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A practical four-step sequence for the synthesis of α,δ-dioxoesters with high enantiomeric excess was developed. It makes use of a regio- and stereoselective Michael addition of a chiral ketimine to ethyl 2-(phenylthio)-2-propenoate as a key transformation. The synthetic elaboration of the Michael adduct provides the new ethyl 3-(1-methyl-2-oxo-cyclohexyl)-2-oxopropanoate, bearing a quaternary stereocenter with 95% ee and high yield.

A practical four-step sequence for the synthesis of α,δ-dioxoesters with high enantiomeric excess was developed. It makes use of a regio- and stereoselective Michael addition of a chiral ketimine to ethyl 2-(phenylthio)-2-propenoate as a key transformation. The synthetic elaboration of the Michael adduct provides the new ethyl 3-(1-methyl-2-oxo-cyclohexyl)-2-oxopropanoate, bearing a quaternary stereocenter with 95% ee and high yield.

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu4N+HSO4– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials.

The N-heterocyclic carbene(NHCs)-catalyzed aza-benzoin condensation reaction is an efficient, single step strategy which employs easily available substrates, such as aldehydes and imines, to provide α-amino ketones. The multifunctionality and high reactivity of α-amino ketones makes these structures attractive for medicinal chemistry and as precursors of a variety of amine derivatives. The different electrophilic characteristics of aldehydes and imines ensure a high regioselective reaction. Enantiomerically-enriched α-amino ketones have been synthesized through stereoselective couplings promoted by chiral N-heterocyclic carbenes. One-pot domino procedures, including an aza-benzoin step, allow valuable complex molecules to be accessed.

A 77-year-old male presented with headache and underwent magnetic resonance imaging, which revealed a large mass in the left parieto-temporal region with an axial diameter of 41 mm (Fig. 1), with an irregular morphology, a necrotic central portion, and margins with intense contrast enhancement, surrounded by an area of hyperintense signal in long repetition time sequences. The patient underwent neurosurgery, and intraoperative evaluation was decided. Intraoperative touch imprint cytology showed a neoplasm composed of medium/small, hyperchromic, lymphoblast-like cells with many mitoses and some ‘cannibalistic’ cells (Fig. 2); the cytology specimen also contained elements that could not be well evaluated, probably due to fixation. A malignant neoplasm, not otherwise specified, was diagnosed intraoperatively without excluding a haemato-lymphoid nature. Histology revealed a biphasic lesion with two distinct cellular components: one consisted of round, hyperchromic, medium/small cells with scant cytoplasm and a high mitotic rate (blue cell component), and the other consisted of pleomorphic, occasionally multinucleated giant cells, absent on intraoperative examination (Fig. 3). Immunohistochemistry showed GFAP positivity (Fig. 4A), IDH1-R132 negativity (molecularly corresponding to an IDH-wildtype profile) and strong/diffuse nuclear positivity for p53 in both components (Fig. 4C). Of note was the zonal positivity for synaptophysin, which was expressed only in the blue cell component. (Fig. 4B). In addition, foci of necrosis (non-palisading) and vascular endothelial proliferation were present.View full text...

We present a case involving a 70-year-old Latina woman who experienced a sud-den onset of lightheadedness, diplopia, vertigo, and loss of balance. Imaging studies revealed a right thalamic intracerebral haemorrhage that obstructed the velum interpositum. Following unsuccessful embolisation, the thalamic region was surgically resected. Histopathological and immunohistochemical analyses of the resected brain tissue demonstrated abnormal blood vessels permeating through excessively cellular brain parenchyma, raising significant concern for a glial neoplasm. This case also illustrates a rare occurrence of an arteriovenous malformation within the velum interpositum, which, when acutely filled with blood, can expand the cavum and clinically present as a sudden onset of headache and vertigo.

SMARCA4-deficient undifferentiated tumours exhibit undifferentiated and rhabdoid features. These highly aggressive neoplasms pose significant diagnostic challenges. They are characterised by an inactivating mutation of SMARCA4, leading to the loss of expression of Brahma-related gene 1 ( BRG1 ). Despite their rareness and poor differentiation as thoracic tumours, it is important to recognise these tumours because, despite being highly aggressive, there are potential treatment options for the future, such as immunotherapy and SMARCA4-targeted therapies. This case presentation aims to raise awareness of this rare neoplasm when evaluating cases presenting undifferentiated morphology.

This case report describes a rare and challenging glioblastoma variant with a bi-phasic morphology comprising both giant cell and primitive neuronal components. The tumour exhibited aggressive features and was difficult to diagnose during the intraoperative evaluation due to the predominance of small blue cell morphology, which complicated differentiation from haematological and metastatic lesions. Im-munohistochemistry and molecular profiling confirmed a glioblastoma, IDH-wild-type, with combined giant cell and primitive neuronal features, and the p53 muta-tion in both components is a novel finding with potential implications for diagnosis and treatment. This report emphasises the importance of recognising morpholog-ical diversity in glioblastoma to avoid misdiagnosis and enable appropriate clinical management.

To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan–Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.