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Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a-d and 12a-e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a-d) or 4-methyl-5-(aryldiazenyl)thiazole (12a-e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site.

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Type 2 diabetes mellitus (T2DM) is a chronic disease with ever-increasing prevalence worldwide. In our study, we evaluated the prevalence of the risk of developing T2DM in Saudi Arabia and investigated associations between that risk and various sociodemographic characteristics. To those ends, a web-based cross-sectional survey of Saudi nationals without diabetes, all enrolled using snowball sampling, was conducted from January 2021 to January 2022. The risk of developing T2DM was evaluated using a validated risk assessment questionnaire (ARABRISK), and associations of high ARABRISK scores and sociodemographic variables were explored in multivariable logistic regression modeling. Of the 4559 participants, 88.1% were 18 to 39 years old, and 67.2% held a college or university degree. High ARABRISK scores were observed in 7.5% of the sample. Residing in a midsize city versus a large city was associated with a lower ARABRISK risk score (p = 0.007), as were having private instead of governmental insurance (p = 0.005), and being unemployed versus employed (p < 0.001). By contrast, being married (p < 0.001), divorced or widowed (p < 0.001), and/or retired (p < 0.001) were each associated with a higher ARABRISK score. A large representative study is needed to calculate the risk of T2DM among Saudi nationals.

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In the current work, we designed and synthesized three families of non-fused and fused compounds based on cyanopyridone: derivatives of 6-amino-1,2-dihydropyridine-3,5-dicarbonitrile (5a-f) and 3,4,7,8-tetrahydro pyrimidine-6-carbonitrile (6a-b and 7a-e). The newly synthesized compounds' structure were determined using a variety of techniques, including 1H NMR, 13C NMR, mass spectrum, infrared spectroscopy, and elemental analysis. The developed compounds were tested for the ability to inhibit the growth of breast adenocarcinoma (MCF-7) and hepatic adenocarcinoma (HepG2) cell lines using MTT assay. Some of the synthesized compounds were more effective towards the cancer cell lines than the standard treatment taxol. The best antiproliferative activities were demonstrated by non-fused cyanopyridones 5a and 5e against the MCF-7 cell line (IC50 = 1.77 and 1.39 µM, respectively) and by compounds 6b and 5a against the HepG2 cell line (IC50 = 2.68 and 2.71 µM, respectively). We further explored 5a and 5e, the two most potent compounds against the MCF-7 cell line, for their ability to inhibit VEGFR-2 and HER-2. Finally, docking and molecular dynamics simulations were performed as part of the molecular modeling investigation to elucidate the molecular binding modes of the tested compounds, allowing for a more thorough comprehension of the activity of compounds 5a and 5e.

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In this work, different series of benzothiazole-based sulphonamides 8a-c, 10, 12, 16a-b and carboxylic acids 14a-c were developed as novel SLC-0111 analogues with the goal of generating potent carbonic anhydrase (CA) inhibitors. The adopted strategy involved replacing the 4-fluorophenyl tail in SLC-0111 with a benzothiazole motif that attached to the ureido linker to produce compounds 8c and its regioisomers 8a-b. In addition, the ureido spacer was elongated by methylene or ethylene groups to afford the counterparts 10 and 12. In turn, the primary sulfamoyl zinc binding group (ZBG) was either substituted or replaced by carboxylic acid functionality in order to provide the secondary sulphonamide-based SLC-0111 analogues 16a-b, and the carboxylic acid derivatives 14a-c, respectively. All compounds (8a-c, 10, 12, 14a-c and 16a-b) were tested for their ability to inhibit CA isoforms CA I, II, IX and XII. Additionally, the in vitro anticancer properties of the developed CAIs were evaluated.

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OBJECTIVES: As rates of oral and maxillofacial cancer (OMFC) continue to rise, the role of dentists in early detection and prevention has become increasingly important. The present study examined the frequency and pattern of OMFC cases diagnosed at a referral dental hospital. METHODS: A retrospective analysis of all primary malignant neoplasms of the oral and maxillofacial area diagnosed at the Histopathology Laboratory of the Dental University Hospital, Medical City, King Saud University, Saudi Arabia from 1984 to 2020 was performed. RESULTS: A total of 242 patients had histologically diagnosed primary malignant neoplasms of the oral and maxillofacial area, accounting approximately 3.7% of the archives. The mean age of patients was 48.87 years, and the male-to-female ratio was 1.5:1. The most prevalent malignant neoplasm was squamous cell carcinoma (SCC) (58.3%), followed by mucoepidermoid carcinoma (11.6%). The tongue and gingiva were the most prevalent malignancy sites, accounting for 19.8% and 18.2% of the cases, respectively. The prevalence of SCC in patients over 50 years old (68.4%) was highly significantly greater than that in younger subjects (31.5%) (P < 0.0005). SCC was also more common in males (66.7%) than in females (33.3%) (P = 0.026). CONCLUSION: OMFC primarily affecting the tongue and gingiva was the predominant in older male patients. SCC was the most frequent type of OMFC and was significantly associated with age older than 50 years. This study provides baseline data on the frequency of OMFC cases diagnosed for the first time by dental practitioners and warrants the need for increasing OMFC awareness among these clinicians.

