Ante-mortem bovine tuberculosis (bTB) tests for buffaloes include the single comparative intradermal tuberculin test (SCITT), interferon-gamma (IFN-γ) release assay (IGRA) and IFN-γ-inducible protein 10 release assay (IPRA). Although parallel test interpretation increases detection of Mycobacterium bovis-infected buffaloes, these algorithms may not be suitable for screening buffaloes in historically bTB-free herds. In this study, the specificities of three assays were determined using M. bovis unexposed herds, and a high specificity diagnostic algorithm developed. Serial test interpretation using the IGRA and IPRA showed significantly greater specificity (98.3%) than individual tests or parallel testing (73%). When the SCITT was added, the algorithm had a 100% specificity. Since the cytokine assays had imperfect specificity, potential cross-reactivity with nontuberculous mycobacteria (NTM) was investigated. No association was found between NTM presence (in oronasal swab cultures) and positive cytokine assay results. As a proof-of-principle, serial testing was applied to high-value buffaloes (n=153) in a historically bTB-free herd. Buffaloes positive on a single test (n=28) were regarded as test negative. Four buffaloes were positive on IGRA and IPRA, and M. bovis infection was confirmed following culling. These results demonstrate the value of using IGRA and IPRA in series to screen buffalo herds with no previous history of M. bovis infection.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

We present an ontology log-OLOG- representation of the classical Miller-Urey experiment, usually considered as a paradigm for spontaneous generation of biomolecules on the prebiotic Earth and also, as a key in understanding the chemical evolution phenomena linked to the origins of life. Ologging The Miler-Urey experiment enables us, through the categorical notion of fibre product or pullback, to define the concept of Biogenic Space, as a space containing low complexity biogenic units subjected to appropriate physical and chemical conditions, facilitating the synthesis of highly complex organic molecules. Also, we characterize the Biogenic Space as a concrete universal object that could be associated with the preconditions for life inside various structures in the universe such as exoplanets and exomoons located in habitable zones, but also in interstellar and intergalactic organic clouds.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

As with many of the non-deterministic search algorithms, particularly those are analogous to complex biological systems, there are a number of inherent difficulties, and the Bees Algorithm (BA) is no exception. Basic versions and variations of the BA have their own drawbacks. Some of these drawbacks are a large number of parameters to be set, lack of methodology for parameter setting and computational complexity. This paper describes a Grouped version of the Bees Algorithm (GBA) addressing these issues. Unlike its conventional version, in this algorithm bees are grouped to search different sites with different neighbourhood sizes rather than just discovering two types of sites, namely elite and selected. Following a description of the GBA, the results gained for 12 benchmark functions are presented and compared with those of the basic BA, enhanced BA, standard BA and modified BA to demonstrate the efficacy of the proposed algorithm. Compared to the conventional implementations of the BA, the proposed version requires setting of fewer parameters, while producing the optimum solutions much faster.

Miller Fisher Syndrome (MFS) is a rare variant of Guillain-Barré Syndrome (GBS). It is largely a clinical diagnosis based on the classical features of ataxia, areflexia, and opthalmoplegia. Its clinical evolution is most often favorable. However, other neurological signs and symptoms may also be present. Supportive laboratory studies (positivity of antibodies, CSF albumin-cytological dissociation and nerve conduction studies) are useful especially in uncommon presentations. We report a case of a 74-year-old patient who exhibited dysphonia and difficulty to swallowing previously to the classic triad of ataxia, areflexia, and opthalmoplegia, characteristic of MFS. CSF analysis demonstrates an albumin-cytological dissociation but anti-GQ1b antibody were negative. The patient has spontaneously and completely recovered after several weeks.

Although different assessments and evaluations of Dual-Miller cycle performed, specified output power and thermal performance associated with engine determined. Besides, multi objective optimization of thermal efficiency, Ecological Coefficient of performance ( ) and Ecological function ( ) by the mean of NSGA-II technique and thermodynamic analysis performed. The Pareto optimal frontier obtaining the best optimum solution is chosen by fuzzy Bellman-Zadeh, LINMAP, and TOPSIS decision-making techniques. Based on the results, performances of dual-Miller cycles and their optimization are improved.

The key links of face recognition are digital image preprocessing, facial feature extraction and pattern recognition, this article aimed at the current problem of slow speed and low recognition accuracy of face recognition , from the above three key links, on the basic of analyzing the therories of Fractional Differential Masks Operator (FDMO), Principal Component Analysis (PCA) and Support Vector Machine (SVM), design a kind of FDMO+PVA+SVM coupling algorithm that applies to face recognition to improve the speed and accuracy of it. To realize FDMO+PCA+SVM coupling algorithm, first, we should apply FDMO to face image processing binary marginalization, the purpose is getting face contour; Then, we apply PCA to get the feature of face image which is disposed by binary marainalization. At last, we can apply One-Against All of the SVM classifier and LibSVM software package to realize face recognition. Beside, the article with nine different coupling algorithm design four groups of experimental reaults on the ORL face database verified by comparative analysic FDMO+PCA+SVM coupling algorithm in the superiority of face recognition accuracy and speed.

With the increasing concern of environment, the energy-efficiency scheduling of manufacturing industry is becoming urgent and popular. In turning processes, both spindle speed and processing time can affect the final energy consumption and thus the spindle speed and scheduling scheme need to be optimized simultaneously. Since the turning workshop can be regarded as the flexible flow shop, this paper formulates a mixed integer linear programming model for energy-efficient scheduling of flexible flow shop. Accordingly, a new decoding method is developed by considering of the optimization of spindle speed and scheduling scheme simultaneously, and an estimation of distribution algorithm adopting the new decoding method is proposed to solve large-size problems. The parameters of this algorithm are determined by statistical technique with a simplified practical case. In order to validate the proposed method, a case from practical factories is studied, in which the makespan can be shortened by 25.22%, and the consumed energy can be saved by 5.48%. These results demonstrate the effectiveness of the proposed mathematical model and algorithm.

In order to overcome the limitation of the traditional adaptive Unscented Kalman Filtering (UKF) algorithm in noise covariance estimation for statement and measurement, we propose a hybrid adaptive UKF algorithm based on combining Maximum a posteriori (MAP) criterion and Maximum likelihood (ML) criterion, in this paper. First, to prevent the actual noise covariance deviating from the true value which can lead to the state estimation error and arouse the filtering divergence, a real-time covariance matrices estimation algorithm based on hybrid MAP and ML is proposed for obtaining the statement and measurement noises covariance, respectively; and then, a balance equation the two kinds of covariance matrix is structured in this proposed to minimize the statement estimation error. Compared with the UFK based MAP and based ML, the proposed algorithm provides better convergence and stability.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Earth observation satellites can capture images of specific areas in Earth's orbit based on user requirements. Despite the high demand for satellite imagery, satellites remain a scarce resource. When there are many observation tasks that are large and dense, they may interfere with each other due to satellite mobility. To address this issue, a multi-satellite scheduling algorithm based on a task merging mechanism has been proposed. This paper proposes a two-stage approach to the problem: task merging phase and merging task scheduling phase. The task merging phase introduces two methods based on Mean Shift and Complete Graph to generate the merging task set. In the merging task scheduling phase, a multi-satellite scheduling algorithm based on merging tasks is employed to solve the problem. Finally, certain measurement experiments suggest the effectiveness of the algorithm.

In wireless sensor networks (WSNs), each sensor node can estimate the global parameter from the local data in distributed manner. This paper proposed a robust diffusion estimation algorithm based on minimum error entropy criterion with self-adjusting step-size, which are referred to as diffusion MEE-SAS (DMEE-SAS) algorithm. The DMEE-SAS algorithm has fast speed of convergence and is robust against non-Gaussian noise in the measurements. The detailed performance analysis of the DMEE-SAS algorithm is performed. By combining the DMEE-SAS with diffusion minimum error entropy (DMEE) algorithms, an Improving DMEE-SAS algorithm is proposed, in non-stationary environment where tracking is very important. The Improving DMEE-SAS algorithm can avoid insensitivity of the DMEE-SAS algorithm due to the small effective step-size near the optimal estimator, and obtain a fast convergence speed. Numerical simulations are given to verify the effectiveness and advantages of these proposed algorithms.

We develop an optimized force-field for poly(3-hexylthiophene) (P3HT) and demonstrate its utility for predicting thermodynamic self-assembly. In particular, we consider short oligomer chains, model electrostatics and solvent implicitly, and coarsely model solvent evaporation. We quantify the performance of our model to determine what the optimal system sizes are for exploring self-assembly at combinations of state variables. We perform molecular dynamics simulations to predict the self-assembly of P3HT at ~350 combinations of temperature and solvent quality. Our structural calculations predict that the highest degrees of order are obtained with good solvents just below the melting temperature. We find our model produces the most accurate structural predictions to date, as measured by agreement with grazing incident X-ray scattering experiments.

