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.

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

Purpose: This study investigates the impact of different intensity normalization (IN) methods on the overall survival (OS) radiomics models’ performance of MR sequences in primary (pHGG) and recurrent high-grade glioma (rHGG). Methods: MR scans acquired before radiotherapy were retrieved from two independent cohorts (rHGG C1: 197, pHGG C2: 141) from multiple scanners (15, 14). The sequences are T1 weighted (w), contrast-enhanced T1w (T1wce), T2w, and T2w-FLAIR. Sequence-specific significant features (SF) associated with OS, extracted from the tumour volume, were derived after applying 15 different IN methods. Survival analyses were conducted using Cox proportional hazard (CPH) and Poisson regression (POI) models. A ranking score was assigned based on the 10-fold cross-validated (CV) concordance index (C-I), mean square error (MSE), and the Akaike information criterion (AICs), to evaluate the methods’ performance. Results: Scatter plots of the 10-CV C-I and MSE against the AIC showed an impact on the survival predictions between the IN methods and MR sequences (C1/C2 C-I range: 0.62-0.71/0.61-0.72, MSE range: 0.20-0.42/0.13-0.22). White stripe showed stable results for T1wce (C1/C2 C-I: 0.71/0.65, MSE: 0.21/0.14). Combat (0.68/0.62, 0.22/0.15) and histogram matching (HM, 0.67/0.64, 0.22/0.15) showed consistent prediction results for T2w models. They were also the top-performing methods for T1w in C2 (Combat: 0.67, 0.13; HM: 0.67, 0.13), however, only HM achieved high predictions in C1 (0.66, 0.22). After eliminating IN impacted SF using Spearman’s rank-order correlation coefficient, a mean decrease in the C-I and MSE of 0.05 and 0.03 was observed in all four sequences. Conclusion: The IN method impacted the predictive power of survival models. Thus, performance is sequence-dependent.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Glioma accounts for 80% of all malignant brain tumors and is the most common adult primary brain tumor. Age is an important factor affecting the development of cancer as somatic mutations accumulate with age. In this study, we aimed to analyze the significance of age-related non-silent somatic mutations in glioma prognosis. Histological tumor grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wildtype counterpart. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. In conclusion, among the many somatic mutations, those in IDH1, TP53, ATRX, and EGFR are important for glioma classification based on histological grade. Patients with EGFR mutation had the poorest prognosis, whereas those with only IDH1 mutation showed the best prognosis.

A right frontoparietal neoplastic lesion was found in a young-aged patient with analgesic refractory headache. Surgical resection was performed, and the pathologist analysis turned out a cellular ependymoma with signs of anaplasia. In the follow-up, a MRI showed a suspicious lesion, so a [18F]Fluorocholine PET/CT was performed. An increased uptake was described in the right parietal region on the margin of residual cystic lesion. The patient got a complete resection which was confirmed later by MR. In the pathology analysis, a focally congestive cerebral parenchyma with a central histiocytic reaction to foreign body area was described. Foreign body reaction in brain tissue is a very rare immune response that has not been well studied. Haemostatic material has been reported as a possible trigger of this response in other organs and could be detected by [18F]FDG PET/CT. Following the experience of the current case report, [18F]Fluorocholine PET/CT could also show a false positive related to foreign body reaction.

Effects of oxygen content on microstructure and creep property of FGH96 superalloy were investigated. When oxygen content increased from 135ppm to 341ppm, prior particle boundary (PPB) rose from degree 2 to degree 3, and the size of γ′ phase on PPB enlarged from 1.07μm to 1.27μm, and MC carbide size grew from 77.4nm to 104.0nm. Meanwhile, the steady creep rate accelerated form 4.34×10-3 h-1 to 1.87×10-2 h-1, and the creep rupture life shortened from 176h to 94h, and the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twins formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries and its micro-twins cross slipped instead of single direction slip in lower oxygen content superalloy. Consequently, specimen with higher oxygen content creeped faster and raptured earlier.

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study，anoikis-related genes (ANRGs) were used to identify LGG subtypes and to construct a prognostic model for LGG patients. In addition, we explored the immune microenvironment and enrichment pathways between different subtypes. We constructed an anoikis-related gene signature using the TCGA cohort and investigated the differences in clinical features, mutational landscape, immune cell infiltration, etc. between different risk groups. Kaplan-Meier analysis showed that the characteristics of ANRGs in the high-risk group were associated with poor prognosis in LGG patients. The risk score was identified as an independent prognostic factor. The high-risk group had higher immune cell infiltration, tumor mutation load, immune checkpoint gene expression, and ICB treatment response. Functional analysis showed that these high- and low-risk groups had different immune statuses and drug sensitivity. Risk scores were used together with LGG clinicopathological features to construct a nomogram, and DCA analysis showed that the model could enable patients to benefit from clinical treatment strategies.

Patients with low-grade appendiceal mucinous carcinomas (LAMN) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have a favorable prognosis. A subgroup presents a clinically aggressive course with disease progress despite any treatment. The purpose of the study is to report the experience with clinically aggressive LAMN patients treated by the same team and review the literature. Four patients with clinically aggressive LAMN were reviewed. Clinical and histopathological characteristics were re-examined. Recurrences and the time of recurrence, as well as the survival time, were recorded. There were 4 men with clinically aggressive LAMN treated with CRS plus HIPEC. One of them underwent CC-0 surgery, two underwent CC-1, and one CC-3 surgery. All received systemic chemotherapy after surgery. Recurrence was recorded in 3 patients in 4-23 months after initial treatment. Two of them underwent secondary CRS. Three patients died of disease recurrence in 13-23 months, and one is alive with disease relapse 49 months after initial surgery. LAMN was identified in both initial specimens and in specimens of reoperation. The prognosis of LAMN patients treated with CRS plus HIPEC is favorable. A small number of them presents clinically aggressive course unresponsive to any treatment. Molecular and genetic studies are required to identify this group of LAMN patients who have an unfavorable prognosis.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Microscopic vision plays an important role in automated micro-assembly. However, some uncertain factors in the assembly process, such as occlusion and stains can lead to the mistakes of feature extraction. Herein, to solve the problem, the deep learning techniques are introduced into the feature recognition tasks, focusing on the attention mechanism and visualizing CNNs for DL-based microscopic vision. The main contributions are summarized as follows: The CBAM attention mechanism is combined with the YOLOv5 algorithm to improve the accuracy and robustness of feature extraction. The micropart feature occlusion experiment results show that at 70% occlusion degree, YOLOV5-CBAM can reach 97.9% [email protected], which is 4.6% higher than the original one. Visualization analysis of DL-based model is conducted using Grad-CAM to make the decision result more transparent and avoid potential visual detection risks during assembly. The heatmap matching degree between GT area and high-light area is increased by 27.81% on average, which further verify the effectiveness of attention mechanism in micropart feature localization. Additionally, micropart surface stain and droplet quality classification models based on ResNet50 are trained to replace the manual sorting. The visual results are consistent with human eye discernment and judgement, confirming the reliability of parts and droplets sorting.

The Eastern Kunlun Fault Zone (EKFZ) is located in a seismic blank area. This study investigates the hydrogeochemical characteristics of varied-temperature springs in the EKFZ to understand the relationship between fractures, fluids and earthquakes. It aids in establishing their induction mechanisms and assists in monitoring the earthquake precursors of the EKFZ. In this study, the main elements, trace elements, hydrogen and oxygen isotopes and strontium isotopes of 23 varied-temperature springs in the EKFZ were analyzed. The results reveal the source of groundwater recharge, hydrochemical types, mineral saturation, and for a select few springs indicative of geothermal activity, collected geothermal reservoir temperatures. The study also explores the relationship between earthquakes and springs, identifying sensitive chemical indicators. Based on continuous monitoring at Maqu Station, we found that before the occurrence of the Maerkang Ms 6.0 earthquake, the concentration of Cl− rose by 2.9 times, and 46 days before the Gande earthquake (Ms = 4.7), the concentrations of Na+ and SO42− significantly increased. Finally, a conceptual model of the hydrogeochemistry of springs is presented to describe the groundwater circulation in the study area. This research is of great significance for the analysis of fluid geochemistry in this area and for assessing the seismic hazards of the EKFZ.

Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.

