Computational Chemistry: Prediction of Compound Accessibility of Targeted Synthesized Compounds.

INTRODUCTION: In the present work, a series of novel pyridine carboxamides 3(a-h) were synthesized and screened with antibacterial activity. This research explores the application of Density Functional Theory (DFT) in studying biological systems at the quantum mechanical level, particularly in the context of drug design. DFT offers a streamlined approach to quantum mechanical calculations, making it indispensable in various scientific fields, and for its exceptional accuracy, reduced computational time, and cost-effectiveness has become a pivotal tool in computational chemistry. This research work highlights the integration of DFT studies with POM analyses, which effectively identify pharmacophoric sites. Moreover, the research incorporates in silico pharmacokinetics analyses to assess the pharmacokinetic properties of synthesized compounds. The paper focused on a series of compounds previously reported, aiming to provide a comprehensive understanding of their electronic structure, pharmacophoric features, and potential as drug candidates. This study not only contributes to the evolving field of computational chemistry but also holds implications for advancing drug design processes by combining theoretical insights with practical analyses. METHODS: The compounds 3(a-h) were subjected to Density Functional Theory (DFT) computations using the B3LYP/6-31G(d) basis set to get optimized geometric structures. GaussViewis used to display the contributions of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The determination of energy gaps was conducted using Gaussian 09W. The pharmacokinetic profiles were evaluated using existing techniques such as Osiris, Petra, and Molinspiration, as well as a novel platform called POM Analyse. RESULTS: The computational studies DFT, POM and in silico pharmacokinetics studies revealed that the studied compounds are biologically active, non-toxic, non-carcinogenic in nature and may be utilized as drug candidates. CONCLUSION: Density functional theory (DFT) investigations emphasize the exceptional stability of complex 3d, which possesses the biggest energy gap and the lowest softness. In contrast, compound 3h demonstrates poorer stability among the tested compounds, characterized by the lowest energy gap and the highest softness values. These findings are further substantiated by absolute energy calculations. The negligible energy difference in compound 3h indicates an increased transfer of electric charge within the molecule, which is associated with its enhanced biological effectiveness. The drug-likeness of the compounds is confirmed by POM and in silico pharmacokinetics investigations, with compound 3h being identified as the most biologically active among the investigated compounds.

Diagnostic Performance of Pointwise Encoding Time Reduction with Radial Acquisition Subtraction-based MR Angiography in the Follow-up of Intracranial Aneurysms after Clipping.

PURPOSE: While follow-up assessment of clipped aneurysms (CAs) using magnetic resonance angiography (MRA) can be challenging due to susceptibility artifacts, a novel MRA sequence pointwise encoding time reduction with radial acquisition (PETRA) subtraction-based MRA, has been developed to reduce these artifacts. The aim of the study was to validate the diagnostic performance of PETRA-MRA by comparing it with digital subtraction angiography (DSA) as a reference for follow-up of CAs using a 3T MR scanner. METHODS: Patients with clipping who underwent both PETRA-MRA and DSA between September 2019 and December 2021 were retrospectively included. Two neuroradiologists independently reviewed with the reconstructed images of PETRA-MRA to assess the visibility of the arteries around the clips and aneurysm recurrence or remnants of CA using a 3-point scale. The diagnostic accuracy of PETRA-MRA was evaluated in comparison to DSA. RESULTS: The study included 34 patients (28 females, mean age 59 ± 9.6 years) with 48 CAs. The PETRA-MRA allowed visualization of the parent vessels around the clips in 98% of cases, compared to 39% with time-of-flight (TOF) MRA (p < 0.0001). The DSA confirmed 14 (29.2%) residual or recurrent aneurysms. The PETRA-MRA demonstrated a high accuracy, specificity, positive predictive value, and negative predictive value of 99.2%, 100%, 100%, and 97.8%, respectively, while the sensitivity was 66.7%. CONCLUSION: This retrospective study demonstrates that PETRA-MRA provides excellent visibility of adjacent vessels near clips and has a high diagnostic accuracy in detecting aneurysm remnants or recurrences in CAs. Further prospective studies are warranted to establish its utility as a reliable alternative for follow-up after clipping.

