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Automobiles and motorcycles that run on conventional fuels are currently not the greatest for transportation because to the rising awareness of pollution and the energy shortage concerns. There is a demand for a less expensive and more effective mode of transportation because the cost of petroleum goods is soaring right now. Additionally, it is becoming more and more crucial to conserve energy in order to assess the issue of leftover fuel depletion. Even large-scale manufacturing and industrial operations restrict their employees' use of transportation within the premises in order to reduce the risk of air pollution. Research on environmentally friendly transport has increased to fulfil these demands. Technology for electrically powered vehicles is a step in the right direction. One such environmentally friendly vehicle that aids employees in covering large distances inside of their organisations is the monowheel. A monowheel is a single-track, one wheeled vehicle that looks a lot like a unicycle. The rider sits inside the wheel as opposed to being above it like on a unicycle. The wheel is a ring that is often propelled by smaller wheels contacting its inner rim. The smaller wheels are powered by an electric motor and a battery to turn. Changes to the frame's design and the addition of solar panels as a backup power source are proposed. Then, the car can also be powered by solar energy. Software from CATIA and ANSYS, respectively, are used for the design and analysis of the inner and exterior fames.

This study focuses on the preparation of Al-based hybrid composites using AA7475 as the main alloy reinforced with two materials, ZrO2 and SiC. The combination of stir-squeeze processing techniques was employed to create various specimens by varying four parameters: Stir-speed, Stir-time, reinforcements, and squeeze pressure. Taguchi design was utilized to generate specimens for analyzing their mechanical properties, specifically tensile strength, hardness, and porosity.The results indicated that the highest porosity (4.44%) was observed in the L16 test, with a combination of 700rpm stir speed, 25 mins stir time, 2wt% reinforcements, and 80MPa squeeze pressure. On the other hand, the lowest porosity (2.61%) was found in the L7 test, with 800rpm stir speed, 30 mins stir time, 2wt% reinforcements, and 100 MPa squeeze pressure.Regarding tensile strength (UTS), the maximum value (285.23MPa) was achieved in the L13 experiment, while the minimum value (187.58 MPa) was observed in the L1 experiment. This variation in UTS can be attributed to the applied load, the strengthening effect of the reinforcements, and the grain size of SiC.

Background The normal ability to distinguish two points from one is known as the two-point discriminative (2PD) sense. This forms an extremely important assessment in patient with injuries to the nerves distributed to the upper extremity. Objective The aim of this study was to estimate the normal reference values of static 2PD in healthy adults and children. Materials and Methods A total of 624 normal adults comprising 380 men and 244 women were recruited randomly for the study at three different centers. Additionally, 172 healthy children, comprising 110 boys and 62 girls, were studied. Eight sensory areas in the palmar surface of the hand were delineated. The ability to distinguish the static 2PD was estimated in millimeters by using disk discriminator. The results were tabulated and statistically analyzed. Results The mean static 2PD in the adult population ranged from 2.78 to 3.5 mm in the fingertips and 5.39 to 7.13 mm in the mid-palm. There was a statistically significant difference between men and women in zones 6, 7, and 8. In children, the observed 2PD values were 2.15 to 3.63 mm in the fingertips and 4.10 to 5.77 mm in the palm. Children have a significantly better 2PD sense when compared with adults. Conclusion The normal value of static 2PD in the palmar surface of the hand among the Indian pediatric and adult populations was established in the study. [ABSTRACT FROM AUTHOR]

Strong crosswinds can cause catastrophic accidents like overturning and derailment in extreme circumstances, therefore the train's capacity to tolerate their impacts is crucial. Despite the significance of this issue, there exists a notable research gap in understanding the specific effects of various positions of a high-speed train within a tunnel on its aerodynamic loads and flow structure under different crosswind conditions. To address this gap, numerical simulations were performed using computational fluid dynamics. The crosswind angles (Ψ) were 15°, 30°, 45°, and 60° and the number of coaches exiting the tunnel was one to three coaches, respectively. The incompressible flow around the train was simulated using the Unsteady Reynolds-Averaged NavierStokes (URANS) equations in conjunction with the k-epsilon (k-ε) turbulence model. The Reynolds number employed in the simulation was 1.3 x 106, calculated based on the height of the train and the freestream velocity. With regard to aerodynamic performance due to the crosswind, force coefficients such as drag, side, and lift and moment coefficients of rolling, pitching, and yawing were measured. The higher crosswind angles including ψ = 45° and ψ = 60° cases produced the worse results of aerodynamic load coefficients compared to the lower crosswind angles of ψ = 15° and ψ = 30°. For instance, the highest side force coefficient (Cs) was recorded at a crosswind angle of ψ = 45°, with a value of 23.6. Meanwhile, the flow structure revealed that the leading coach of the train experienced intricate flow patterns during crosswinds, characterized by vortices and flow separation. These findings indicate that aerodynamic instabilities can potentially affect the overall performance of the train. Additionally, this increases the risk of derailment or overturning to be high, particularly when the majority of coaches are exiting the tunnel under strong crosswind conditions. [ABSTRACT FROM AUTHOR]