Accurate classification of objects in 3D point clouds is a significant problem in several applications, such as autonomous navigation and augmented/virtual reality scenarios, which has become a research hot spot. In this paper, we presented a deep learning strategy for 3D object classification in augmented reality. The proposed approach is a combination of the GRU and LSTM. LSTM networks learn longer dependencies well, but due to the number of gates, it takes longer to train; on the other hand, GRU networks have a weaker performance than LSTM, but their training speed is much higher than GRU, which is The speed is due to its fewer gates. The proposed approach used the combination of speed and accuracy of these two networks. The proposed approach achieved an accuracy of 0.99 in the 4,499,0641 points dataset, which includes eight classes (unlabeled, man-made terrain, natural terrain, high vegetation, low vegetation, buildings, hardscape, scanning artifacts, cars). Meanwhile, the traditional machine learning approaches could achieve a maximum accuracy of 0.9489 in the best case.

Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p&lt;0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.

In this paper, we first discuss the research status and application progress of the finite element method and the smoothed particle method. By analyzing the advantages of the smoothed particle method and the finite element method, a new coupling algorithm, namely FEM-SPH algorithm, is proposed. By the method of comparison, it shows that finite element method and SPH method in the simulation of large deformation problems each have advantages and disadvantages, the finite element method smoothed particle coupling algorithm is effective to achieve the performance of high computational efficiency and can naturally simulate large deformation problems across. In the process of calculation, the large deformation unit can be freely into an algorithm to facilitate the calculation accuracy and efficiency of three methods of numerical simulation. Through the study found, FEM-SPH algorithm not only overcome the defect of smooth particle tensile instability, but also overcomes the problem of low efficiency of finite element computation. To further test the FEM-SPH algorithm has advantages in the practical engineering, we have carried out the actual test to the example of the super high speed collision, concluded that, since the target of most of the computational domain is always finite element, smoothed particle focused only in contact with the projectile and target of local area, particle number is not much, the whole calculation process just ten minutes, computational efficiency has been greatly improved, at the same time in the simulation of large deformation, the advantage is very obvious .This provides a criterion for the actual project, depending on the specific material deformation mode and choose a more appropriate conversion algorithm.

Background—In 2011, Miller and Goldman published a study in Human and Experimental Toxicology that found a counterintuitive, positive correlation, r = 0.70 (r² = 0.49, p < .0001), demonstrating that as nations require more vaccine doses for their infants, infant mortality rates (IMRs) tend to increase (worsen). The dataset (n = 30) included the United States, a nation that required the most vaccines for their infants, and all nations with better IMRs than the United States. Dr. E. Bailey, a professor at BYU, and her students, recently read the Miller-Goldman study and found it "troublesome that this manuscript is in the top 5% of all research outputs" and falsely claimed that its findings were due to "inappropriate data exclusion," i.e., failure to analyze the "full dataset" of all 185 nations. The "Bailey reanalysis," titled Infant vaccination does not predict increased infant mortality rate: correcting past misinformation, was posted to the medRxiv preprint server on September 10, 2021 (version 1) and October 5, 2021 (version 3) and Europe PMC preprint server on September 10, 2021. Objective—This present study examines the various claims postulated by the Bailey reanalysis and assesses the robustness of their methodology, analyses, and reported results and conclusions. Methods—Data discussed in this paper are based on the previously mentioned study by Miller and Goldman and the Bailey reanalysis. Results—Linear regression analysis of IMR and the number of vaccine doses for each country yield a statistically significant positive correlation of r = 0.70 (p < .0001) for the top nations (n = 30) chosen by Miller-Goldman and r = 0.16 (p < .04) for the "entire dataset" chosen by Bailey et al (n = 185). Bailey also conducted linear regression analyses (for the year 2019) of IMRs as a function of vaccination rates for each of eight different vaccines and reported statistically significant inverse correlations for 7 of 8 vaccines over the entire range of vaccination rates. However, Miller and Goldman reanalyzed the Bailey analyses for nations with vaccination rates below 60% and found no statistically significant correlation for six vaccines (DPT, Hib, hepatitis B, polio, rotavirus, and measles) and statistically significant positive correlations for tuberculosis (r = 0.8, p < .005) and pneumococcal (r = 0.6 p < .023) vaccines. Conclusions—Bailey’s reanalysis corroborates a statistically significant positive correlation originally reported by Miller and Goldman. However, Bailey’s reported correlation (r = +0.16, p < .04) is small, likely due to poor methodology (failing to account for covariates, i.e., disparities among numerous socioeconomic factors that add uncertainty to their conclusion). The r-value reported by the Bailey reanalysis demonstrates an effect size that is about one-fourth (0.16/0.70) that reported by Miller-Goldman—underscoring how critically important it is for Bailey's reanalysis to eliminate confounding variables. Moreover, Bailey’s linear regression analyses of IMR as a function of vaccination rates for each of eight different vaccines demonstrate that some countries with low vaccination rates have low IMRs, while other countries with high vaccination rates have high IMRs. Rather than supporting a strong inverse correlation, the Bailey reanalysis demonstrates high vaccination rates are neither necessary nor sufficient to cause low IMR.

This paper proposes a new approach for multi-focus images fusion based on Region Mosaicing on Contrast Pyramids (REMCP). A density-based region growing method is developed to construct a focused region mask for multi-focus images. The segmented focused region mask is decomposed into a mask pyramid, which is then used for supervised region mosaicking on a contrast pyramid. In this way, the focus measurement and the continuity of focused regions are incorporated and the pixel level pyramid fusion is improved at the region level. Objective and subjective experiments show that the proposed REMCP is more robust to noise than compared algorithms and can fully preserves the focus information of the multi-focus images meanwhile reducing distortions of the fused images.

Since certain Mycobacterium tuberculosis complex (MTBC) members, like M. bovis, are endemic in specific South African wildlife reserves and zoos, cases of clinically important nontuberculous mycobacteria (NTM) in wildlife may be neglected. Additionally, due to the inability of tests to differentiate between host responses to MTBC and NTM, the diagnosis of MTBC may be confounded by the presence of NTMs. This may hinder control efforts. These constraints highlight the need for enhanced rapid detection and differentiation methods for MTBC and NTM, especially in high MTBC burden areas. We evaluated the use of the GeneXpert MTB/RIF Ultra, the Hain CMdirect V1.0, and novel amplicon sequencing PCRs targeting the mycobacterial rpoB and ku gene targets, directly on antemortem respiratory samples from known MTBC-infected and NTM culture-positive African elephants (n=26 animals) and rhinoceros (n=23 animals). Our findings suggest that the Ultra is the most sensitive diagnostic test for MTBC DNA detection directly in raw antemortem respiratory specimens and that the rpoB PCR is ideal for Mycobacterium genus DNA detection and species identification through amplicon sequencing.

Pavement crack detection is one of the key links in highway pavement maintenance management. In the current road crack detection, the network model easily ignores the shallow geometric features of cracks and cannot extract the key feature information of cracks. Aiming at the above problems, an EC-YOLOX network model is proposed. The CFPN is constructed to cross-fuse different scale features to solve the feature scale invariance. In the strengthen feature extraction layer, ECANet is fused to enhance the ability to pay attention to key information. The WEIoU loss function is proposed, which assigns different penalty terms to the target box in the vertical and horizontal directions. In terms of data, geometric distortion constraint correction is performed on the single-point perspective pavement image. The experimental data show that the accuracy of EC-YOLOX on the self-built data set reaches 76.34% [email protected], which is 4.45% higher than that of YOLOX. The loss curve of EC-YOLOX is smoother than that of YOLOX, and the minimum training loss value is 2.136, which is 0.648 lower than the minimum loss value 2.784 of YOLOX. Many experiments have verified the effectiveness of EC-YOLOX in improving the detection effect in pavement crack detection.

This study was to identify clinical cancer biomarkers for recurrent gastric cancer survivors using artificial intel-ligence. From a hospital-based cancer registry database in Taiwan, the datasets of the incidence of recurrence and clinical risk features were included in 2476 gastric cancer survivors. We benchmarked Random forest with MLP, C4.5, AdaBoost, and Bagging algorithms on metrics and leveraged synthetic minority oversampling technique (SMOTE) for imbalanced dataset issues, cost-sensitive learning for risk assessment, and SHapley Additive ex-Planations (SHAP) for feature importance analysis in this study. Our proposed Random forest outperformed the other models with an accuracy of 87.9%, a recall rate of 90.5%, an accuracy rate of 86% and F1 of 88.2% on re-current category by a 10-fold cross-validation in a balanced dataset. We identified clinical features of recurrent gastric cancer, which are the top five features, stage, number of regional lymph node involvement, Helicobacter pylori, BMI(body mass index), and gender, which significantly affect the prediction model's output, are worth paying attention to in the following causal effect analysis. Using an artificial intelligence model, the risk factors for recurrent gastric cancer could be identified and cost-effectively ranked according to their feature importance. In addition, they should be crucial clinical features to provide physicians with the knowledge to screen high-risk patients in gastric cancer survivors as well.

