Utility of diffusion tensor imaging in differentiating benign from malignant thyroid nodules.

Purpose: To assess diffusion tensor imaging (DTI) in differentiating benign from malignant thyroid nodules. Methods: A retrospective analysis was done on 55 patients with thyroid nodules who had undergone DTI. The fraction anisotropy (FA) and mean diffusivity (MD) of the thyroid nodules were measured using region of interest (ROI) by two observers. The final diagnosis was malignant and benign, as proved by pathological examination. Results: The mean MD of benign thyroid nodules (1.84 ± 0.42 and 1.90 ± 0.37 × 10-3mm2/s) was significantly higher (p < .001) than malignant nodules (0.95 ± 0.46 and 0.97 ± 0.41 × 10-3mm2/s) as scored by both observers. The cut-off values of 1.45 and 1.50 × 10-3mm2/s were used to differentiate malignant from benign thyroid nodules with the areas under the curve (AUC) of 0.926 and 0.937, respectively. The mean FA of benign thyroid nodules (0.23 ± 0.07 and 0.24 ± 0.08) was significantly lower (p < .001) than malignant nodules (0.48 ± 0.21 and 0.49 ± 0.18). The FA cut-off value of ≤0.32 and 0.33 was used for differentiating malignant from benign thyroid nodules with an AUC of 0.877 and 0.881, respectively. A combination of MD and FA values was used to differentiate benign from malignant thyroid nodules with an AUC of 0.932 and an accuracy of 87%. There was an excellent agreement between both observers for FA and MD (K = 0.939, 0.929). Conclusion: The DTI is a non-invasive, non-contrast imaging tool that can differentiate benign from malignant thyroid nodules.

Quinazolines and thiazolidine-2,4-dions as SARS-CoV-2 inhibitors: repurposing, in silico molecular docking and dynamics simulation.

This paper presents an extensive analysis of COVID-19 with a specific focus on VEGFR-2 inhibitors as potential treatments. The investigation includes an overview of computational methodologies employed in drug repurposing and highlights in silico research aimed at developing treatments for SARS-CoV-2. The study explores the possible effects of twenty-eight established VEGFR-2 inhibitors, which include amide and urea linkers, against SARS-CoV-2. Among these, nine inhibitors exhibit highly promising in silico outcomes (designated as 3-6, 11, 24, 26, 27, and sorafenib) and are subjected to extensive molecular dynamics (MD) simulations to evaluate the binding modes and affinities of these inhibitors to the SARS-CoV-2 Mpro across a 100 ns timeframe. Additionally, MD simulations are conducted to ascertain the binding free energy of the most compelling ligand-pocket complexes identified through docking studies. The findings provide valuable understanding regarding the dynamic and thermodynamic properties of the interactions between ligands and pockets, reinforcing the outcomes of the docking studies and presenting promising prospects for the creation of therapeutic treatments targeting COVID-19.

Anticancer evaluations of iodoquinazoline substituted with allyl and/or benzyl as dual inhibitors of EGFRWT and EGFRT790M: design, synthesis, ADMET and molecular docking.

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFRWT and EGFRT790M. The new derivatives were designed according to the target of structural requirements of receptors. Cytotoxicity of our compounds was evaluated against MCF-7, A549, HCT116 and HepG2 cell lines using MTT assay. Compounds 18, 17 and 14b showed the highest anticancer effects with IC50 = 5.25, 6.46, 5.68 and 5.24 µM, 5.55, 6.85, 5.40 and 5.11 µM and 5.86, 7.03, 6.15 and 5.77 µM against HepG2, MCF-7, HCT116 and A549 cell lines, respectively. The eight highly effective compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 were inspected against VERO normal cell lines to evaluate their cytotoxicity. Our conclusion was that compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 possessed low toxicity against VERO normal cells with IC50 increasing from 43.44 to 52.11 µM. All compounds were additionally assessed for their EGFRWT and EGFRT790M inhibitory activities. Additionally, their ability to bind with EGFRWT and EGFR receptors was confirmed by molecular docking. Compound 17 exhibited the same inhibitory activity as erlotinib. Compounds 10, 13, 14b, 16 and 18 excellently inhibited VEGFR-2 activity with IC50 ranging from 0.17 to 0.50 µM. Moreover, compounds 18, 17, 14b and 16 remarkably inhibited EGFRT790M activity with IC50 = 0.25, 0.30, 0.36 and 0.40 µM respectively. As planned, compounds 18, 17 and 14b showed excellent dual EGFRWT/EGFRT790M inhibitory activities. Finally, our compounds 18, 17 and 14b displayed good in silico ADMET calculated profiles.

