Regioselective synthesis and DFT study of novel fused heterocyclic utilizing Thermal heating and Microwave Irradiation

Regioselective facile synthesis of innovative heterocycles from the reaction of 2-cyano-N-cyclohexylacetamide (3) with N, N- dimethylformamide dimethylacetal (DMF-DMA) to afford (E)-2-cyano-N-cyclohexyl-3-(dimethylamino) acrylamide (4) under microwave irradiation. Enaminonitrile 4 reacts with hydrazine derivatives affords the corresponding pyrazole derivatives 5a-c, furthermore the behavior of enaminone 4 reacts with guanidine to give the corresponding 2,4 diaminopyrimidine derivative (7). Moreover (E)-2-cyano-N-cyclohexyl-3-(dimethylamino) acrylamide (4) reacts with amino pyrazoles 8a-f, 1,2,4-aminotriazole (11) and 2-aminobenzimidazole (13) to afford the corresponding pyrazolo[1,5-a]pyrimidine 9a-f, andtriazolo[4,3-a]pyrimidine 12, pyrimido[1,2-a]benzimdazole14; respectively. Density functional theory calculations at the B3LYP/6-31G (d) levels of theory have been carried out to investigate the equilibrium geometry of the novel fused pyrazoles 5a and 9a. Moreover, the total energy, the energy of the HOMO and LUMO and Mulliken atomic charges were considered. Additionally,the measurements of their interactions with hydrazine hydrate to form fused pyrazoles 5a and 9a have been calculated. Also, comprehensive theoretical and experimental structural studies of 7-amino-Ncyclohexyl-2-methyl-3-phenylpyrazole[1,5-a]pyrimidine-6-carboxamide (9a) have been carried out by elemental analysis, FTIR, 1H NMR and Mass. Optimized molecular structure and harmonic vibrational frequencies have been reconnoitered by DFT/B3LYP and HF methods combined with 6-31G(d) basis set

Effect of Implantation Time of Cupper Nitride onto ITO Thin Films: Structural, Morphological, Electrical, and Optical Properties

Copper nitride (Cu3N) thin films have been implanted onto an electron beam evaporated films of indium tin oxide (ITO) from Cu metal target using reactive dc Magnetron Sputtering (dcMS) technique in a nitrogen/argon atmosphere at room temperature. The implantation parameter was kept constant excepting the implantation time. The effect of implantation time upon microstructural, morphological, electrical, and optical properties have been studied. The elemental composition of the as-deposited and Cu3N implanted has been studied by using the EDXS technique, and the spectrum shows peaks belonging to In, Sn, O, Cu, and N. A zinc blend structure was observed for all the investigated films with no sign of impurities. The optical direct energy bandgap E_g^opt is found to decreases from 3.49 eV to 2.62 eV with increasing the implantation time of Cu3N. The refractive index n is increased with increasing the exposure time of implantation. The refractive index has abnormal behavior in the infrared region due to the strong absorption in this region that appears in transmission spectra. The electrical resistivity decreases from 1908.22 .cm to 165.24 .cm with increasing the duration time of implantation

Assessment of clinical trial protocols for pathology content using the SPIRIT-Path guidelines highlights areas for improvement

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence-based recommendations for the minimum content of clinical trial protocols. The Cellular Molecular Pathology Initiative, hosted by the UK National Cancer Research Institute, developed an extension, SPIRIT-Path, describing how to effectively incorporate pathology support into clinical trial protocols. The current study assessed the inclusion of SPIRIT-Path items in protocols of active clinical trials. Publicly available clinical trial protocols were identified for assessment against the new guidelines using a single UK hospital as the ‘test site’. One hundred and ninety interventional clinical trials were identified as receiving support from the pathology department. However, only 38 had publicly available full trial protocols (20%) and following application of the inclusion/exclusion criteria, 19 were assessed against the SPIRIT-Path guidelines. The reviewed clinical trial protocols showed some areas of compliance and highlighted other items that were inadequately described. The latter lacked information about the individuals responsible for the pathology content of the trial protocol, how pathology activities and roles were organised in the trial, where the laboratory work would be carried out, and the accreditation status of the laboratory. Only one trial had information specific to digital pathology, a technology certain to become more prevalent in the future. Adoption of the SPIRIT-Path checklist will facilitate comprehensive trial protocols that address all the key cellular and molecular pathology aspects of interventional clinical trials. This study highlights once again the lack of public availability of trial protocols. Full trial protocols should be available for scrutiny by the scientific community and the public who participate in the studies, increasing the transparency of clinical trial activity and improving quality

European guidelines for the diagnosis, treatment and follow-up of breast lesions with uncertain malignant potential (B3 lesions) developed jointly by EUSOMA, EUSOBI, ESP (BWG) and ESSO

