method easily to polish the complex holes and the curved surface of the hard machining shapes. Although abrasive media dominate the polishing behavior in AFM process, the mechanism of the abrasive media are not easy to understand because of the high viscous gels, therefore, many finishing works need lots of time to design AFM process. Power laws of the abrasive gels is studied here to evaluate the non-Newtonian flow of abrasive gels in complex holes polishing firstly, at the mean time different abrasive gels are utilized to finish the complex holes to follow the results by non-Newtonian flow calculation. Moreover, traditional AFM has difficulty to achieve a uniform roughness of radial distribution in the complex holes polishing because of the non-uniform abrasive forces. So a helical passageway is proposed to create a multiple motion of abrasive medium and to obtain the even surface of the complex holes in AFM process.

The evolutionary conserved STING-cGAS pathway represents one of the most important cytosolic DNA sensing systems that is activated in response to viral invasion and/or damaged integrity of the nuclear envelope. The key outcome of this pathway is the production of IFN, which subsequently stimulates hundreds of genes. In oncology, the situation is a complex one since this pathway may serve either anti- or pro-oncogenic roles in a context-dependent fashion. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as from ruptured micronuclei, it results in the production of interferon which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression. In these cells, the pathway initiates a non-canonical nuclear factor κB transcriptional response, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in conjunction with cancer progression and development of new treatment modalities.

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using web-server tool PADLOC (Prokaryotic Antiviral Defense Locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring the resistance.

In this paper, we introduce a new generalization of the Hermite polynomials via (p, q)-exponential generating function and investigate several properties and relations for mentioned polynomials including derivative property, explicit formula, recurrence relation, integral representation. We also de…ne a (p, q)-analogue of the Bernstein polynomials and acquire their some formulas. We then provide some (p, q)-hyperbolic representations of the (p, q)-Bernstein polynomials. In addition, we obtain a correlation between (p, q)-Hermite polynomials and (p, q)-Bernstein polynomials.

To investigate the process and chemistry of reaction zone formation, we conducted detailed petrographic observations and major-trace element analysis of rocks and minerals of lherzolite xenoliths from basanites of Tumusun volcano (Baikal Rift Zone). The reaction zones gradually disappear from contact toward center of xenoliths. This indicates their formation as a result of lherzolite-basanite interaction. The influence of basanite melt on major-trace element composition of secondary minerals of reaction zones is notable only at distance up to 100-200 μm from the contact. The major-trace element composition of secondary clinopyroxenes from orthopyroxene reaction zone indicates their formation from a melt formed by dissolution of orthopyroxene and influenced by element diffusion from basanite melt. Inside xenoliths the secondary minerals have Mg# values equal to or higher than Mg# of primary minerals. The secondary clinopyroxenes inherit their depleted or enriched REE pattern from primary pyroxenes. The major-trace element variations in secondary clinopyroxenes testify melt heterogeneity. Secondary clinopyroxene has slightly higher LILE and similar abundances of other trace elements compared to unreacted part of clinopyroxene grain. This is consistent with model developed from experimental studies: due to the interaction with basanite, incongruent dissolution of orthopyroxene occurs to form a melt which circulates in lherzolite and leads to pyroxenes and spinel dissolution. Non-dissolved centers of minerals are homogenous and similar in major-trace element composition to primary minerals. The process of peridotite-basanite interaction is not isochemical: even the centers of large xenoliths become enriched in LILE.