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity.

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.

Design, synthesis, docking, ADMET and anticancer evaluations of N-alkyl substituted iodoquinazoline derivatives as dual VEGFR-2 and EGFR inhibitors.

Fifteen new 1-alkyl-6-iodoquinazoline derivatives 5a-d to 9a-e were designed and synthesized and their anticancer activities were evaluated against HepG2, MCF-7, HCT116 and A549 cancer cell lines via dual targeting of EGFR and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. Compound 9c showed the highest anticancer activities with EC50 = 5.00, 6.00, 5.17 and 5.25 µM against HepG2, MCF-7, HCT116 and A549 cell lines correspondingly. Moreover, compounds 5d, 8b, 9a, 9b, 9d, and 9e exhibited very good anticancer effects against the tested cancer cell lines. The highly effective seven derivatives 5d, 8b, 9a-e were examined against VERO normal cell lines to estimate their cytotoxic capabilities. Compounds 9c, 9b, 9d, 9a, 9e and 5d excellently inhibited VEGFR-2 activity with IC50 = 0.85, 0.90, 0.90, 1.00, 1.20 and 1.25 µM respectively. Moreover, compounds 9c, 9d, 9e, 5d, 8b and 9b excellently inhibited EGFRT790M activity with IC50 = 0.22, 0.26, 0.30, 0.40, 0.45 and 0.50 µM respectively. Also, compounds 9c, 9d and 9e excellently inhibited EGFRWT activity with IC50 = 0.15, 0.20 and 0.25 µM respectively. As planned, compound 9c showed excellent dual EGFR/VEGFR-2 inhibitory activities. Consonantly, ADMET study was calculated in silico for the supreme three worthwhile compounds 9b, 9c and 9e in contrast to sorafenib and erlotinib as reference drugs. The obtained results concluded that, our compounds might be useful as prototype for design, optimization, adaptation and investigation to have more powerful and selective dual VEGFR-2/EGFRT790M inhibitors with higher antitumor activity.

Five and six membered heterocyclic rings endowed with azobenzene as dual EGFRT790M and VEGFR-2 inhibitors: design, synthesis, in silico ADMET profile, molecular docking, dynamic simulation and anticancer evaluations.

Novel azobenzene scaffold-joined heterocyclic isoxazole, pyrazole, triazole, and/or triazine moieties have been developed and synthesized utilizing microwave and traditional methods. Our compounds were tested for growth inhibition of A549, MCF-7, HCT-116, and HepG2 tumors by dual targeting the VEGFR-2 and EGFRT790M enzymes. The suggested compound's manner of binding with EGFRT790M and VEGFR-2 active sites was explored through molecular design and MD modeling. The information from the results of the biological screening and the docking studies was highly correlated. The A549 cell line was the one that responded to the novel compound's effects most effectively. Having IC50 values of 5.15, 6.37, 8.44 and 6.23 µM, respectively, 14 was the most effective derivative on the four A549, MCF-7, HCT116 and HepG2 cancer cells. It had greater activity than erlotinib and slightly inferior activities on the tested cell lines than sorafenib, respectively. The cytotoxicity of the most effective derivatives, 5, 6, 10 and 14, was evaluated against typical VERO cell lines. Having IC50 values ranging from 42.32 to 55.20 µM, the results showed that the investigated drugs have modest toxicity against VERO normal cells. Additionally all derivatives were assessed for their dual VEGFR-2 and EGFRT790M inhibitory effects. Among them, derivatives 14, 5 and 10 were established as the greatest inhibitors of VEGFR-2 at IC50 values of 0.95, 1.25 and 1.50 µM correspondingly. As well, derivatives 14, 6, 5 and 10 could inhibit EGFRT790M activity demonstrating strongest effects with IC50 = 0.25, 0.35, 0.40 and 0.50 µM respectively. Furthermore, the ADMET profile was evaluated for compounds 5, 6, 10 and 14 in contrast to reference drugs sorafenib and erlotinib.