Abstract In this study, a landslide susceptibility assessment is performed by combining two machine learning regression algorithms (MLRA), such as support vector regression (SVR) and categorical boosting (CatBoost), with two population-based optimization algorithms, such as grey wolf optimizer (GWO) and particle swarm optimization (PSO), to evaluate the potential of a relatively new algorithm and the impact that optimization algorithms can have on the performance of regression models. The Kerala state in India has been chosen as the test site due to the large number of recorded incidents in the recent past. The study started with 18 potential predisposing factors, which were reduced to 14 after a multi-approach feature selection technique. Six susceptibility models were implemented and compared using the machine learning algorithms alone and combining each of them with the two optimization algorithms: SVR, CatBoost, SVR-PSO, CatBoost-PSO, SVR-GWO, and CatBoost-GWO. The resulting maps were validated with an independent dataset. The performance rankings, based on the area under the receiver operating characteristic curve (AUC) metric, are as follows: CatBoost-GWO (AUC = 0.910) had the highest performance, followed by CatBoost-PSO (AUC = 0.909), CatBoost (AUC = 0.899), SVR-GWO (AUC = 0.868), SVR-PSO (AUC = 0.858), and SVR (AUC = 0.840). Other validation statistics corroborated these outcomes, and the Friedman and Wilcoxon-signed rank tests verified the statistical significance of the models. Our case study showed that CatBoost outperformed SVR both in case the models were optimized or not; the introduction of optimization algorithms significantly improves the results of machine learning models, with GWO being slightly more effective than PSO. However, optimization cannot drastically alter the results of the model, highlighting the importance of setting up of a rigorous susceptibility model since the early steps of any research.

Abstract EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 fusion proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks and target genes. We show that EWS-WT1 is a powerful chromatin activator controlling an oncogenic gene expression program that characterizes primary tumors. Similar to wild type WT1, EWS-WT1 has two isoforms that differ in their DNA binding domain and we find that they have distinct DNA binding profiles and are both required to generate viable tumors that resemble primary DSRCT. Finally, we identify candidate EWS-WT1 target genes with potential therapeutic implications, including CCND1, whose inhibition by the clinically-approved drug Palbociclib leads to marked tumor burden decrease in DSRCT PDXs in vivo. Taken together, our studies identify gene regulation programs and therapeutic vulnerabilities in DSRCT and provide a mechanistic understanding of the complex oncogenic activity of EWS-WT1.

Benign gastric epithelial lesions, known as gastric hyperplastic polyps, include concomitant inflammatory alterations and elongated or convoluted foveolae and cystically dilated glands. It is believed that polypoid foveolar hyperplasia, a regenerative lesion associated with both acute and chronic mucosal damage, as well as, chronic gastritis, may serve as a precursor to gastric hyperplastic polyps. In the presented case, a 64-year-old female with a history of Helicobacter pylori (H. pylori)-associated chronic gastritis complained of abdominal pain, heartburn and regurgitation for one year. During endoscopy, three polyps were identified, one at the gastroesophageal junction, another below the gastroesophageal junction, and a third at the distal body of the stomach, of which only two polyps were sent for HPE. Gross inspection revealed that both soft-tissue masses were globular, with the cut-section of the polyp from the stomach’s distal body showing haemorrhagic areas. Under the microscope, the polyp from the stomach’s distal body revealed hyperplastic foveolar epithelium that was distorted, branching, elongated and dilated, situated in an oedematous, inflammatory stroma. The polyp just below the gastroesophageal junction displayed characteristics of polypoid foveolar hyperplasia, including elongated pits devoid of dilation features. The final diagnosis for the polyp from the distal body of the stomach was gastric hyperplastic polyp, and the polyp from just below the gastroesophageal junction was diagnosed as polypoid foveolar hyperplasia. Malignant transformation affects hyperplastic polyps, but foveolar polypoid hyperplasia remains unaffected, underscoring the importance of careful and diligent examination to distinguish between the two conditions.

The potential for waste management can be enhanced by the recovery and utilisation of waste biomass. In this work, we used analytical n-hexane to chemically extract sandbox oil, and we followed it up with a single transesterification step to turn it into biodiesel. Diesel and biodiesel were mixed to make five fuel samples (diesel, B20, B40, B50, and B100). These fuel samples were then burned in a compression ignition engine test bed to assess their performance and ascertain their emission characteristics. The test fuels yielded 5.2 kW of rated power from an unmodified single-cylinder diesel engine. It has been found that combustion–ignition engines can effectively use sandbox biodiesel as a biofuel. Pollution is also decreased by burning biofuels. As to the test findings, B20 (20% biodiesel and 80% diesel) outperformed other automobiles with respect to high cylinder pressure and heat release rate, reducing hydrocarbon, carbon monoxide, and smoke emissions by 12.5%, 35.5%, and 38.5%, respectively. The results so far are similar to diesel.

