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BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

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PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) and reticular pseudodrusen (RPD) in very old individuals. METHODS: The population-based Ural Very Old Study consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85 + years. All individuals living in the study regions and having an age of 85 + years were eligible for the study. The presence of AMD and RPDs was assessed on color fundus photographs, red-free fundus images, and optical coherence tomographic images. RESULTS: The study included 932 (61.1% of 1526) individuals (age:88.6 ± 2.7 years) with available fundus images. Prevalence of any, early, intermediate and late AMD was 439/932 (47.1%; 95%CI:44.0,50.0), 126/932 (13.5%; 95% CI:11.0,16.0), 185/932 (19.8%; 95% CI:17.3,22.3) and 128/932 (13.7%; 95% CI:11.7,15.7), respectively. Neovascular AMD was present in 63 eyes (6.8%;95%CI:5.3,8.3) and geographic atrophy in 65 eyes (7.0%;95%CI:5.0,9.0). Higher prevalence of any AMD and late AMD was significantly correlated with urban region of habitation (OR:3.34; 95% CI:2.37,4.71; P < 0.001), and with older age (OR:1.12; 95% CI:1.04,1.19; P = 0.001), female sex (OR:1.63; 95%CI:1.02,2.60; P = 0.04), and urban region of habitation (OR:2.89; 95% CI:1.59,5.26; P < 0.001), respectively. RPDs (assessed in 889 (58.3%) study participants) were present in 220/889 participants (24.7%; 95%CI:21.7,27.7). Higher RPD prevalence was associated (multivariable analysis) with higher serum concentration of the rheumatoid factor (OR:1.15; 95% CI:1.04,1.28; P = 0.008), shorter axial length (OR:0.84;95%CI:0.71,0.00;P = 0.04), and higher degree of nuclear cataract (OR:1.06; 95% CI:1.01,1.12; P = 0.02). AMD was the main cause for vision impairment in 230 (24.7%) participants, for moderate-to-severe vision impairment in 75 (8.0%; 95% CI: 6.4, 10.0) individuals, and for blindness in 15 (1.6%; 95%CI: 0.8, 2.5) persons respectively. CONCLUSIONS: In this ethnically mixed, very old population, AMD prevalence (any AMD:47.1%;late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher RPD prevalence correlated with shorter axial length. KEY MESSAGES: What is known The prevalence of age-related macular degeneration (AMD) has been explored in many studies and societies. Information is missing about its prevalence and associations in very old individuals. The same holds true for reticular pseudodrusen of the macula. What is new In an ethnically mixed, very old population in Bashkortostan / Russia, the prevalence of AMD (any AMD: 47.1%; late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher prevalence of reticular pseudodrusen correlated with shorter axial length.

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During the Mesolithic and Neolithic, foragers dwelling in the Eastern Baltic, Scandinavia and Fennoscandia regions buried some of their dead on lake islands or other coastal sites. Based on ethnographic accounts, these sites are often understood as liminal places where water separates the lands of the dead and the living. In this paper, we take a more relational view of place and suggest that a particular combination of spatial perception of landscape and the dynamic nature of coastal sites might have contributed to the social agency of these places, resulting in their use as places for ritual activity. By exploring two Mesolithic-Neolithic burial places, Donkalnis and Spiginas (western Lithuania), with sensory archaeological and artistic approaches, we suggest that the ancient foragers of this region buried human bodies in these locations to be part of the place itself. Similar to other depositional acts, this could have been done to mark the location or communicate with the surrounding world.

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Tumor deposits (TD) are tumor nodules in the lymphatic drainage area of colorectal cancer patients, and they are currently classified in the N category in the TNM classification. However, due to the associated poor prognosis, some small cohort studies suggest that TD belong in the M category. A retrospective study using The Surveillance, Epidemiology, and End Results program (SEER) data was performed in Stages III and IV colon carcinoma (CC) patients to evaluate the prognostic impact of TD. In multivariate analysis, TD have significantly negative effect on survival in both stages (Stage III HR = 1.4 [95% CI 1.4-1.5] and Stage IV HR = 1.3 [95% CI 1.2-1.3]). In Stage III, 5-year overall survival (OS) for patients with TD 49%, whereas it was 64% for patients without TD (p < .001). Additionally, in Stage IV patients without TD, the 5-year OS rates are superior at 21% compared to patients with TD, who show 5-year OS rate of 10% (p < .001). Stage III patients with TD (5-year OS 49%) have a significantly better prognosis compared to Stage IV patients (5-year OS 17%, p < .001). Therefore, despite the previous suggestions, this large scale study (n = 52,332) on outcomes in CC does not support the classification of TD in Stage IV.