Classifying network flow subsequences in an Industrial IoT gateway is an effective method for identifying Industrial IoT faults. This paper proposes a subsequence classification algorithm SSGBUL-IKNN based on unsupervised learning encoding to address the problem of low classification accuracy. Firstly, we built a network module based on unsupervised learning to encode the flow sequence of the Industrial IoT gateway. In the encoding module, a subsequence calibration algorithm controls the increasing error during the coding process. Then, the specific fault type is obtained through an improved KNN classification algorithm based on the indication distance source from the integrated coding sequences converted by multi-dimensional network flow sequences. The test result on three Industrial IoT datasets of a sewage treatment plant shows that the accuracy of SSGBUL-IKNN in this paper exceeds 92%, significantly higher than the algorithm DTW and TSF. It reaches the classification requirements of Industrial IoT fault diagnosis.

Diagnosis of bovine tuberculosis (bTB) may be confounded by immunological cross-reactivity to Mycobacterium bovis antigens when animals are sensitised by certain nontuberculous mycobacteria (NTMs). Therefore, this study aimed to investigate NTM species diversity in African buffalo (Syncerus caffer) respiratory secretions and tissue samples, using a combination of novel molecular tools. Oronasal swabs were collected opportunistically from 120 immobilised buffaloes in historically bTB-free herds. In addition, bronchoalveolar lavage fluid (BALF; n=10) and tissue samples (n=19) were obtained during post-mortem examination. Mycobacterial species were identified directly from oronasal swab samples using the Xpert MTB/RIF Ultra qPCR (14/120 positive) and GenoType CMdirect (104/120 positive). In addition, all samples underwent mycobacterial culture, and PCRs targeting hsp65 and rpoB were performed. Overall, 55 NTM species were identified in 36 mycobacterial culture-positive swab samples with presence of esat-6 or cfp-10 detected in 20 of 36 isolates. The predominant species were M. avium complex and M. komanii. Nontuberculous mycobacteria were also isolated from 6 of 10 culture-positive BALF and 4 of 19 culture-positive tissue samples. Our findings demonstrate that there is a high diversity of NTMs present in buffaloes, and further investigation should determine their role in confounding bTB diagnosis in this species.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.

The paper presents an error model of a measurement chain containing link performing discrete wavelet transform algorithm which is most often the last stage of measurement signal processing. The goal is to determine the uncertainty budget of the input quantities of the wavelet transform algorithm. The error model takes into account parts of analog, analog-to-digital and digital processing, describing the properties of subsequent fragments of the chain using their transmittance and processing functions. The proposed model enables the description of both deterministic and non-deterministic properties of signal errors. The proposed model was validated using an example measurement chain created for this purpose.

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

We define the notions of strong and strict recurrency for actions of countable ordered groups on $\sigma$-finite non atomic measure spaces with quasi-invariant measures. We show that strong recurrency is equivalent to non existence of weakly wandering sets of positive measure. We also show that for certain p.m.p ergodic actions the system is not strictly recurrent, which shows that strong and strict recurrency are not equivalent.

Depth-sensing technology has led to broad applications of inexpensive depth cameras that can capture human motion and scenes in 3D space. Background subtraction algorithms can be improved by fusing color and depth cues, thereby allowing many issues encountered in classical color segmentation to be solved. In this paper, we propose a new fusion method that combines depth and color information for foreground segmentation based on an advanced color-based algorithm. First, a background model and a depth model are developed. Then, based on these models, we propose a new updating strategy that can eliminate ghosting and black shadows almost completely. Extensive experiments have been performed to compare the proposed algorithm with other, conventional RGB-D algorithms. The experimental results suggest that our method extracts foregrounds with higher effectiveness and efficiency.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

Insulated Gate Bipolar Transistor (IGBT) may convey high current and sustain high breakdown voltages; it may provide high power control. In a sense, how IGBT demonstrates the capability of power control was not specifically described, and the equivalent bipolar junction transistors (BJT) activated by an applied bias to the insulated gate is intriguing. As seen in Figure 1, IGBT shows an equivalent circuit structure containing two types of BJT, (NPN-type Bipolar transistor and PNP-type Bipolar transistor), which can be modeled as diode-associated transistor. Apparently, as a bias applies to the controlling gate, the channel beneath the gate oxide gets strongly inversed and turns out to be conductive just like what happens on metal-oxide-silicon field effect transistor (MOSFET), which provides necessary igniting currents to both BJTs and thus causes high current gain flowing through them-selves from the bottom. A proposed and renewed formula provides addressing the above scenario and successfully fitting the measured data that forms the characteristic curves. Some parameters in the proposed formula, which includes size and mobility associated constant, threshold voltage, and Early-Voltage-related lambda for MOSFET, explain and explore the underlying physics. IGBT thus enjoy high input impedance and high current gain due to MOSFET (Insulated Gate) and BJT, respectively. This formula combines both merits of MOSFET and BJT in order to fit the measured data. Indeed, the formula intimately fits IGBT electrical characteristic curves, and thus may be qualified and served as a model. The new model is then advisable for designing power integrated circuit to exactly achieve power saving, power control, and power efficiency.

Primates have an unparalleled ability to produce a wide range of dexterous movements, each sensitive to context and robust to perturbation. Recent progress in understanding the neural basis of movement generation comes from two largely independent ideas, “Optimal Feedback Control” and “Neural Dynamical Systems”. The optimal control framework was largely inspired by research programs from the ‘80s showing that the brain doesn’t seem to plan a simple desired movement trajectory, but instead produces movements by transforming sensory information into motor output that satisfies an optimality criterion. The more recent idea that the motor cortex acts as a dynamical system came about only as it became possible to analyze large numbers of simultaneously recorded single neurons. These two framings of the motor system have been largely incommensurate, neither able to contribute much to the understanding of the other. In this review, we reconcile these two views into a single model we call “Dynamical Feedback Control”. We propose that the dynamics in the motor cortex emerge from a sensorimotor transformation that couples the motor cortex to sensory input from the periphery, and to contextual inputs from other cortical and subcortical areas. Dynamics in motor cortex can be thought to approximate gains of a feedback controller, and by moving the neural state to different regions of state space, the motor system can rapidly alternate between different controllers. The DFC framework presents a new lens to interpret neural dynamics, and to understand how ensembles of neurons generate flexible and responsive patterns of muscle activity.

Recently, coastal swamps have been acknowledged for their capability to alleviate shorelines and defend coastal communities. Mangroves play a prominent role in obstructing water currents in riverbanks, shorelines, and coastal areas. Mangrove roots have the significant contribution to the resiliency of the vegetation structure. Yet, mangrove model has lately been called into question by lab experimental evidence. In this paper, the flow characteristics past root models are reviewed. coastal swamps are among the most fruitful and carbon‐rich ecosystems on the planet. Long‐term carbon putting away in coastal wetlands happens mostly below ground as soil organic matter. Mangrove servs as a carbon sink, impacts wetland ecosystem configuration, purpose, and firmness. To expect and ease the properties of climate change, there is a necessity to advance considerate of environmental controls on wetland. The impact of four soil formation factors are reviewed. Across the shorelines, soil organic matter was highest in mangrove forests and it was lower areas.