Two Pyranopyrazole derivatives, namely, methyl-11-(2-chlorophenyl)-16-methyl-8-[(4-methylbenzene)sulfonyl], -14-phenyl-12-oxa-8,14,15-triazatetracyclo[8.7.0.02,7.013,17] heptadeca-2(7), 3, 5, 13(17), 15-pentaene-10-carboxylate, C38H37N3S1O5 and butyl‑16-methyl-8-[(4-methylbenzene)sulfonyl]-11,14-diphenyl-12-oxa-8,14,15-triazatetracyclo[8.7.0.02,7.013,17] heptadeca-2(7),3,5, 13(17), 15-pentaene-10-carboxylate, C35 H30 Cl N3 O5 S with phenyl and chlorophenyl substitutions were synthesized successfully, and crystallized by the slow evaporation technique. The pyranopyrazole derivatives were characterized by spectroscopic techniques including UV–visible, FTIR, and mass spectroscopy, and their 3D-structural arrangements were also confirmed by single crystal XRD studies. Both compounds crystallize in the triclinic crystal system with the centrosymmetric space group P-1, which is identified by the X-ray single-crystal structure. These compounds were examined for in vitro and molecular docking studies with the enzymes 1hny, 1pgg, and 4 cox and thus correspond to diabetes and inflammation. The observed results showed better binding energy and inhibition constants for inflammation involving enzymes. The chemical reactivity and electronic arrangement of the compounds have been revealed by DFT studies.

The most frequently used sulfonamide is sulfamethazine (SMZ) because it is often found in foods made from livestock, which is hazardous for individuals. Here, we have developed an easy, quick, selective, and sensitive analytical technique to efficiently detect SMZ. Recently, transition metal oxides have attracted many researchers for their excellent performance as a promising sensor for SMZ analysis because of their superior redox activity, electrocatalytic activity, electroactive sites, and electron transfer properties. Further, Cu-based oxides have a resilient electrical conductivity; however, to boost it to an extreme extent, a composite including two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanosheets needs to be constructed and ready as a composite (denoted as g-C3N4/Cu2Y2O5). Moreover, several techniques, including X-ray diffraction analysis, scanning electron microscopy analysis, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy were employed to analyze the composites. The electrochemical measurements have revealed that the constructed g-C3N4/Cu2Y2O5 composites exhibit great electrochemical activity. Nevertheless, the sensor achieved outstanding repeatability and reproducibility alongside a low limit of detection (LOD) of 0.23 µM, a long linear range of 2 to 276 µM, and an electrode sensitivity of 8.86 µA µM−1 cm−2. Finally, the proposed GCE/g-C3N4/Cu2Y2O5 electrode proved highly effective for detection of SMZ in food samples, with acceptable recoveries. The GCE/g-C3N4/Cu2Y2O5 electrode has been successfully applied to SMZ detection in food and water samples.

Flooding is a recurrent hazard occurring worldwide, resulting in severe losses. The preparation of a flood susceptibility map is a non-structural approach to flood management before its occurrence. With recent advances in artificial intelligence, achieving a high-accuracy model for flood susceptibility mapping (FSM) is challenging. Therefore, in this study, various artificial intelligence approaches have been utilized to achieve optimal accuracy in flood susceptibility modeling to address this challenge. By incorporating the grey wolf optimizer (GWO) metaheuristic algorithm into various models—including recurrent neural networks (RNNs), support vector regression (SVR), and extreme gradient boosting (XGBoost)—the objective of this modeling is to generate flood susceptibility maps and evaluate the variation in model performance. The tropical Manimala River Basin in India, severely battered by flooding in the past, has been selected as the test site. This modeling utilized 15 conditioning factors such as aspect, enhanced built-up and bareness index (EBBI), slope, elevation, geomorphology, normalized difference water index (NDWI), plan curvature, profile curvature, soil adjusted vegetation index (SAVI), stream density, soil texture, stream power index (SPI), terrain ruggedness index (TRI), land use/land cover (LULC) and topographic wetness index (TWI). Thus, six susceptibility maps are produced by applying the RNN, SVR, XGBoost, RNN-GWO, SVR-GWO, and XGBoost-GWO models. All six models exhibited outstanding (AUC above 0.90) performance, and the performance ranks in the following order: RNN-GWO (AUC: 0.968) > XGBoost-GWO (AUC: 0.961) > SVR-GWO (AUC: 0.960) > RNN (AUC: 0.956) > XGBoost (AUC: 0.953) > SVR (AUC: 0.948). It was discovered that the hybrid GWO optimization algorithm improved the performance of three models. The RNN-GWO-based flood susceptibility map shows that 8.05% of the MRB is very susceptible to floods. The modeling found that the SPI, geomorphology, LULC, stream density, and TWI are the top five influential conditioning factors.