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Hepatic glomerulosclerosis, a renal complication of liver cirrhosis, presents challenges in diagnosis and management. This case report discusses the rarity of kidney biopsy findings resembling lecithin-cholesterol acyltransferase (LCAT) deficiency post liver transplantation. We present the case of a patient with end-stage liver disease (ESLD) from alcohol-related cirrhosis, who underwent orthotopic liver transplantation (OLT) with persistent proteinuria after transplantation. Kidney biopsy revealed features of hepatic glomerulopathy resembling both IgA nephropathy (IgAN) and LCAT deficiency. The histopathological similarities between hepatic glomerulosclerosis and LCAT deficiency suggest a potential link between liver disease and lipid deposition in the kidneys. The clinical course and outcomes of such renal alterations post liver transplantation remain uncertain, highlighting the need for further research in glomerular pathology in the context of liver transplantation. This case underscores the importance of kidney biopsy in ESLD patients and the necessity for more attention to glomerular pathology post liver transplantation, especially in the current era of increasing liver transplantation rates.

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Introduction: One of the most common causes of vision loss in the elderly population worldwide is age-related macular degeneration (AMD). Subsequently, the number of people affected by AMD is estimated to reach approximately 288 million by the year 2040. The aim of this study was to develop an ex vivo model that simulates various aspects of the complex AMD pathogenesis. Methods: For this purpose, primary porcine retinal pigment epithelial cells (ppRPE) were isolated and cultured. One group was exposed to medium containing sodium iodate (NaIO3) to induce degeneration. The others were exposed to different supplemented media, such as bovine serum albumin (BSA), homogenized porcine retinas (HPR), or rod outer segments (ROOS) for eight days to promote retinal deposits. Then, these ppRPE cells were cocultured with porcine neuroretina explants for another eight days. To assess the viability of ppRPE cells, live/dead assay was performed at the end of the study. The positive RPE65 and ZO1 area was evaluated by immunocytochemistry and the expression of RLBP1, RPE65, and TJP1 was analyzed by RT-qPCR. Additionally, drusen (APOE), inflammation (ITGAM, IL6, IL8, NLRP3, TNF), oxidative stress (NFE2L2, SOD1, SOD2), and hypoxia (HIF1A) markers were investigated. The concentration of the inflammatory cytokines IL-6 and IL-8 was determined in medium supernatants from day 16 and 24 via ELISA. Results: Live/dead assay suggests that especially exposure to NaIO3 and HPR induced damage to ppRPE cells, leading in a significant ppRPE cell loss. All supplemented media resulted in decreased RPE-characteristic markers (RPE65; ZO-1) and gene expression like RLBP1 and RPE65 in the cultured ppRPE cells. Besides, some inflammatory, oxidative as well as hypoxic stress markers were altered in ppRPE cells cultivated with NaIO3. The application of HPR induced an enhanced APOE expression. Pre-exposure of the ppRPE cells led to a diminished number of cones in all supplemented media groups compared to controls. Discussion: Overall, this novel coculture model represents an interesting initial approach to incorporating deposits into coculture to mimic AMD pathogenesis. Nevertheless, the effects of the media used need to be investigated in further studies.

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Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare disease without standardized treatment modalities. Daratumumab is a human IgG monoclonal anti-CD38 antibody that has been demonstrated to be highly effective and safe in the treatment of PGNMID. This article reports a 66-year-old female who suffered from edema in both lower limbs and face for 6 years with mild proteinuria and hypoproteinemia. Renal biopsy displayed eight glomeruli, among which two presented with glomerulosclerosis, and the remaining six exhibited moderate diffuse hyperplasia of glomerular mesangial cells and stroma with endothelial cell proliferation. Immunofluorescence microscopy revealed lumpy and diffuse deposits of C3, C1q, IgG, and κ light chain in the glomerular mesangium, with strongly positive staining for IgG3 and varying degrees of weak to negative staining for IgG1, IgG2, IgG4, and λ light chain. Additionally, ultrastructural analysis unveiled that the glomerular basement membrane was segmentally thickened, accompanied by diffuse pedicle fusion, segmental tethered insertion, subendothelial deposits, and electron-dense material in tethered areas. The patient received a total dose of 800 mg of daratumumab (400 mg daily for two consecutive days), as well as daily prednisone (25 mg) and valsartan (80 mg), for treatment and achieved complete remission after three-month follow-up. This case represents an early attempt to treat PGNMID with low-dose daratumumab but requires long-term follow-up.