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Different 2,4-thiazolidinedione-tethered coumarins 5a-b, 10a-n and 11a-d were synthesised and evaluated for their inhibitory action against the cancer-associated hCAs IX and XII, as well as the physiologically dominant hCAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins 10a, 10 h, and 2-thienyl/furyl-bearing coumarins 11a-c exhibited the best hCA IX (KIs between 0.48 and 0.93 µM) and hCA XII (KIs between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target hCA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins 10a, 10 h and 11a-c, were assessed in an in vitro antiproliferative assay, and then the most potent antiproliferative agent 11a was tested to explore its impact on the cell cycle phases and apoptosis in MCF-7 breast cancer cells to provide more insights into the anticancer activity of these compounds.

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Background: Since the beginning of COVID-19 pandemic, many associated factors have been investigated to clarify the susceptibility and severity among the affected individuals. Biological markers can play an important role in identification of individual susceptibility to such pandemic. Growing evidence suggest the influence of different blood group systems on susceptibility to COVID-19 virus, with a particular blood type conferring selection advantage. Objectives: The study aimed to determine the association of ABO, Rhesus (D) and P1 blood groups with COVID-19 susceptibility in Taif city, Western Saudi Arabia. Methods: ABO, D and P1 blood antigens were determined in 104 blood samples of COVID-19 patients versus 100 control samples using either automated immunohematology analyser or test tube method. Statistical differences between patients and control samples were calculated based on p-value where results of ≤ 0.05 were considered significant. Results: O+ve blood group constituted the predominant type among the studied samples. Determination of P1 antigen showed significant association where Anti-P1 was positive in 76.9% of patients compared to 61.0% of controls with a P value of 0.01 conferring the susceptibility of P1+ve patients to COVID-19. Conclusion: Although our study showed no significant association between ABO and D, and susceptibility to COVID-19, there was a significant association between P1+ve and COVID-19. P1+ve participants were 2.131 times more associated with the risk of COVID-19 infection than those with Anti P1-ve. Thus, P1 antigen can be used as a biological marker for identification of individuals susceptibility to COVID-19. It is strongly advised that such individuals should consider extra protective measures. Further studies on other contributing factors should also be considered for more scientific clarity.

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SARS-CoV-2 (COVID-19), a novel coronavirus causing life-threatening pneumonia, caused a pandemic starting in 2019 and caused unprecedented economic and health crises all over the globe. This requires the rapid discovery of anti-SARS-CoV-2 drug candidates to overcome this life-threatening pandemic. Strawberry (Fragaria ananassa Duch.) and ginger (Zingiber officinale) methanolic extracts were used for silver nanoparticle (AgNPs) synthesis to explore their SARS-CoV-2 inhibitory potential. Moreover, an in silico study was performed to explore the possible chemical compounds that might be responsible for the anti-SARS-CoV-2 potential. The characterization of the green synthesized AgNPs was carried out with transmission electron microscope (TEM), Fourier-transform infrared, spectroscopy ultraviolet-visible spectroscopy, zeta potential, and a dynamic light-scattering technique. The metabolic profiling of strawberry and ginger methanolic extract was assessed using liquid chromatography coupled with high-resolution mass spectrometry. The antiviral potential against SARS-CoV-2 was evaluated using an MTT assay. Moreover, in silico modeling and the molecular dynamic study were conducted via AutoDock Vina to demonstrate the potential of the dereplicated compounds to bind to some of the SARS-CoV-2 proteins. The TEM analysis of strawberry and ginger AgNPs showed spherical nanoparticles with mean sizes of 5.89 nm and 5.77 nm for strawberry and ginger, respectively. The UV-Visible spectrophotometric analysis showed an absorption peak at λmax of 400 nm for strawberry AgNPs and 405 nm for ginger AgNPs. The Zeta potential values of the AgNPs of the methanolic extract of strawberry was -39.4 mV, while for AgNPs of ginger methanolic extract it was -42.6 mV, which indicates a high stability of the biosynthesized nanoparticles. The strawberry methanolic extract and the green synthesized AgNPs of ginger showed the highest antiviral activity against SARS-CoV-2. Dereplication of the secondary metabolites from the crude methanolic extracts of strawberry and ginger resulted in the annotation of different classes of compounds including phenolic, flavonoids, fatty acids, sesquiterpenes, triterpenes, sterols, and others. The docking study was able to predict the different patterns of interaction between the different compounds of strawberry and ginger with seven SARS-CoV-2 protein targets including five viral proteins (Mpro, ADP ribose phosphatase, NSP14, NSP16, PLpro) and two humans (AAK1, Cathepsin L). The molecular docking and dynamics simulation study showed that neohesperidin demonstrated the potential to bind to both human AAK1 protein and SARS-CoV-2 NSP16 protein, which makes this compound of special interest as a potential dual inhibitor. Overall, the present study provides promise for Anti-SARS-CoV-2 green synthesized AgNPs, which could be developed in the future into a new anti-SARS-CoV-2 drug.

