Geo-spatial analysis of acute ischemic stroke reperfusion treatment in India: An assessment of distribution and access to centers.

Background: Stroke is a leading cause of global mortality and disability, with a disproportionately high burden in low- and middle-income countries. Access to intravenous thrombolysis (IVT) and endovascular treatment (EVT) remains extremely limited.

Aims: We evaluated the spatial distribution and geographic accessibility of stroke centers in India.

Identification of structural features of surface modifiers in engineered nanostructured metal oxides regarding cell uptake through ML-based classification.

Nanoparticles (NPs) are considered as versatile tools in various fields including medicine, electronics, and environmental science. Understanding the structural aspects of surface modifiers in nanoparticles that govern their cellular uptake is crucial for optimizing their efficacy and minimizing potential cytotoxicity. The cellular uptake is influenced by multiple factors, namely, size, shape, and surface charge of NPs, as well as their surface functionalization.

A sensitive LC-MS/MS assay to quantitate free payload Aur0101 from ADC PYX-201 in rat and monkey plasma.

Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody-drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d were used in this LC-MS/MS method.

Quantitation of total antibody (tAb) from antibody drug conjugate (ADC) PYX-201 in rat and monkey plasma using an enzyme-linked immunosorbent assay (ELISA) and its application in preclinical studies.

PYX-201 is an investigative ADC oncology drug composed of a monoclonal human immunoglobulin G (IgG) antibody targeting the extra domain B splice variant of fibronectin (EDB + FN) conjugated to an auristatin payload through a cleavable linker. Effective measurement of PYX-201 tAb is the key to ADC drug PYX-201 preclinical pharmacokinetics (PK) assessment. PYX-201 monoclonal antibody (mAb) was used as the reference standard, goat anti-human IgG polyclonal antibody (pAb) or rabbit anti-human Kappa light chain mAb was employed as the capture antibody, and mouse mAb or goat pAb anti-human IgG the crystallizable fragment (Fc) (horseradish peroxidase (HRP)) was utilized as the detection antibody in this ELISA.

Quantification of antibody-drug conjugate PYX-201 in rat and monkey plasma via ELISA and its application in preclinical studies.

PYX-201 is a novel antibody-drug conjugate targeting the extra domain B splice variant of fibronectin in the tumor microenvironment. Accurate quantification of PYX-201 is critical for PYX-201 pharmacokinetics profiling in preclinical studies. ELISA was performed using reference standard PYX-201, mouse monoclonal anti-monomethyl auristatin E antibody, mouse IgG1, mouse monoclonal anti-human IgG horseradish peroxidase and donkey anti-human IgG horseradish peroxidase.

Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non-small cell lung cancer.

In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR.

Clinicopathological study of annexin A5 & apelin in pre-eclamptic placentae with emphasis on foetal outcome.

Background & Objectives: Pre-eclampsia has remained an elusive disease with serious impacts on both maternal and foetal health. Two novel markers, annexin A5 (ANXA5) and apelin are currently of considerable interest. The present study aimed to determine the placental expression of ANXA5 and apelin in pre-eclamptic placentae and also to elucidate if there is any correlation between the expression of these markers and the clinical features of both, mother and neonate.

Clinicopathological study and immunohistochemical analysis of expression of annexin A5 and apelin in human placentae of gestational diabetes mellitus.

Background And Aims: Gestational diabetes mellitus (GDM) is one of the commonest medical complications of pregnancy. Annexin A5 (ANXA5) is a protein, found in apical surfaces of syncytiotrophoblasts, which prevents fetal and placental vascular thrombosis in GDM. Apelin is a bioactive peptide which has been linked to GDM.

Penumbra quantification from MR SWI-DWI mismatch and its comparison with MR ASL PWI-DWI mismatch in patients with acute ischemic stroke.

In acute-ischemic-stroke patients, penumbra assessment plays a significant role in treatment outcome. MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch ratio can provide penumbra assessment. Recently reported studies have shown the potential of susceptibility-weighted imaging (SWI) in the qualitative assessment of penumbra.

Mobocertinib (TAK-788): A Targeted Inhibitor of Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer.

Most exon 20 insertion (ex20ins) driver mutations in non-small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting -mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating ex20ins mutations with selectivity over wild-type EGFR. The and activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse ex20ins mutations.

Tenecteplase-induced Nonaneurysmal Subarachnoid Hemorrhage in a Patient with Acute Ischemic Stroke: A Case Report and Literature Review.

Recently, tenecteplase (TNK) has been used for intravenous thrombolysis in acute ischemic stroke (AIS). Although spontaneous subarachnoid hemorrhage (SAH) following thrombolysis with tissue plasminogen activator has been reported, there is a lack of literature regarding TNK-induced nonaneurysmal spontaneous SAH. Our index case received intravenous TNK within an hour of symptom onset of AIS.

Router design for nano-communication using actin quantum cellular automata.

Logic expressions can be designed from actin filaments. It is a protein that makes the cellular structure and plays an important role in intracellular communication. Nano communication technique has been established using actin cellular automata.

GFNB: Gini index-based Fuzzy Naive Bayes and blast cell segmentation for leukemia detection using multi-cell blood smear images.

The blood cell counting and classification ensures the evaluation and diagnosis of a number of diseases. The analysis of white blood cells (WBCs) permits us to detect the acute lymphoblastic leukemia (ALL), a type of blood cancer that causes fatality when untreated. At present, the morphological analysis of blood cells is performed manually by skilled operators, which holds numerous drawbacks.

An Unusual Cause of Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a clinical radiographic diagnosis of heterogeneous etiologies. The pathogenesis of PRES remains unclear, but may be related to impaired cerebral autoregulation and endothelial dysfunction. We present a case of intravascular nonionic contrast-induced PRES observed after cerebral angiography.

Dissecting Aneurysm of Vertebral Artery Involving the Origin of Posteroinferior Cerebellar Artery Treated with Retrograde Stent Placement and Coil Embolization in the Era of Flow Diverter.

Ruptured vertebral artery (VA) dissecting aneurysm carries high risk of rerupture and mortality if not treated immediately. Dissecting aneurysm of the VA involving the posteroinferior cerebellar artery (PICA) origin is difficult to treat by surgical and endovascular route. With the availability of flow diversion device for reconstructive procedure, endovascular treatment has now become easy to treat difficult aneurysm while maintaining the patency of the PICA.

Surpass Flow Diverter in the Treatment of Ruptured Intracranial Aneurysms-A Single-Center Experience.

Background: Use of a Surpass flow diverter (FD) device in the treatment of acutely ruptured aneurysm has not been well studied and reported in the literature.

Methods: We retrospectively reviewed patients with subarachnoid hemorrhage who were treated by Surpass FD placement at our hospital between June 2016 and March 2018. Detailed analysis of medical records was performed to obtain patient age, gender, clinical history, Hunt and Hess grade, Fisher grade, results of radiographic and procedural details including technical success and complication, clinical outcome, and follow-up angiographic results.