The authors attempt to addresses the importance of timely detection and management of cervical intraepithelial neoplasia (CIN) to prevent cervical cancer. The study focuses on the potential of electrical impedance spectroscopy (EIS) as an adjunct to colposcopy, aiming to enhance the accuracy of identifying high-grade cervical lesions. Colposcopy, a widely used technique, exhibits variable sensitivity in detecting high-grade lesions, which relies on the expertise of the operator. The study's primary objective is to evaluate the effectiveness of combining colposcopy with EIS in detecting high-grade cervical lesions among patients initially diagnosed with low-grade CIN based on cytology. We employ a cross-sectional observational design, recruiting 101 women with abnormal cervical cytology results. The participants undergo colposcopy with acetic acid and subsequent EIS using the ZedScan device. The ZedScan results are categorized into color-coded probability levels, with red indicating the highest likelihood of high-grade squamous intraepithelial lesions (HSIL) occurrence. Results reveal that ZedScan exhibits a sensitivity rate of 89.5% and a specificity rate of 84% for detecting high-grade lesions. Colposcopy, on the other hand, records a sensitivity rate of 85.5% and a specificity rate of 92%. The agreement rate between ZedScan and biopsy is 79.2%, as indicated by a kappa coefficient of 0.71, while the agreement rate between colposcopy and biopsy is 74.3%, with a kappa coefficient of 0.71.

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLME-Resnet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial and spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3\%) and Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and adjustment of treatment, by providing physicians with insights into the underlying pathological organization of gliomas.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

This study aimed to evaluate the effects of Blazepod technology when incorporated with various training regimens on the essential elements of physical fitness in volleyball, such as agility, speed, visual response time, and vertical leap. Thirty-six participants (age :17.33±0.48 y, height: 183.78±6.34 cm, weight: 77.14±5.16 kg) were in-volved in this study. In randomized design, three equal groups with two experimental groups and one control group were involved in the study over a period of six weeks: (GE1) used Blazepod technology to workout at a low level; (GE2) used Blazepod technology to workout at a higher intensity; (CG) did not employ Blazepod technology, but it adhered to the same fundamental training curriculum. We conducted agility, speed, reaction time, and vertical jump tests before, midway and after the study to determine optimal training volume, intensity, and frequency. A significant main effect of time (P0.01), and time×group interaction (P>0.001) were found for all tests. Post hoc test showed that the two experimental groups gadget significantly improved in all performance variables (P

Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and human cancer patients. To develop an appropriate combination of immunotherapy and OV for dogs with soft tissue sarcoma (STS), canine cancer cells were inoculated with myxoma viruses (MYXVs) and gene transcripts were quantified. Next, cytokine concentrations in canine cancer cells were altered to evaluate their effect on MYXV replication. These studies indicated that, as in murine and human cells, type I interferons (IFN) play an important role in limiting MYXV replication in canine cancer cells. To reduce type I IFN production during OV, oclacitinib (a JAK1 inhibitor) was administered twice daily to dogs for 14 days starting ~7 days prior to surgery. STS tumors were excised and MYXV deleted for serp2 (MYXV∆SERP2) was administered at the surgical site at two time points post-operatively to treat any remaining microscopic tumor cells. Tumor regrowth in dogs treated with OV was decreased relative to historical controls. However, regrowth was not further inhibited in patients given combination therapy.

The numerical simulation of entropy generation at mixed natural free and forced convection flow in a square lid-driven cavity filled with an eletrically conducting binary fluids saturated porous media in the presence of a magnetic field is performed in this investigation. Both the top and bottom horizontal walls of the cavity are kept at constant and different temperatures while the left and right vertical walls are adiabatic and insulated. The magnetic field is applied in normal direction to the cavity. The Darcy model, including Brinkman term relative to viscous effects and Forchheimer term due to inertial forces, is used for the momentum equations, and the SIMPLER algorithm, based on the control volume finite-element method approach is used to solve the pressure –velocity coupling. The flow pattern and the heat transfer characteristics inside the cavity are presented in the form of isotherms, streamlines and isentropic lines and average Nusselt number trend. The entropy generation rate is determined for various values of Darcy number (10^-3 ≤ Da ≤ 1) and for a range of Hartmann number (0 ≤ Ha ≤ 10²). This study is limited to Pr = 7 which corresponds to water. It is observed that entropy generation is very affected by the variations of dimensionless control parameters considered.

Background: Coronavirus disease (COVID-19) related pneumonia is leaded by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which infects host cells through receptors named Angiotensin-converting enzyme 2 (ACE2). Smoking is thought to be related to poor disease prognosis, as a large amount of evidence highlights the negative effects of smoking on lung health and its causal relationship with various respiratory diseases. Methods: We first evaluated the role of ACE2 expression level with tobacco effect. And correlation analyses were used to identify the related genes of ACE2 both in smoker trait and human normal multi-tissues. After intersections, hub genes were later used to further GSEA and co-regulated mechanisms were explored by GeneMANIA. We used UALCAN to perform survival curves of pan-cancers included 33 types of cancers. New clinical model of top co-occurrence cancer type was constructed and validated. Results: Effected by cigarette smoking, the expression level of ACE2 expressed statistically upwards in current smokers compared with never smokers, upwards in groups after acute smoke exposed compared with normal control. But no strong evidence detected in third-hand smoke, as poor amounts of samples, only 4. A little trend of expressing upwards became in groups after third-hand smoke compared with groups after clean air exposing. 4 genes included PIR, ADH7, AKR1C2 and AKR1C3 were identified as ACE2 related genes in smoker trait and human normal multi-tissues. Then, we made the survival curves of pan-cancers in 4 genes. Brain lower grade glioma was the co-occurrence type as both ACE2, PIR and AKR1C3 had the significantly prognostic situation. Later, we made the new clinical prediction model as the C-index was 0.827 and the Area Under Curves (AUCs) of 1-year survival, 2-year survival and 3-year survival were 0.921(95%CI, 0.882-0.961), 0.911(95%CI, 0.860-0.962) and 0.878(95%CI, 0.818-0.939). In inner validation, the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.777(95%CI, 0.640-0.914), 0.916(95%CI, 0.842-0.990) and 0.888(95%CI, 0.768-1.000). In outer validation one, the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.764(95%CI, 0.672-0.856), 0.848(95%CI, 0.783-0.913) and 0.748(95%CI, 0.656-0.841). And in outer validation two the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.740(95%CI, 0.654-0.826), 0.766(95%CI, 0.688-0.843) and 0.794(95%CI, 0.721-0.866). Conclusions: In our study, we compared the ACE2 expression level between smokers and non-smokers crowds and identified associated hub genes. Then we explored the further role of hub genes in tumor fields to identify the correlation and influence between the avoidable host factors such as smoking on COVID-19 contamination and tumor. ACE2 and AKR1C3 are potential prognostic genes for brain lower grade glioma, and we created the web dynamic nomogram and encapsulation app through validations.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

Mutual exclusion algorithms are at the heart of concurrent, distributed/parallel, real-time and operating systems. It is well-known that such algorithms are very difficult to analyze and in the literature different conjectures about starvation-freedom and the number of by-passes (also said the overtaking factor), which in turn affects the (hopefully) bounded waiting time that a process competing for entering the critical section has to suffer before accessing the shared resource, have been formulated for specific algorithms. This paper proposes a novel modelling approach based on Timed Automata and the Uppaal toolset, which proves effective for studying all the properties of a mutual exclusion algorithm for N≥2 processes, by exhaustive model checking. Although the approach, as already confirmed by similar experiments reported in the literature, is not scalable due to state explosion problems, and can be practically applied until N≤5, it is of great value for revealing true properties of analyzed algorithms. For dimensions N>5 the statistical model checker of Uppaal can be used which, although based on simulations, can confirm properties by estimations and probabilities. The paper describes the proposed modelling and verification method and applies it to several mutual exclusion algorithms, thus retrieving known properties but also showing new results about properties often studied only by peer-review and intuitive reasoning.

Isothermal interrupted hot compression tests of 5754 aluminum were conducted on Gleeble-3500 thermo-mechanical simulator at temperature 350 °C and 450 °C, strain rate 0.1 s-1 and 1s−1. These tests simulated flat rolling to investigate how softening behaviors respond to controlled parameters, such as deformation temperature, strain rate and delay times. This data allowed the parameters for the hot rolling process to be optimized. The delay times during interrupted compression vary between 5s and 60s. The dynamic softening at each pass and metadynamic recrystallization at the intervals of deformation passes were analyzed in detail. 0.2% offset yield strength is applied to calculate the softening fraction undergoing metadynamic recrystallization. A kinetic model was developed to describe metadynamic recrystallization behaviors of the hot deformed 5754 aluminum alloy. Furthermore, the time constant for 50% recrystallization was expressed as functions related to the temperature and the strain rate. The experimental and calculated results were found to be in close agreement, which verified the developed model.