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels. This research endeavors to identify promising inhibitory candidates that target the allosteric site of PCSK9 through an in silico approach. To start with, the FDA-approved Drug Library from Selleckchem was selected and virtually screened by docking studies using Glide extra-precision (XP) docking mode and Smina software (Version 1.1.2). Subsequently, rescoring of 100 drug compounds showing good average docking scores were performed using Gnina software (Version 1.0) to generate CNN Score and CNN binding affinity. Among the drug compounds, amikacin, bestatin, and natamycin were found to exhibit higher docking scores and CNN affinities against the PCSK9 enzyme. Molecular dynamics simulations further confirmed that these drug molecules established the stable protein–ligand complexes when compared to the apo structure of PCSK9 and the complex with the co-crystallized ligand structure. Moreover, the MM-GBSA calculations revealed binding free energy values ranging from −84.22 to −76.39 kcal/mol, which were found comparable to those obtained for the co-crystallized ligand structure. In conclusion, these identified drug molecules have the potential to serve as inhibitors PCSK9 enzyme and these finding could pave the way for the development of new PCSK9 inhibitory drugs in future in vitro research.

Regulatory T cells (Treg) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity toward CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wild-type mice and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity., (©2024 American Association for Cancer Research.)

Research Question: What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis?, Design: Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models., Results: Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers., Conclusion: The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

An effective approach to producing sophisticated miniaturized and nanoscale materials involves arranging nanomaterials into layered hierarchical frameworks. Nanostructured layered materials are constructed to possess isolated propagation assets, massive surface areas, and envisioned amenities, making them suitable for a variety of established and novel applications. The utilization of various techniques to create nanostructures adorned with metal nanoparticles provides a secure alternative or reinforcement for the existing physicochemical methods. Supported metal nanoparticles are preferred due to their ease of recovery and usage. Researchers have extensively studied the catalytic properties of noble metal nanoparticles using various selective oxidation and hydrogenation procedures. Despite the numerous advantages of metal-based nanoparticles (NPs), their catalytic potential remains incompletely explored. This article examines metal-based nanomaterials that are supported by layers, and provides an analysis of their manufacturing, procedures, and synthesis. This study incorporates both 2D and 3D layered nanomaterials because of their distinctive layered architectures. This review focuses on the most common metal-supported nanocomposites and methodologies used for photocatalytic degradation of organic dyes employing layered nanomaterials. The comprehensive examination of biological and ecological cleaning and treatment techniques discussed in this article has paved the way for the exploration of cutting-edge technologies that can contribute to the establishment of a sustainable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these interactions with tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow to identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed to recapitulate genes and proteins, some borrowed and others tumor-intrinsic, induced in cancer cells by direct contact. Protein-protein interaction networks revealed the rich connectome between 'borrowed' and 'intrinsic' components. Bioinformatics prioritized one of the 'borrowed' components, CCDC88A/GIV, a multi-modular metastasis-related protein that has recently been implicated in driving a hallmark of cancer, growth signaling autonomy. MSCs transferred GIV protein to ER+ breast cancer cells (that lack GIV) through tunnelling nanotubes via connexin (Cx)43-facilitated intercellular transport. Reinstating GIV alone in GIV-negative breast cancer cells reproduced approximately 20% of both the 'borrowed' and the 'intrinsic' gene induction patterns from contact co-cultures; conferred resistance to anti-estrogen drugs; and enhanced tumor dissemination. Findings provide a multiomic insight into MSC→tumor cell intercellular transport and validate how transport of one such candidate, GIV, from the haves (MSCs) to have-nots (ER+ breast cancer) orchestrates aggressive disease states.

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR. In patient OC databases, high ZNFX1 expression levels correlate with advanced stage disease. ZNFX1 expression alone significantly correlates with an increase in overall survival in a phase 3 trial for therapy-resistant OC patients receiving bevacizumab in combination with chemotherapy. In correlative RNA-seq data, inflammasome signaling through ZNFX1 correlates with abnormal vasculogenesis. ZNFX1 controls PMR signaling through the mitochondria and may serve as a biomarker to facilitate offering personalized therapy in OC patients, highlighting the strong translational significance of our findings., Significance Statement: DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors upregulate expression of a novel nucleic-acid sensor, ZNFX1 that serves as a mitochondrial gateway to STING-dependent interferon/inflammasome signaling with tumor suppressor properties in ovarian cancer.