Coordination of cellular biological processes is regulated in part via metabolic enzymes acting to match cellular metabolism to current conditions. The acetate activating enzyme, acyl-coenzyme A synthetase short-chain family member 2 (Acss2) has long been considered to have a predominantly lipogenic function. More recent evidence suggests that this enzyme has regulatory functions in addition to its role in providing acetyl-CoA for lipid synthesis. We used Acss2 knockout mice (Acss2-/-) to further investigate the roles this enzyme plays in three physiologically distinct organ systems that make extensive use of lipid synthesis and storage including the liver, brain and adipose tissue. We examined the resulting transcriptomic changes resulting from Acss2 deletion and assessed these changes in relation to fatty acid constitution. We find that loss of Acss2 leads to dysregulation of numerous canonical signaling pathways, upstream transcriptional regulatory molecules, cellular processes, and biological functions, which were distinct in the liver, brain and mesenteric adipose tissues. The detected organ-specific transcriptional regulatory patterns reflect the complementary functional roles of these organ systems within the context of systemic physiology. While alterations in transcriptional states were evident, the loss of Acss2 resulted in few changes in fatty acid constitution in all three organ systems. Overall, we demonstrate Acss2 loss institutes organ-specific transcriptional regulatory patterns reflecting the complementary functional roles of these organ systems. Collectively, these findings provide further confirmation that Acss2 regulates key transcription factors and pathways under well-fed, non-stressed conditions, and acts as a transcriptional regulatory enzyme.

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining disease pre-antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we will discuss evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model is providing insights into the pathogenesis of JCPyV CNS disease.

Astrocytes have been implicated in a wide range of neurodegenerative diseases, with the literature indicating harmful or beneficial roles on a case-by-case basis. On such conditions, these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including metabotropic glutamate receptor (mGluR5). However, mGluR5 activation in astrocytes under neuroinflammatory conditions can be neuroprotective or have the opposite effect. In this work, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP is capable of reducing pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) release in rTNF-α-stimulated astrocytes, but, in contrast, leads to an augmented expression of the pan-reactive marker SERPINA3. Additionally, CTEP enhances synaptoneurosomes phagocytosis by astrocytes in both non-stimulated and TNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation leads to a reduction in the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockage may have beneficial and detrimental effects under inflammatory conditions.

Ice-binding proteins are crucial for adaptation of various organisms to low temperatures. Some of these, called antifreeze proteins, are usually thought to inhibit growth and/or recrystallization of ice crystals. However, prior to these events, ice must somehow appear in the organism, either coming from outside or forming inside through the nucleation process. Unlike most other works, our paper is focused on ice nucleation rather than the behavior of the already existing ice. The nucleation kinetics is studied both theoretically, with special attention paid to ice nucleation on ice-binding surfaces, and experimentally. For experimental studies, we use the ice-binding protein mIBP83, a previously constructed mutant of a spruce budworm Choristoneura fumiferana antifreeze protein. We show that mIBP83 does not affect the ice nucleation temperature in the buffer in test tubes, but hinders the impact of potent ice nucleators of various chemical natures, namely CuO powder and ice-nucleating bacteria Pseudomonas syringae. Additional experiments on human cells show that mIBP83 is concentrated in some regions, but only in cooled cells. Thus, the antifreeze protein not only binds to ice, but also blocks various sites that act or can act as ice nucleators. Such ice-preventing binding may be the crucial biological task of antifreeze proteins.

Accelerating, exact, explicit and simple solutions of relativistic hydrodynamics allow for a simple and natural description of highly relativistic p+p collisions. These solutions yield a finite rapidity distribution, thus they lead to an advanced estimate of the initial energy density of high energy collisions. We show that such an advanced estimate yields an initial energy density in $\sqrt{s}=7$ and 8 TeV p+p collisions at LHC around or above the critical energy density from lattice QCD, and a corresponding initial temperature above the critical temperature from QCD and the Hagedorn temperature. This suggests that the collision energy of the LHC corresponds to a large enough initial energy density to create a non-hadronic perfect fluid even in pp collisions. %We also show, that several times the %critical energy density may have been reached in high multiplicity events, hinting at a non-hadronic medium created in %high multiplicity $\sqrt{s}=7$ and 8 TeV p+p collisions.