Age and Gender-Dependence of Single-and Bi-Exponential T1ρ MR Parameters in Knee Ligaments.

BACKGROUND: There is limited understanding of differences in the composition and structure of ligaments between healthy males and females, and individuals of different ages. Females present higher risk for ligament injuries than males and there are conflicting reports on its cause. This study looks into T1ρ parameters for an explanation as it relates to proteoglycan, collagen, and water content in these tissues. PURPOSE: To investigate gender-related and age-related differences in T1ρ parameters in knee joint ligaments in healthy volunteers using a T1ρ -prepared zero echo-time (ZTE)-based pointwise-encoding time-reduction with radial acquisition (T1ρ -PETRA) sequence. STUDY TYPE: Prospective. POPULATION: The study group consisted of 22 healthy subjects (11 females, ages: 41 ± 18 years, and 11 males, ages: 41 ± 14 years) with no known inflammation, trauma, or pain in the knee joint. FIELD STRENGTH/SEQUENCE: A T1ρ -prepared 3D-PETRA sequence was used to acquire fat-suppressed images with varying spin-lock lengths (TSLs) of the knee joint at 3T. ASSESSMENT: Monoexponential, biexponential, and stretched-exponential 3D-PETRA-T1ρ parameters were measured in the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and patellar tendon (PT) by manually drawing ROIs over the entirety of the tissues. STATISTICAL TESTS: Mann-Whitney U-tests were used to compare 3D-PETRA-T1ρ parameters in the ACL, PCL, and PT between males and females. Spearman correlation coefficients were used to determine the association between age and T1ρ parameters. Statistical significance was defined as P < 0.05. RESULTS: Significant correlations with age were found the three ligaments with most of the measured T1ρ parameters (rs = 0.28-0.74) with the exception of the short fraction in the PCL (P = 0.18), and the short relaxation time in the ACL (P = 0.58) and in the PCL (P = 0.14). DATA CONCLUSION: 3D-PETRA-T1ρ can detect age-related differences in monoexponential, biexponential, and stretched-exponential T1ρ parameters in three ligaments of healthy volunteers, which are thought to be related to changes in tissue composition and structure during the aging process. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Usefulness of PETRA-MRA for Postoperative Follow-Up of Stent-Assisted Coil Embolization of Cerebral Aneurysms.

Objective: Image evaluation after stent-assisted coil embolization (SAC) for a cerebral aneurysm is difficult with conventional MRA or CTA because of metal artifacts. Pointwise encoding time reduction with radial acquisition (PETRA)-MRA is a noninvasive imaging examination that can reduce metal artifacts. This study aimed to examine whether PETRA-MRA can be used as a follow-up imaging after SAC. Methods: Twelve patients (eight women and four men; mean age, 66.9 ± 13.2 years) underwent SAC for unruptured aneurysms and were retrospectively evaluated using time-of-flight (TOF)- and PETRA-MRA data from the same follow-up session. Two neurosurgeons independently compared the aneurysm occlusion status and flow visualization score in the stented parent artery (4-point scale, where 4 points represented excellent visualization) between TOF- and PETRA-MRA images. If DSA was performed within 3 months before or after PETRA-MRA, the aneurysm assessment was compared between MRA and DSA. The interobserver agreement for each MRA was evaluated. Results: Nine of the 12 patients underwent DSA within 3 months before and after TOF- and PETRA-MRA. The aneurysm occlusion status on DSA was more consistent with PETRA-MRA (eight of nine cases) than with TOF-MRA (one of nine cases; P = 0.023). The median visualization score of the stented parent artery was significantly higher for PETRA-MRA (4 [interquartile range {IQR} 3-4]) than for TOF-MRA (1 [IQR 1-1], P = 0.003). The interobserver agreement for evaluation of the aneurysm occlusion status and visualization score of the parent artery for PETRA-MRA were excellent (κ = 0.98 and 0.93, respectively). In one case, PETRA-MRA was able to detect aneurysm recurrence, leading to subsequent retreatment. Conclusion: PETRA-MRA is a noninvasive examination that can be used to evaluate the occlusion status of aneurysms after SAC and visualize the stented parent artery. PETRA-MRA is useful for repeated follow-up examinations after SAC.