Skin is an important vital organ that must be given proper care and protection from external damage and harmful microbes. If injured, it must be treated with an ideal wound dressing material with potent hemostatic and non-toxic properties. In the present study, fish collagen (FC) was extracted from the fins and tails of Black pomfret (Parastromateus niger). The isolated fish collagen was homogenized with pectin (P) and freeze dried to obtain fish collagen/pectin (FC/P) scaffolds. Scanning electron microscopic analysis showed the porous nature of scaffolds with intermittent holes. UV-Visible and Fourier infrared spectroscopic analyses demonstrated the physicochemical properties of FC/P scaffolds. Hemolytic assay performed using human blood demonstrated the percentage of hemolysis as 0.5 %. In vitro blood clotting assay carried out to determine the hemostatic behaviour displayed the formation of blood clot within 60 s in the presence of FC/P scaffolds. 95 % of cells were viable with the highest concentration of FC/P scaffold used for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Scratch wound assay demonstrated complete closure of wound in FC/P scaffold treated cells after 48 h of treatment. Chick embryo chorioallantoic membrane (CAM) assay showed the development of new blood vessels within 6 h of incubation with the FC/P scaffolds, thereby proving their angiogenic potency. These results indicate the potential use of FC/P scaffolds as effective biomaterials for tissue regenerative applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This research investigates the manufacturing and characterisation of polyester-based composites reinforced with jute fibres and red mud particulates. The motivation stems from the need for sustainable, high-performance materials for applications in industries, like aerospace and automotive, where resistance to erosion is critical. Jute, a renewable fibre, combined with red mud, an industrial byproduct, offers an eco-friendly alternative to conventional composites. The composites were fabricated using compression moulding with varying red mud contents (10, 20, and 30 wt.%) and a fixed 40 wt.% of jute fibre. Fibre treatments included sodium hydroxide (NaOH) and silane treatments to improve bonding and performance. Erosion tests were performed using an air-jet erosion tester, examining the effects of the red mud content, fibre treatment, and impact angles. Scanning Electron Microscope (SEM) analysis provided insights into the erosion mechanisms. A distinctive reduction in erosion rates at higher impact angles (30°-60°) was observed, attributed to the semi-ductile nature of the composites. The addition of red mud enhanced erosion resistance, although an excess of 30 wt.% reduced resistance due to poor surface bonding. Silane-treated composites showed the lowest erosion rates. This study provides new insights into the interplay among material composition, fibre treatment, and erosion dynamics, contributing to the development of optimised, eco-friendly composite materials.

Objective: There is significant practice variation in the use of antithrombotic therapy after endovascular intervention for lower limb peripheral arterial disease, with differences in medication choice and duration. Prescriber decision making is complex, and patient factors have been shown to substantially contribute to prescribing variation. To determine the influence of patient factors on antithrombotic prescribing, a discrete choice experiment was distributed to vascular surgeons and trainees across Australia and Aotearoa New Zealand., Methods: After pilot testing, the discrete choice experiment questionnaire was distributed to 300 vascular surgeons and trainee members of the Australian and New Zealand Society for Vascular Surgery. Multinomial logistic regression models were used to analyse patient factors that had the most influence on decisions to prescribe a second antithrombotic agent, and the preferred choice of antithrombotic (clopidogrel 75 mg daily or rivaroxaban 2.5 mg twice daily) in addition to aspirin 100 mg daily. The odds ratio (OR) with 95% confidence interval (CI) reported preference strength., Results: A total of 44 questionnaires were completed between September and October 2023, reaching the 15% targeted response rate. Prescribing a second antithrombotic was more likely after femoropopliteal stenting compared with angioplasty (OR 1.89, 95% CI 1.20 - 2.13), and in chronic limb threatening ischaemia compared with intermittent claudication (OR 1.58, 95% CI 1.20 - 2.13). Most respondents preferred clopidogrel over rivaroxaban (62%), with over a third of respondents exclusively prescribing clopidogrel. Patients with stents (OR 1.77, 95% CI 1.32 - 2.37) or moderate bleeding risk (OR 1.38, 95% CI 0.97 - 1.84) were more likely to receive clopidogrel than rivaroxaban., Conclusion: This study demonstrates that vascular surgeons primarily prioritise antithrombotic prescribing decisions by procedure type. Clopidogrel is more likely to be prescribed than rivaroxaban as a second agent in combination with aspirin, especially after stenting. Knowing these clinician preferences can target implementation strategies towards supporting decision making in subgroups of patients according to individual risk profiles., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