It is increasingly common for experiments in biology and medicine to involve large numbers of hypothesis tests. A natural graphical method for visualizing these tests is to construct a histogram from the p-values of these tests. In this article, we examine the shapes, both normal and abnormal, that these histograms can take on, as well as present simple inferential procedures that help to interpret the shapes in terms of diagnosing potential problems with the experiment. We examine potential causes of these problems in detail, and discuss potential remedies. Throughout, examples of abnormal-looking p-value histograms are provided and based on case studies involving real biological experiments.

The objective was to conduct a scoping review and produce a publicly available database characterizing the design and reporting elements of the literature on dietary added sugars and select health outcomes. Relevant studies published from 1990 – 2021 were identified to create a database containing information on study and population characteristics, reported added sugars source and concentrations, diet energy balance, total energy intake, and outcome measures related to body composition, obesity, cardiovascular disease, and diabetes mellitus. There were 245 publications identified, 22% of which describe interventions and 78% describe observational studies. Publications pertaining to added sugars have risen dramatically since 2010, led by studies primarily assessing body composition (36%) or cardiovascular health (32%), including adults (65%), measuring liquid-only sources of added sugars (56%). Over 65% of studies reported total energy intake, 61% controlled for total energy intake in the design and analysis, and fewer than 5% of studies reported the energy balance of subjects. There has been a significant increase in research on added sugars since 2010, with substantial heterogeneity across all facets of methodology – study designs, exposures and outcomes of interest, terminology, and reporting of dietary intake data – thus limiting the ability to synthesize evidence in this scope of literature. This evidence map highlights gaps and important areas for improvement to strengthen the state of research to better inform future policies and dietary recommendations on added sugars.

The goal of our article was to systematize studies that investigated the impact of living conditions in large national regions on individual alcohol consumption. We sought publications on the research topic in PubMed, Google Scholar, OpenGrey, Crossref and eLibrary databases from the moment they were created until December 31, 2021. After removal of duplicates and unsuitable publications, and full-text review of remaining published sources, the final sample included 81 publications. The majority of ultimately selected papers were published after 2010, represented the United States of America, and considered samples of children and youths, either the younger population or the general adult population. High quality was characteristic for 19 studies, while satisfactory quality was exhibited by 46 publications. The most consistent associations with individual alcohol consumption were revealed for the legislative environment (especially for integral scales and indices), alcohol pricing policy, the prevalence of alcohol consumption and binge drinking in the population, and unemployment rate. Among the shortcomings of the reviewed articles, we should mention the prevailing assessment of the impact of only one type of regional characteristics, as well as the lack of studies analyzing the interaction of environmental influence at the territorial level of different scales. Protocol PROSPERO CRD42021234874.

P versus NP is considered as one of the most fundamental open problems in computer science. This consists in knowing the answer of the following question: Is P equal to NP? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the P versus NP problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity class is NP-complete. It is well-known that P is equal to NP under the assumption of the existence of a polynomial time algorithm for some NP-complete. We show that the Monotone Weighted Xor 2-satisfiability problem (MWX2SAT) is NP-complete and P at the same time. Certainly, we make a polynomial time reduction from every directed graph and positive integer k in the K-CLOSURE problem to an instance of MWX2SAT. In this way, we show that MWX2SAT is also an NP-complete problem. Moreover, we create and implement a polynomial time algorithm which decides the instances of MWX2SAT. Consequently, we prove that P = NP.

The objectives of this study are threefold. First, we evaluate the applicability of the information–motivation–behavioral skills (IMB) model for predicting organic food purchase intention (OFPI) in adults with chronic conditions. Second, we examine the indirect effects of organic food knowledge, attitudes toward organic food purchase, and subjective norms on OFPI through self-efficacy. Third, we examine whether these indirect effects are moderated by gender and educational attainment. Data were collected from Indian adults with chronic conditions using a self-administered questionnaire. The results show significant indirect effects of organic food knowledge, attitude toward organic food purchase, and subjective norm on OFPI through self-efficacy. Moreover, the mediating effect of knowledge was moderated by gender and education attainment, with the effect being stronger for females and among individuals with a lower level of education. Organic food marketers, social marketers, and public health agencies promoting organic food consumption to people with chronic conditions should aim to increase their confidence in comprehending organic food. This study contributes to the literature by assessing the applicability of Fisher and Fisher’s (1992) IMB model in understanding behavioral intention toward organic food.