As Artificial Intelligence (AI) technology, particularly Machine Learning algorithms, becomes increasingly ubiquitous, our abilities to understand and interpret AI and machine learning algorithms are becoming increasingly desirable. Visualization has been used as a common tool to view and understand complex machine learning processes. In this paper, we will focus on developing a general framework for the visualization of machine learning models as a scalar valued multi-dimensional function to help users understand how the models behave over different viewing spaces. We first give a formal definition of the visualization problem. Interpolation-based morphing and subspace sampling techniques are applied to generate various renderings through projections and cross-sections of the model space as 3D surfaces or heatmap images. This method will be applied to two real-world datasets and applications: the diagnosis of Alzheimer's Disease (AD) using a human brain networks dataset and a real-world benchmark dataset for predicting home credit default risks. The visualizations show that different machine learning algorithms can behave quite differently under different conditions.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Abstract: Purpose: High-grade isthmic spondylolisthesis (HGISL) is a severe condition, associated with low-back pain (LBP) and radiculopathies. The present study is a monocentric prospective observational study investigating the clinical-radiological outcomes of a bilateral minimally invasive TLIF (bm-TLIF) for HGISL. Material and Methods: Patients who underwent bm- TLIF for HGISL at our institution, were considered for inclusion. Clinical-radiological outcomes and complications were collected. Results: Twenty-one patients (14M:7F) were included and the mean clinical follow-up (FU) time was 27(±6) months. There was a significative improvement of the mean VAS-back, VAS-legs, ODI, and SF-36 PCS scores, comparing pre- and last FU measurements. The mean pelvic tilt (p0,05). The univariate analysis showed that residual slip angle (> or  10°) may independently influence VAS-b (p

Background: Glioma surgery was remarkably renewed in the past 2 decades, with improved safety and limited but yet improved life expectations. Fluorescence-guided resection of high-grade gliomas (HGG) plays a central role in this sense, by allowing higher degrees of extent of resection (EOR). The introduction of the exoscopic guided surgery may be considered an im-plementation for fluorescence techniques over the traditional microscopes. We present the appli-cation and the advantages of the exoscopic guided surgery compared to the microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGG. Methods: ten consecutive patients underwent a surgery for HGG resection. The surgery was per-formed via an exoscopic-guided procedure (Olympus Orbeye) and after oral administration of Gliolan 5 hours before the procedure. During surgery, the procedure was shifted to microscope (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different was subjectively measured in different picture samples during the surgery in a 1 to 5 (from minimum to maxi-mum) scale. The brightness of the surgical field and the detailing of the anatomy were also ana-lyzed comparatively. Results: among the ten patients the histopathological diagnosis was an high grade glioma in all cases. In 9 cases was possible to achieve the gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the exoscope group and 3.5 in the microscope group (p

The GPA is a universally recognised and utilised metric of academic performance that is considered to also measure a student’s potential for academic performance in the future. In this short communication we examine to what extent the GPA of the first grade of high school predicts performance in the later grades of high school, either generally (as classified in excellent student, strong student, weak student or very weak student) or more accurately (as indicated by the exact GPA in the next grade). We also put to the test the widely held notion that it might be best if core courses such as language and mathematics contributed more to the calculation of the GPA compared to secondary courses such as physical education or music. Our findings confirm the predictive properties of the GPA but strongly rebut the notion that a weighted GPA might achieve a better reflection of students’ potential. The study is based on the academic records of every student in Greece that progressed from first to third grade of high school in the 2016-2019 period. This data set contains records of more than 85,000 students, making it one of the most extensive studies ever conducted on the topic of the properties of the GPA.

The study aimed to investigate the impact of incorporating deep learning strategies in mathematics instruction on students' problem-solving abilities, critical thinking skills, academic achievement, and mathematical skills development. The study population consisted of 280 students, with a sample size of 162 participants. Employing a purely quantitative approach, data collection utilized questionnaires and achievement tests as instruments. Data analysis involved simple linear regression, descriptive analysis, and Pearson correlation. The results of the study revealed that there was no significant enhancement observed in students' problem-solving abilities and critical thinking skills when deep learning strategies were incorporated into mathematics instruction. Additionally, students' attitudes towards deep learning activities in mathematics showed no effect on their academic achievement. Furthermore, students' engagement levels in deep learning activities did not impact their development of mathematical skills. Lastly, the frequency of deep learning activities in the mathematics classroom did not show a significant relationship with students' academic performance. These findings suggest that the implementation of deep learning strategies in mathematics instruction did not yield notable improvements in the specified areas based on the study outcomes.

This review centers on the pivotal role of the oncoprotein FOSL1, within the dimeric AP-1 transcription factor consisting of FOS-related elements. FOSL1 emerges as a key regulator governing invasion and metastatic dissemination, therefore making it a promising target for therapeutic intervention in cancer patients. The review provides a comprehensive survey of the regulatory mechanisms that exert influence over FOSL1. These encompass a spectrum of transcriptional and post-translational modifications. Notably, we unveiled the intricate involvement of diverse non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the modulation of FOSL1 expression through targeted interactions with its mRNA transcripts. Furthermore, an exploration into the functional dimensions of FOSL1 unfolds, encompassing apoptosis, proliferation, and migration. This investigation is accompanied by a thorough examination of the elaborate signaling pathways that underpin these multifaced roles. Additionally, emphasis is placed on the role of FOSL1 in orchestrating the stimulation of various cytokines, including TGF-beta, and the initiation of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that transverse into the tumor microenvironment. A distinct focus is dedicated to appraising the prognostic implications associated with FOSL1. Finally, insights emerge into the evolving roles of FOSL1 in the context of mechanisms governing resistance and dependency on targeted therapeutic modalities.

The goal of classroom English instruction is to educate students on how to use the English language effectively for communication in any scenario. It is identified by presenting various teaching tactics and speaking activities to encourage students to participate more actively in conversations. The study intended to identify the problems in the speaking performance of Grade 8 Jade in Tagum City National High School. The study was conducted using a quantitative non-experimental descriptive survey method. Results revealed that the problems in speaking performance have garnered a mean of 3.20 (moderate) as descriptive equivalent and it was found out that the prevailing speaking problem is anxiety with a mean of 3.84, interpreted as high. Thus, an intervention program is designed to address the problems in the speaking performance of the respondents. This program is divided into two: Overcoming Speaking Anxiety Seminar-Workshop and Speaking Enhancement Activities.

The genetic aetiology of familial glioma is largely unknown. To gain further insight into the role of rare disruptive variants we performed whole exome sequencing (WES) of 17 glioma families, identifying two families where loss of function mutations in dynein axonemal heavy chain 11 (DNAH11) co-segregated with glioma (DNAH11 p.Ser1470ArgfsTer6 and p.Thr3900Lys) and single families implicating Telomere Replication Complex Component 1 (CTC1 p.Leu1058ProfsTer32) and filamin alpha (FLNA p.Ser1356Phe). We complemented linkage analysis by WES of 150 additional unrelated familial glioma cases and conducting gene burden tests leveraging WES data on 691 cases of glioma from TCGA. Our analysis does not provide support for a hitherto unidentified major cancer gene for glioma but highlights a series of novel candidate predisposition variants/genes, worthy of further investigation to shed light on glioma risk.

Nickel is widely used in industrial processes and plays a crucial role in many applications. However, most of the nickel resource mainly exists as nickel oxide in laterite nickel ore with complex composition, resulting in difficulty in upgrading the nickel content using physical separation methods. In this study, high-grade ferronickel concentrates were obtained through a carbothermal reduction and magnetic separation using laterite nickel ore and anthracite as raw materials. The effects of different types of additives (CaF2, Na2SO4 and H3BO3), carbon ratio (nc/no in metal oxides) and grinding time on the recoveries and grades of ferronickel concentrates were experimentally investigated, along with the microstructure and chemical composition of the products. CaF2 was proved to be the primary active additive in the aggregation and growth of the ferronickel particles, and the improvement of the grade of the product. Under the optimal conditions of CaF2 addition of 12 wt.%, carbon ratio of 1.4, and grinding time of 240 s, high-grade magnetically separable ferronickel concentrate with nickel grade 8.93 wt.% and iron grade 63.96 wt.% was successfully prepared. This work presents a practical method for the highly efficient recovery and utilization of iron and nickel from low-grade laterite nickel ore, contributing to the development of strategies for the sustainable extraction and utilization of nickel resources.

