Search

Background: Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy. Methods: We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential PIK3CA mutations using Sanger sequencing. Results: High HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression. Conclusion: Our findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.

Analysing complex diseases such as chronic inflammatory joint diseases (CIJDs), where many factors influence the disease evolution over time, is a challenging task. CIJDs are rheumatic diseases that cause the immune system to attack healthy organs, mainly the joints. Different environmental, genetic and demographic factors affect disease development and progression. The Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) Foundation maintains a national database of CIJDs documenting the disease management over time for 19'267 patients. We propose the Disease Activity Score Network (DAS-Net), an explainable multi-task learning model trained on patients' data with different arthritis subtypes, transforming longitudinal patient journeys into comparable representations and predicting multiple disease activity scores. First, we built a modular model composed of feed-forward neural networks, long short-term memory networks and attention layers to process the heterogeneous patient histories and predict future disease activity. Second, we investigated the utility of the model's computed patient representations (latent embeddings) to identify patients with similar disease progression. Third, we enhanced the explainability of our model by analysing the impact of different patient characteristics on disease progression and contrasted our model outcomes with medical expert knowledge. To this end, we explored multiple feature attribution methods including SHAP, attention attribution and feature weighting using case-based similarity. Our model outperforms temporal and non-temporal neural network, tree-based, and naive static baselines in predicting future disease activity scores. To identify similar patients, a k-nearest neighbours regression algorithm applied to the model's computed latent representations outperforms baseline strategies that use raw input features representation.

Abstract Graphene presents practical applications in energy storage devices, especially supercapacitors. However, mainstream synthesis of graphene includes toxic chemical usage, which threatens the environment. With the recent attention shift to synthesizing nanomaterials from agro-waste due to their easy availability, cost-effectiveness, and, most importantly, their environmental friendliness, we present, in this work for the first time, a novel and green synthesis of few-layered graphene sheets using pomegranate peels as a precursor at a low temperature of 80 °C. The surface morphology and microstructural properties are determined by Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray spectroscopy (EDX), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), UV–visible spectroscopy (UV–vis), and the electrical properties determined by Hall Effect Measurement. The application as a supercapacitor is also examined using Cyclic Voltammetry (CV), Charge–Discharge Cycling (GCD), and Electrochemical Impedance Spectroscopy (EIS). The resulting supercapacitor delivers an areal capacitance of $$3.39 mF{cm}^{-2}$$ 3.39 m F cm - 2 at a current density of 15.6 μA $${cm}^{-2}$$ cm - 2 , making our synthesized graphene a good choice for electrochemical storage devices.

Abstract Introduction Stereotactic body radiotherapy (SBRT) is an ablative method for lung malignancies. Here, the definition of the gross target volume (GTV) is subject to interobserver variation. In this study, we aimed to evaluate the interobserver variability during SBRT and its dosimetric impact, as well as to introduce a semi‐automated delineation tool for both planning computer tomography (P‐CT) and cone beam CT (CBCT) to help to standardise GTV delineation and adaptive volume‐change registration. Methods The interobserver variation of GTV manual contours from five physicians was analysed in 15 patients after lung SBRT on free breathing (FB) P‐CT (n = 15) and CBCT (n = 90) before and after each fraction. The dosimetric impact from interobserver variations of GTV based on the original treatment plan was analysed. Next, the accuracy of an in‐house easy‐to‐use semi‐automated‐segmentation algorithm for pulmonary lesions was compared with gold standard contours in FB P‐CT and CBCT, as well as 4D P‐CT of additional 10 patients. Results The interobserver variability in manual contours resulted in violations of dose coverage of the planning target volume (PTV), which, in turn, resulted in compromised tumour control probability in contours from four physicians. The validation of the semi‐automated delineation algorithm using thorax phantom led to a highly reliable accuracy in defining GTVs. Comparing the unsupervised auto‐contours with the gold standard delineation revealed high equal high concordance for FB P‐CT, 4D P‐CT and CBCT, with a DSC of 0.83, 0.76 and 0.8, respectively. The supervised use of the semi‐automated delineation tool improved its accuracy, with DSCs of 0.86, 0.86 and 0.8 for FB P‐CT, 4D P‐CT and CBCT, respectively. The use of the algorithm was associated with a significantly shorter working time. The semi‐automated delineation tool can accurately register volume changes in CBCTs. Conclusion The segmentation algorithm provides a reliable, standardised and time‐saving alternative for manual delineation in lung SBRT in P‐CT and CBCT.