Reassessment of the fatigue life for wind turbines structural components is typically performed using deterministic methods with the same partial safety factors as used for the original design. However, in relation to life extension, the conditions are generally different from the assumptions used for calibration of partial safety factors; and using a deterministic assessment method with these partial safety factors might not lead to optimal decisions. In this paper, the deterministic assessment method is compared to probabilistic and risk-based approaches, and the economic feasibility is assessed for a case wind farm. Using the models also used for calibration of partial safety factors in IEC61400-1 ed. 4 it is found that the probabilistic assessment generally leads to longer additional fatigue life than the deterministic assessment method. The longer duration of the extended life can make life extension feasible in more situations. The risk-based model is applied to include the risk of failure directly in the economic feasibility assessment and it is found that the reliability can be much lower than the target for new turbines, without compromising the economic feasibility.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

Evaluating new, promising organic molecules to make next-generation organic optoelectronic devices necessitates the evaluation of charge carrier transport performance through the semi-conducting medium. In this work, we utilize quantum chemical calculations (QCC) and kinetic Monte Carlo (KMC) simulations to predict the zero-field hole mobilities of ~100 morphologies of the benchmark polymer poly(3-hexylthiophene), with varying simulation volume, structural order, and chain-length polydispersity. Morphologies with monodisperse chains were generated previously using an optimized molecular dynamics force-field and represent a spectrum of nanostructured order. We discover that a combined consideration of backbone clustering and system-wide disorder arising from side-chain conformations are correlated with hole mobility. Furthermore, we show that strongly interconnected thiophene backbones are required for efficient charge transport. This definitively shows the role "tie-chains" play in enabling mobile charges in P3HT. By marrying QCC and KMC over multiple length- and time-scales, we demonstrate that it is now possible to routinely probe the relationship between molecular nanostructure and device performance.

Deadlock is a real problem that can cause expensive, time-dependent hang-ups or failures in distributed computing systems. Some studies have been conducted with deadlock detection and resolution in generalized request computing models, most of these studies are based on the diffusing computation scheme, where forward and backward propagated probe and reply messages respectively are diffused between dependent processes. The replies carry the dependency information between processes for the initiator. Using this dependency information initiator can detect and resolve the deadlock cycle. It has been proven in the literature that a deadlock cycle length distribution is skewed with a large majority of cycles (90%) having length two. Based on this fact an improved algorithm is proposed for handling deadlock detection in distributed computing systems under the distributed request model where each process has several requests at a time. The improved algorithm depends mainly on message propagation and timeout policy. Probe and reply messages are propagated between the initiator and its successors only to detect deadlock cycles between them. Global timeout policy is used to detect potential deadlock cycles with large length distribution. The proposed algorithm can handle concurrent executions. Simulation experiments are performed to see the effectiveness of the improved algorithm. It is found that the improved algorithm compares favorably with other existing algorithms and it shows better results for several performance metrics especially in reducing deadlock latency and execution time.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

Detection of subsurface archaeological remains using a range of remote sensing methods, poses several challenges until today. Recent studies regarding the detection of archaeological proxies like those of cropmarks highlight the complexity of the phenomenon. In this work we present three different methods, and associated indices, for identifying stressed reflectance signatures indicating buried archaeological remains, based on a dataset of measured ground spectroradiometric reflectance. Several spectral profiles between the visible and near infrared part of the spectrum, were taken over a controlled environment in Cyprus during the 2011-2012 and are re-used in this study. The first two (spectral) methods are based on a suitable analysis of the spectral signatures in (1) the visible part of the spectrum, and in particular in the neighborhood of 570 nm, and (2) the red edge-near infrared part of the spectrum, in the neighborhood of 730 nm. Machine learning (decision trees) allows for the deduction of suitable wavelengths to focus on, in order to formulate the proposed indices and the associated classification criteria (decision boundaries) that can enhance the detection probability of stressed vegetation. Noise in the signal is taken into account by simulating reflectance signatures perturbed by white noise. Applying decision tree classification on the ensemble of simulations and basic statistical analysis we refine the formulation of the indices and criteria for the noisy signatures. The success rate of the proposed methods is over 90%. The third method rests on the estimation of vegetation/canopy reflectance parameters through inversion of the physical-based PROSAIL reflectance model and the associated classification through machine learning methods. The obtained results provide further insights into the formation of stress vegetation that occurred due to the presence of shallow buried archaeological remains, which are well aligned with physical-based models and existing empirical knowledge. To the best of the authors' knowledge, this is the first study demonstrating the usefulness of radiative transfer models such as PROSAIL for understanding the formation of cropmarks. Similar studies can support future research directions towards the development of regional remote sensing methods and algorithms if systematic observations are adequately dispersed in space and time.

Quaking aspen (Populus tremuloides Michx.) landscapes are valued for their biodiversity, water retention, fire mitigation, aesthetics, and recreation opportunities. Across North America, some aspen populations are experiencing population declines as they face uninhibited ungulate browsing, drought, fire suppression, insects, disease, and inappropriate management. Increased human development and recreational use within aspen landscapes can serve as additive stressors, though there is a dearth of literature examining these elements. At a popular recreational area in Utah, USA, identifying the cause of apparent decline within a larger aspen community is complicated by development upstream and recreation-related activities. We sought to: 1) assess the overall condition of the aspen at the site, 2) understand key variables that influence aspen conditions, and 3) elucidate how aspen fitness varies across the site. We collected data from forty-five plots using established aspen sampling methods, including ungulate presence, tree characteristics, soil chemistry, and environmental descriptors. Results suggest that a combination of higher levels of browsing and elevated soil sodium may be causing premature mortality and limiting aspen recruitment in a portion of the study area. These findings will inform future management at this site, as well as similar recreational forest settings experiencing compound stressors.

Amid the swift progression of the global automobile industry, the aspiration for lightweight vehicle design has surfaced as a crucial approach to boost fuel efficiency and curtail environmental impact. The objective of this study revolves around achieving holistic optimization of vehicle structure via detailed scrutiny of vehicle process characteristics, amalgamated with a Back Propagation neural network (BPNN) optimized by a genetic algorithm (GA) and a topology optimization (TO) method.The process initiates with an examination of the vehicle's technical characteristics, succeeded by an optimization protocol that couples GA with BPNN. This exhaustive optimization procedure derives the best-fit values of design parameters and identifies the globally optimal lightweight design approach. Subsequently, a comprehensive structural optimization is actualized by modifying the topological distribution of the structure.A simulation experiment of the conceptual car body beam skeleton is conducted as a conclusive step, and the anti-collision capacity of the car body beam skeleton is assessed by measuring deformation intrusion. The findings reveal that in the vehicle topology optimization, a comparative analysis of pre and post-optimization results indicates an improved topological density across diverse sections. The topological density of the vehicle's frontal structure escalates from 0.75 to 0.8. Following optimization, the stiffness assessment records a marginal increase (within the range of 0.02–0.05), implying that the lightweight design does not compromise the general rigidity of the structure.The optimized body structure manifests superior crashworthiness in the crash test: the deformation intrusion diminishes by 27% in front-end collisions. In side impacts, the deformation and intrusion at critical points are reduced by 13.15% to 10% respectively. The comprehensive method proposed herein proves to be an efficient strategy to actualize the lightweight design of vehicles.

Gaze tracking of high-speed moving targets is a novel application mode for low Earth orbit microsatellites. In this mode, small satellites are equipped with high-resolution narrow-field-of-view video cameras for stable gaze-tracking imaging of high-speed moving targets. This paper proposes a high-precision attitude adaptive integral sliding mode control method with a feedforward compensation disturbance observer to enhance the capability of a microsatellite attitude control system for gaze tracking of high-speed moving targets. Specifically, first, we present the attitude control system model for microsatellites and the calculation method for the desired attitude of target tracking based on image feedback. Then, an adaptive integral sliding mode attitude control algorithm with a feedforward compensation disturbance observer, which meets the requirements of high-precision tracking control, is designed. The developed algorithm utilizes the disturbance observer to observe the friction torque of the flywheel and compensates for it through feedforward control. It also employs the adaptive integral sliding mode control algorithm to reduce the impact of uncertain disturbances, decrease the steady-state error of the system, and enhance the attitude control precision. Simulation experiments demonstrated that the designed disturbance observer can successfully observe the frictional disturbance torque of the flywheel. The attitude Euler angle control precision for high-speed moving target tracking reached 0.009°, and the angular velocity control precision reached 0.005°/s, validating the effectiveness of the proposed approach.

Pheochromocytoma is a rare neuroendocrine tumor that affects people in the 4th and 5th decades of life. It can be benign or malignant, and present as isolated tumors or along with other neuroendocrine syndromes. We present a case of an elderly man who underwent laparoscopic adrenalectomy for pheochromocytoma when he was 58 years only to have a recurrence of metastatic malignant pheochromocytoma in his seventies. We also conducted a literature review to understand the epidemiology and presentation of the tumor and to emphasize that there should be a low threshold of suspicion for timely diagnosis and management of recurrent pheochromocytoma.