For several decades, products derived from marine natural sources (PMN) have been widely identified for several therapeutic applications due to their rich sources of bioactive sub-stances, unique chemical diversity, biocompatibility and excellent biological activity. For the past 15 years, our research team explored several PMNs, especially fungi fibrinolytic compounds (FGFCs). FGFC is an isoindolone alkaloid derived from marine fungi, also known as staplabin analogs or Stachybotrys microspora triprenyl phenol (SMTP). For instance, our previous studies explored different types of FGFCs such as FGFC 1, 2, 3 and 4 from the marine fungi Stachybotrys longispora FG216 derived metabolites. The derivatives of FGFC are potentially employed in several disease treatments, mainly for stroke, cancer, ischemia, acute kidney injury, inflammation, cerebral infarction, thrombolysis and hemorrhagic activities, etc. Due to the increasing use of FGFCs in pharmaceutical and biomedical applications, it is important to understand the fundamental signaling concept of FGFCs. Hence, for the first time, this review collectively summarizes the background, types, mode of action and biological applications of FGFCs and their current endeavors for future therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeevithan, Diao, Hu, Elango, Wu, Mate Sanchez de Val, Rajendran, Sundaram and Rajamani Sekar.)

Assessing fertilized human embryos is crucial for in vitro fertilization, a task being revolutionized by artificial intelligence. Existing models used for embryo quality assessment and ploidy detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we develop and compare various embryo ploidy status prediction models across distinct embryo development stages. We present BELA, a state-of-the-art ploidy prediction model that surpasses previous image- and video-based models without necessitating input from embryologists. BELA uses multitask learning to predict quality scores that are thereafter used to predict ploidy status. By achieving an area under the receiver operating characteristic curve of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists' manual scores. While not a replacement for preimplantation genetic testing for aneuploidy, BELA exemplifies how such models can streamline the embryo evaluation process., (© 2024. The Author(s).)

Context: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined., Objective: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities., Methods: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023., Results: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04)., Conclusion: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes., (© 2024 John Wiley & Sons Ltd.)

Background: Low-dose colchicine reduces the risk of cardiovascular events after myocardial infarction (MI). The purpose of this study was to assess the effect of colchicine post-MI on coronary plaque morphology in non-culprit segments by optical coherence tomography (OCT)., Methods and Results: COCOMO-ACS was a double-blind, placebo-controlled trial that randomized 64 patients (median age 61.5 years; 9.4% female) with acute non-ST-segment elevation MI to colchicine 0.5 mg daily or placebo for a median of 17.8 months in addition to guideline-recommended therapy. Participants underwent serial OCT imaging within a matched segment of non-culprit coronary artery which contained at least one lipid-rich plaque causing ≥20% stenosis. The primary outcome was the change in minimum fibrous cap thickness (FCT) in non-culprit segments from baseline to final visit. Of those randomized, 57 (29 placebo, 28 colchicine) had evaluable imaging at baseline and follow-up. Overall, colchicine had no effect on relative (placebo +48.0±35.1% vs. colchicine +62.4±38.1%, P=0.18) or absolute changes in minimum FCT (+29.2±20.9 µm vs. +37.2±21.3 µm, P=0.18), or change in maximum lipid arc (-38.8±32.2° vs. -54.8±46.9°, P=0.18) throughout the imaged non-culprit segment. However, in patients assigned colchicine, cap rupture was less frequent (placebo 27.6% vs. colchicine 3.6%, P=0.03). In post-hoc analysis of 43 participants who had been followed for at least 16 months, minimum FCT increased to a greater extent in the colchicine group (placebo +38.7±25.4% vs. colchicine +64.7±34.1%, P=0.005)., Conclusion: In this study, OCT failed to detect an effect of colchicine on the minimum FCT or maximum lipid arc of plaques in non-culprit segments post-MI. The post-hoc observation that minimum FCT increased to a greater extent with colchicine after more prolonged treatment suggests longer-term studies may be required to detect the effect of anti-inflammatory therapies on plaque morphology by OCT., Trial Registration: Australian New Zealand Clinical Trials Registry Identifier, ACTRN12618000809235, registered on the 11th of May 2018., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The second most common type of malignant tumor worldwide is colorectal cancer. Histopathology image analysis offers crucial data for the clinical diagnosis of colorectal cancer. Currently, deep learning techniques are applied to enhance cancer classification and tumor localization in histopathological image analysis. Moreover, traditional deep learning techniques might loss integrated information in the image while evaluating thousands of patches recovered from whole slide images (WSIs). This research proposes a novel colorectal cancer detection network (CCDNet) that combines coordinate attention transformer with atrous convolution. CCDNet first denoises the input histopathological image using a Wiener based Midpoint weighted non-local means filter (WMW-NLM) for guaranteeing precise diagnoses and maintain image features. Also, a novel atrous convolution with coordinate attention transformer (AConvCAT) is introduced, which successfully combines the advantages of two networks to classify colorectal tissue at various scales by capturing local and global information. Further, coordinate attention model is integrated with a Cross-shaped window (CrSWin) transformer for capturing tiny changes in colorectal tissue from multiple angles. The proposed CCDNet achieved accuracy rates of 98.61% and 98.96%, on the colorectal histological image and NCT-CRC-HE-100 K datasets correspondingly. The comparison analysis demonstrates that the suggested framework performed better than the most advanced methods already in use. In hospitals, clinicians can use the proposed CCDNet to verify the diagnosis., (© 2024. The Author(s).)