The objective of this study was to assess the ability of producing laminated edible films manufactured using the following proteins; gelatin (G), whey protein isolate (WPI), and polysaccharide; sodium alginate (SA), and to evaluate their physical properties. Additionally, films’ preparation employing these ingredients was optimized through the addition of corn oil (O), Overall, 8-types of laminated films (G-SA, G-WPI, SA-WPI, SA-G-WPI, GO-SAO, GO-WPIO, SAO-WPIO, SAO-GO-WPIO were developed in this study. The properties of the prepared films were characterized through the measurement of; tensile strength (TS), elongation at break point (EB), puncture resistance (PR), tear strength (TT), water vapour permeability (WVP) and oxygen permeability (OP). The microstructure of cross-sections of laminated films was investigated by scanning electron microscopy (SEM). Mechanical properties of films were dramatically enhanced through the addition of film layers. GO-SAO laminate showed the best barrier properties to water vapour (22.6 ± 4.04 g mm/kPa d m2) and oxygen (18.2 ± 8.70 cm3 mm/kPa d m2). SAO-GO-WPIO laminate film was the strongest of all laminated films tested, having the highest TS of 55.77 MPa, PR of 41.36 N and TT of 27.32 N. SA-G-WPI film possessed the highest elasticity with an EB value of 17.4%.

Leptospirosis is a zoonotic disease of global importance. The current killed vaccine provides serovar-specific protection without sterilizing immunity. Several surface antigens, including Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as subunit vaccine candidates; however, they require potent adjuvants. Bacterial Lipopolysaccharide (LPS), including lipid A, is a well-known immunostimulatory agent, and the formulation of Monophosphoryl Lipid A (MPLA) in Alum is a clinical adjuvant. Being less endotoxic, we tested the adjuvant activity of lipid A purified from L. interrogans serovar Pomona (PLA) for its ability to activate innate and enhance antigen-specific adaptive immune response. PLA-induced activation of macrophages similar to levels induced by MPLA, albeit at a much higher dose, indicating that it is less stimulatory than MPLA. Mice immunized with a Variable portion of LigA (LAV) formulated in Alum and PLA (LAV-Alum-PLA) induced significantly higher levels of LAV-specific humoral and cellular immune response than Alum but similar to levels induced by Alum-MPLA. The adjuvant activity of PLA seems to be quite similar to MPLA and primarily mediated through enhanced recruitment, activation, and uptake of antigens by innate immune cells. Moreover, like MPLA, the PLA formulation was able to generate a long-term memory response. Most importantly, PLA demonstrated better potency than MPLA formulation and generated sterilizing immunity against challenge in a hamster model of leptospirosis. Altogether, our study has provided important insight into the adjuvant activity of Leptospira lipid A and has opened avenues for the development of LPS-based vaccines against this dreadful zoonosis.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

Marine sediment sample was collected and the total aerobic population was counted and probiotic Bacillus cereus was isolated. Then it was mixed with formulated feed by spraying, while control diet was purchased from a local aquarium. 30 days of feeding experiment was conducted. Carassius auratus fishes were randomly divided into two experimental groups in rectangular tanks. The first group served as a control in which fishes were fed with commercial feed. The second group of fish were fed with probiotic incorporated feed. After 40 days, their survival and growth performance were detected. Bacillus cereus incorporated feed significantly yielded higher survival rate of the fish compared to control. Food conversion ratio (FCR) was significantly lower than the control group. The main aim of this work is to investigate the effect of a marine probiotic bacteria, Bacillus cereus on the survival and growth performance of gold fish Carassius auratus.