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

In silico and POM analysis for potential antimicrobial agents of thymidine analogs by using molecular docking, molecular dynamics and ADMET profiling.

Nucleoside analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we designed to explore the synthesis and spectral characterization of 5'-O-(myristoyl)thymidine esters (2-6) for in vitro antimicrobial, molecular docking, molecular dynamics, SAR, and POM analyses. An unimolar myristoylation of thymidine under controlled conditions furnished the 5'-O-(myristoyl)thymidine and it was further converted into four 3'-O-(acyl)-5'-O-(myristoyl)thymidine analogs. The chemical structures of the synthesized analogs were ascertained by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests along with PASS, prediction indicated expectant antibacterial functionality of these thymidine esters compared to the antifungal activities. In support of this observation, their molecular docking studies have been performed against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) and significant binding affinities and non-bonding interactions were observed. The stability of the protein-ligand complexes was monitored by a 100 ns MD simulation and found the stable conformation and binding mode in a stimulating environment of thymidine esters. Pharmacokinetic predictions were studied to assess their ADMET properties and showed promising results in silico. SAR investigation indicated that acyl chains, lauroyl (C-12) and myristoyl (C-14), combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. The POM analyses provide the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving each activity and selectivity of designed drugs targeting potentially drug-resistant microorganisms. It also opens avenues for the development of newer antimicrobial agents targeting bacterial and fungal pathogens.

A novel series of 5´-O-(myristoyl)thymidine derivatives were synthesized and characterized by FTIR, ¹H-NMR, 2D-NMR, ¹³C-NMR, mass and physicochemical studies.In vitro antimicrobial susceptibility revealed that alkyl chain and aromatic substituents can improve the antimicrobial efficacy of the thymidine structure which was also supported by PASS enumeration.Molecular docking study against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) exhibited a promising binding score and interaction in the catalytic active site.A 100ns MD simulation revealed the stable conformation and binding pattern in a stimulating environment of thymidine derivatives.ADMET analysis revealed that most of the compounds are non-toxic and most of them have an inhibitory property to the CYP1A2 and CYP3A4In silico and POM analyses provide substantial ideas about the structural features responsible for their combined antibacterial/antifungal agents and provide guidelines for further modifications.

The value of magnetic resonance ultrashort echo time imaging to evaluate non-calcified cartilage of the knee joint and its damage.

Objectives: To image knee osteochondral specimens using magnetic resonance (MR) ultrashort echo time imaging with pointwise encoding time reduction with radial acquisition combined fat suppression (PETRA-FS) sequence to determine whether it can reveal non-calcified cartilage, including the deep radial layer, and to assess its effectiveness in cartilage damage diagnosis. Materials and methods: PETRA-FS imaging was performed on 58 osteochondral specimens of the lower femur and upper tibia to observe depth of cartilage damage, combined with histological results to observe signal intensity composition. Sensitivity, specificity, and reliability of PETRA-FS sequence for diagnosing cartilage damage were evaluated using histological results as the gold standard. Diagnostic efficacy was assessed using receiver operating characteristic (ROC) curve. Results: MR ultrashort echo time imaging PETRA-FS sequence showed non-calcified cartilage, including tangential, transitional, and radial layers, which showed a high signal. PETRA-FS sequence showed 37 cases of cartilage damage and 21 cases of no damage among 58 specimens, kappa value of 0.75. Histological analysis of the 58 osteochondral specimens revealed 38 cases of cartilage injury and 20 cases of undamaged cartilage. Using histological results as the gold standard, PETRA-FS sequence had a sensitivity of 87.00%, specificity of 80.00%, kappa value of 0.81, and an area under the ROC curve (AUC) of 0.83 for cartilage injury diagnosis. Conclusion: MR ultrashort echo time imaging PETRA-FS sequence can show non-calcified cartilage, including the deep radial layer (which cannot be shown by conventional MR), by exhibiting a high signal in knee osteo-chondral specimens. Thus, PETRA-FS sequences may have important diagnostic value for cartilage injury diagnosis.