Introduction: Breast lesions of uncertain malignant potential (B3) include atypical ductal and lobular hyperplasias, lobular carcinoma in situ, flat epithelial atypia, papillary lesions, radial scars and fibroepithelial lesions as well as other rare miscellaneous lesions. They are challenging to categorise histologically, requiring specialist training and multidisciplinary input. They may coexist with in situ or invasive breast cancer (BC) and increase the risk of subsequent BC development. Management should focus on adequate classification and management whilst avoiding overtreatment. The aim of these guidelines is to provide updated information regarding the diagnosis and management of B3 lesions, according to updated literature review evidence.Methods: These guidelines provide practical recommendations which can be applied in clinical practice which include recommendation grade and level of evidence. All sections were written according to an updated literature review and discussed at a consensus meeting. Critical appraisal by the expert writing committee adhered to the 23 items in the international Appraisal of Guidelines, Research and Evaluation (AGREE) tool. Results: Recommendations for further management after core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB) diagnosis of a B3 lesion reported in this guideline, vary depending on the presence of atypia, size of lesion, sampling size, and patient preferences. After CNB or VAB, the option of vacuum-assisted excision or surgical excision should be evaluated by a multidisciplinary team and shared decision-making with the patient is crucial for personalizing further treatment. De escalation of surgical intervention for B3 breast lesions is ongoing, and the inclusion of vacuum-assisted excision (VAE) will decrease the need for surgical intervention in further approaches. Communication with patients may be different according to histological diagnosis, presence or absence of atypia, or risk of upgrade due to discordant imaging. Written information resources to help patients understand these issues alongside with verbal communication is recommended. Lifestyle interventions have a significant impact on BC incidence so lifestyle interventions need to be suggested to women at increased BC risk as a result of a diagnosis of a B3 lesion.Conclusions: These guidelines provide a state-of-the-art overview of the diagnosis, management and prognosis of B3 lesions in modern multidisciplinary breast practice

Robust diffraction-limited near-infrared-to-near-ultraviolet wide-field imaging from stratospheric balloon-borne platforms — super-pressure balloon-borne imaging telescope performance

At a fraction of the total cost of an equivalent orbital mission, scientific balloon-borne platforms, operating above 99.7% of the Earth’s atmosphere, offer attractive, competitive, and effective observational capabilities—namely, space-like seeing, transmission, and backgrounds—which are well suited for modern astronomy and cosmology. The Super-pressure Balloon-borne Imaging Telescope (SUPERBIT) is a diffraction-limited, wide-field, 0.5 m telescope capable of exploiting these observing conditions in order to provide exquisite imaging throughout the near-infrared to near-ultraviolet. It utilizes a robust active stabilization system that has consistently demonstrated a 48 mas 1σ sky-fixed pointing stability over multiple 1 h observations at float. This is achieved by actively tracking compound pendulations via a three-axis gimballed platform, which provides sky-fixed telescope stability at < 500 mas and corrects for field rotation, while employing high-bandwidth tip/tilt optics to remove residual disturbances across the science imaging focal plane. SUPERBIT’s performance during the 2019 commissioning flight benefited from a customized high-fidelity science-capable telescope designed with an exceptional thermo- and opto-mechanical stability as well as a tightly constrained static and dynamic coupling between high-rate sensors and telescope optics. At the currently demonstrated level of flight performance, SUPERBIT capabilities now surpass the science requirements for a wide variety of experiments in cosmology, astrophysics, and stellar dynamics

Modified Mathieu repair for failed surgery for hypospadias: Perimeatal-based flap with a subdermal vascular dartos pedicle

Objectives: To present our experience with the use of modified Mathieu urethroplasty for failed hypospadias repair. Patients and methods: Thirty-eight patients aged between 2 and 10 (mean 5) years underwent modified Mathieu urethroplasty for salvage hypospadias repair. Modifications included a wide subdermal vascular dartos pedicle attached to the perimeatal-based flap, running subcuticular urethral sutures and coverage of the urethroplasty using a redundant dartos flap. Twenty patients presented with complete dehiscence after previous hypospadias repair, while a coronal fistula was present in 18. The meatal position was coronal in 22 patients and anterior penile in 16. Twenty-six patients underwent a single operation and 12 underwent multiple operations. The urethral plate was supple in 28 patients but altered in 10. The length of the flap was ≤20 mm in 23 patients and ≥20 mm in 15. Results: Follow-up ranged from 3 to 9 years (mean 64 months). Overall success was achieved in 31/38 patients (82%). Meatal stenosis occurred in one patient (3%), while urethrocutaneous fistulas developed in six (16%). A history of previous surgery for hypospadias, an altered urethral plate and associated distal stenosis were associated with an increased incidence of postoperative fistulas, whereas the meatal location and the length of the flap had no effect on fistula formation. Conclusions: Our modified Mathieu urethroplasty proved to be excellent in repairing failed hypospadias surgery. However, a proper patient selection is mandatory to achieve satisfactory results

Elucidating the chemical and structural composition of breast cancer using raman micro-spectroscopy

The current gold standard for breast cancer (BC) diagnosis is the histopathological assessment of biopsy samples. However, this approach limits the understanding of the disease in terms of biochemical changes. Raman spectroscopy has demonstrated its potential to provide diagnostic information and facilitate the prediction of the biochemical progression for different diseases in a rapid non-destructive manner. Raman micro-spectroscopy was used to characterize and differentiate breast cancer and normal breast samples. In this study, tissue microarrays of breast cancer biopsy samples (n=499) and normal breast (n=79) were analyzed using Raman micro-spectroscopy, and principal component analysis (PCA) was used for feature extraction. Linear discriminant analysis (LDA) was used for feature validation. Normal breast and breast cancer were successfully differentiated with a sensitivity of 90 % and specificity of 78 %. Dominance of lipids, specifically fatty acids, was identified in the normal tissue whereas proteins dominated the malignant spectra. Higher intensities of carotenoids, β-carotenoids, and cholesterol were identified in the normal breast while ceramide related peaks were mostly visible in the BC spectra. The biochemical characterization achieved with Raman micro-spectroscopy showed that this technique is a powerful and reliable tool for the monitoring and diagnosis of BC, regardless of the cohort heterogeneity. Raman spectroscopy also provided a powerful insight into the biochemical changes associated with the BC progression and evolution