Abstract: Background: Surgery on varicose veins (crossectomy and stripping) leads to recurrence and has clinical and socio-economic repercussions. Their etiopathogenesis has yet to fully under-stood. Objective: Study the expression of endoglin and other molecules involved in the neovascu-larisation process in patients suffering from this disease. Methods: 43 patients that have undergone surgery for varicose veins (24 primary and 19 recurrent). They were identified on the venous wall (proximal -saphenofemoral junction- and distal), via real-time RT-PCR, and in serum, via ELISA: Endoglin (Eng), Vascular Endothelial Growth Factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLT1), (VEGFR2 or FLK), and the Hypoxia-Inducible Factor (HIF-1A). All the patients signed a con-sent form. Results: The recurrent group recorded a higher expression of Eng, VEGF-A, VEGFR1 and VEGFR2 at the level of proximal venous wall compared to the primary group. HIF-1A did not record any differences. As regards the determination of the distal venous wall, no markers recorded differ-ences between the groups. Among the serum determinations, only sFLT1 recorded a significant drop among the patients with recurrent varicose veins. Conclusions: Patients with recurrent vari-cose veins record a higher expression of endoglin and other markers of angiogenesis in proximal veins. Endoglin in the blood (sEng) has not proven to be of any use in recurrent varicose veins.

The nucleation and dynamics of Josephson and Abrikosov vortices determine the critical currents of layered high-T_c superconducting (HTS) thin films, grain boundaries, and coated conductors, so understanding their mechanisms is of crucial importance. Here we treat pair creation of Josephson and Abrikosov vortices in layered superconductors as a secondary Josephson effect, in which each full vortex is viewed as a composite fluid of micro-vortices, such as pancake vortices, which tunnel coherently via a tunneling matrix element. We introduce a two-terminal magnetic (Weber) blockade effect that blocks tunneling below a threshold current, and simulate time-correlated vortex tunneling above threshold. The model shows nearly precise agreement with voltage-current (V-I) characteristics of HTS cuprate grain boundary junctions, which becomes more concave rounded as temperature decreases, and also explains the piecewise linear V-I behavior observed in iron-pnictide bicrystal junctions and other HTS devices. When applied to either Abrikosov or Josephson pair creation, the model explains a plateau seen in plots of critical current vs. thickness of HTS coated conductors. The observed correlation between theory and experiment strongly supports the proposed quantum picture of vortex nucleation and dynamics in layered superconductors.

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

Count data analysis presents unique challenges due to its discrete nature, often exhibiting excessive zeros and overdispersion. To address these complexities, count models, such as Poisson regression and Negative Binomial regression, have been developed, enabling modeling and prediction of count-based phenomena. Additionally, it’s important to notice that zero inflation, a phenomenon commonly observed in count data, requires specialized techniques for robust analysis. This article provides an overview of count data and count models, explores zero inflation, introduces Likelihood Ratio Tests, and explains how the Vuong Test can be used as a model selection criteria. Furthermore, we created a Vuong Test implementation from scratch using the Python programming language. This implementation enhances the accessibility and applicability of the Vuong Test in real-world scenarios, providing a valuable contribution to the academic community, since Python didn’t have an implementation of this statistical test.

The article discusses issues related to the optimization of the operation of medium voltage networks, focusing on the optimization of network division points and the selection of the optimal network configuration aimed at reducing power and energy losses. The article provides a critical review of selected scientific works from recent years on the issue of network configuration optimization. The developed solution uses non-deterministic network models and statistical and probabilistic approaches. Optimization studies were carried out using heuristic optimization methods and proprietary algorithms for forecasting the load and power generated from renewable energy sources. The solution proposed in the article has many application possibilities. It can be used to optimize the location of network division points (reducing economic costs related to the modernization of network infrastructure) as well as to optimize the reconfiguration process in order to reduce power losses while maintaining voltage criteria.

The development of autonomous vehicles is becoming increasingly popular and gathering real world data is considered a valuable task. Many datasets have been published recently in the autonomous vehicle sector, with synthetic datasets gaining particular interest due to availability and cost. For a real implementation and correct evaluation of vehicles at higher levels of autonomy it is also necessary to consider human interaction, which is precisely something that lacks in existing datasets. In this article the UPCT dataset is presented, a public dataset containing high quality, multimodal data obtained using state of the art sensors and equipment installed onboard the UPCT’s CICar autonomous vehicle. The dataset includes data from a variety of perception sensors including 3D LiDAR, cameras, IMU, GPS, encoders, as well as driver biometric data and driver behaviour questionnaires. In addition to the dataset, the software developed for data synchronisation and processing has been made available. The quality of the dataset was validated using an end-to-end neural network model with multiple inputs to obtain speed and steering wheel angle and obtained very promising results.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

Accurate electricity price forecasting has become a substantial requirement since the liberalization of the electricity markets. Due to the challenging nature of the electricity prices, which includes high volatility, sharp price spikes and seasonality, various types of electricity price forecasting models still compete and can not outperform each other consistently. Neural Networks have been successfully used in machine learning problems and Recurrent Neural Networks (RNNs) have been proposed to address time-dependent learning problems. In particular, Long Short Term Memory and Gated Recurrent Units (GRU) are tailor-made for time series price estimation. In this paper, we propose to use Gated Recurrent Units as a new technique for electricity price forecasting. We have trained a variety of algorithms with rolling 3-year window and compared the results with the RNNs. In our experiments, 3-layered GRUs outperformed all other neural network structures and state of the art statistical techniques in a statistically significant manner in the Turkish day-ahead market.

This paper describes the feasibility and probable benefits associated with greening the Tahliah Channel, a concrete drainage channel that was originally built to relieve urban flooding in Jeddah City, Saudi Arabia. It includes an estimation of irrigation needs for channel greening based on a standardized planting specification. The study also demonstrates alternative strategies for meeting the required irrigation demand, including water harvesting and graywater reuse on a residential scale. The study shows that greening Tahliah Channel is possible relying mainly on graywater reuse from the surrounding buildings. Also, the study shows that rainwater harvesting is not a reliable source for irrigation. Rather, it can cover only part of the irrigation needs (6%) and so can be used as a secondary supporting source. The positive results of this case study will be of interest to those in arid countries who are looking to upgrade and replace traditional, single function drainage infrastructure with more sustainable, green infrastructure systems. More specifically, the objectives of the study are consistent with the goals of the Saudi government’s ongoing initiative that advocates for more resilient and sustainable cities. (Vision 2030 year).

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.

Accurate forecasting of icing thickness has a great significance for ensuring the security and stability of power grid. In order to improve the forecasting accuracy, this paper proposes an icing forecasting system based on fireworks algorithm and weighted least square support vector machine (W-LSSVM). The method of fireworks algorithm is employed to select the proper input features with the purpose of eliminating the redundant influence. In addition, the aim of W-LSSVM model is to train and test the historical data-set with the selected features. The capability of this proposed icing forecasting model and framework is tested through the simulation experiments using real-world icing data from monitoring center of key laboratory of anti-ice disaster, Hunan, South China. The results show that the proposed W-LSSVM-FA method has a higher prediction accuracy and it may be a promising alternative for icing thickness forecasting.

Breastmilk is the only recommended source of nutrition for infants below six-months of age. However, a significant proportion of children are either on supplemental breastfeeding(SBF) or weaned due to the early introduction of solid/semi-solid/soft food and liquids(SSF) before 6 months of age. There is good evidence that Exclusive Breastfeeding(EBF) in infants below six-months of age protects them from preventable illnesses, including malnutrition. The relationship between infant feeding practices and coexisting forms of malnutrition(CFM) has not yet been explored. This study examined the association of different feeding indicators(continuation of breastfeeding, predominant feeding, and SSF) and feeding practices(EBF, SBF, and complete weaning) with CFM in infants aged below six-months of age in Pakistan. National and regional datasets of Pakistan from the last ten years were retrieved from the Demographic Health Surveys(DHS) and UNICEF data repositories. In Pakistan, 34.5%(n=6131) of infants have some form of malnutrition. Among malnourished infants, 44.7%(~15.4% of the total sample) had a CFM. Continuation of breastfeeding was observed in more than 85% of infants, but less than a quarter were on EBF, and the rest were either SBF(65.4%) or weaned infants(13.7%). Compared to EBF, complete weaning increased the odds of coexistence of underweight with wasting and underweight with both wasting and stunting by 1.96(1.12-3.47) and 2.25(1.16-4.36), respectively. Overall, breastfed children had lower odds of various forms of CFM (compared to non-breastfed), except for the coexistence of stunting with overweight/obesity. Continuation of any breastfeeding protects infants in Pakistan from various types of CFM during the first six months of life.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic cause of cholestasis. It is considered as part of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC), and intrahepatic cholestasis of pregnancy. BRIC is presented in infancy or in early adulthood. It is characterized by exacerbations and remissions of jaundice with accompanying intense itching, lasting from weeks to years throughout lifetime. Normal gamma-glutamyl transferase (GGT) is a characteristic laboratory finding. Contrary to PFIC, which may progress to cirrhosis, BRIC does not progress to chronic liver disease or cirrhosis. However, incessant episodes of cholestasis result in marked reduction in quality of life and distinct mutations increase the risk of hepatobiliary malignancy. In intervals between the exacerbations, the histological findings of centrilobular cholestasis together with the abnormal laboratory parameters return to normal. In this context, liver biopsy might be avoided. In this review, we will focus on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis of this autosomal recessive genetically determined cholestatic disorder. Moreover, triggering factors as well as treatment options will be further elucidated.