: In the automotive industry, high-strength plates have been increasingly used to reduce the vehicle body weight due to stringent regulations on fuel economy and safety. Such plates achieve tensile strengths as high as 1.5 GPa owing to the hot-stamping process. However, these plates suffer from scale generation and surface decarburization because of the surface oxidation of the material. Recently, studies on materials subjected to high-frequency induction heating have reported strength improvement owing to the coil shape and cooling method. This study presents the surface temperature changes, mechanical properties, and microstructures of boron steels subjected to longitudinal heating, which uses eddy currents generated from high-frequency induction heating. The surface temperature data were analyzed under different high-frequency induction heating powers (15, 18, 21, 24, 27, and 30 kW) and distances from the specimen (6, 9, and 15 mm). The mechanical properties and microstructures were also analyzed in different high-frequency induction heating coil directions. The correlations between the high-frequency induction heating power and the distance from the specimen with the maximum tensile strength were determined.

The statistical analysis of impact of the top 50 solar flares of X-class (1997-2023) on the global seismic activity, as well as on the earthquake preparation zones located in illuminated part of the globe and in the area of 5000 km radius around the subsolar point was carried out. It is shown by a method of epoch superposition that for all cases the increase of seismicity is observed, especially in the region around the subsolar point (up to 38%) during 10 days after the solar flare in comparison with preceding 10 days. The case study of aftershock sequence of strong M=9.1 earthquake (Su-matra-Andaman Islands, 26.12.2004) after the solar flare of X7.2 class (20.01.2005) demonstrated that the number of aftershocks with magnitude M≥2.5 increases more than 20 times after the solar flare with a delay of 7 days. For the case of the Darfield earthquake (M=7.1, 04.09.2010, New Zealand) it was shown that strong solar flares of class X and M probably triggered two strong aftershocks (M>6) with the same delay of 6 days on the Port Hills fault, which is the most sensitive to external electromagnetic impact from point of view of the fault electrical conductivity and orientation. Based on the obtained results the possible application of natural electromagnetic triggering of earthquakes is discussed for a short-term earthquake prediction using confidently recorded strong external electromagnetic triggering impacts on the specific earthquake preparation zones, as well as ionospheric perturbations due to aerosol emission from the earthquake sources recorded by satellites.

The performance of OpenFOAM in strong scaling tests on HPC systems with AMD EPYC processors exhibits a pronounced superlinear speedup. Simple test cases show superlinear speedups of over 300%, which significantly impacts the efficient use of computing resources. With the last generation of HPC architectures, a superlinear speedup of about 10% to 20% was well expected and accepted by CFD users. The measured superlinear speedup is much more pronounced and withstands the communication overhead to even larger scales. A detailed performance analysis of OpenFOAM follows, employing various High-Performance Computing (HPC) architectures, including AMD, ARM and Intel systems. The performance metric FVOPS (Finite VOlumes solved Per Second) is introduced to compare the performance of Computational Fluid Dynamics (CFD) applications when varying the grid size, as occurs in a strong scaling test. The achievable FVOPS depends on various factors, including the simulation type, boundary conditions, and especially the grid size of a use case. Analysing FVOPS on a single node level with varying grid size shows a significant difference in performance and cache utilization, which explains the large superlinear speedups seen in the strong scaling tests. Furthermore, FVOPS can be used as a simple benchmark to determine the optimal number of grid elements per rank to simulate a given use case at peak efficiency on a given platform, resulting in time, energy, and cost savings. The FVOPS metric also facilitates the direct comparison between different HPC architectures. The tests using AMD, ARM, and Intel processors show a peak in performance when employing around 10,000 grid elements per core. The presence of a large L3 cache on AMD processors is particularly advantageous, as indicated by L3 cache miss rates observed on AMD EPYC processors. Our results suggest that future HPC architectures with larger caches and higher memory bandwidth would benefit the CFD community.

Beginning with the discovery of the BRCA ovarian cancer susceptibility genes and subsequent detailed examination of risk reduction salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous cancer - serous tubal intraepithelial carcinoma or STIC - has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in fallopian tubes of women with advanced malignancy. This paradox, a high-frequency of tubal involvement early and a low-frequency late in the disease process has spurred interest in other potential sources, such as the ovarian surface or secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by TP53 mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that nonmalignant but TP53 mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a 2nd component of the paradigm by which cells from early lesions can escape the fallopian tube and undergo future malignant transformation later, emerging suddenly as widespread malignancy. This dualistic model thus explains the paradox and opens new questions pertaining to the challenge of both early detection and prevention of this lethal malignancy.

Glioma tumors are one of the most devastating cancer types. Of the different glioma tumors, glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advantages in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OV) in cancer treatment is one of those immune-therapeutic alternatives. OV have a double oncolytic action by both, directly destroying the cancer cells, sparing the patient’s life, and stimulating a tumor specific immune response to revert the ability of tumors to escape the control of the immune system. OV are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility to use some viruses to specifically infect tumors eluding undesired toxic effects in the patient. Here we have revisited the literature in order to describe the main OV proposed so far as therapeutic alternatives to destroy glioma cells in vitro and trigger tumor destruction in vivo. Some clinical trials are exploring the use of this therapy as an alternative were other approaches provide limited hope.

Background: A prognostic index validated for the outcomes of advanced high-grade serous ovarian cancer (HGSOC) patients with neoadjuvant chemotherapy (NACT) is still lacking. We therefore developed an ovarian neoadjuvant chemotherapy prognostic index (ONCPI) to enhance predictive accuracy. Methods: We analyzed clinicopathologic feature of advanced HGSOC patients receiving platinum-based NACT. Blood inflammatory composite markers were calculated and binary-transformed by optimal cutoffs. The omental hematoxylin and eosin (H&E) stained slides were selected for the assessment of chemotherapy response score (CRS). Logistic regression analyses and Cox proportional hazard regression model were utilized to develop a prognostic index. Results: Multivariate analysis showed that CRS and neutrophils-to-lymphocyte ratio (NLR) are independent risk factors for platinum-chemotherapy response. Meanwhile, Kaplan–Meier and Cox regression analysis revealed that CRS score was significantly correlated with PFS and OS, and NLR-high patients was associated with poor OS. We further developed an ONCPI model based on the CRS score and NLR level. Survival analysis suggested that patients with score 0 and 1 of ONCPI were significantly associated with improved PFS and OS. Conclusions: The ONCPI score emerges as a significant prognostic marker for predicting NACT outcomes in advanced HGSOC patients. Its integration into clinical practice and risk-stratified trial design is conceivable.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study gliomagenesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

In this paper, the synthesis of two novel luminescent Eu3+ ion complexes [Eu(TFT)3(phen) (1) and Eu(TFT)3(bpy)•Hex (2)] based on the combination of 2-(2,2,2-trifluoroethyl)-1-tetralone (TFT), containing n-donor ligands (1,10-phenanthroline or 2,2'-Bipyridine) and Eu3+ ion is reported herein, and their structural features are discussed on the basis of X-ray crystallographic and thermal analyses. We observed that the ligands transfer energy effectively to the metal center by fluorescence, IR and UV spectrograms studies. The structures and properties of complexes 1-2 were optimized by the DFT theoretical calculation, and the calculation results were consistent with the experimental X-ray structure data and spectral analysis.

In this paper, we focus on the impact of financial liberalization on stability of emerging stock market. We identify crises in a group of Latin American (Argentina, Brazil and Chile) and Asian countries (Philippines, Korea, Taiwan and Thailand) during 1975–2005. This paper aims to apply the methodology of CMAX method. Our results indicate that liberalization triggers more unstable stock market in the short run and generate several crises. Still, liberalization seems to generate more stable financial markets in the long run. Financial liberalization does not increase the frequency of crises in emerging countries and at long-term, crises are less several.