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Objective Post-operative infection after cardiac surgery causes prolonged hospital stay and increased mortality. In patients with diabetes, peri-operative and pre-operative glycemic control have been associated with increased risk of post-operative infection. Saudi Arabia is the 7th highest country in the world for the prevalence of diabetes. In our surgical population the incidence of diabetes is 77%. We were aware of a high incidence of post-operative infections in our institution. The aim of this work was to assess how peri-operative and pre-operative glycemic control was related to the six-week incidence of post-operative infection. Method We retrospectively collected data for 174 adult patients with diabetes undergoing cardiac surgery between January 2017 and June 2019. For group analysis of peri-operative glycemic control, a mean value of ≤10 mmol/l was categorized as optimal control and a mean value of >10 mmol/l as sub-optimal control. The admission glucose value, the maximum glucose value and glycosylated hemoglobin A1c (HbA1c) were separately recorded. Admission HbA1c was used for optimal long-term control group (HbA1c ≤ 7%) and sub-optimal long-term control group (HbA1c > 7%). Results Of the 174 patients 60 (34%) developed infection in the six-week post-operative period. No statistically significant difference in infections was seen in the optimal peri-operative control group (n = 24, 14%) compared to sub-optimal peri-operative control group (n = 36, 21%; p = 0.113). However, patients with infection had a significantly higher mean glucose (10.4 mmol/l versus 9.9 mmol/l, p = 0.0316) than no infection. Grouping according to their HbA1c: well controlled group (41, 24.0%) and poor control group (130, 76.0%) showed no difference in infections. However, patients with lower HbA1c had better glycemic control as measured by: initial glucose (r = 0.52, p=<0.001); mean peri-operative glucose (r = 0.45, p=<0.001); maximum recorded glucose (r = 0.41, p=<0.001). Conclusion The majority of our patients presented with sub-optimal long-term glycemic control which we linked to poor stress glycemic control perioperatively. Patients with post-operative infections had higher mean peri-operative blood glucose. With the high incidence of diabetes in Saudi Arabia we have demonstrated the importance of good pre-operative assessment which allows tighter peri-operative glycemic control to reduce post-operative morbidity.

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Human health in the current medical era is facing numerous challenges, especially cancer. So, the therapeutic arsenal for cancer should be unremittingly enriched with novel small molecules that selectively target tumour cells with minimal toxicity towards normal cells. In this context, herein a new series of 3,6-disubstituted pyridazines 11a-r has been synthesised and evaluated for in vitro anticancer activity. They possessed good anti-proliferative action towards human breast cancer T-47D (IC50 range: 0.43 ± 0.01 - 35.9 ± 1.18 µM) and MDA-MB-231 (IC50 range: 0.99 ± 0.03 - 34.59 ± 1.13 µM) cell lines, whereas they displayed weak activity against the tested ovarian cancer cell line SKOV-3. Among the studied compounds, the methyltetrahydropyran-bearing pyridazine 11m emerged as the unique submicromolar growth inhibitor herein reported towards both T-47D (IC50 = 0.43 ± 0.01 µM) and MDA-MB-231 (IC50 = 0.99 ± 0.03 µM) cell lines. In addition, the biological results indicated that pyridazines 11l and 11m exerted an efficient alteration within the cell cycle progression as well as induction of apoptosis in both T-47D and MDA-MB-231 cells. Moreover, pyridazines 11l and 11m displayed good mean tumour S. I. values of 13.7 and 16.1 upon assessment of their cytotoxicity towards non-tumorigenic breast MCF-10A cells. Furthermore, an in silico study proposed CDK2 as a probable enzymatic target for pyridazines 11, and explored their binding interactions within the vicinity of CDK2 binding site. Subsequently, pyridazines 11e, 11h, 11l, and 11m were selected to be evaluated for their ability to inhibit CDK2, where they exerted good inhibitory activity (IC50 = 151, 43.8, 55.6 and 20.1 nM, respectively). Finally, the in silico study implied that target pyridazines 11 exhibited not only an efficient anticancer activity but also an acceptable ADME, physicochemical and druglikeness properties, specifically pyridazines 11l and 11m. Overall the obtained results from this study quite sustained our strategy and gave us a robust opportunity for further development and optimisation of 3,6-disubstituted pyridazine scaffold to enrich therapeutic arsenal with efficient and safe anticancer CDK inhibitors.