High-grade gliomas (HGGs) and glioblastomas (GBMs) are the most aggressive and lethal brain tumors. The current standard of care (SOC) includes gross safe surgical resection followed by chemoradiotherapy. The main chemotherapeutic agents are the DNA-alkylating agent temozolomide (TMZ) and adjuvants. Due to the outdated therapeutic protocols and lack of specific treatments, there is an urgent and rising need to improve our understanding of tumor biology and design more effective therapeutic strategies. In vitro models are essential for investigating glioma biology and testing novel therapeutic approaches. While using commercially available and patient-derived glioma cell lines for in vitro studies is common practice, they exhibit several limitations, including failing to maintain the genetic and phenotypic diversity of primary tumors, undergo genetic drift over time, and often lacking the invasive and stem-like characteristics of patient tumors. These limitations can lead to inconsistent and non-reproducible results, hampering translational research progress. In this study, we established a novel primary murine HGG cell line, isolated from an immunocompetent HGG-bearing RCAS/T-va mouse. We characterized the transcriptome and phenotype to ensure that this cell line resembles the nature of HGGs and retains the ability to reprogram primary murine T lymphocytes., Competing Interests: P.R. and K.C. are associate editors of Molecular Therapy Oncology., (© 2024 The Author(s).)

Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Bacterial fermentation is considered to be a cost-effective means of generating desired flavour compounds from plant-based substrates. However, the wide range of substrates present in plants makes it challenging to understand how individual components impact on flavour volatile organic compound (VOC) production. To simplify this, a defined medium can be used to better understand VOCs production with regard to individual compounds. In the current study, the VOCs produced by the lactic acid bacterium, Levilactobacillus brevis WLP672, growing in a defined medium containing different carbon sources (either glucose (DM), fructose (DMFr) or citrate (DMCi)) under a range of fermentation conditions (time: 0, 7, and 14 days; and temperature: 25 and 35 °C) were assessed using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). Among the detected mass peaks ( m / z ), after 7 days of fermentation, the concentrations of m / z 45.033 (t.i. acetaldehyde), m / z 49.011 (t.i. methanethiol), and m / z 89.060 (t.i. ethyl acetate) were significantly ( p < 0.05) higher in DM at 35 °C than all other treatments at either temperature. The knowledge obtained will help to produce desirable LAB fermentation flavour VOCs or VOC mixtures that could be used in developing plant-based analogues with acceptable sensory properties.