Obesity is associated with serious comorbidities and economic implications. Bariatric surgery, most commonly Roux-en-Y gastric bypass and sleeve gastrectomy, are effective options for weight loss and improvement of obesity-related comorbidities. With the growing obesity epidemic, there has been a concomitant rise in bariatric surgeries, particularly in sleeve gastrectomy, which has been the most widely performed bariatric surgery since 2013. Gastroesophageal reflux disease (GERD) is highly prevalent in obese individuals, can significantly impact quality of life and may lead to serious complications. Obesity and GERD both improve with weight loss. However, as the incidence of sleeve gastrectomy rises, recent data has revealed a risk of exacerbation of pre-existing GERD or the development of de novo GERD following sleeve gastrectomy. We performed a detailed review of GERD post-sleeve gastrectomy, including its overall incidence, pathophysiology and current treatment paradigms.

In this paper, I investigate Hyers-Ulam-Rassias stabilities of the general quintic functional equation and the general sextic functional equation.

This study presents a transversal investigation, that we performed at Fundeni hospital, into the therapeutic benefits and efficacy of Emicizumab, a non-factor therapy, in the context of hemophilia A. Ten patients diagnosed with hemophilia A were closely monitored, using clinical and laboratory resources, during the course of Emicizumab treatment, with an average of 12.8 months. Among these patients, six exhibited anti-factor VIII inhibitors, changing the medical approach and adding complexity to their clinical profiles. A comprehensive approach was adopted to assess the coagulation status of patients under Emicizumab therapy. The study employed several key coagulation monitoring tools, of which including thrombin generation time (TGT) and thrombelastography (TEG). These methodologies proved highly valuable results in evaluating the patients' coagulation profiles during the treatment regimen. Additionally, traditionally coagulation assays were utilized to gain a comprehensive understanding of the overall coagulation dynamics. Noteworthy, impressive outcomes emerged from the study. During prophylaxis with Emicizumab all patients had experienced a reduced number of bleeding events. Moreover, a subset of these patients underwent major surgical procedures (orthopedic joint replacements) with successful outcomes. These findings underscore the potential of Emicizumab therapy as an effective option for hemophilia A patients, including those that presented a prompt production of anti-factor VIII inhibitors. As for the outcomes, this transversal study sheds some light on the positive impact of Emicizumab therapy in addressing the coagulation challenges posed by hemophilia A. The utilization of global coagulation assays, such as thrombin generation time, thrombelastography and combined with traditional coagulation assays, used as monitoring tools highlights their significance once more in evaluating the therapeutic response. This research contributes by providing physicians with valuable insights to the field, offering a potential avenue for improved patients’ care and treatment strategies that translate in enhanced quality of life for hemophilia A patients undergoing Emicizumab therapy.

Polyvinyl Alcohol (PVA)/ Graphene Quantum Dots (GQDs) polymer nanocomposite films have been prepared, and the relationship between their structural, thermal and nanoscale morphologi-cal properties, and their photoluminescent response, has been investigated. Although according to X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Thermal Analysis (DTA) the incorporation of GQDs does not significantly affect the percentage crystallinity of the PVA matrix, for a range of added GQD concentrations, Atomic Force Micros-copy (AFM) showed the formation of islands with apparent crystalline morphology on the surface of the PVA/GQD films, with GQD presumably acting as a nucleating agent for island growth. The incorporation of GQD also led to the formation of characteristic surface pores with increased stiffness and frictional contrast, according to Ultrasonic Force Microscopy (UFM) and Frictional Force Microscopy (FFM) data. The photoluminescence (PL) spectra of the films were found to de-pend both on the amount of GQD incorporated and on the film morphology. For GQD loads > 1,2wt%, a GQD-related band was observed at ~ 1650 cm-1 in FT-IR, along with an increase in the PL band at lower energy. For a load of ~2wt% GQD, the surface morphology was characterized by extended cluster aggregates with lower stiffness and friction than the surrounding matrix, and the PL signal decreased.