A pair of carbazate derivatives as novel Schiff base ligands: DFT and POM theory supported spectroscopic and biological evaluation.

Schiff bases are mentioned as strongly important molecular scaffolds of industrial and medicinal purposes. Due to wide range applications of carbazate derivatives herein synthesis and characterization of a new Schiff base ligand, (E)-ethyl 2-(4-methoxybenzylidene)hydrazinecarboxylate and 4-(nitrobenzaldehyde)ethylcarbazate are reported. The compound was characterized on the basis of experimental and density functional theory calculations (using the B3LYP and 6-31 G(d,p)formalism combination). Among characterization techniques elemental analysis, FT-IR, UV-Vis and NMR spectroscopic evaluations were mainly employed to carry out the formulation of the compound. In addition to computational validation of characterization other significant molecular parameters were also evaluated including geometry optimization, frontier molecular orbital analysis (FMO) and Columbic interaction of different constituent atoms of the title compound. A good agreement has been found between DFT and experimental outcomes confined to prove the structure of the compound. Moreover, molecular docking and antimicrobial studies have proven the Schiff base as an effective bioactive compound.Communicated by Ramaswamy H. Sarma.

In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site.

An array of computational approaches DFT/QSAR/POM methods has been used for a better understanding of drug properties regarding 13 inhibitor derivatives containing either P2 cyclopentane P1 carboxylic acid moiety (1-9) or a P1 cyclopropyl acyl sulfonamide (10-13). To further recognize binding interactions and their activity trends, molecular docking studies were carried out with the use of HCV, which can be used to accurately predict the interactions of ligands with the receptor. The QSAR models are developed through the use of Multiple Linear Regression (MLR) together with Principal Component Analysis (PCA) methods. The statistical results indicate the multiple correlation coefficient R2 = 0.840, which shows favorable estimation stability, as well as showing a significant correlation between the HCV NS3 protease of the studied compounds and their electron-accepting ability. The POM analysis of the Physico-chemical properties of compounds 1-13, shows that they are bearing (O1, O2) and/or (O1, O2, O3) antiviral pockets, whereby all oxygen atoms are Osp2 and bearing negative charges. Similar to the reference ligand (F9K), the most active compound 10 was bound deeply into the binding cavity of NS3 protease making interactions with the residues Gly137, His57, Ala157, and His528. The anti-hepatitis pharmacophore site is similar to the anti-HIV pharmacophore site.Communicated by Ramaswamy H. Sarma.

[Evaluation of Enhanced 3D Brain Image Using Ultrashort TE Sequence with Inversion Recovery for Preoperative Examination of Brain Tumor: Phantom Study Compared with MPRAGE].

It is important to obtain accurate anatomical information with little distortion in preoperative examination of brain tumors. Using PETRA, which is an ultrashort echo time (UTE) sequence that is less affected by magnetic susceptibility artifacts, we determined the optimal imaging conditions (radial views [RV] and inversion time [TI]) for IR-PETRA using the inversion recovery (IR) method and compared it with MPRAGE. IR-PETRA was found to be slightly inferior to MPRAGE in sharpness under the optimum conditions (RV=100,000 and TI=500 ms), but it was significantly improved by using a high RV value, and SNR and CNR were higher than or equal to MPRAGE. It is suggested that IR-PETRA may be an alternative sequence of MPRAGE in preoperative examination of brain tumors.