Myxobacteria are predatory bacteria with antimicrobial activity, utilizing complex mechanisms to kill their prey and assimilate their macromolecules. Having large genomes encoding hundreds of secondary metabolites, hydrolytic enzymes and antimicrobial peptides, these organisms are widely studied for their antibiotic potential. MyxoPortal is a comprehensive genomic database hosting 262 genomes of myxobacterial strains. Datasets included provide genome annotations with gene locations, functions, amino acids and nucleotide sequences, allowing analysis of evolutionary and taxonomical relationships between strains and genes. Biosynthetic gene clusters are identified by AntiSMASH, and dbAMP-generated antimicrobial peptide sequences are included as a resource for novel antimicrobial discoveries, while curated datasets of CRISPR/Cas genes, regulatory protein sequences, and phage associated genes give useful insights into each strain's biological properties. MyxoPortal is an intuitive open-source database that brings together application-oriented genomic features that can be used in taxonomy, evolution, predation and antimicrobial research. MyxoPortal can be accessed at http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Database URL:  http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Graphical Abstract., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: To investigate how the shift of the United States Medical Licensing Examination (USMLE) Step 1 to a Pass/Fail (P/F) scoring system impacts the perceptions of Urology Program Directors (PDs) on evaluating urology residency applicants., Methods and Materials: A cross-sectional survey was sent to 117 PDs, including questions about program characteristics, perceptions of shelf scores and medical school rank post-transition, beliefs about the predictive value of Step 1 and Step 2 Clinical Knowledge (CK) scores for board success and residency performance, and changes in applicant parameter ranking., Results: Forty-five PDs (38% response rate) participated. Notably, 49% favored releasing quantitative clerkship grades, and 71% valued medical school rank more. Opinions on Step 1 scores' correlation with board success were split (49% agreed), and 44% endorsed Step 2 CK scores' connection to board performance. As predictors of good residents, only 9% and 22% considered Step 1 and Step 2 CK scores, respectively, indicative. Clerkship grades and Urology rotation recommendation letters maintained significance, while research experience gained importance. Step 2 CK scores' importance rose but did not match Step 1 scores' previous significance., Conclusion: The transition to P/F for USMLE Step 1 adds intricacies to urology residency selection, exposing PDs' uncertainties regarding clerkship grades and the relevance of medical school rank. This research underscores the dynamic nature of urology residency admissions, emphasizing the increasing importance of research in evaluating applicants and a diminishing emphasis on volunteering and leadership., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate bone char's physicochemical transformations through co-torrefaction and co-pyrolysis processes with biomass. Additionally, it aimed to analyze the carbon sequestration process during co-torrefaction of bone and biomass and optimize the process parameters of co-torrefaction. Finally, the study sought to evaluate the arsenic sorption capacity of both torrefied and co-torrefied bone char. Bone and biomass co-torrefaction was conducted at 175 °C-300 °C. An orthogonal array of Taguchi techniques and artificial neural networks (ANN) were employed to investigate the influence of various torrefaction parameters on carbon dioxide sequestration within torrefied bone char. A co-torrefied bone char, torrefied at a reaction temperature of 300 °C, a heating rate of 15 °C·min -1 , and mixed with 5 g m of biomass (wood dust), was selected for the arsenic (III) sorption experiment due to its elevated carbonate content. The results revealed a higher carbonate fraction (21%) in co-torrefied bone char at 300 °C compared to co-pyrolyzed bone char (500-700 °C). Taguchi and artificial neural network (ANN) analyses indicated that the relative impact of process factors on carbonate substitution in bone char followed the order of co-torrefaction temperature (38.8%) > heating rate (31.06%) > addition of wood biomass (30.1%). Co-torrefied bone chars at 300 °C exhibited a sorption capacity of approximately 3 mg g -1 , surpassing values observed for pyrolyzed bone chars at 900 °C in the literature. The findings suggest that co-torrefied bone char could serve effectively as a sorbent in filters for wastewater treatment and potentially fulfill roles such as a remediation agent, pH stabilizer, or valuable source of biofertilizer in agricultural applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A previously elusive organocatalytic protocol for the esterification of amides is disclosed. DABCO (10 mol%) is identified as an effective catalyst for the esterification of N -pivaloyl amides. Although N -pivaloyl amides are nearly planar (amide bond twist ( τ ) = 4.54° and pyramidalization ( χ N = 6.39°)) and resonance stabilized, esterification is achieved with high efficiency. The developed protocol is generic, phenols, thiophenols, aliphatic alcohols, and thiols were identified as effective substrates. Furthermore, the reaction features a broad substrate scope and excellent functional group tolerance. To exemplify the practical applicability of the developed protocol, the esterification of bioactive natural products, pterostilbene and menthol, is demonstrated. In addition, a series of competitive experiments were conducted to establish the reactivity pattern of alcohols, thiols, and phenols, which could serve as selectivity principles for future synthetic design. Our findings signify a notable advancement in utilizing amides as versatile synthetic building blocks in organic synthesis under metal-free conditions.

Sugarcane (Saccharum officinarum) is an important crop, native to tropical and subtropical regions and it is a major source of sugar and Bioenergy in the world. Abiotic stress is defined as environmental conditions that reduce growth and yield below the optimum level. To tolerate these abiotic stresses, plants initiate several molecular, cellular, and physiological changes. These responses to abiotic stresses are dynamic and complex; they may be reversible or irreversible. Waterlogging is an abiotic stress phenomenon that drastically reduces the growth and survival of sugarcane, which leads to a 15-45% reduction in cane's yield. The extent of damage due to waterlogging depends on genotypes, environmental conditions, stage of development and duration of stress. An improved understanding of the physiological, biochemical, and molecular responses of sugarcane to waterlogging stress could help to develop new breeding strategies to sustain high yields against this situation. The present review offers a summary of recent findings on the adaptation of sugarcane to waterlogging stress in terms of growth and development, yield and quality, as well as biochemical and adaptive-molecular processes that may contribute to flooding tolerance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: Update on the most recent clinical evidence on CDK4/6 inhibitors (CDK4/6i) in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer., Recent Findings: Over the past decade, CDK4/6i have become part of the standard of care treatment of patients with both metastatic and high-risk early HR + /HER2- breast cancers. The three available CDK4/6i (palbociclib, ribociclib and abemaciclib) have been extensively studied in combination with endocrine therapy (ET) in metastatic breast cancer (mBC) with consistent prolongation of progression free survival; however, ribociclib has emerged as the preferred first line agent in mBC given overall survival benefit over endocrine monotherapy. In early BC, abemaciclib is the only currently approved agent while ribociclib has early positive clinical trial data. Toxicities and financial burden limit the use of CDK4/6i in all patients and resource-poor settings, and optimal timing of their use in mBC remains unclear. There is considerable evidence for the use of CDK4/6i in metastatic and early HR + /HER2- breast cancer, but knowledge gaps remain, and further research is necessary to better define their optimal use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)