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Amyloidosis cutis dyschromica is a very rare form of primary cutaneous amyloidosis characterized by prepubertal onset of hyper and hypopigmented spots and amyloid deposits in the papillary dermis. We report two cases of this condition highlighting its dermoscopic findings.

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Introduction: Inside oil and gas pipelines, native microbial communities and different solid compounds typically coexist and form mixed deposits. However, interactions between these deposits (primarily consisting of mineral phases) and microorganisms in oil and gas systems remain poorly understood. Here, we investigated the influence of magnetite (Fe3O4), troilite (FeS), and silica (SiO2) on the microbial diversity, cell viability, biofilm formation, and EPS composition of an oil-recovered multispecies consortium. Methods: An oilfield-recovered microbial consortium was grown for 2 weeks in separate bioreactors, each containing 10 g of commercially available magnetite (Fe3O4), troilite (FeS), or silica (SiO2) at 40°C ± 1°C under a gas atmosphere of 20% CO2/80% N2. Results: The microbial population formed in troilite significantly differed from those in silica and magnetite, which exhibited significant similarities. The dominant taxa in troilite was the Dethiosulfovibrio genus, whereas Sulfurospirillum dominated in magnetite and silica. Nevertheless, biofilm formation was lowest on troilite and highest on silica, correlating with the observed cell viability. Discussion: The dissolution of troilite followed by the liberation of HS- (H2S) and Fe2+ into the test solution, along with its larger particle size compared to silica, likely contributed to the observed results. Confocal laser scanning microscopy revealed that the EPS of the biofilm formed in silica was dominated by eDNA, while those in troilite and magnetite primarily contained polysaccharides. Although the mechanisms of this phenomenon could not be determined, these findings are anticipated to be particularly valuable for enhancing MIC mitigation strategies currently used in oil and gas systems.

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KEY MESSAGES     : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative.

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For LiCoO2 (LCO) operated beyond 4.55 V (vs Li/Li+), it usually suffers from severe surface degradation. Constructing a robust cathode/electrolyte interphase (CEI) is effective to alleviate the above issues, however, the correlated mechanisms still remain vague. Herein, a progressively reinforced CEI is realized via constructing Zr─O deposits (ZrO2 and Li2ZrO3) on LCO surface (i.e., Z-LCO). Upon cycle, these Zr─O deposits can promote the decomposition of LiPF6, and progressively convert to the highly dispersed Zr─O─F species. In particular, the chemical reaction between LiF and Zr─O─F species further leads to the densification of CEI, which greatly reinforces its toughness and conductivity. Combining the robust CEI and thin surface rock-salt layer of Z-LCO, several benefits are achieved, including stabilizing the surface lattice oxygen, facilitating the interface Li+ transport kinetics, and enhancing the reversibility of O3/H1-3 phase transition, etc. As a result, the Z-LCO||Li cells exhibit a high capacity retention of 84.2% after 1000 cycles in 3-4.65 V, 80.9% after 1500 cycles in 3-4.6 V, and a high rate capacity of 160 mAh g-1 at 16 C (1 C = 200 mA g-1). This work provides a new insight for developing advanced LCO cathodes.