Background. The treatment for patients with high-grade gliomas includes radiation therapy and temozolomide. However, some patients do not respond to temozolomide because they have a methylation reversal mechanism through the enzyme O6-methylguanine-DNA-methyltransferase. This biomarker has been used as a prognostic factor in patients receiving treatment with temozolomide. However, not all patients respond in the same way, which suggests the existence of other genes involved in resistance to temozolomide. Materials and Methods. A group of 31 patients with high-grade gliomas was recruited and were clinically, image pattern, and pathologically characterized. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment. Results. The genes related to the second relapse of patients with high-grade glioma after the use of temozolomide according to Stupp protocol and metronomic dose were PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. Considering the results obtained, we suggest that the mutations in the four genes and the methylation of the gene promoter that codes for MGMT protein could be related to the clinical evolution of patients with high-grade gliomas and its response to treatment with temozolomide.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

ABSTRACT Lubricants play a crucial role in reducing friction and wear between surfaces in relative motion. Engine oil, as a lubricant, is specifically designed to minimize friction and wear between the moving parts of different equipment and machinery. Engine oil blending serves the purpose of adjusting the variety of lubricants available to meet specific performance requirements. Through blending, it is possible to tailor the characteristics of the lubricating oil, such as viscosity, stability, and additive content, to optimize its effectiveness in reducing friction, protecting engine components, and enhancing overall equipment performance. By customizing lubricant formulations through blending, manufacturers can address the diverse lubrication needs of modern engines and machinery, ensuring smooth operation, longevity, and efficiency.To enhance the quality of the lubricant and achieve the desired high-performance multi-grade engine oil, a systematic approach was followed. The process began with testing the specific gravity of the oil using a hydrometer and thermometer to ensure accurate measurements. Subsequently, 5 liters of base oil were carefully measured and poured into a stainless steel reactor pot to serve as the blending vessel. Following this, 1 liter of paraffin oil (100N) was added to the base oil to introduce specific properties to the blend. To further optimize the formulation, 0.42 kg (7% of the total blend) of additives, including a selection of specific performance-enhancing compounds, was incorporated. These additives, such as Aspen, Tackifier, and other essential components like anti-wear, corrosion inhibitors, detergents, dispersants, and antioxidants, were meticulously measured and added to the mix. Through this precise blending process, the goal was to craft a high-quality multi-grade engine oil that meets the stringent performance requirements for various operating conditions and equipment types. After the melted Aspen and dissolved tackifier were added to the mixture, thorough stirring was carried out to ensure uniform distribution until a homogeneous blend was achieved. The mixture was then exposed to heat to facilitate the reaction between the base oil and additives, reaching a temperature of 70°C for optimal blending. Subsequently, 0.5 kg of viscosity index improver was introduced into the mixture and stirred continuously for a period of 5 minutes to ensure proper integration. Following this step, 5 grams of dye were carefully added to the mixture, and stirring was continued to evenly disperse the coloring agent throughout the blend. This meticulous process aimed to ensure that all components were effectively incorporated, facilitating the production of a high-quality, customized multi-grade engine oil with enhanced performance characteristics and optimal lubricating properties. After subjecting the mixture to a temperature of 70°C, the heat source was removed, allowing the product to gradually cool down to room temperature, which was estimated to be around 30°C. Following this cooling process, the product underwent a filtration step to remove any residual impurities present in the mixture. A sample of the purified product was then extracted for further analysis. Quality control tests were meticulously carried out on the sample to ensure that the product met the rigorous standards set by the Standard Organization of Nigeria (SON). The results obtained from the quality control tests were highly promising, indicating that the product indeed complied with the stringent specifications outlined by the regulatory body. This adherence to quality standards is essential in ensuring the product's reliability and performance in various applications. The successful outcome of the quality control test underscores the meticulous attention to detail and commitment to excellence in the production process. The rigorous quality control procedures implemented in the analysis of the product highlight the commitment to upholding high standards of quality and safety in the manufacturing process. By consistently meeting and exceeding industry regulations and standards, the product not only demonstrates its reliability but also reflects a dedication to customer satisfaction and product excellence. The adherence to the SON standards showcases a commitment to producing top-quality products that meet the needs and expectations of consumers and industry stakeholders alike.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n=18) and IDH1 mutant (IDH1-mt) astrocytoma (n=12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical mem-braneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vascula-ture are shown to have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Overproduction of lipids by the tumor is suspected to be due to a combination of two processes: i) dysfunctional oxidative phosphorylation in mitochondria that causes metabolic backup and ac-cumulation of acetyl-CoA, as well as ii) the overproduction of pyruvate due to the tumor cell reli-ance on overactive glycolysis. Tumor cells use lipids for structural components but cannot use them for energy if their oxidative phosphorylation is dysfunctional, which seems to be the case in the tumor cells we examined. This lipid-rich environment, however, offers tumor cells certain advantages: protection from the immune system, non-lipophilic drugs, and oxidative stress. Our research highlights the significant presence of lipid overproduction in both IDH1-wild type glio-blastoma and IDH1-mutant astrocytoma tumors, leading to diverse lipid accumulations in var-ious cellular compartments and structures. This lipid excess stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune re-sponses, non-lipophilic drugs, and free radicals.

Glioblastoma multiforme (GBM) is a glioma and the most aggressive type of brain tumor with a dismal average survival time, despite the standard of care. One promising alternative therapy is boron neutron capture therapy (BNCT), which is a noninvasive therapy for treating locally invasive malignant tumors, including glioma. BNCT involves boron-10-released radiation directly into tumor cells with minimal damage to healthy tissues. This therapy lacks clinically approved targeted blood-brain-barrier-permeating delivery vehicles for therapeutic drug/ boron-10. Nanoparticles, particularly gold nanoparticles (GNPs), are selective and effective drug-delivery vehicles because of their desirable properties, facile synthesis, and biocompatibility. This review discusses historical and current GNP therapeutic applications as a drug delivery vehicle for treating glioma. Furthermore, GNPs loaded with therapeutic drugs, imaging agents, and GBM-targeting antibodies/ peptides to treat GBM will be discussed. Additionally, the importance of upper and lower limits on therapeutic efficacy will be described and explored followed by highlighting their advantages, limitations, and possible toxicity. Recent research and selected important findings for GNP-mediated pharmaceutics in GBM will also be considered.

Solid waste management in Accra is a major challenge to the Metropolitan Authorities and inhabitants. The rapidly increasing population coupled with poor capacity of the municipal and private waste management companies to management waste effectively has created issues of environmental concern. Due to poor waste managements systems, most household dispose waste indiscriminately leading to floods and health issues. The study showed that about 60% of household waste is organic materials which has the potential to be converted to compost for agriculture purpose. Meanwhile plastics and rubbers which litters the environment as well as blocking major storm drains and gutters hence creating huge environmental hazard is made of 11% of the total component of most household waste generated daily. The study also revealed that among the methods of disposing waste, dumping waste in skip containers located at authorized places was the preferred means of disposing waste by household though others also dispose waste by other means such as burying and burning. Inadequate skip containers per population of household in an area coupled with irregularity of tracks picking these containers makes skip containers dumping site ugly scene, hence creating health issues. Among the constraints that impact negatively on sustainable waste management in Accra Metropolis, economic constraints was perceived as the main challenge which affect efficient waste management. Currently the country is going through serious economic challenges so government does not release money timely to fund projects which waste management is key. Most donor partners that use to support the government with funds have either reduced or redrawn their services as they have no confidence in the state of Ghana economy. Aside the constrains, the study also indicated that factors such as poor public attitude towards waste management, poor enforcement of sanitation by-laws, inadequate and untimely release of government funds were also seen as the main factors affecting waste management.