Design, Synthesis, In Vitro, and In Silico Studies of New N5-Substituted-pyrazolo[3,4-d]pyrimidinone Derivatives as Anticancer CDK2 Inhibitors.

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N5-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC50 values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development.

Development of Novel Class of Phenylpyrazolo[3,4-d]pyrimidine-Based Analogs with Potent Anticancer Activity and Multitarget Enzyme Inhibition Supported by Docking Studies.

Phenylpyrazolo[3,4-d]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2. Some of these compounds showed potent cytotoxicity, with variable degrees of potency and cell line selectivity in antiproliferative assays with low resistance. As the analogs carry the pyrazolopyrimidine scaffold, which looks structurally very similar to tyrosine and receptor kinase inhibitors, the potent compounds were evaluated for their inhibitory effects on three essential cancer targets: EGFRWT, EGFRT790M, VGFR2, and Top-II. The data obtained revealed that most of these compounds were potent, with variable degrees of target selectivity and dual EGFR/VGFR2 inhibitors at the IC50 value range, i.e., 0.3-24 µM. Among these, compound 5i was the most potent non-selective dual EGFR/VGFR2 inhibitor, with inhibitory concentrations of 0.3 and 7.60 µM, respectively. When 5i was tested in an MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibited cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Molecular docking studies were performed to explore the binding mode and mechanism of such compounds on protein targets and mapped with reference ligands. The results of our studies indicate that the newly discovered phenylpyrazolo[3,4-d]pyrimidine-based multitarget inhibitors have significant potential for anticancer treatment.

Utility of diffusion tensor imaging in differentiating benign from malignant hepatic focal lesions.

OBJECTIVES: To assess the diagnostic accuracy of diffusion tensor imaging (DTI) in the characterization of hepatic focal lesions (HFLs) and compare it to diffusion-weighted imaging (DWI). METHODS: Prospective analysis was done for 49 patients (23 male and 26 female) with 74 HFLs who underwent dynamic MRI, DWI, and DTI. Apparent diffusion coefficient (ADC) values from DWI, fractional anisotropy (FA) values, and mean diffusivity (MD) values from DTI were measured by two independent radiologists. HFLs were classified into benign and malignant HFLs; the latter were subdivided into HCC and non-HCC lesions. Binary logistic regression was performed to analyze the associations between the DTI parameters and the distinction of malignant lesions. RESULTS: The ADC, MD, and FA at cutoff values of ≤ 1.17 × 10-3 mm2/s, ≤ 1.71 × 10-3 mm2/s, and > 0.29, respectively, are excellent discriminators for differentiating malignant and benign HFLs. The mean ADC and MD values of hemangiomas were significantly higher than HCC and non-HCC malignant lesions. In contrast, the mean FA values of hemangiomas were significantly lower than those of non-HCC malignant lesions and HCCs. The ADC and MD were very good discriminators at cutoff values of > 1.03 × 10-3 mm2/s and > 1.12 × 10-3 mm2/s, respectively. The FA at a cutoff value > 0.38 is an excellent discriminator for HCC versus non-HCC malignant lesions. Only FA value > 0.38 was a statistically significant independent predictor of HCC versus non-HCC lesions among the three parameters. There was an excellent inter-observer agreement with ICC > 0.9. CONCLUSION: MD and FA of DTI are non-invasive, very good, and excellent discriminators superior to ADC measured by DWI for the differentiation of HFLs. KEY POINTS: • The ADC, MD, and FA at cutoff values of ≤ 1.17 × 10-3 mm2/s, ≤ 1.71 × 10-3 mm2/s, and > 0.29, respectively, are excellent discriminators for differentiating malignant and benign HFLs. • The mean ADC and MD values of hemangiomas were significantly higher than those of HCC and non-HCC malignant lesions. In contrast, the mean FA values of hemangiomas were significantly lower than those of non-HCC malignant lesions and HCCs, respectively. • Multivariate regression analysis revealed that only FA value > 0.38 was a statistically significant independent predictor of HCC vs. non-HCC lesions. A lesion with FA > 0.38 has 34 times higher odds of being HCC rather than non-HCC lesions.