The pathogenesis of transient global amnesia (TGA), a dramatic but self-limiting episode of anterograde amnesia with a variable duration of retrograde amnesia, remains unknown. Although most episodes are single, TGA has a finite recurrence rate. Studies of case series and large patient cohorts have typically been used to investigate possible precipitating and predisposing factors for TGA. Study of recurrent TGA episodes in single cases might provide another way to address pathogenetic factors. A patient with recurrent TGA is presented to illustrate such considerations with respect to possible chronobiological factors in TGA pathogenesis.

The long-term resilience of Pyrenean forests in the face of historical anthropogenic clearing remains largely unknown. The palynological study of the varved sediments from a mid-elevation (1027 m) karstic lake provides a high-resolution record of three major century-scale deforestation/recovery (DR) cycles that occurred in the last two millennia, during Roman, Medieval and Modern times. Each DR cycle is characterized considering three different levels: overall forest trends, by forest type and by individual taxa. Overall, the studied forests exhibited high resilience, as they recovered almost completely after each deforestation event (bulk resilience). The critical point of no return (tipping point) beyond which forests would have irreversibly disappeared from the region was never reached, even after deforestation magnitudes above 60%. The different forest types identified (conifer, sclerophyll and deciduous) persisted over time, showing similar heterogeneous patterns with minor spatial reorganizations (mosaic resilience). Individually, the main forest taxa underwent minor variations in their relative abundances, always within the same attraction domains (community resilience). The high levels of resilience documented in these Pyrenean forests are attributed to the action of metapopulation and metacommunity processes and mechanisms in a highly dynamic patchy environment. Conservation actions should be focused on the maintenance of these spatial patterns and the associated ecological dynamics.

In this paper we develop a forecasting algorithm for recurrent patterns in consumer demand. We study this problem in two different settings: pull and push models. We discuss several features of the algorithm concerning sampling, periodic approximation, denoising and forecasting.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

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.

This paper compares a series of traditional and deep learning methodologies for the segmentation of textures. Six well-known texture composites first published by Randen and Hus{\o}y were used to compare traditional segmentation techniques (co-occurrence, filtering, local binary patterns, watershed, multiresolution sub-band filtering) against a deep-learning approach based on the U-Net architecture. For the latter, the effects of depth of the network, number of epochs and different optimisation algorithms were investigated. Overall, the best results were provided by the deep-learning approach. However, the best results were distributed within the parameters, and many configurations provided results well below the traditional techniques.

Human milk (HM) is the gold standard for feeding infants but has been associated with slower growth in preterm infants compared with preterm formula. This systematic review and meta-analysis summarises the post-1990 literature to examine the effect of HM feeding on growth during the neonatal admission of preterm infants with birth weight ≤1500g and/or born ≤28 weeks’ gestation. Medline, PubMed, CINAHL and Scopus were searched, and comparisons grouped as: exclusive human milk (EHM) vs exclusive preterm formula (EPTF), any HM vs EPTF and higher vs lower doses of HM. We selected studies that used fortified HM and compared that with a PTF; studies comparing unfortified HM and term formula were excluded. Experimental and observational studies were pooled separately. The GRADE system was used to evaluate risk of bias and certainty of evidence. Forty-four studies were included with 37 (n =9,963 infants) included in the meta-analyses. In general, due to poor quality studies, evidence of the effect of any HM feeds or higher versus lower doses of HM was inconclusive. There was a possible effect that lower doses of HM compared with higher doses of HM improved weight gain during the hospital admission, and separately, a possible effect of increased head circumference growth in infants fed EPTF vs any HM. The clinical significance of this is unclear. There was insufficient evidence to determine the effects of an exclusive HM diet on any outcomes.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

Prostate cancer is the most common non-cutaneous malignancy in men, with the majority of newly diagnosed patients eligible for active surveillance. Despite definitive treatment, a considerable percentage of men will experience biochemical recurrence and even regional and distant metastatic recurrence after radiation therapy or radical prostatectomy. Salvage prostatectomy, while oncologically effective, poses significant morbidity with poor functional outcomes. Salvage cryotherapy has emerged as a promising alternative for localized recurrence, demonstrating safety and efficacy. This review examines the oncologic and functional outcomes of whole-gland and focal salvage cryotherapy, including disease-free survival, cancer-specific survival, and overall survival. The crucial role of multiparametric prostate MRI and evolving role of next-generation PSMA-targeted PET imaging is also examined. Comparison of outcomes of cryotherapy to other salvage ablation modalities, such as high-intensity focused ultrasound (HIFU) is also explored.

This article introduces a novel nature-inspired metaheuristic algorithm called Frilled Lizard Optimization (FLO), which emulates the hunting behavior of frilled lizards in their natural habitat. FLO draws in-spiration from the sit-and-wait strategy observed in frilled lizards during hunting. The underlying theory of FLO is presented and mathematically formulated in two phases: (i) an exploration phase, simulating the frilled lizard's attack towards prey, and (ii) an exploitation phase, simulating the lizard's retreat to the top of the tree after feeding. To assess FLO's efficacy in solving optimization problems, the algorithm's performance is evaluated across fifty-two standard benchmark functions, encompassing unimodal, high-dimensional multimodal, fixed-dimensional multimodal, and the CEC 2017 test suite. Comparative analyses with twelve existing metaheuristic algorithms are conducted. The simulation results reveal that FLO, distinguished by its adeptness in exploration, exploitation, and balancing them during search process, outperforms competing algorithms. Additionally, FLO is implemented on twenty-two constrained optimization problems from the CEC 2011 test suite and four engineering design problems, demonstrating its effectiveness in addressing real-world optimization applications.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Objective The aim of this study was to explore the prognosis and influencing factors of recurrent ependymoma in children. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched to collect studies on survival outcomes and influencing factors of recurrent ependymoma in children. The search time frame was from the establishment of the database to September 2023. Two evaluators independently screened the literature, extracted data, and evaluated the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. Results A total of 11 studies involving 1120 patients were included. The integrated results of mOS from the 11 studies showed significant heterogeneity (I2 = 92%). Therefore, a random-effects model was used for merging, and the results showed statistically significant differences (P < 0.00001). In all the studies, the pooled estimate of median OS from the time of recurrence was 15.54 months (95% CI 8.80-27.45; P < 0.00001), and the combined median progression-free survival (PFS) from the time of first recurrence was 6.7 months (95% CI 5.59-7.64; P < 0.0001). The median OS for patients who underwent surgery at the time of recurrence was 20.7 months (95% CI 12.40–34.72; P < 0.00001), while the mOS for patients who received radiation therapy was 29.5 months (95% CI 18.97–46.00; P < 0.0001), and for patients who received chemotherapy mOS was 18.0 months (95% CI 8.62–37.75; P < 0.00001). The mOS for patients under 3 years old at the time of recurrence was 20.1 months (95% CI 1.98-204.50; P < 0.00001), while for patients over 3 years old at the time of recurrence mOS was 16.6 months (95% CI 9.40-29.35; P < 0.00001). Conclusion The results of the study show poor prognosis for children with recurrent ependymoma, and there are significant differences in these results. The influencing factors include patient age, tumor recurrence location, and treatment methods. These findings can further guide clinical research on new treatment methods and strategies to improve the prognosis of this population.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

Most police Mental Health Act (Section 136) detentions in England and Wales relate to suicide prevention. Despite attempts to reduce detention rates, numbers have risen almost continually. Although Section 136 has been subject to much academic and public policy scrutiny, the topic of individuals being detained on multiple occasions remains under-researched and thus poorly understood. A mixed methods study combined six in-depth interviews with people who had experienced numerous suicidal crises and police intervention, with detailed police and mental health records. A national police survey provided wider context. Consultants with lived experience of complex mental health problems jointly analysed interviews. Repeated detention is a nationally recognised issue. In South East England it almost exclusively relates to suicide or self-harm and accounts for a third of all detentions. Females are detained with the highest frequencies. The qualitative accounts revealed complex histories of unresolved trauma that had catastrophically damaged interviewee’s relational foundations, rendering them disenfranchised from services and consigned to relying on police intervention in repeated suicidal crises. A model is proposed that offers a way to conceptualise the phenomenon of repeated detention, highlighting that long-term solutions to sustain change are imperative, as reactive-only responses can perpetuate crisis cycles.