In the follow-up of treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions, cer-vical cytology has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing showed high sensitivity and lower specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) seems to be an indicator of viral integration and it allows the identification of severe lesions. Our objective was to assess the clinical utility of E6/E7 mRNA determination in the follow-up of patients treated for HSIL/CIN. A retrospective obser-vational study including 407 patients treated for HSIL/CIN was performed. The recurrence rate and the validity of E6/E7 mRNA testing were evaluated. The recurrence rate of high-grade lesions was 1.7%. The sensitivity of the test was 88% in the first clinical revision and 100% in the second and third revisions. Specificity was 91% in the first revision, 92% in the second revision, and 85% in the third revision. The positive predictive value was 18% in the first medical revision, 10% in the second and 14% in the third. The negative predictive value was 100% in all follow-up visits. In conclusion, the E6/E7 mRNA test seems to be effective in ruling out recurrence after treatment for HSIL/CIN lesions.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but it is unknown the degree to which such cultures retain the characteristics of the source tumors. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

Glioblastoma (GBM) still presents as one of the most aggressive tumors in the brain, which despite enormous research efforts remains incurable until today. As many theories evolve around the persistent recurrence of this malignancy the assumption of a small population of cells with a stem-like phenotype remains as a key driver of its infiltrative nature. In this article we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of Bone Morphogenic Protein 4 (BMP4), which induces GSC differentiation and hence reduces tumorigenicity. We therefore employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell based assays (MTT, limiting dilution and sphere formation assays), western blots, irradiation procedures and quantitative real-time PCR that depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1-expression might also serve as a marker protein to determine BMP4-susceptibility.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluate the pathology and molecular characteristics of DIPG, the current and future approaches to DIPG treatment; and, lastly, we will discuss clinical trials that have been completed to develop successful treatment options.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy (p=0.005), poor platinum sensitivity (p<0.001), and poor PFS (p<0.001) and OS (p<0.001). Multiva-riate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity (p=0.005) and shorter OS (p<0.001). Instead, no correlation was observed between NY-ESO-1 protein expression and response to platinum-based chemotherapy (p=0.832), platinum sensitivity (p= 0.168), PFS (p=0.126) and OS (p=0.335). MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted im-munotherapy could represent an important alternative therapeutic option in these cancers.

A PLS-based quality prediction method is proposed for batch processes using two-dimensional extended windows. To realize the adoption of information in the direction of sampling time and batch, a new definition region of support (ROS), k-i-back-extended region of support (KIBROS), is proposed to establish the extended window, which including the data of the previous sampling times in the same batch, the data of the same sampling time in the historical batches, the data of the previous sampling times in the historical batches and the data of the later sampling times in the historical batches. According to these regions of support, extended windows are established, and different models are proposed based on the extended windows for batch processes quality prediction. Further, using a typical batch process as an example, the injection molding process, the proposed quality prediction method is experimentally verified, proving that the proposed methods have higher prediction accuracy than the traditional method and the prediction stability is also improved.

The association between obesity and the risk of gliomas remains unclear. We sought to evaluate the potential association between general and abdominal obesity and the risk of gliomas based on a nationwide population-based cohort study of Koreans. Using data from the Korean National Health Insurance System cohort, 6,833,744 people older than 20 years who underwent regular national health examination in both 2009 and 2011 were followed until the end of 2017. We documented 4,771 glioma cases based on an ICD-10 code of C71 during the median follow-up period of 7.30 years. Individuals with a body mass index (BMI) ≥ 25.0 kg/m2 were at significantly higher risk of gliomas than those with a BMI < 25.0 kg/m2 (HR 1.08 CI 1.02-1.15). Individuals with a waist circumference (WC) ≥ 90 cm (males)/85 cm (females) also had a significantly higher risk of gliomas than those with a WC < 90 cm (males)/85 cm (females) (HR 1.16 CI 1.09-1.24). In the group with a BMI ≥ 25.0 kg/m2, individuals with abdominal obesity were at significantly higher risk of gliomas (HR 1.18 CI 1.09-1.27) than those without abdominal obesity. The role of abdominal obesity in this association was stronger in women than in men. To our knowledge, this is the first demonstration that obese people may be at higher risk of gliomas, especially centrally obese people from an Asian population with a BMI ≥ 25.0 kg/m2. Loss of visceral fat in people with abdominal obesity may reduce their risk of gliomas.

Chondrosarcoma, represents approximately 0.1% of all neoplasms of the head and neck, being considered a rare disease, but with a relatively good prognosis. The 5-year overall survival (OS) rate is estimated at 70-80%, being considered a disease with a low growth rate. About 13% of all cases of chondrosarcoma, are located in the region of the head and neck. We present the case of a young patient treated multimodally, lost from the oncological records less than two years after the diagnosis, without evidence of disease progression. The early loss from the oncological follow-up programs of patients with a lower risk of early repalpse, without evidence of a recurrence or metastasis could be the consequence of a major complication among which we could assume an aspiration pneumonia secondary to a dysphagia, associated with an aggressive multidisciplinary treatment. Large tumor size and positive resection margins (R1 resection) are risk factors that support an intensive adjuvant approach in order to reduce the risk of recurrence, but the low grade of tumor, associating a lower risk of recurrence as well as the adverse events (AE) of adjuvant radiotherapy and chemotherapy justifies a more reserved therapeutic approach. Taking into account the longer life expectancy of these patients, it is recommended to use a more conformal irradiation technique in order to reduce doses to radiosensitive structures as well as to omit elective neck irradiation, taking into account the lower risk of lymph node involvement. The lack of guidelines that include very rare tumors including low grade chondrosarcoma of head and neck make a unified approach difficult, but the data presented even in case reports could contribute to choosing the regimen that offers the best therapeutic ratio.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

This paper introduces an innovative Particle Swarm Optimization (PSO) Algorithm in-corporating Sobol and Halton Random number samplings. It evaluates the enhanced PSO's performance against conventional PSO employing Monte Carlo Random Number Samplings. The comparison involves assessing the algorithms across nine benchmark problems and the renowned Travelling Salesman Problem (TSP). The re-sults reveal consistent enhancements achieved by the enhanced PSO utilizing Sob-ol/Halton samplings across the benchmark problems. Particularly noteworthy are the substantial improvements demonstrated by the enhanced PSO in solving the Travel-ling Salesman Problem. These findings underscore the efficacy of employing Sobol and Halton random number generation methods in enhancing algorithm efficiency.

The mechanism underlying microbiologically induced carbonate precipitation have not been thoroughly characterized, although numerous scholars and experts have specifically investigated questions regarding minerals induced by bacteria. The study of the precipitation of carbonate minerals induced by halophilic bacteria has aroused wide concern. The present study aimed to investigate the characterization and process of biomineralization in high salt systems by a halophilic bacterium, Chromohalobacter israelensis strain LD532 (GenBank: KX766026), which was isolated from the Yinjiashan Saltern in China. Carbonate minerals induced by LD532 were investigated in several sets of comparative experiments that employed magnesium sulfate and magnesium chloride as Mg resources. Magnesium calcite and aragonite were induced by LD532 bacteria, whereas these minerals did not appear in the control group. The mineral phases, micromorphologies, and crystal structures were analysed using X-ray powder diffraction, scanning electron microscopy, and energy dispersive X-ray detection. The carbonic anhydrase and urease secreted by strain LD532 through metabolism increased the pH value of the liquid medium and promoted the process of carbonate precipitation. Further study using high resolution transmission electron microscopy, energy dispersive X-ray detection and analysis of ultrathin slices showed that the nucleation sites of carbonate minerals were located on extracellular polymeric substances and the membranes of intracellular vesicles of LD532 bacteria, which provided favourable conditions for the growth of carbonate mineral crystals. The morphologies and compositions of minerals formed in solutions of MgSO₄ and MgCl₂ display significant differences, indicating that different sources of Mg²⁺ may also affect the physiological and biochemical activities of microorganisms and thus mineral deposition. This study will be of some interest for the interpretation of carbonate biomineralization in natural salt environments and has some value as a reference in understanding sedimentary carbonates in ancient marine environments, such as tidal flats.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

In this paper we introduce a computational model for the simulation of hypervelocity impact (HVI) phenomena which is based on the Discrete Element Method (DEM). Our paper constitutes the first application of DEM to the modeling and simulating of impact events for velocities beyond 5 kms⁻¹. We present here the results of a systematic numerical study on HVI of solids. For modeling the solids, we use discrete spherical particles that interact with each other via potentials. In our numerical investigations we are particularly interested in the dynamics of material fragmentation upon impact. We model a typical HVI experiment configuration where a sphere strikes a thin plate and investigate the properties of the resulting debris cloud. We provide a quantitative computational analysis of the resulting debris cloud caused by impact and a comprehensive parameter study by varying key parameters of our model. We compare our findings from the simulations with recent HVI experiments performed at our institute. Our findings are that the DEM method leads to very stable, energy–conserving simulations of HVI scenarios that map the experimental setup where a sphere strikes a thin plate at hypervelocity speed. Our chosen interaction model works particularly well in the velocity range where the local stresses caused by impact shock waves markedly exceed the ultimate material strength.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect in stabilizing symptoms. In silico and preclinical studies identified ONC201, as a cytotoxic agent against some human cancer cell lines, including DIPG ones. Single crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed to identify hClpP as its main target. Hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients, receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β -carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based Virtual Screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