This study addresses the problem of accurately predicting azimuth and elevation angles of signals impinging on an antenna array employing Machine Learning (ML). Using the information obtained at a receiving system when a transmitter’s signal hits it, a Decision Tree (DT) model is trained to estimate azimuth and elevation angles simultaneously. Simulation results demonstrate the robustness of the proposed DT-based method, showcasing its ability to predict the Direction of Arrival (DOA) in diverse conditions beyond the ones present in the training dataset, i.e., the results display the model’s generalization capability. Additionally, the comparative analysis reveals that DT-based DOA estimation outperforms the state-of-the-art MUltiple SIgnal Classification (MUSIC) algorithm, establishing DTs as competitive alternatives for DOA estimation in signal reception systems.

Methionine 77 in calmodulin can be stereospecifically oxidized to methionine sulfoxide by mammalian methionine sulfoxide reductase A. Whether this has in vivo significance is unknown. We therefore created a mutant mouse in which wild-type calmodulin-1 was replaced by a calmodulin containing a mimic of methionine sulfoxide at residue 77. Total calmodulin levels were unchanged in the homozygous M77Q mutant, which is viable and fertile. No differences were observed on learning tests, including the Morris water maze and associative learning. Cardiac stress test results were also the same for mutant and wild type mice. .However, young male and female mice were 20% smaller than wild type mice, although food intake was normal for their weight. Young M77Q mice were notably more active and exploratory than wild type mice. This behavior difference was objectively documented on the treadmill and open field tests. The mutant mice ran 20% longer on the treadmill than controls, and in the open field test, the mutant mice explored more than controls and exhibited reduced anxiety These phenotypic differences bore a similarity to those observed in mice lacking calcium/calmodulin kinase Iiα (CaMKIIα). We then showed that M77Q calmodulin was less effective in activating CaMKIIα than wild type calmodulin. Thus, characterization of the phenotype of a mouse expressing a constitutively active mimic of calmodulin led to the identification of the first calmodulin target that can be differentially regulated by the oxidation state of Met77. We conclude that reversible oxidation of methionine 77 in calmodulin by MSRA can regulate cellular function.

Wooden breast is a muscle disorder affecting modern commercial broiler chickens that causes a palpably firm pectoralis major muscle and severe reduction in meat quality. Most studies have focused on advanced stages of wooden breast apparent at market age, resulting in limited insights into the etiology and early pathogenesis of the myopathy. Therefore, the objective of this study was to identify early molecular signals in the wooden breast transcriptional cascade by performing gene expression analysis on the pectoralis major muscle of two-week-old birds that may later exhibit the wooden breast phenotype by market age at 7 weeks. Biopsy samples of the left pectoralis major muscle were collected from 101 birds at 14 days of age. Birds were subsequently raised to 7 weeks of age to allow sample selection based on the wooden breast phenotype at market age. RNA sequencing was performed on 5 unaffected and 8 affected female chicken samples, selected based on wooden breast scores (0 to 4) assigned at necropsy where affected birds had scores of 2 or 3 (mildly or moderately affected) while unaffected birds had scores of 0 (no apparent gross lesions). Differential expression analysis identified 60 genes found to be significant at an FDR-adjusted p value of 0.05. Of these, 26 were previously demonstrated to exhibit altered expression or genetic polymorphisms related to glucose tolerance or diabetes mellitus in mammals. Additionally, 9 genes have functions directly related to lipid metabolism and 11 genes are associated with adiposity traits such as intramuscular fat and body mass index. This study suggests that wooden breast disease is first and foremost a metabolic disorder characterized primarily by ectopic lipid accumulation in the pectoralis major.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ²(1) = 93.82, p-value < 2.2 × 10⁻¹⁶) and the H-bonds (χ²(1) = 91.93, p-value < 2.2 × 10⁻¹⁶). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

The present study was aimed at revealing the influence of the mechanical stress induced by water molecules adsorption on the composition of crystalline phases in the ZrO2–3mol%Y2O3-nanoparticles. Three basic methods have been used to determine the phase transition: neutron diffraction, Raman microspectroscopic scanning, and X-ray diffraction. The fact of phase-structural β → α transformation and the simultaneous presence of two polymorphic structural modifications (β is the phase of the tetragonal syngony and α of monoclinic syngony in nanosized particles (9nm)) under normal physical conditions was established by these methods. Satisfactory consistency was achieved between the results obtained using different techniques.