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Background/purpose: Periapical lesions of endodontic origin are often diagnosed based on the clinical and radiological presentations that may be different from the histological diagnoses. The purpose of this study was to assess the concordance between the clinical diagnosis of these lesions and the histopathological diagnoses and to analyze their clinical and pathological features. MATERIALS AND METHODS: Biopsies of periapical lesions of endodontic origin diagnosed in the histopathology laboratory between 2006 and 2017 were retrieved from the database and used to conduct this retrospective review. Clinical data were obtained, and tissue samples were re-evaluated. The overall agreement between the clinical and histological diagnoses was tested utilizing the Cohen kappa (k). RESULTS: A total of 317 periapical biopsy specimens were included in this study which consisted of 137 periapical granulomas, 174 periapical cysts, and six periapical scars. Generally there was weak overall agreement between the clinical and histological diagnoses of periapical granuloma and periapical cysts (Cohen kappa, k = 0.059). CONCLUSION: The findings of this study indicate that clinical/radiographic examinations are not able to preoperatively determine whether a periapical lesion is a cyst or a granuloma and highlights the importance of developing a reliable nonsurgical diagnostic method to differentiate periapical lesions.

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As a continuation for our previous work, a novel set of N-alkylindole-isatin conjugates (7, 8a-c, 9 and 10a-e) is here designed and synthesised with the prime aim to develop more efficient isatin-based antitumor candidates. Utilising the SAR outputs from the previous study, our design here is based on appending four alkyl groups with different length (ethyl and n-propyl), bulkiness (iso-propyl) and unsaturation (allyl) on N-1 of indole motif, with subsequent conjugation with different N-unsubstituted isatin moieties to furnish the target conjugates. As planned, the adopted strategy achieved a substantial improvement in the growth inhibitory profile for the target conjugates in comparison to the reported lead VI. The best results were obtained with N-propylindole -5-methylisatin hybrid 8a which displayed broad spectrum anti-proliferative action with efficient sub-panel GI50 (MG-MID) range from 1.33 to 4.23 µM, and promising full-panel GI50 (MG-MID) equals 3.10 µM, at the NCI five-dose assay. Also, hybrid 8a was able to provoke cell cycle disturbance and apoptosis in breast T-47D cells as evidenced by the DNA flow cytometry and Annexin V-FITC/PI assays. Furthermore, hybrid 8a exhibited good inhibitory action against cell cycle regulator CDK2 protein kinase and the anti-apoptotic Bcl-2 protein (IC50= 0.85 ± 0.03 and 0.46 ± 0.02 µM, respectively). Interestingly, molecular docking for hybrid 8a in CDK2 and Bcl-2 active sites unveiled that N-propyl group is involved in significant hydrophobic interactions. Taken together, the results suggested conjugate 8a as a promising lead for further development and optimisation as an efficient antitumor drug.

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Pursuing our effort for developing effective inhibitors of the cancer-related hCA IX isoform, here we describe the synthesis of novel benzofuran-based carboxylic acid derivatives, featuring the benzoic (9a-f) or hippuric (11a,b) acid moieties linked to 2-methylbenzofuran or 5-bromobenzofuran tails via an ureido linker. The target carboxylic acids were evaluated for the potential inhibitory action against hCAs I, II, IX, and XII. Superiorly, benzofuran-containing carboxylic acid derivatives 9b, 9e, and 9f acted as submicromolar hCA IX inhibitors with KIs = 0.91, 0.79, and 0.56 µM, respectively, with selective inhibitory profile against the target hCA IX over the off-target isoforms hCA I and II (SIs: 2 to >63 and 4-47, respectively). Compounds 9b, 9e, and 9f were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. In particular, 9e displayed promising antiproliferative (IC50 = 2.52 ± 0.39 µM), cell cycle disturbance, and pro-apoptotic actions in MDA-MB-231 cells.