Culture exploits the acquisition of meaningful content by crafting regimes of shared attention, determining what is relevant, valuable, and salient. Culture changes the field of relevant social affordances worthy of being acted upon in a context-sensitive manner. When relevant affordances are highly weighted, their attentional capture and their salience increase the probability of them being enacted due to the associated expectation for minimizing prediction error. This process is known as active inference. In the digital era, individuals need to infer the action-related attributes of digital cues, here characterized as digital affordances. The digital affordances of digital social platforms are of particular interest here. Digital social affordances are defined as online possibilities of social interactions. By their own nature, these are salient because they are related to social interactions and relevant social cues. However, the problem of digital social platforms is that they are not equivalent to situated social interactions because their structure is built, mediated, and defined by third-parties with diverse interests. The third-parties behind the digital social platforms are using the same mechanism exploited by culture to manipulate the shared patterns of attention. Moreover, digital social platforms are deliberately designed to be hyper-stimulating, making digital social affordances highly rewarding and increasingly salient. This appropriation, for economic purposes, is an issue of great importance, especially as the COVID-19 pandemic brought deep global changes, pushing societies to an online digital way of life. Here, we examined different types of digital social affordances under an active inference view, placing them into two categories, those for self-identity formation, and those for belief-updating. This paper aims to analyze digital social affordances in light of the prediction error dynamics they might elicit to their users. Although each of the analyzed digital social affordances allows different epistemic and instrumental digital actions, they all share the characteristic of having an "easy" and a fast expected rate of error reduction. Here, we aim to provide a new hypothesis about how the design behind digital social affordances is built on our natural attractiveness to minimize prediction error and the resulting positive embodied feelings when doing so. Finally, it is suggested that because digital social affordances are becoming highly weighted in the field of affordances, this might be putting at risk our context-sensitive grip on a rich, dynamic and varied field of relevant affordances.

The prevalence of type-2 diabetes mellitus (T2D) is increasing worldwide and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be integrated daily in the diet are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially-available yogurt (control yogurt). Interestingly, we found that feeding of this synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the composition of gut microbiota compared to milk; conversely, the control yogurt negatively modulated the gut microbiota by significantly increasing the abundance of detrimental bacteria like Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected intact pancreatic islet morphology compared to the milk control, while the commercial yogurt demonstrated worse effects on pancreatic physiology. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a modality to prevent diabetes progression.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

The United States is plagued with the highest rates of preventable metabolic diseases it has ever seen, and while poor nutrition is increasingly recognized as a critical contributing factor, good nutrition has been shown to be a potent factor in prevention and management of these illnesses. Notably, nutrition is inextricably intertwined with farming practices and the stewardship of our environment – particularly its soil. In this proposal, we propose a method to expose medical students to basic agricultural and environmental knowledge regarding the production of food, as well as educate them in practical nutrition education within the interactive, case-based, and longitudinal preclinical curriculum at Case Western Reserve University School of Medicine (CWRU SOM). We propose a two-part approach; first: integrating relevant topics in nutrition, culinary medicine, and farming practices into the preclinical blocks through Official Learning Objectives, and second: an optional 8-week, zero credit elective for students interested in pursuing a deeper understanding of these topics. Through these interventions, we believe courses like this will support a generation of physicians able to understand health from soil to plate with a consideration for the environment in addition to exemplifying healthful lifestyles themselves. We believe these kinds of future physicians will be the most effective in treating (and ideally reversing) the chronic disease epidemic.

ABSTRACT: Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neurooncology, and the survival status of patients after relapse usually means rapid deterioration, and also the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulate the body's immune system to recognize and attack cancer cells , which could be used as a in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma, This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and focus on the rGBM especially.

Video super-resolution, which utilizes the relevant information of several low-resolution frames to generate high-resolution images, is a challenging task. One possible solution called sliding window method tries to divide the generation of high-resolution video sequences into independent sub-tasks, and only adjacent low-resolution images are used to estimate the high-resolution version of the central low-resolution image. Another popular method named recurrent algorithm proposes to utilize not only the low-resolution images but also the generated high-resolution images of previous frames to generate the high-resolution image. However, both methods have some unavoidable disadvantages. The former one usually leads to bad temporal consistency and requires higher computational cost while the latter method always can not make full use of information contained by optical flow or any other calculated features. Thus more investigations need to be done to explore the balance between these two methods. In this work, a bidirectional frame recurrent video super-resolution method is proposed. To be specific, a reverse training is proposed that the generated high-resolution frame is also utilized to help estimate the high-resolution version of the former frame. With the contribution of reverse training and the forward training, the idea of bidirectional recurrent method not only guarantees the temporal consistency but also make full use of the adjacent information due to the bidirectional training operation while the computational cost is acceptable. Experimental results demonstrate that the bidirectional super-resolution framework gives remarkable performance that it solves the time-related problems when the generated high-resolution image is impressive compared with recurrent-based video super-resolution method.

PPARgamma belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARgamma is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARgamma under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion & 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARgamma. Expression changes were evaluated by immunohistochemistry and RT-PCR in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using CD68 as marker for macrophages. The intermediate villous trophoblast revealed a significantly lower PPARgamma expression in spontaneous and recurrent abortion. Maternal macrophages express PPARgamma. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARgamma only in very few cases. PPARgamma is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARgamma in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

Pyrolysis is a combustion process of woody biomass conducted under low or no oxygen conditions. New innovations and the need to limit open burning has resulted in numerous mobile and fixed plant pyrolysis methods that burn a variety of woody residues. Production technologies that reduce the need for open burning, the main source of potential pollutants, fall under the regulations in the Clean Air Act of 1990. This Act is the legal instrument to regulate air pollution at its source across the United States of America and it is implemented and enforced through the Environmental Protection Agency, in coordination with sister agencies. One newer innovation for reducing woody residues and emissions is an air curtain incinerator. Currently, the Clean Air Act regulates stationary solid waste incinerators, and this is also applied to mobile air curtain incinerators burning woody biomass. However, other woody biochar production methods (e.g., flame cap kilns) are not subject to these regulations. Discrepancies in the interpretation of definitions related to incineration and pyrolysis and the myriad of differences related to stationary and mobile air curtain incinerators, type of waste wood from construction activities, forest residues, and other types of clean wood make the permitting regulations confusing as permits can vary by jurisdiction. This review summarizes the current policies, regulations, and directives related to in-woods biochar production and the required permits.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Abstract: 1) Background. This research examined feasibility, acceptability and outcomes of delivering a 6-week yoga-based meditation intervention to clinical teams of hospice professionals (HPs) at a large non-profit hospice organization. The intervention was designed to increase mind-body integration and combat burnout. The manuscript was written for different audiences including research scientists who study interoception, burnout, meditation, or yoga, designers of meditation interventions, and hospice organizations looking for ways to mitigate HP burnout. 2) Methods. The intervention was launched within clinical teams, beginning with a half hour online introduction to the program and exposure to the week 1 meditation at each team’s monthly all-staff meeting. Throughout the program, HPs could access the meditations on their own via their workplace computers, tablets, and smartphones. Online pre- and post-intervention surveys with 151 HPs assessed burnout using the Professional Fulfillment Index and mind-body integration using the Multidimensional Assessment of Interoceptive Awareness sub-scales. 3) Results. Half of HPs expressed a desire to continue to have access to the meditations after the 6-week program ended. Due to covid-19 work from home restrictions, three-fourth of HPs did a meditation at home, 29% in a car between patient visits (not while driving), and 23% at the office. Higher interoceptive awareness was significantly related to lower burnout, particularly lower work exhaustion. Meditation frequency was significantly related to higher interoceptive awareness but not to burnout. 4) Conclusions. Findings showed that yoga-based meditation intervention was feasible and acceptable and associated with higher interoceptive awareness. The results point to a role for interoceptive awareness in reducing the risk for burnout.

When implementing SVMs, two major problems are encountered: (a) the number of local minima increases exponentially with the number of samples and (b) the quantity of required computer storage, required for a regular quadratic programming solver, increases by an exponential mag-nitude as the problem size expands. The Kernel-Adatron family of algorithms gaining attention lately which has allowed it to handle very large classification and regression problems. Howev-er, these methods treat different types of samples (Noise, border, and core) in the same manner, which causes searches in unpromising areas and increases the number of iterations. In this work, we introduce a hybrid method to overcome these shortcomings, namely Optimal Recurrent Neu-ral Network Density Based Support Vector Machine (Opt-RNN-DBSVM). This method consists of four steps: (a) characterization of different samples, (b) elimination of samples with a low probability of being a support vector, (c) construction of an appropriate recurrent neural network based on an original energy function, and (d) solution of the system of differential equations, managing the dynamics of the RNN, using the Euler-Cauchy method involving an optimal time step. The RNN remembers the regions explored during the search process thanks to its recurrent architecture. We demonstrated that RNN-SVM converges to feasible support vectors and Opt-RNN-DBSVM has a very low time complexity compared to RNN-SVM with constant time step, and KAs-SVM. Several experiments were performed on academic data sets. We used several classification performances measures to compare Opt-RNN-DBSVM to different classification methods and the results obtained show the good performance of the proposed method.

