A rationale for the poor response to alectinib in a patient with adenocarcinoma of the lung harbouring a fusion by artificial intelligence and molecular modelling: a case report.

Background: Non-small cell lung cancers (NSCLCs) with fusions are effectively treated with tyrosine kinase inhibitors (TKIs). The widespread use of next-generation sequencing (NGS) assays to study the molecular profile of NSCLCs, can identify rare fusion partners of . Therapy decisions are made without considering which fusion partner is present and its potential oncogenic properties.

Cytotoxic ROS-Consuming Mn(III) Synzymes: Structural Influence on Their Mechanism of Action.

ROS (i.e., reactive oxygen species) scavenging is a key function of various Mn-based enzymes, including superoxide dismutases (SODs) and catalases, which are actively linked to oxidative stress-related diseases.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour.

Depression and cardiovascular diseases are two of the world's major health problems. Escitalopram (ESC) is widely used because of its safety in relation to other drugs in that class; however, it can affect the cardiovascular system. The present study evaluated the cardiovascular parameters of depressive-like male rats and the cardiovascular effects of ESC treatment on that condition.

Enalapril induces muscle epigenetic changes and contributes to prevent a decline in running capacity in spontaneously hypertensive rats.

Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can improve muscle function and exercise capacity, as well as preventing, attenuating or reversing age-related losses in muscle mass, however, the exact mechanisms by which these drugs affect muscle cells, are not yet fully elucidated. Moreover, the potential epigenetic alterations induced in skeletal muscle tissue are also largely unexplored. The aim of this study was to evaluate if enalapril or losartan can change the physical performance and epigenetic profile of skeletal muscle in spontaneously hypertensive rats (SHRs).

Transient Adaptation of to Exposure by Thiosemicarbazone Drugs That Target Ribosomal Proteins Is Associated with the Upregulated Expression of Tachyzoite Transmembrane Proteins and Transporters.

Thiosemicarbazones and their metal complexes have been studied for their biological activities against bacteria, cancer cells and protozoa. Short-term in vitro treatment with one gold (III) complex (C3) and its salicyl-thiosemicarbazone ligand (C4) selectively inhibited proliferation of . Transmission Electron Microscopy (TEM) detected transient structural alterations in the parasitophorous vacuole membrane and the tachyzoite cytoplasm, but the mitochondrial membrane potential appeared unaffected by these compounds.

Anticancer activity of new water-soluble sulfonated thiosemicarbazone copper(II) complexes targeting disulfide isomerase.

Copper complexes have shown promising anticancer properties, but they are often poorly soluble in aqueous solutions, thus limiting their possible medical developments and applications. We have recently isolated some copper(II) complexes with salicylaldehyde thiosemicarbazone ligands exhibiting remarkable nanomolar cytotoxic activity, but in vivo tests evidenced several difficulties related to their poor solubility. To overcome these limitations and increase solubility in aqueous solution, herein we report the synthetic strategy that led to the introduction of the sulfonic group on the ligands, then separated as salts (NaHL - NaHL), as well as the synthesis and characterization of the related copper(II) complexes.

SMARCB1/INI1-deficient undifferentiated tumour of the thorax: a case report and review of the literature.

The 5th WHO classification of thoracic tumours includes thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) among the "other epithelial tumours of the lung" chapter. Herein, we present a case of undifferentiated thoracic neoplasm with retention of SMARCA4 expression, lack of NUT fusion protein and loss of SMARCB1/INI1 expression. After presenting the clinical and pathological features of the tumour, we carried out a review of the literature on the same topic.

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

Background: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers.

Patients And Methods: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm.

Head-to-head: Should Ki67 proliferation index be included in the formal classification of pulmonary neuroendocrine neoplasms?

The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low- to intermediate-grade neuroendocrine tumours (NETs), while large-cell neuroendocrine carcinoma (NEC) and small-cell lung carcinoma are high-grade NECs. In small-sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively.

Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC.

Introduction: The emergence of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC) has revolutionized targeted therapy. This dynamic landscape, featuring novel ALK inhibitors and combination therapies, necessitates a profound understanding of resistance mechanisms for effective treatment strategies. Recognizing two primary categories - on-target and off-target resistance - underscores the need for comprehensive assessment.

Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle.

Aminocatalysis is a well-established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored.

Discovery of antibacterial manganese(i) tricarbonyl complexes through combinatorial chemistry.

The continuous rise of antimicrobial resistance is a serious threat to human health and already causing hundreds of thousands of deaths each year. While natural products and synthetic organic small molecules have provided the majority of our current antibiotic arsenal, they are falling short in providing new drugs with novel modes of action able to treat multidrug resistant bacteria. Metal complexes have recently shown promising results as antimicrobial agents, but the number of studied compounds is still vanishingly small, making it difficult to identify promising compound classes or elucidate structure-activity relationships.

Biphenotypic lung carcinoma with coexpression of TTF-1 and ΔNP63/P40 within most of the same individual cells: a further case confirming poor prognosis and a review of literature.

The WHO Classification of Tumors, Thoracic Tumors, 5th edition, has outlined the use of TTF-1 and ΔNP63/P40 to discriminate between adenocarcinoma and squamous cell carcinoma. In 2015, the first description of a rare non-small cell lung carcinoma featuring co-expression of glandular and squamous differentiation within most of the same individual tumor cells was reported on, with ultrastructural and molecular demonstration of such a biphenotypic differentiation. We herein describe an additional case of this rare tumor entity, which is confirmed to be an aggressive neoplasm despite potential targets of therapy.

Plasma lipidomics and coronary plaque changes: a substudy of the SMARTool clinical trial.

Aims: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA).

Methods And Results: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.

Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency.

Recombination activating genes () are tightly regulated during lymphoid differentiation, and their mutations cause a spectrum of severe immunological disorders. Hematopoietic stem and progenitor cell (HSPC) transplantation is the treatment of choice but is limited by donor availability and toxicity. To overcome these issues, we developed gene editing strategies targeting a corrective sequence into the human gene by homology-directed repair (HDR) and validated them by tailored two-dimensional, three-dimensional, and in vivo xenotransplant platforms to assess rescue of expression and function.

Lack of imbalance between the master regulators TTF1/NKX2-1 and ΔNp63/p40 implies adverse prognosis in non-small cell lung cancer.

The transcription factors TTF1/NKX2-1 and ΔNp63/p40 are the counterposed molecular markers associated with the main Non-Small Cell Lung Cancer subtypes: TTF1 for adenocarcinoma, p40 for squamous cell carcinoma. Although they generally display a mutually exclusive expression, some exceptions exist simultaneously lacking or (very rarely) expressing both markers, either pattern being associated to poor prognosis. Hence, we quantitatively analyzed the relationship between their coordinated activity and prognosis.

New Stable Gallium(III) and Indium(III) Complexes with Thiosemicarbazone Ligands: A Biological Evaluation.

The aim of this work is to explore a new library of coordination compounds for medicinal applications. Gallium is known for its various applications in this field. Presently, indium is not particularly important in medicine, but it shares a lot of chemical traits with its above-mentioned lighter companion, gallium, and is also used in radio imaging.

An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53 mutations or copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.

Graph-guided Gaussian Process-based Diagnosis of CVD Severity with Uncertainty Measures.

The severity of coronary artery disease can be assessed invasively using the Fractional Flow Reserve (FFR) index which is a useful diagnostic tool for the clinicians to select the treatment approach. The present work capitalizes a Gaussian process (GP) framework over graphs for the prediction of FFR index using only non-invasive imaging and clinical features. More specifically, taking the per-node one-hop connectivity vector as input, we employed a regression-based task by applying an ensemble of graph-adapted Gaussian process experts, with a data-adaptive fashion via online training.