Gliomas, the most prevalent and lethal form of brain cancer, are known to exhibit metabolic alterations that facilitate tumor growth, invasion, and resistance to therapies. Peroxisomes, essential organelles responsible for fatty acid oxidation and reactive oxygen species (ROS) homeostasis, rely on the receptor PEX5 for the import of metabolic enzymes into their matrix. However, the prognostic significance of PEX5 for glioma patients remains unclear. We developed a robust prognosis model based on PEX5-dependent signature. This signature not only serves as a robust prognosis model capable of accurately predicting outcomes for glioma patients but also effectively distinguishes several clinicopathological features, including the grade, isocitrate dehydrogenase (IDH) mutation, and 1p19q codeletion status. Furthermore, we developed a nomogram that integrates the prognostic model with other clinicopathological factors, demonstrating highly accurate performance in estimating patient survival. Patients classified into the high-risk group based on our prognostic model exhibit an immunosuppressive microenvironment. Finally, we validated that the peroxisomal localization of the signature genes depends on PEX5 and demonstrated that PEX5 is required for cell growth, migration and invasion of glioma cells. These findings identify the PEX5-dependent signature as a promising prognostic tool for gliomas.

Background: Diffuse glioma is a malignant human brain cancer that is hard to overcome. This represents a high risk of mortality. The current challenge is limited to the control of tumor progression and survival improvement. Immunotherapy consists of stimulating the immune system in order to eliminate the non-self-elements that damage the human body, including cancer cells. However, in human glioma, the current immunotherapeutic targets did not show significant benefit. In this study, we aimed at evaluating the expression and potential role of a new immunosuppressive molecule, TIGIT in glioma patients. Methods: A cohort of 667 patients from the TCGA database along with a cohort of 53 Moroccan patients, were analyzed in order to assess the role of TIGIT in human glioma progression and to estimate whether blocking this immune checkpoint molecule would be of a potential therapeutic benefit. Real time RT-PCR from fresh human biopsies and RNAseq data analysis were performed in this study. Results: Our results showed that high expression of TIGIT had prognostic value with some known clinical glioma risk factors such as sex, age and IDH mutation status. High expression of TIGIT was positively associated with advanced grades of glioma. Interestingly, elevated rates of TIGIT were significantly associated to elevated levels of other inhibitory immune checkpoint molecules (PD-1, VISTA and Tim-3) in human glioma patients, also TIGIT showed strong association with Treg cell-secreted cytokines (TGF-beta and IL-10), indicating the high potential involvement of TIGIT in immunosuppression in human glioma. Moreover, we reported that high TIGIT expressing CD8 T-cells displayed more surface inhibitory molecules and, elevated levels of Treg cells and FoxP3 were linked to higher rates of TIGIT, supporting the likely involvement of TIGIT in the suppression of the intra-tumoral immune cells. Finally, high expression of TIGIT was significantly linked to advanced histological subtypes of glioma and was associated with poor overall survival in human glioma. Conclusion: TIGIT blockade might be of valuable therapeutic benefit in patients with advanced glioma.

Objective:The Glioma brain tumor detection and segmentation methods are proposed in this paper using machine learning approaches. Methods:The boundary edge pixels are detected using Kirsch’s edge detectors and then contrast adaptive histogram equalization method is applied on the edge detected pixels. Then, Ridgelet transform is applied on this enhanced brain image in order to obtain the Ridgelet multi resolution coefficients. Further, features are derived from the Ridgelet transformed coefficients and the features are optimized using Principal Component Analysis (PCA) method and these optimized features are classified into Glioma or non-Glioma brain images using Co-Active Adaptive Neuro Fuzzy Expert System (CANFES) classifier.Results:The proposed method with PCA and CANFES classification approach obtains 97.6% of se, 98.56% of sp, 98.73% of Acc, 98.85% of Pr, 98.11% of FPR and 98.185 of FNR, then the proposed Glioma brain tumor detection method using CANFES classification approach only.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking, chemo and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to 1) optimize delivery of oncolytic viruses beyond the blood brain barrier; 2) trigger inflammatory immune responses in and around tumors; and 3) use of multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

This study provides designs for a low-cost, easily replicable open source lab-grade digital scale that can be used as a precision balance. The design is such that it can be manufactured for use in most labs throughout the world with open source RepRap-class material extrusion-based 3-D printers for the mechanical components and readily available open source electronics including the Arduino Nano. Several versions of the design were fabricated and tested for precision and accuracy for a range of load cells. The results showed the open source scale was found to be repeatable within 0.1g with multiple load cells, with even better precision (0.01g) depending on load cell range and style. The scale tracks linearly with proprietary lab-grade scales, meeting the performance specified in the load cell data sheets, indicating that it is accurate across the range of the load cell installed. The smallest loadcell tested(100g) offers precision on the order of a commercial digital mass balance. The scale can be produced at significant cost savings compared to scales of comparable range and precision when serial capability is present. The cost savings increase significantly as the range of the scale increases and are particularly well-suited for resource-constrained medical and scientific facilities.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

The origin and significance of the tonalite–trondhjemite–granodiorite (TTG) units and the familiar metabasite xenoliths they host in the Yangtze Craton, China, remain controversial, and resolving these issues is important if we are to understand the evolution of the early Yangtze Craton. We focused on biotite–tremolite schist xenoliths in the Archean TTG units of the Kongling high-grade metamorphic terrane, and U–Pb dating of their zircons yielded ²⁰⁷Pb/²⁰⁶Pb ages of ca. 3.00 Ga, which provides a minimum age for the formation of the pre-metamorphic basic igneous rock. The host TTGs and late intrusive granitic dikes yield three groups of upper intercept ages at 2.87–2.88, 2.91–2.94, and 3.07 Ga, and a concordant age at 2.94 Ga, which suggest that the Yangtze continental nucleus underwent three important metamorphic–magmatic events in the Mesoarchean at ca. 3.00, 2.94, and 2.87 Ga. The biotite–tremolite schists have high ratios of K₂O/Na₂O and high contents of CaO, Cr, and Ni, thus showing the characteristics of high-K calc-alkaline island-arc volcanic rocks (basalt–andesite) that form by the partial melting of subducted oceanic crust. The data also provide further proof that a Mesoarchean metamorphic basement exists in the Yangtze Plate. Derivation of the magmatic protoliths of the biotite–tremolite schist enclaves from an oceanic crust during slab subduction, and the presence of these xenoliths within the TTG suite, indicate the existence of the initiation of plate tectonics during the Mesoarchean (≤2.94 Ga).

Three-dimensional V₂O₅ hollow structures have been prepared through a simple synthesis strategy combining solvothermal treatment and a subsequent thermal annealing. The V₂O₅ materials are composed of microspheres 2–3 μm in diameter and with a distinct hollow interior. The as-synthesized V₂O₅ hollow microspheres, when evaluated as a cathode material for lithium-ion batteries, can deliver a specific capacity as high as 273 mAh·g⁻¹ at 0.2 C. Benefiting from the hollow structures that afford fast electrolyte transport and volume accommodation, the V₂O₅ cathode also exhibits a superior rate capability and excellent cycling stability. The good Li-ion storage performance demonstrates the great potential of this unique V₂O₅ hollow material as a high-performance cathode for lithium-ion batteries.

This research focuses on the Hopf bifurcation occurring at a singular point with high-order degeneracy in a class of three-dimensional systems. Based on center manifold theorem, by expanding the technique for determining singular point values of degenerate singularities in two-dimensional systems, the formal series method to determine the singular point values at the high-order degenerate critical point is discussed. Furthermore, a class of specific three-dimensional differential systems with high-order degenerate singularities is explored. By computing the singular point values and determining center conditions, we proved that a minimum of 5 small-amplitude limit cycles in the vicinity of the origin. This research provides new perspectives on the center problem and limit cycle bifurcation in high-dimensional systems with high-order degenerate singular points.