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

The motivation for investigating the issues presented in this article stemmed from a need to understand better the relationship in long-established physics formulas and extract the information they provided using conventional methods. Based on the definition of magnetic flux quantization, which is based on a combination of fundamental physical constants, the Planck constant, and the particle’s elementary charge, this work explores the results that arise when this equation is combined with the equation of the Bohr-level electrostatic force acting on the electron, which leads to a new mathematical relationship between the combined expressions. The new relationship yields novel theoretical findings related to the known universal constants. Following this insight, the formalism developed in this paper indicates that the mass of the electron and other subatomic particles is associated with the magnitude of the square of the magnetic flux quantum, which makes up the particle. This conclusion is not as strange as it may seem, as the square of the magnetic flux quantum appears in the context of magnetic energy in a current loop and, according to Einstein’s special theory of relativity, energy is equivalent to mass. Another aspect described at the end of this paper demonstrates the connection between the square of the magnetic flux quantum through the Bohr radius and the significance of the wave function in the atom. The theoretical results are in full accordance with experimental results published by NIST CODATA 2018 that I’ve used, which validates the existence of the relationship.

The selection of biomaterials for biomedical application is a significant challenge. In the last few decades, various bioabsorbable and stable biopolymers have been applied for use as biomedical devices in orthopedic applications. Ultra-high molecular weight polyethylene (UHMWPE) has been extensively used in medical implants, notably in the bearings of hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the ACL graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and its extremely high tensile strength. Despite the appeal of new advanced materials such as carbon fiber, poly-ether-ether ketone, and other load-bearing materials, UHMWPE remains a primary load-bearing candidate material for ACL reconstructions because of its extremely high strength, the simplicity of the fabrication process, its biocompatibility, and low friction. However, some significant problems are observed in UHMWPE based implants, such as wear debris, and oxidative degradation due to the generation of free radicals when exposed to irradiation with gamma rays for grafting or sterilization. Various innovative methodologies have been developed to resolve those problems and enhance the properties of UHMWPE. In this review, we will explore in detail the methods for surface functionalization of UHMWPE and will apply these findings to the case study of UHMWPE for Anterior Cruciate Ligament repair.

Deep eutectic solvents (DESs) have emerged as novel alternatives to common solvents and VOCs. Their employment as electrolytes in battery has been an area of intense research. In this context, understanding changes in physicochemical properties of DESs in the presence of Li salts becomes of utmost importance. Solvatochromic probes have potential to gauze such changes. It is reported herein that one such uv-vis molecular absorbance probe, Reichardt’s betaine dye 33, effectively manifests changes taking place in a DES Glyceline, composed of H-bond accepting salt choline chloride and H-bond donor glycerol in 1 : 2 molar ratio, as salt LiCl is added. Lowest energy intramolecular charge-transfer absorbance band of this dye exhibits 17 nm hypsochromic shift as up to 3.0 molal LiCl is added to Glyceline. The estimated ETN parameter shows linear increase with LiCl mole fraction. Spectroscopic responses of betaine dye 33, N,N-diethyl-4-nitroaniline and 4-nitroaniline are used to assess empirical Kamlet-Taft parameters of dipolarity/polarizability (π*), H-bond donating acidity (α) and H-bond accepting basicity (β) as a function of LiCl concentration in Glyceline. LiCl addition to Glyceline results in increase in α and no change in π*and β. It is proposed that added lithium interacts with oxygen of the –OH functionalities on the glycerol rendering the solvent with increased H-bond donating acidity. It is observed that pyrene, a popular fluorescence probe of solvent polarity, does respond to the addition of LiCl to Glyceline, however, the change in pyrene response starts to become noticeable only at higher LiCl concentration (mLiCl ≥ 1.5 m). Reichardt’s betaine dye is found to be highly sensitive and versatile in gauzing physicochemical properties of DESs in the presence of LiCl.