Triazoloquinoxalines-based DNA intercalators-Topo II inhibitors: design, synthesis, docking, ADMET and anti-proliferative evaluations.

Sixteen [1, 2, 4]triazolo[4,3-a]quinoxalines as DNA intercalators-Topo II inhibitors have been prepared and their anticancer actions evaluated towards three cancer cell lines. The new compounds affected on high percentage of MCF-7. Derivatives 7e, 7c and 7b exhibited the highest anticancer activities. Their activities were higher than that of doxorubicin. Molecular docking studies showed that the HBA present in the chromophore, the substituted distal phenyl moiety and the extended linkers enable our derivatives to act as DNA binders. Also, the pyrazoline moiety formed six H-bonds and improved affinities with DNA active site. Finally, 7e, 7c and 7b exhibited the highest DNA affinities and act as traditional intercalators of DNA. The most active derivatives 7e, 7c, 7b, 7g and 6e were subjected to evaluate their Topo II inhibition and DNA binding actions. Derivative 7e exhibited the highest binding affinity. It intercalates DNA at IC50 = 29.06 µM. Moreover, compound 7e potently intercalates DNA at an IC50 value of 31.24 µM. Finally, compound 7e demonstrated the most potent Topo II inhibitor at a value of 0.890 µM. Compound 7c exhibited an equipotent IC50 value (0.940 µM) to that of doxorubicin. Furthermore, derivatives 7b, 7c, 7e and 7g displayed a high ADMET profile.

Diagnostic performance of chest computed tomography for COVID-19 in children: a systematic review and meta-analysis of clinical and computed tomography features in 987 patients.

Purpose: The outbreak of a new coronavirus is still spreading worldwide, affecting children and adults. However, COVID-19 in children shows distinctive characteristics in clinical and radiological presentation. We aimed to assess the diagnostic performance of chest CT and clarify the clinicoradiological CT features of COVID-19 among children with COVID-19. Material and methods: Adhering to PRISMA-DTA guidelines, we searched databases (PubMed, Google Scholar, and Web of Science) to identify relevant articles. The search keywords were: "Chest CT" AND "COVID-19" OR "coronavirus" OR "SARS-COV-2" AND "Children" OR "Pediatric". Published reports providing clinical and imaging findings of paediatric COVID-19 were included. Results: Twenty-eight studies were included, with 987 patients. Most of the patients were symptomatic (76.9%; 95% CI: 69.2-84.7%), with fever being the most frequent manifestation (64%; 95% CI: 58.0-71.2%). Only 2.3% of the cases were critical, and mortality was reported in one case. The proportion of COVID-19 detected by chest CT among children is relatively high (658/987), with ground-glass opacity (GGO) being the most prevalent feature (52.5%; 95% CI: 40.5-64.7%). The pooled sensitivity of chest CT in all patients was 67%; however, it was different between symptomatic and asymptomatic patients (71% and 33%, respectively). The pooled specificity was (67%), which was calculated after considering the symptomatic PCR-positive patients as the gold standard. Conclusions: Chest CT showed moderate pooled sensitivity and specificity among symptomatic children with COVID-19 and low sensitivity among asymptomatic children. This means that CT is not to be used as a screening tool or for confirmation of the diagnosis in children and should be reserved for specific clinical situations.

Relationship of the pulmonary disease severity scoring with thromboembolic complications in COVID-19.