Abstract Background Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy. Methods This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients. Discussion The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.

The spinning and weaving industry is one of the oldest industries known to man, and it began as a handicraft to which man was guided by his instinct, making for himself what he used to cover his body and protect it from the cold of winter, then it developed after a period of time using mechanical processes in this industry (5)The production of pile textiles represents a wide sector of the textile production sectors because of its importance in covering many functional and aesthetic dimensions of the consumer, It is unique from the common and commonly used types of textiles with its structural theories, design rules, and technical methods for its production, represented by the stages of production and equipment for the production of pile. (1)Webbing textiles are distinguished among all other textiles by their effectiveness towards highlighting and confirming the technical, aesthetic and functional trends of the third dimension of the fabric represented in thickness, which arises mainly from achieving the pile appearance of that type of fabrics, whether cut pile or uncut, each of which plays a major role in determining dimensions and performance rules Functional and aesthetic of pile weaving product (3).The research aims to take advantage of the applied methods of hand tufted carpets as a source for the design and production of textile pendants with Egyptian character and identity, and to achieve the objectives of the study, a group of (10) designs were made, through the foundations of design and technology of hand tufted carpets, using some Islamic of geometric, vegetarian, and Islamic Mafroka, to emphasize and enrich the aesthetic values of the fabric hanging design.A number of designs were selected and implemented using hand tufted carpet techniques (Tuft), and to determine the quality level of designs, their relevance implementation technology, and the achievement of the Egyptian identity, a tool (evaluation form) was designed and applied by referees specialized in the field, after the application of the questionnaire, its data were statistically processed and the best (5) designs were reached, in the end, the study reached a set of conclusions and recommendations, if applied, it can achieve an advanced level in the quality of hand tufting carpet industry in general, and the design and production of pile textile in particular.

In animal production systems around the world, brucellosis is a serious zoonotic disease that creates public health hazards and losses in economic terms. The aim of the study is to genotype and molecularly characterize Brucella melitensis (B. melitensis) and Brucella abortus (B. abortus) collected from different animal species and humans. A total of 50 isolates of Brucella species (16B. melitensis and 34B. abortus) were isolated from 1081 animal and human samples using a culture technique, followed by biochemical identification using the Vitek 2 compact system and proteomic identification using mass spectrometry technology. Molecular genotyping was performed on all isolates using multiplex real-time PCR. Six isolates from each genotype of Brucella species were selected and genetically evaluated by IS711 insertion sequences. Microchips-based real-time PCR for Brucella species identification was performed on twelve genetically characterized isolates as a first attempt. Forty-four (88%) isolates of Brucella species were detected using multiplex real-time PCR. Based on IS711 nucleotide sequencing, twelve isolates were phylogenetically clustered into their specific clusters. The results of the comparative analysis of conventional real time and microchips-based real time indicated that the later is faster and qualitatively more sensitive than conventional real time; however, further studies are needed to ensure that it is capable of serving as a gold standard alternative for Brucella species monitoring.

This study aimed to evaluate the possible protective effect of platelet-rich plasma (PRP) on ischemia reperfusion (I/R)-induced ovarian injury in a rat model. Forty adult female albino rats were randomly assigned to four groups: control, ischemia, I/R, and I/R + intraperitoneal PRP. Induction of ischemia was done by bilateral ovarian torsion for 3 h, while reperfusion was done by subsequent detorsion for another 3 h. PRP was injected 30 min before detorsion. Histological assessment and measurement of ovarian anti-Mullerian hormone (AMH) were done to assess the degree of tissue damage and the remaining ovarian reserve. Ovarian malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured to evaluate the oxidant-antioxidant balance. Tumor necrosis factor-α (TNF-α) was measured to assess degree of inflammation. Immunohistochemical assessment of ovarian vascular endothelial growth factor-A (VEGF-A) was also done. PRP treated I/R group revealed a significant decrease in MDA (P = 0.007), TNF-α (P = 0.001), and a significant increase in TAC (P = 0.001) and VEGF-A (P = 0.003) in comparison to the untreated I/R group. Furthermore, limited vascular congestion and inflammatory infiltration were observed after PRP treatment. However, no significant difference was detected in AMH after PRP treatment. Our results denoted that PRP may help in preservation of ovarian function and structure during surgical conservative detorsion of the torsioned ovary. These protective effects could be attributed to its ability to reduce oxidative stress, inflammation and also to its high content of growth factors especially VEGF.