Drug design of new therapeutic agents: molecular docking, molecular dynamics simulation, DFT and POM analyses of new Schiff base ligands and impact of substituents on bioactivity of their potential antifungal pharmacophore site.

Since Schiff base derivatives have a wide range of biological activities, novel Schiff base derivatives were designed and synthesized in satisfactory yields. 1H NMR, 13C NMR, IR, mass and elemental analysis were used to provide a complete structural characterization of the new synthesized Schiff bases (3-6). The antiproliferative activity properties of compounds were tested against two human cancer cell lines including breast (MDA-MB-231) and colon (DLD-1). The compounds overall did not show high cytotoxic activity against both cancer cell lines compared to the positive control drug cisplatin. The synthesized Schiff base compounds were further screened for their in vitro antimicrobial activities against five bacterial strains (Escherichia coli (ATTC 25922), Salmonella thyphimurium (ATTC 14028), Staphylococcus aureus (ATCC 25923), Bacillus subtilis (ATCC 6633), Bacillus cereus (ATCC 11778)) and two fungal strains (Candida albicans (ATCC 10231) and Candida glabrata (ATCC 90030)) using broth micro dilution techniques. The mode of action for the antimicrobial effect in the experimental part was explored through molecular docking. The stability of target-ligand complexes obtained from the docking were assessed through molecular dynamics simulation. The binding affinity of the compounds toward the target protein were also investigated using MMPBSA. Furthermore, electrochemical properties of some compounds was analyzed by DFT calculations. By using POM theory, it becomes more easy to control the bioactivity of drugs. Here, how the physicochemical properties play a crucial role in the orientation of their bioactivity was demonstrated.Communicated by Ramaswamy H. Sarma.

Postmortem sampling time effect on toxicity biomarkers in rats exposed to an acute lethal methomyl dose.

Regulations often are imposing long postmortem times before autopsy leading to certain toxicity-unrelated changes in biomarkers, which in turn may affect the reliability of toxicity evaluation during forensic investigations. Since methomyl pesticide shows significant toxicity and is frequently encountered in poisoning cases, the current study evaluated different parameters in methomyl intoxicated rats at three different postmortem intervals (Hour 0, Hour 3 and Hour 6). Eighteen adult Sprague Dawley rats were poisoned with methomyl to simulate actual methomyl poisoning cases. The time of death was assigned as Hour 0. The animals were divided into 3 groups (n = 6) to collect blood and tissue samples at the selected time points. Body weight, relative organ weight, protein concentration, methomyl concentration and acetylcholinesterase activity (AChE) were assessed in blood and different tissues (liver, spleen, kidney, brain, eye, and bone marrow) to evaluate the effect of postmortem sampling time. Outcomes revealed significant decreases in methomyl concentration in blood and bone marrow with advanced sampling time (P < 0.001). Similarly, there were significant reductions in AChE activity in the kidney (P < 0.01), while the enzyme activity significantly increased in brain samples (P < 0.05). Findings illustrated the importance of sampling time in toxicity studies because it could alter experimental results and impact consequent interpretations, as well as it may alter postmortem biomarkers in related forensic cases.

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity.

The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O δ-, O δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.

First pointwise encoding time reduction with radial acquisition (PETRA) implementation for catheter detection in interstitial high-dose-rate (HDR) brachytherapy.

PURPOSE: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient. METHODS AND RESULTS: Empty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were < 1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was < 1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation. CONCLUSIONS: PETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

Comparison of contrast-enhanced T1-weighted imaging using DANTE-SPACE, PETRA, and MPRAGE: a clinical evaluation of brain tumors at 3 Tesla.