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Lymph node metastases (LNM) play a central role in the tumour-node-metastasis (TNM) classification for colorectal cancer (CRC), with extranodal extension (ENE) as an adverse feature. ENE has never been directly compared to tumour deposits (TD). The aim of this study was to perform an up-to-date systematic review, including a network meta-analysis to compare their prognostic value. A comprehensive search was conducted on PubMed, Embase, Web of Science and Cochrane databases to identify all prognostic studies on ENE and TD. A total of 20 studies were included, with 7719 cases. The primary outcome was 5-year disease-free survival (DFS); secondary outcomes were overall survival (OS) and disease-specific survival (DSS). Frequentist paired and network meta-analyses were performed using the netmeta package in R. For univariable DFS analysis, LNM + TD+ cases had a significantly worse outcome compared with LNM + ENE+ cases [hazard ratio (HR) = 1.27, 95% confidence interval (CI) = 1.06-1.53], which was no longer significant for multivariable DFS analysis (HR = 1.13, 95% CI = 0.87-1.46). All OS and multivariable DSS analyses showed a significantly worse outcome for LNM + TD+ cases compared with LNM + ENE cases. For all outcomes, both LNM + TD+ and LNM + ENE+ had a significantly increased hazard compared with LNM+ cases. This study shows that there is a trend towards worse outcome for LNM + TD+ than LNM + ENE+, not statistically significant in multivariable DFS analysis. Both groups perform significantly worse than cases with LNM only. To improve the accuracy of CRC staging, we recommend to put more emphasis on both ENE and TD in the TNM classification, with the most prominent role for TD.

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PURPOSE: To characterize fundus autofluorescence (FAF) in complete (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) by fluorescence lifetime imaging ophthalmology (FLIO). METHODS: Overall, 98 macular atrophy (MA) lesions in 42 eyes of 37 age-related macular degeneration (AMD) patients (mean age: 80.9 ± 5.8 years), 25 of them classified as iRORA and 73 as cRORA by OCT, were investigated by FLIO in a short (SSC: 498-560 nm) and a long wavelength channel (LSC: 560-720 nm). Differences of FAF lifetimes and peak emission wavelength (PEW) between atrophic lesions and intact retinal pigment epithelium (RPE) in the outer ring of the ETDRS grid were considered. RESULTS: FAF lifetimes in MA were longer and PEW were significantly (p < 0.001) shorter than in intact RPE by 112 ± 78 ps (SSC), 91 ± 64 ps (LSC), 27 ± 18 nm (PEW) in iRORA and by 227 ± 112 ps (SSC), 167 ± 81 ps (LSC), and 54 ± 17 nm (PEW) in cRORA. 37% of iRORA and 24% of cRORA were hyperautofluorescent in SSC. Persistent sub-RPE-BL material in MA was newly found as a hyperautofluorescent entity with lifetimes considerably longer than that of drusen and RPE. CONCLUSIONS: Despite RPE and, thus, lipofuscin are greatly absent in MA, considerable FAF, preferably at short wavelengths, was found in those lesions. Drusen, persistent sub-RPE-BL material, basal laminar deposits, persistent activated RPE, and sclera were identified as putative sources of this fluorescence. FLIO can help to characterize respective fluorophores.

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Tumour deposits (TDs) significantly impact colorectal cancer (CRC) prognosis. Integrating TDs into the TNM staging system can enhance individualized disease management. Keeping abreast of evolving TDs research is pivotal for clinical advancement. We comprehensively reviewed both recent and popular literature to grasp the field's essence. Subsequently, a data retrieval sourced articles on TDs in CRC for bibliometric analysis, spanning from 1 January 1935 to 30 April 2023. Bibliometrix software facilitated paper analysis and visualization. Bibliometric indicators, the trends and hotspots were determined. A total of 2147 articles were successfully retrieved. Brown G emerged as the most productive author, and the USA as the most prolific country. Central South University and Memorial Sloan Kettering Cancer Center led productivity. Bradford's law categorized 48 journals into zone 1. Keywords co-occurrence analysis identified three main clusters: the application of TDs in TNM staging, the pathogenesis of TDs, and the assessment of TDs. The trend topic analysis highlighted research focused on refining TDs incorporation into tumour staging. TDs wield enduring medical significance, shaping ongoing research. Much literature focused on confirming TD's prognostic value and optimizing TNM integration. Additionally, it is worth highlighting that TD's enigmatic pathogenesis demands research priority, as it holds the potential to unveil concealed knowledge regarding their development.

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PURPOSE: This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. METHODS: Narrative review of the literature published until May 2024. RESULTS: The early onset age of EMAP (50-55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. CONCLUSION: EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management.