The environmental issues we are currently facing require long-term prospective efforts for sustainable growth. Renewable energy sources seem to be one of the most practical and efficient alternatives in this regard. Understanding a nation's pattern of energy use and renewable energy production is crucial for developing strategic plans. No previous study has been performed to explore the dynamics of power consumption with the change in renewable energy production on a country-wide scale. In contrast, a number of deep learning algorithms demonstrated acceptable performance while handling sequential data in the era of data-driven predictions. In this study, we developed a scheme to investigate and predict total power consumption and renewable energy production time series for eleven years of data using a Recurrent Neural Network (RNN). The dynamics of the interaction between the total annual power consumption and renewable energy production are investigated through extensive Exploratory Data Analysis (EDA) and a feature engineering framework. The performance of the model is found satisfactory through the comparison of the predicted data with the observed data, visualization of the distribution of the errors and Root Mean Squared Error (RMSE) value of 0.084. Higher performance is achieved through the increase in the number of epochs and hyperparameter tuning. The proposed framework can be used and transferred to investigate the trend of renewable energy production and power consumption and predict the future scenarios for different communities. Incorporation of the cloud-based platform into the proposed pipeline may lead to real-time forecasting.

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes to a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure under the above described constraints.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

Online transactions are becoming more popular in present situation where the globe is facing an unknown disease COVID-19. Now authorities of Countries requested peoples to use cashless transaction as far as possible. Practically it is not always possible to use it in all transactions. Since number of such cashless transactions have been increasing during lockdown period due to COVID-19, fraudulent transactions are also increasing in a rapid way. Fraud can be analysed by viewing a series of customer transactions data that was done in his/her previous transactions. Normally banks or other transaction authorities warned their customers about the transaction If any deviation is noticed by them from available patterns. These authorities think that it is possibly of fraudulent transaction. For detection of fraud during COVID-19, banks and credit card companies are applying various methods such as data mining , decision tree, rule based mining, neural network, fuzzy clustering approach and machine learning methods. These approaches is try to find out normal usage pattern of customers based on their past activities. The objective of this paper is to find out such fraud transactions during such unmanageable situation.Digital payment schemes are often threatened by fraudulent activities. Detecting fraud transaction in during money transfer may save customers from financial loss. Mobile based money transactions are focused in this paper for fraud detection. A Deep Learning (DL) framework is suggested in this paper that monitors and detects fraudulent activities. Implementing and applying recurrent neural network on PaySim generated synthetic financial dataset, deceptive transactions are identified. The proposed method is capable to detect deceptive transactions with an accuracy of 99.87%, F1-Score of 0.99 and MSE of 0.01.

Purpose: This review features a generalized overview of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The increasing number of reported cases indicated the worldwide distribution of the mosquito vectors, which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. However, the 4 different viral serotypes increases the risk of a life-threatening secondary infection due to the varying serotypes. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

Phylogenies depict shared evolutionary patterns and structures on a tree topology, enabling the identification of hierarchical and historical relationships. Recent analyses indicate that phylogenetic signals extend beyond the primary structure of protein or DNA, and various aspects of codon usage biases are phylogenetically conserved. Several functional biases exist within genes, including the number of codons that are used, the position of the codons, and the overall nucleotide composition of the genome. Codon usage biases can significantly affect transcription and translational efficiencies, leading to differential gene expression. Although systematic codon usage biases originate from the overall GC content of a species, ramp sequences, codon aversion, codon pairing, and tRNA competition also significantly affect gene expression and are phylogenetically conserved. We review recent advances in analyzing codon usage biases and their implications in phylogenomics. We first outline common phylogenomic techniques. Next, we identify several codon usage biases and their effects on secondary structure, gene expression, and implications in phylogenetics. Finally, we suggest how codon usage biases can be included in phylogenomics. By incorporating various codon usage biases in common phylogenomic algorithms, we propose that we can significantly improve tree inference. Since codon usage biases have significant biological implications, they should be considered in conjunction with other phylogenetic algorithms.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first- and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical popu-lation of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: The Korean ver-sion of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression In-ventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experi-encing their first episode (n=22, mean age: 15.09±1.44 years) and those with recurrent episodes (n=39, mean age: 15.95±1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first-episode 26.18±10.54 and recurrent episode 25.90±10.59, STAI-S: first-episode 56.91±12.12 and recurrent episode 57.49±11.93, STAI-T: first-episode 60.36±11.63 and recurrent episode 59.09±12.10, SPAQ-total: first-episode 6.59±4.86 and recurrent episode 6.77±5.23, KtCS: first-episode 30.32±5.83 and recurrent episode 28.13±7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r=0.26), KtCS (r=-0.48), K-BRIAN-sleep (r=0.58), K-BRIAN-activity (r=0.64), K-BRIAN-social (r=0.71) and K-BRIAN-eating (r=0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

Background/Aims: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). Methods: This study used two databases for different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS database converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study. Results: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8,201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1,216 patients with history of MI during 1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 [95% confidence interval (CI); 1.83-2.38], and the RR showed an increasing trend with PPI duration. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group [Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, P=0.04]. The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, P=0.23). The impact of individual PPIs on stroke and MI showed different patterns. Conclusions: PPI co-prescription with clopidogrel was associated with recurrent stroke; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by a shift in the vaginal microbiota from lactobacillus dominance to a diverse array of facultative and strict anaerobic bacteria which form a multi-species biofilm on vaginal epithelial cells. The rate of recurrence after therapy is high, often >60%. While the BV biofilm itself likely contributes to recurrent and/or refractory disease after treatment by reducing antimicrobial penetration, antimicrobial resistance in BV-associated bacteria including those, both within the biofilm and the vaginal canal, may be the result of independent, unrelated bacterial properties which are discussed in this paper. Our current recommendations for the treatment of refractory and recurrent BV are also provided.

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione], a component of Curcuma longa L. rhizomes, displays various biological and pharmacological activities. However, it is poorly bioavailable and unstable in physiological pH, which has led more stable and effective curcumin analogs (e.g., monoketone curcuminoids, or MKCs) to be synthesized, and their biological activities to be described. In this review, we cover papers published between 2019 and 2023 on the antimicrobial, anticancer, antioxidant, and antiparasitic actions as well as other less common MKC biological and pharmacological activities. We also address the Claisen-Schmidt condensation as a standard procedure to synthesize MKCs.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG) with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. We investigated the antiviral effect of NTP using an in vitro model for HSV-1 cold sores, involving the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. We found NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggest the potential of NTP as a therapeutic agent effective against HSV-1 infection.

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.

Background and Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised 8 pediatric patients (ages 3-18) and 2 adult patients (ages 19-75). Median age at the time of SRS was 13 years, median tumor volume accounted for 1.9 cc, median biologically equivalent dose (BED) was 126 Gy, and single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusion: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (ARE) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.

The effects of four cycles of recurrent selection on simple sequence repeat (SSR) marker allele frequencies and population structure were examined in the Maksimir 3 Synthetic (M3S) maize population (Zea mays L.). Genotyping of 32 plants from each cycle of selection at 38 SSR loci revealed that the mean number of alleles per locus and the mean expected heterozygosity were preserved over cycles of selection, indicating maintenance of sufficient genetic variability in the population needed for future genetic gain. Waples test of selective neutrality revealed that genetic drift was the main force in changing allele frequencies in the population. The proportion of selectively nonneutral loci in single cycles of selection varied between 16% and 37%. Some nonneutral loci shared the same genomic locations with previously published QTLs controlling important agronomic traits. Between 5% and 29% of loci were found to be in significant Hardy-Weinberg (HW) disequilibrium with the majority showing an excess of homozygosity. Excess of homozygosity at several loci was highly consistent across cycle populations suggesting positive assortative mating as the possible cause of the observed HW disequilibrium. Linkage disequilibrium (LD) tests revealed that the M3S population was essentially in linkage equilibrium. The proportion of pairs of loci in significant LD varied across cycles of selection between 0.1% and 1.8% probably due to the effects of genetic drift and epistatic selection.

Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.