BACKGROUND: We aimed to compare the performance of three contrast-enhanced T1-weighted three-dimensional (3D) magnetic resonance (MR) sequences to detect brain tumors at 3 Tesla. The three sequences were: (I) delay alternating with nutation for tailored excitation sampling perfection with application-optimized contrasts using different flip angle evolution (DANTE-SPACE), (II) pointwise encoding time reduction with radial acquisition (PETRA), and (III) magnetization-prepared rapid acquisition with gradient echo (MPRAGE). METHODS: This study involved 77 consecutive patients, including 34 patients with known primary brain tumors and 43 patients suspected of intracranial metastases. All patients underwent each of the three sequences with comparable spatial resolution and acquisition time post-injection. Signal-to-noise ratios (SNRs) for gray matter (GM) and white matter (WM), contrast-to-noise ratios (CNRs) for lesion/GM, lesion/WM, and GM/WM were quantitatively compared. Two radiologists determined the total number of enhancing lesions by consensus. Intraclass correlation coefficients (ICCs) between the two radiologists for metastases presence, qualitative ratings for image quality, and acoustic noise level of each sequence were assessed. RESULTS: Among the three sequences, SNRs and CNRs between lesions and surrounding parenchyma were highest using DANTE-SPACE, but CNRWM/GM was the lowest with DANTE-SPACE. SNRs for PETRA images were significantly higher than those for MPRAGE (P<0.001). CNRs between lesions and surrounding parenchyma were similar for PETRA and MPRAGE (P>0.05). Significantly more brain metastases were detected with DANTE-SPACE (n=94) compared with MPRAGE (n=71) and PETRA (n=72). The ICCs were 0.964 for MPRAGE, 0.975 for PETRA, and 0.973 for DANTE-SPACE. Qualitative scores for lesion imaging using DANTE-SPACE were significantly higher than those obtained with PETRA and MPRAGE (P=0.002 and P=0.004, respectively). The acoustic noise level for PETRA (64.45 dB) was significantly lower than that for MPRAGE (78.27 dB, P<0.01) and DANTE-SPACE (80.18 dB, P<0.01). CONCLUSIONS: PETRA achieves comparable detection of brain tumors with MPRAGE and is preferred for depicting osseous metastases and meningeal enhancement. DANTE-SPACE with blood vessel suppression showed improved detection of cerebral metastases compared with MPRAGE and PETRA, which could be helpful for the differential diagnosis of tumors.

How to face COVID-19: proposed treatments based on remdesivir and hydroxychloroquine in the presence of zinc sulfate. Docking/DFT/POM structural analysis.

Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.

IRIXS Spectrograph: an ultra high-resolution spectrometer for tender RIXS.

The IRIXS Spectrograph represents a new design of an ultra-high-resolution resonant inelastic X-ray scattering (RIXS) spectrometer that operates at the Ru L3-edge (2840 eV). First proposed in the field of hard X-rays by Shvyd'ko [(2015), Phys. Rev. A, 91, 053817], the X-ray spectrograph uses a combination of laterally graded multilayer mirrors and collimating/dispersing Ge(111) crystals optics in a novel spectral imaging approach to overcome the energy resolution limitation of a traditional Rowland-type spectrometer [Gretarsson et al. (2020), J. Synchrotron Rad. 27, 538-544]. In combination with a dispersionless nested four-bounce high-resolution monochromator design that utilizes Si(111) and Al2O3(110) crystals, an overall energy resolution better than 35 meV full width at half-maximum has been achieved at the Ru L3-edge, in excellent agreement with ray-tracing simulations.

The Value of PETRA in Pulmonary Nodules of <3 cm Among Patients With Lung Cancer.