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

Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

The oscillating heat pipe (OHP) is a new member in the family of heat pipes, and it has great potential applications in energy conservation. However, the fluid flow and heat transfer in the OHP as well as the fundamental effects of inner diameter on them have not been fully understood, which are essential to the design and optimization of the OHP in real applications. Therefore, by combining the high-speed visualization method and infrared thermal imaging technique, the fluid flow and thermal performance in the OHPs with inner diameters of 1, 2 and 3 mm are presented and analyzed. The results indicate that three fluid flow motions, including small oscillation, bulk oscillation and circulation, coexist or, respectively, exist alone with the increasing heating load under different inner diameters, with three flow patterns occurring in the OHPs, viz. bubbly flow, slug flow and annular flow. These fluid flow motions are closely correlated with the heat and mass transfer performance in the OHPs, which can be reflected by the characteristics of infrared thermal images of condensers. The decrease in the inner diameter increases the frictional flow resistance and capillary instability while restricting the nucleate boiling in OHPs, which leads to a smaller proportion of bubbly flow, a larger proportion of short slug flow, a poorer thermal performance, and easier dry-out of working fluid. In addition, when compared with the 2 mm OHP, the increasing role of gravity induces the thermosyphon effect and weakens the 'bubble pumping' action, which results in a little smaller and bigger thermal resistances of 3 mm OHP under small and bulk oscillation of working fluid, respectively.

In the recent years, tubular nanostructures have been related with immense advances in various fields of science and technology. Considerable research efforts have been centered on the theoretical prediction and manufacturing of non-carbon nanotubes (NTs), which meet modern requirements for the developing of novel devices and systems. In this context, diatomic inorganic nanotubes formed by atoms of elements from the 13th group of the periodic table (B, Al, Ga, In, Tl) and nitrogen (N), have received much research attention. In the present work, the elastic properties of single-walled boron nitride, aluminium nitride, gallium nitride, indium nitride and thallium nitride nanotubes were numerically evaluated using the nanoscale continuum modelling approach (also called molecular structural mechanics). The elastic properties (rigidities, surface Young´s and shear moduli, and Poisson´s ratio) of nitride nanotubes are discussed with respect to the bond length of the corresponding diatomic hexagonal lattice. The results obtained contribute to a better understanding of the mechanical response of nitride compound-based nanotubes, covering a broad range from the well-studied boron nitride NTs to the hypothetical thallium nitride NTs.

Cuproptosis, a copper-dependent cellular death mechanism, is typically overlooked in glioblastoma diagnosis. Lipoylation is needed for cuproptosis, and FDX1 controls this process. Cuproptosis in prognostic models may drive cancer treatment. This study evaluated cuproptosis and glioblastoma cell proliferation. The Cancer Genome Atlas provided annotated clinical, genetic mutation, and RNA sequencing data for the TCGA_GBM and TCGA_LGG cohorts. Patients with gliomas were randomly allocated to the validation or training cohort. Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models were utilized to evaluate which model best predicted prognosis in the training cohort. The models' independent predictive power was evaluated throughout the cohort. A previous study revealed 19 genes related to ferroptosis. LncRNAs associated with cuproptosis were identified by coexpression analysis. Cox discovered 17 cuproptosis-associated lncRNAs and established a predictive model. The median risk score classified patients as high- or low-risk. K‒M survival analysis demonstrated significant differences in overall survival among risk categories. Principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis were used to test the model’s predictive power. Univariate and multivariate Cox regression analyses revealed risk score-related independent prognostic factors. Multivariate Cox regression analysis was used to construct a nomogram for marker-based prognosis. The risk category affected the tumour mutation rate. High-risk glioma patients benefit from immunotherapy. Glioma drug sensitivity was also substantially linked with the risk score. The expression of 17 cuproptosis-related long noncoding RNAs (lncRNAs) may assist in the stratification of glioma patient prognosis, molecular characteristics, cell cycle gene regulation pathways, the TME, and clinicopathological aspects. Our clinical sample and database analysis revealed that cuproptosis influences glioma prognosis and may guide therapy.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

This paper presents a review on numerical and experimental methods to predict fracture of ad-vanced high strength steels (AHSS). AHSS are widely processed through sheet metal forming processes. Although being an excellent choice when lightweight, high strength and ductility are critical factors, their multi-phase microstructure accentuates forming challenges. To accurately model forming behavior, necking based failure criteria as well as direct fracture models require improvements. As a necking based failure model, the conventional forming limit diagram/curve (FLD/FLC) presents limitations such as in estimating direct fracture (surface cracks, edge cracks, shear cracks), as well as deformation histories under nonlinear strain paths. Thus, significant re-search efforts are being made towards the needs of advanced fracture constitutive models capa-ble of predicting fracture scenarios without necking, more frequently observed in the realm of AHSS. Scientific community research is divided into several directions aiming at improving the forming and fracture behavior accuracy of parts subjected to sheet metal forming operations. In this review paper, a comprehensive overview on ductile fracture modeling is presented. Firstly, the FLD/FLC limitations modeling fracture behavior in sheet metal forming operations are stud-ied. Followed by the recent trends in constitutive material modeling. Afterwards, material char-acterization methods advancements to cover a broad range of stress states are comprised. Final-ly, damage and fracture models predicting failure in AHSS are investigated. This review paper supplies relevant information on the current issues the sheet metal forming community is chal-lenged with due to the trend towards AHSS employment in the automotive industry.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

This study presents the utilization of the Microwave InfraRed Thermography (MIRT) technique to identify and analyze the defects in the carbon-fiber-reinforced polymer (CFRP) composite rein-forcement of concrete specimens. At first, a set of the numerical models was created, comprising of the broadband pyramidal horn antenna and the analyzed specimen. The utilization the system operating at a power of 1000W in a continuous mode, operating at frequency of 2.45 GHz was analyzed. The specimen under examination comprised a compact concrete slab that was covered with an adhesive layer, thereafter, topped with a layer of CFRP. An air gap represented a defect at the interface between the concrete and CFRP within the adhesive layer. In the modelling stage the study investigated three separate scenarios: a sample with no defects, a sample with a defect located at the center, and a sample with a numerous additional random defects located at the rim of the CFRP matte, to analyze the effect of the natural reinforcement degradation in this area. The next phase of the study involved conducting experiments to confirm the results obtained from nu-merical modeling. In the experiments the concrete sample aged for 10 years with the defect in the center and naturally developed defects at the CFRP rim was used. The study employed numerical modeling to explore the phenomenon of microwave heating in complex structures. The aim was to assess the chosen antenna design and identify the most effective experimental setup. These con-clusions were subsequently confirmed through experimentation. The observations made during the heating process were particularly remarkable, since they deviated from earlier studies that solely conducted measurements of the sample post-heating phase. The findings demonstrate that MIRT has the capacity to be employed as a technique for detecting flaws in concrete structures reinforced with CFRP.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p&lt;0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers expression in low (LGG) and high-grade gliomas (HGG). In 39 glioma cases, we assessed protein expression of autophagy markers LC3B, p62, and DRAM by immunohistochemistry (IHC) and mRNA expression of autophagy genes; PI3K, AKT, m-TOR, PTEN, ULK1, ULK2, UVRAG, Beclin 1 and VPS34 using RT-qPCR. Livak’s method was used to analyze the relative changes in gene expression and multi-variate Anova test and Spearman's correlation tests were performed for statistical significance. LC3B, p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases respectively. The expression of LC3B and p62 was notably higher in HGG compared to LGG. VPS34 exhibited a significant differential expression and increased fold change and demonstrated strong positive correlations with Beclin1 (rs=0.768), UVRAG (rs=0.802), and ULK2 (rs=0.786) in HGG compared to LGG, thus highlighting the potential link between autophagy and glioma progression. We Provide preliminary data for functional analysis of autophagy using cell culture model and to identify potential targets for therapeutic interventions

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Human detection from Unmanned Aerial Vehicles (UAV) is gaining popularity in the field of disaster management, crowd counting, people monitoring. Real time human detection from UAV is a challenging task, because of many constraints involved. This study proposes a system for real time detection of humans on videos captured from UAVs addressing three of these constraints namely, flying height, computation time and scale of viewing. The proposed method integrated an android application with a binary classifier based on Haar-features to automatically detect human / non-human class from UAV images. The video frames were parsed and detected humans from image frames were geo-localized and visualized on Google Earth. The performance was evaluated for geo-localization accuracy, computation time and detection accuracy, considering human coverage – pixel size relationship for various heights and scale factor. Based on flying height - human size relationship and tradeoff between detection accuracy vs computation time, the study came up with optimal parameters for OpenCV’s cv2.cascadeClassifier. detectMultiScale function. This paper establishes a strong ground for further research relating to real time human detection from UAV.

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.