This research, entitled (Combining the Two Prizes in a House with One Novel Syntactic Morphological Study) is an attempt to find out a linguistic phenomenon mentioned in our poetic heritage, and I wanted it to study its images, reasons, and motives for it with the arrangement of what was mentioned and its classification grammatically, morphologically and semantically, and the phenomenon of collecting the poet came between The winners in a house with a single novel are scattered in the stomachs of books and references, without collecting their scattered or surveying their pictures. I intended to write on this topic a study that clarifies his feelings, clarifies his concept, collects what is dispersed from him and reveals his rulings. It became clear to me that the motive for this phenomenon is to show the poet's ability to speak the language and to familiarize him with its grammar, his knowledge of the languages and dialects of Arabs, and to inform him of the ex-poems and their simulations, and his use of it if he had to adjust his weights in the face of some of his Arabic hues. I gathered twenty-five verses from the eyes of authentic and authentic Arabic poetry, and I ask God for success

Abstract Background Drug–drug interactions (DDIs) refer to processes triggered by the administration of two or more drugs leading to side effects beyond those observed when drugs are administered by themselves. Due to the massive number of possible drug pairs, it is nearly impossible to experimentally test all combinations and discover previously unobserved side effects. Therefore, machine learning based methods are being used to address this issue. Methods We propose a Siamese self-attention multi-modal neural network for DDI prediction that integrates multiple drug similarity measures that have been derived from a comparison of drug characteristics including drug targets, pathways and gene expression profiles. Results Our proposed DDI prediction model provides multiple advantages: (1) It is trained end-to-end, overcoming limitations of models composed of multiple separate steps, (2) it offers model explainability via an Attention mechanism for identifying salient input features and (3) it achieves similar or better prediction performance (AUPR scores ranging from 0.77 to 0.92) compared to state-of-the-art DDI models when tested on various benchmark datasets. Novel DDI predictions are further validated using independent data resources. Conclusions We find that a Siamese multi-modal neural network is able to accurately predict DDIs and that an Attention mechanism, typically used in the Natural Language Processing domain, can be beneficially applied to aid in DDI model explainability.

Base editors enable precise genetic alterations but vary in efficiency at different loci. Here the authors analyse ABEs and CBEs at over 28,000 integrated sequences to train BE-DICT, a machine learning model capable of predicting base editing outcomes.

Trapezoidal cross-sectional spiral microfluidic channels showed high resolution and throughput in cell separation in bio-applications. The main challenges are the complexity and high cost of the fabrication process of trapezoidal cross-sectional channels on the micro-scale. In this work, we present the application of grayscale in microfluidic channel design to overcome the complexity of the fabrication process. We also use direct engraving with a CO2 laser beam on polymethyl methacrylate (PMMA) material to drastically reduce the microfluidic chip’s cost (to

PurposeTo describe the survival and toxicity outcome from a single-centre experience in patients with squamous cell cancer of the anal canal (SCC-AC), related to the impact of technological advances in diagnostics and radiation techniques.Material and MethodsA retrospective cohort study was performed after the approval of the institutional ethical committee (EK 478-21). We identified 142 patients in our registry, who received radical treatment for SCC-AC between 2000 and 2020. Fifty-five patients had FDG PET/CT for initial staging and target volume delineation, 87.33% received concomitant chemoradiotherapy (CRT), 64 patients were treated with 3-dimensional conformal radiotherapy (3DRT) between 2000-2009, and 78 patients with intensity-modulated radiotherapy (IMRT) between 2009-2020. Endpoints for the analysis included locoregional relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Acute and late toxicities were also reported.ResultsAt a median follow-up of 31.2 months, the median overall survival was 135 months, 5-year LRFS was 73.1%, 5-year DFS was 65.3%, and 5-year CSS was 75.3%. The use of IMRT was associated with shorter treatment duration. In the univariate analysis, IMRT was associated with significantly improved DFS and CSS for the whole cohort and significantly improved DFS, OS, and CSS for patients who received CRT. In the multivariate analysis, IMRT was associated with the improvement of all survival paraments. The use of FDG PET/CT did not translate into an improvement in the survival outcomes in both univariate and multivariate analyses. Grade-3 and more dermatological toxicities occurred less frequently, but hematological toxicities were more frequent in the IMRT-group. Late side effects and colostomies were less frequently reported in the IMRT group.ConclusionThe use of IMRT in the management of SCC-AC was associated with improvement of the oncological outcomes with improved toxicity profiles in this long-term single-centre experience.