In the present study, we aimed to determine the antimicrobial resistance and genetic structure of a population of S. aureus recovered from transient and persistent intramammary infections and nares/muzzles. We investigated the antimicrobial resistance of 189 S. aureus strains using a broad antimicrobial susceptibility profile. Furthermore, 107 S. aureus isolates were strain-typed using staphylococcal protein-A (spa) typing. Here, a great proportion of strains exhibited multidrug resistance to antimicrobials, including resistance to critically important antimicrobials, although no methicillin-resistant S. aureus strains were found. Our study did not strengthen the idea that extramammary niches (i.e., nares/muzzles) are an important source for S. aureus. A discrepancy in the antimicrobial resistance between S. aureus strains isolated from nasal/muzzles and milk samples was observed. Furthermore, S. aureus isolates from transient and persistent IMIs did not differ by spa typing, suggesting that the persistence of bovine IMIs was determined by cow factors. Thus, the high level of multidrug-resistant S. aureus found in the two herds studied together with the predominance of a well udder-adapted S. aureus strain may contribute to the history of the high prevalence of mastitis caused by S. aureus, leading to great animal and public health concerns.

Androgen receptor signaling is crucial for prostate cancer growth and is positively regulated in part by intratumoral CYP3A5. As African American (AA) men often carry the wild type CYP3A5 and express high level of CYP3A5 protein, we blocked the wild type CYP3A5 in AA origin prostate cancer cells and tested its effect on androgen receptor signaling. q-PCR based profiler assay identified several AR regulated genes known to regulate AR nuclear translocation, cell cycle progression and cell growth. CYP3A5 processes several commonly prescribed drugs and many of these are CYP3A5 inducers or inhibitors. In this study, we test the effect of these commonly prescribed CYP3A5 inducers/inhibitors on AR signaling. The results show that the CYP3A5 inducers promoted AR nuclear translocation, downstream signaling and cell growth whereas CYP3A5 inhibitors abrogated them. The observed changes in AR activity is specific to alterations in CYP3A5 activity. Both the inducers tested demonstrated increased cell growth of prostate cancer cells, whereas the inhibitors showed reduced cell growth. Further, characterization and utilization of the observation that CYP3A5 inducers and inhibitors alter AR signaling may provide guidance to physicians prescribing CYP3A5 modulating drugs to treat comorbidities in elderly patients undergoing ADT, particularly AA.

A single tree topology is a commonly employed topology for wireless sensor networks (WSN) to connect sensors to one or more remote gateways. However, its many-to-one traffic routing pattern imposes heavy burden on downstream nodes, as the same routes are repeatedly used for packet transfer, from one or more upstream branches. The challenge is how to choose the most optimal routing paths that minimizes energy consumption across the entire network. This paper proposes a proactive energy awareness-based many-to-one traffic routing scheme to alleviate the above said problem referred to as Energy Balance-Based Energy Hole Alleviation in tree topology (EBEHA-T). This protocol combines updated status of variations in energy consumption pattern around sink-hole zones and distribution of joint nodes among the trees. With this approach, EBEHA-T proactively prevents sink-hole formation instead of just a reactive response after they have occurred. Performance evaluation of EBEHA-T against benchmark method RaSMaLai shows increased energy saving across the entire network and a marked improvement in energy consumption balance in energy-hole zones. This precludes energy hole formation and the consequent network partitioning, leading to improved network lifetime beyond that of the RasMaLai. OMNET++ network simulation software has been used for the evaluation.