PURPOSE: To correlate thromboembolic (TE) complications secondary to COVID-19 with the extent of the pulmonary parenchymal disease using CT severity scores and other comorbidities. METHODS: In total, 185 patients with COVID-19 and suspected thromboembolic complications were classified into two groups based on the presence or absence of thromboembolic complications. Thromboembolic complications were categorized based on location. Chest CT severity scoring system was used to assess the pulmonary parenchymal disease severity in all patients. Based into severity scores, patients were categorized into three groups (mild, moderate, and sever disease). RESULTS: The final study cohort consisted of 171 patients (99 male and 72 female) after excluding 14 patients with non-diagnostic CT pulmonary angiography. The TE group included 53 patients with a mean age of 55.1 ± 7.1, while the non-TE group included 118 patients with a mean age of 52.9 ± 10.8. Patients with BMI > 30 kg/m2 or having a history of smoking and HTN were found more frequently in the TE group (p < 0.05). Patients admitted to ICU were significantly higher in the TE group (p < 0.001). There was statistically significant difference (p = 0.002) in chest CT-SS between the TE group (22.8 ± 11.4) and non-TE group (17.6 ± 10.7). The percentage of severe parenchymal disease in the TE group was significantly higher compared to the non-TE group (p < 0.05). Severe parenchymal disease, BMI > 30 kg/m2, smoking, and HTN had a higher and more significant odds ratio for developing TE complications. CONCLUSION: The present data suggest that severe pulmonary parenchymal disease secondary to COVID-19 is associated with a higher incidence of thromboembolic complications.

Design, Synthesis, biological Evaluation, and molecular docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers.

A series of novel hybrid pyrazolo[3,4-d]pyramidine derivatives was designed and chemically synthesized in useful yields. The synthesized compounds were structurally characterized by the usual techniques. All the new synthesized compounds were biologically screened in vitro for their antiproliferative activities against a panel of four cancer cell lines, namely HepG-2, MCF-7, HCT-116, and Hela. The results of cytotoxic evaluation indicated that compound 14d was appeared to be the most prominent broad-spectrum cytotoxic activity and significantly more potent than sorafenib with IC50 values of 4.28, 5.18, 3.97, and 9.85 µM against four cell lines (HePG2, Hela, HCT-116 and MCF-7). In addition, compound 15 was displayed promising antiproliferative effect against all tested cell lines with IC50 value less than 11 µM compared with sorafenib as a control drug. Besides, structurally pharmacophoric features indicated that pyrazolo[3,4-d]pyrimidine scaffold having an amide linker and substituted with phenyl moiety at the 5-position was more potent than those possessing azomethine methyl, azomethine proton and carbomethene linkers, which lead to significant decrease in antiproliferative activity. The most potent compounds were further selected and evaluated for their activities against epidermal growth factor receptor (EGFR) kinase inhibitors according to homogenous time resolved fluorescence (HTRF) assay. The most potent compound 14d exhibited the most promising inhibitory activity against EGFRWT with IC50 value of 56.02 ± 1.38 µM compared with gefitinib as control drug with IC50 value of 41.79 ± 1.07 µM. Moreover, the inhibition of cell cycle progression and induction of apoptosis in the A549 cell line at G2/M and pre-G1 phases of cell cycle might contribute to cancer treatment that evaluated by Annexin V-FITC/PI double staining detection method. Finally, molecular docking studies were conducted to investigate that probable binding conformations of these anticancer agents and ADME properties were calculated to predict pharmacokinetics and toxic properties of the target compounds.

Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies.

Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. These fragments include hydrazone, indoline-2-one, phthalimide, thiourea, oxadiazole, pyrazole, and dihydropyrazole. The synthesized molecules were evaluated for their anticancer activity against the human breast cancer cell line, MCF-7. The obtained results revealed comparable antitumor activity with that of the reference drugs doxorubicin and toceranib. Docking studies were performed along with EGFR-TK and ADMET profiling studies. The results of the docking studies showed the ability of the designed compounds to interact with key residues of the EGFR-TK through a number of covalent and noncovalent interactions. The obtained activity of compound 25 (IC50 = 2.89 µM) suggested that it may serve as a lead for further optimization and drug development.