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Hemochromatosis is a condition marked by excessive iron accumulation, causing dysfunction in various organs. A 50-year-old woman, previously in good health, reported abdominal pain and yellowing of the skin and eyes for one month. Upon examination, she exhibited widespread jaundice, leg swelling, and abdominal distention. Her total bilirubin level was 24.52 mg/dL at admission, indicating hyperbilirubinemia. Imaging studies, including USG and CT scans, revealed mild to moderate ascites and altered liver texture. Elevated serum ferritin (1443 ng/mL) and transferrin saturation (84%) suggested iron overload. A liver biopsy confirmed the presence of iron deposits in hepatocytes, leading to a diagnosis of hemochromatosis. Genetic testing was negative for the C282Y and H63D mutations, resulting in a diagnosis of non-homeostatic iron regulator (non-HFE) related hereditary hemochromatosis. The patient began weekly phlebotomy and was monitored regularly, with a liver transplant being considered as a potential treatment.

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The Twangiza-Namoya Gold Deposit within the Kibaran Belt of the Democratic Republic of the Congo represents a crucial manifestation of the hydrothermal gold system. This review investigates its intricate origin and the subsequent metallogenic evolution that has shaped its present-day characteristics and offers a systematic categorization based on its deposition processes and geotectonic settings. The findings reveal that the gold deposits are predominantly derived from sedimentary fluid sources. Within this vast metallogenic province, two stages of gold deposition have been constrained: (a) the early-stage formation related to the accretion of Rodinia assembly with subduction-collisional event where diagenesis cemented the syngenetic pyrite carbonaceous sediments and (b) the later stage deposition related to the continent-collisional event during the last stage of Rodinia supercontinent amalgamation. Previous isotopic investigations, with a particular emphasis on pyrite sulfur isotopes on both host rocks and vein-bearing sulfides, have been instrumental in tracing the origins of gold-bearing fluids in the study region. The isotopic variance in the four deposits: Twangiza (-5.2 % to +3 %, avg. -0.3 %), Kamituga (-0.6 % to -0.9.1 %, avg. -5%), Lugushwa (+3.0 % to -18.4 %), and Namoya, on the southernmost end, has a vast range but with much heavier isotope compositions, ranging between +1.3 % and to +22.6 %, with an average of +12.2 %. The data predominantly points to the sedimentary origins of ore fluids in the Twangiza-Namoya Gold belt, highlighting the pivotal role of sedimentary processes in shaping the metallogenic landscape of the region. The fluids inclusions depicted the deposits to be formed from H2O-Nacl-H2O with abundant CH4 and N2 ore-forming fluid, moderate temperature (350-500 °C), and low salinity. The overall results confirm the genetic style of the Twangiza-Namoya Gold Belt to be an orogenic gold-style deposit that was emplaced during the early Neoproterozoic era in low greenschist facies terrain.

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This study presents a comprehensive analysis of mineralization exploration in the Egyptian Eastern Desert (ED), one of the most sought-after areas for those interested in mining industry, by integrating Landsat-9 images and geophysical magnetic data. Employing advanced techniques like Principal Component (PC) analysis, Minimum Noise Fraction (MNf) transform, and Band-Ratio (B-Ratio), the research focuses on mapping lithological units, hydrothermal alteration regions, and structural elements. Composite images derived from specific PC, and MNf bands, and B-Ratio exhibit superior lithological unit identification. The findings emphasize that there are significant variations in the types of rocks extend from the southern to the northern parts of the ED. Hydrothermal alteration mapping, guided by B-Ratio results, aids qualitative lithological discrimination. A novel false color composite image optimizes Landsat-9 B-Ratios, enhancing rock unit discrimination. Correlation analyses reveal associations between mineralization types and major lithological units, while exploration of the magnetic anomaly map highlights its role in correlating mineralization sites. Structural features, analyzed through Center for Exploration-Targeting Grid-Analysis (CET-GA) and Center for Exploration-Targeting Porphyry-Analysis (CET-GA) with Tilt Derivative of RTP (TDR) techniques, contribute to a robust association between regions with medium to high structural density and porphyry intrusions and mineralization. The study significantly supports the advanced exploration geoscience, providing insights into the geological structures and dynamics governing mineralization in the Egyptian ED.