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BACKGROUND AND OBJECTIVE: Regional odontodysplasia (RO) is a localized developmental anomaly involving both dentitions. The characteristic clinical findings are soft discolored several contiguous teeth with atypical morphology associated with swelling or abscess formation. Radiographic images of the involved teeth show a ghost-like appearance because enamel and dentin are hypoplastic and hypocalcified. Although RO is known for more than seven decades, the literature on RO is mostly limited to case reports.The objective of this investigation was to provide an updated review of the literature with regards to clinical presentation and epidemiology of RO. Because of its rarity, retrospective analysis of the published reports across the world is considered one of the most appropriate available methods to analyze epidemiological and clinical data of RO. This review was reported and conducted according to the PRISMA guidelines. RESULTS: Between 1953 and 2017, 161 cases were reported in literatures written in English. At the time of diagnosis, the age of the patients ranged between 1 and 25 years. There was slight female predilection with a ratio of 1.37: 1. When examined collectively, the maxilla was commonly affected compared to the mandible. RO occurred in both dentitions in 75 reported cases. While it affects the deciduous teeth alone in 19.3% and the permanent teeth in 34.2% of the cases. Failure of tooth eruption was the most common presenting finding (41.6%) followed by swelling of the affected area (32.3%). CONCLUSION: Although RO was first described almost 80 years ago and the total subsequent case reports were over 160 cases, there is no consensus on its pathogenesis and how it should be treated. The descriptive nature of the examined case reports reveals the limited information on this condition. Further experimental and genetic studies are needed.

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OBJECTIVES: Light microscopy used to be the traditional modality of teaching histology and pathology disciplines. Recent advances and innovations in the information technology field have revolutionized the use of hard- and software in medical education. An example of such an innovation is the so-called virtual microscopy. Many schools have started to adopt virtual microscopy as a new method aimed at enhancing student learning. Nonetheless, few reports have described the experiences of introducing virtual microscopy in dental education. We conducted this study to evaluate student perceptions of virtual microscopy use. MATERIALS AND METHODS: A survey of 9 items with a five-point Likert scale was designed to assess student perceptions of different aspects of virtual microscopy use compared with light microscopy. Eighty-seven 2nd year dental students answered the survey for a response rate of 80%. RESULTS: The majority of the students (85.1%) reported positive feedback for the use of virtual slides as a method of learning. Students reported significantly higher scores in virtual microscopy compared with light microscopy (t test: t86 = 9.832, P < 0.0001); however, a few students reported some technical difficulties when using computers to view the virtual slides. CONCLUSIONS: Although light microscopy is the classical tool of teaching histology and pathology, virtual microscopy is a highly preferred substitute. We believe that virtual microscopy is a valuable teaching tool that enhances student educational experiences.

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OBJECTIVE: Oral and maxillofacial lesions of neural origin are rare soft tissue neoplasms. The aim of the present study is to review the epidemiological data of oral and maxillofacial neurogenic lesions submitted for diagnosis to our laboratory over a 31-year period (August 1984-March 2015). MATERIALS AND METHODS: The available formalin-fixed embedded specimens, Hematoxylin and Eosin slides, demographic and clinical data were retrieved. RESULTS: Thirty-one cases were included in this study, representing 0.6% of the 5161 biopsies submitted. Most of the diagnosed cases 11 (35.5%) were traumatic neuromas. The other cases included 2 (6.5%) solitary circumscribed neuromas, 2 (6.5%) melanotic neuroectodermal tumors of infancy, 2 (6.5%) Schwannomas, 5 (16.1%) granular cell tumors, and 9 (29%) neurofibromas. The patients' ages ranged from 5 months to 78 years. Among these cases, 16 were males (51.61%) and 15 were females (48.38%). CONCLUSION: This analysis showed that neural lesions affecting the oral and maxillofacial region were rare and mostly benign in nature. Such lesions should be carefully diagnosed because of their association with life-threatening syndromes and the possibility of malignant transformation.

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Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that has an exquisitely exclusive affection to the jawbone. It is defined as squamous cell carcinoma arising within the jaw and developing from residual odontogenic epithelium or from a preexisting odontogenic cyst or tumor. The solid-type of this tumor is a central jaw carcinoma arising de novo and has no initial connection with the oral mucosa. Herein, we report a case of solid-type PIOSCC involving the mandible in a 37-year-old male patient elucidating its histopathological and imaging findings. The patient underwent surgical resection followed by post-operative adjuvant radiotherapy. The close 2-year follow up of the patient revealed neither locoregional nor distant metastasis.

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