Mimickers of novel coronavirus disease 2019 (COVID-19) on chest CT: spectrum of CT and clinical features.

COVID-19 (coronavirus disease 2019) is a recently emerged pulmonary infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). It started in Wuhan, China, in December 2019 and led to a highly contagious disease. Since then COVID-19 continues to spread, causing exponential morbidity and mortality and threatening economies worldwide. While the primary diagnostic test for COVID-19 is the reverse transcriptase-polymerase chain reaction (RT-PCR) assay, chest CT has proven to be a diagnostic tool of high sensitivity. A variety of conditions demonstrates CT features that are difficult to differentiate from COVID-19 rendering CT to be of low specificity. Radiologists and physicians should be aware of imaging patterns of these conditions to prevent an erroneous diagnosis that could adversely influence management and patients' outcome. Our purpose is to provide a practical review of the conditions that mimic COVID-19. A brief description of the forementioned clinical conditions with their CT features will be included.

In vivo- and in silico-driven identification of novel synthetic quinoxalines as anticonvulsants and AMPA inhibitors.

The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol-induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED50 values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore-based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.

Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists.

Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC50 values ranging from 1.9 to 6.4 µM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored.

Completeness of Medical Records of Trauma Patients Admitted to the Emergency Unit of a University Hospital, Upper Egypt.

Trauma records in Egyptian hospitals are widely suspected to be inadequate for developing a practical and useful trauma registry, which is critical for informing both primary and secondary prevention. We reviewed archived paper records of trauma patients admitted to the Beni-Suef University Hospital in Upper Egypt for completeness in four domains: demographic data including contact information, administrative data tracking patients from admission to discharge, clinical data including vital signs and Glasgow Coma Scale scores, and data describing the causal traumatic event (mechanism of injury, activity at the time of injury, and location/setting). The majority of the 539 medical records included in the study had significant deficiencies in the four reviewed domains. Overall, 74.3% of demographic fields, 66.5% of administrative fields, 55.0% of clinical fields, and just 19.9% of fields detailing the causal event were found to be completed. Critically, oxygen saturation, arrival time, and contact information were reported in only 7.6%, 25.8%, and 43.6% of the records, respectively. Less than a fourth of the records provided any details about the cause of trauma. Accordingly, the current, paper-based medical record system at Beni-Suef University Hospital is insufficient for the development of a practical trauma registry. More efforts are needed to develop efficient and comprehensive documentation of trauma data in order to inform and improve patient care.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Antimicrobial screening and pharmacokinetic profiling of novel phenyl-[1,2,4]triazolo[4,3-a]quinoxaline analogues targeting DHFR and E. coli DNA gyrase B.

A novel series of [1,2,4]triazolo[4,3-a]quinoxaline derivatives of different heteroaromatization members were synthesized. The newly synthesized molecules were explored for their potential antimicrobial activities against a panel of pathogenic organisms. Among these derivatives, the chalcone compound 6e with a methoxy substituent exhibited broad potent antimicrobial activity against most of the bacterial and fungal strains. Furthermore, the analysis of the SAR disclosed that the linker and terminal aromatic fragments perform critical roles in exerting antibacterial activity. The molecular docking calculations were executed on two of the most bacterial targets, ATP-binding sites of DNA gyrase B, and the folate-binding site of DHFR enzymes. The results presented good binding data to the pockets of both enzymes showing different linkers contributions through the hydrogen-bonding and aromatic stacking interactions that stabilize the compounds in their pockets taking 6e compound as representative of most active analogs. In addition, good pharmacokinetic profiling data for the 6e compound was obtained and compared to reference drugs. Accordingly, our findings suggest that [1,2,4]triazolo[4,3-a]quinoxaline scaffold is an interesting precursor for the design of potent antimicrobial agents with multitarget inhibition.