OBJECTIVE: This study aimed to evaluate the visibility of different subgroups of lung nodules of <3 cm using the pointwise encoding time reduction with radial acquisition (PETRA) sequence on 3T magnetic resonance imaging (MRI) in comparison with that obtained using low-dose computed tomography (LDCT). METHODS: The appropriate detection rate was calculated for each of the different subgroups of lung nodules of <3 cm. The mean diameter of each detected nodule was determined. The detection rates and diameters of the lung nodules detected by MRI with the PETRA sequence were compared with those detected by computed tomography (CT). The sensitivity of detection for the different subgroups of pulmonary nodules was determined based on the location, size, type of nodules and morphologic characteristics. Agreement of nodule characteristics between CT and MRI were assessed by intraclass correlation coefficient (ICC) and Kappa test. RESULTS: The CT scans detected 256 lung nodules, comprising 99 solid nodules (SNs) and 157 subsolid nodules with a mean nodule diameter of 8.3 mm. For the SNs, the MRI detected 30/47 nodules of <6 mm in diameter and 52/52 nodules of ≥6 mm in diameter. For the subsolid nodules, the MRI detected 30/51 nodules of <6 mm in diameter and 102/106 nodules of ≥6 mm in diameter. The PETRA sequence returned a high detection rate (84%). The detection rates of SN, ground glass nodules, and PSN were 82%, 72%, and 94%, respectively. For nodules with a diameter of >6 mm, the sensitivity of the PETRA sequence reached 97%, with a higher rate for nodules located in the upper lung fields than those in the middle and lower lung fields. Strong agreement was found between the CT and PETRA results (correlation coefficients = 0.97). CONCLUSION: The PETRA technique had high sensitivity for different type of nodule detection and enabled accurate assessment of their diameter and morphologic characteristics. It may be an effective alternative to CT as a tool for screening and follow up pulmonary nodules.

The dataset on the clipped cerebral aneurysm and their radiological findings in three-dimensional computed tomography, time-of-flight magnetic resonance angiography (TOF-MRA), and Pointwise Encoding Time Reduction with Radial Acquisition (PETRA)-MRA.

These data present the 141 intracranial arterial branches' visibilities near the 72 cerebral aneurysms in postoperative 58 patients treated with titanium or cobalt-chromium-nickel-molybdenum (CCNM) alloy clips. The visibilities were evaluated using time-of-flight magnetic resonance angiography (TOF-MRA), pointwise encoding time reduction with radial acquisition (PETRA)-MRA, which uses MRA with ultrashort echo time (UTE-MRA) and subtraction technique between saturated and non-saturated images, and three-dimensional computed tomography angiography (3DCTA). We retrospectively acquired the data from the medical records of Suwa Red Cross Hospital. Each method's appearance was compared, and associations between visibility on PETRA-MRA, arterial diameter, clip numbers, clip shapes, clip materials, and amounts of hematoma were summarized. Our article on PETRA-MRA's usefulness for proximal and branched arteries evaluation after cerebral aneurysm clipping [1] was based on these data. This dataset would be useful for reference value for other neurosurgeons or radiologists for further analysis on PETRA-MRA and another UTE-MRA like SILENT-MRA after cerebral aneurysm clipping.

HYFI: Hybrid filling of the dead-time gap for faster zero echo time imaging.

The aim of this work was to improve the SNR efficiency of zero echo time (ZTE) MRI pulse sequences for faster imaging of short-T2 components at large dead-time gaps. ZTE MRI with hybrid filling (HYFI) is a strategy for retrieving inner k-space data missed during the dead-time gaps arising from radio-frequency excitation and switching in ZTE imaging. It performs hybrid filling of the inner k-space with a small single-point-imaging core surrounded by a stack of shells acquired on radial readouts in an onion-like fashion. The exposition of this concept is followed by translation into guidelines for parameter choice and implementation details. The imaging properties and performance of HYFI are studied in simulations as well as phantom, in vitro and in vivo imaging, with an emphasis on comparison with the pointwise encoding time reduction with radial acquisition (PETRA) technique. Simulations predict higher SNR efficiency for HYFI compared with PETRA at preserved image quality, with the advantage increasing with the size of the k-space gap. These results are confirmed by imaging experiments with gap sizes of 25 to 50 Nyquist dwells, in which scan times for similar image quality could be reduced by 25% to 60%. The HYFI technique provides both high SNR efficiency and image quality, thus outperforming previously known ZTE-based pulse sequences, in particular for large k-space gaps. Promising applications include direct imaging of ultrashort-T2 components, such as the myelin bilayer or collagen, T2 mapping of ultrafast relaxing signals, and ZTE imaging with reduced chemical shift artifacts.