Association between higher glucose levels and reduced survival in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Background: Obesity and hypercholesterolemia have been associated with better responses to ICIs in NSCLC, while type 2 diabetes (T2D) has been associated with a worse response. However, the association between glucose levels and outcomes remains unknown. This study investigated the impact of mean baseline glucose levels, T2D, dyslipidemia, and obesity on overall survival (OS) in NSCLC patients undergoing ICI therapy.

Turning the needle into the haystack: Culture-independent amplification of complex microbial genomes directly from their native environment.

High-throughput sequencing (HTS) has revolutionized microbiology, but many microbes exist at low abundance in their natural environment and/or are difficult, if not impossible, to culture in the laboratory. This makes it challenging to use HTS to study the genomes of many important microbes and pathogens. In this review, we discuss the development and application of selective whole genome amplification (SWGA) to allow whole or partial genomes to be sequenced for low abundance microbes directly from complex biological samples.

Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration.

Post-Artesunate Delayed Hemolysis in Pediatric Malaria Patients in the United States.

Post-artesunate delayed hemolysis (PADH) occurred in 6 of 24 children treated with artesunate for severe malaria in the United States; however, severe hemolysis requiring hospitalization or transfusion was rare. In children in the United States treated with artesunate, counseling, and symptom monitoring may be preferred to weekly laboratory surveillance for PADH.

Noteworthy synthesis strategies and applications of metal-organic frameworks for the removal of emerging water pollutants from aqueous environment.

17 global Sustainable Development Goals (SDGs) were established through the adoption of the 2030 Agenda for Sustainable Development by all United Nations members. Clean water and sanitation (SDG 6) and industry, innovation, and infrastructure (SDG 9) are the SDGs focus of this work. Of late, various new companies delivering metal-organic frameworks (MOFs) have blossomed and moved the field of adsorption utilizing MOFs to another stage.

Sustainable approach for the expulsion of metaldehyde: risk, interactions, and mitigation: a review.

All pests can be eliminated with the help of pesticides, which can be either natural or synthetic. Because of the excessive use of pesticides, it is harmful to both ecology and people's health. Pesticides are categorised according to several criteria: their chemical composition, method of action, effects, timing of use, source of manufacture, and formulations.

Carbon and metal based magnetic porous materials - Role in drug removal: A Comprehensive review.

Development of effective adsorbents for the removal of contaminants from wastewater is indispensable due to increasing water scarcity and a lack of pure drinking water, which are prevailing as a result of rapid industrialization and population growth. Recently, the development of new adsorbents and their effective use without generating secondary waste is receiving huge consideration. In order to protect the environment from primary and secondary pollution, the development of adsorbents from wastes and their recycling have become conventional practices aimed at waste management.

Facile synthesis of iron nanoparticles from Camellia Sinensis leaves catalysed for biodiesel synthesis from Azolla filiculoides.

Recent years have seen an increase in research on biodiesel, an environmentally benign and renewable fuel alternative for traditional fossil fuels. Biodiesel might become more cost-effective and competitive with diesel if a solid heterogeneous catalyst is used in its production. One way to make biodiesel more affordable and competitive with diesel is to employ a solid heterogeneous catalyst in its manufacturing.

The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.

The human epidermal growth factor receptor (HER) family consists of four members, activated by two families of ligands. They are known for mediating cell-cell interactions in organogenesis, and their deregulation has been associated with various cancers, including breast and esophageal cancers. In particular, aberrant epidermal growth factor receptor (EGFR) and HER2 signaling drive disease progression and result in poorer patient outcomes.

Ca-dimers, solvent layering, and dominant electrochemically active species in Ca(BH) in THF.

Divalent ions (Mg, Ca, and Zn) are being considered as competitive, safe, and earth-abundant alternatives to Li-ion electrochemistry, but present challenges for stable cycling due to undesirable interfacial phenomena. We explore the formation of electroactive species in the electrolyte Ca(BH)∣THF using molecular dynamics coupled with a continuum model of bulk and interfacial speciation. Free-energy analysis and unsupervised learning indicate a majority population of neutral Ca dimers and monomers with diverse molecular conformations and an order of magnitude lower concentration of the primary electroactive charged species - the monocation, CaBH[Formula: see text] - produced via disproportionation of neutral complexes.

Melvin is a conversational voice interface for cancer genomics data.

Despite large collections of cancer genomics data being openly available, the inability to quickly interrogate this information remains a barrier for researchers and oncologists. Here we present Melvin, an Amazon Alexa skill to explore cancer genomics data through simple conversations.

Approaches and Limitations of Machine Learning for Synthetic Ultrasound Generation: A Scoping Review.

This scoping review examines the emerging field of synthetic ultrasound generation using machine learning (ML) models in radiology. Nineteen studies were analyzed, revealing three primary methodological strategies: unconditional generation, conditional generation, and domain translation. Synthetic ultrasound is mainly used to augment training datasets and as training material for radiologists.

EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.

Background: The epidermal growth factor receptor (EGFR)-K745_E746insIPVAIK and others with XPVAIK amino-acid insertions are exon 19 insertion mutations, which, at the structural modeling level, resemble EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants. An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIK amino-acid insertion mutations to available EGFR TKIs.

Methods: We used preclinical models of EGFR-K745_E746insIPVAIK and more typical EGFR mutations (exon 19 deletion, L858R, L861Q, G719S, A763_Y764insFQEA, other exon 20 insertion mutations) to probe representative 1st (erlotinib), 2nd (afatinib), 3rd generation (osimertinib), and EGFR exon 20 insertion active (mobocertinib) TKIs.

Unsupervised learning of representative local atomic arrangements in molecular dynamics data.

Molecular dynamics (MD) simulations present a data-mining challenge, given that they can generate a considerable amount of data but often rely on limited or biased human interpretation to examine their information content. By not asking the right questions of MD data we may miss critical information hidden within it. We combine dimensionality reduction (UMAP) and unsupervised hierarchical clustering (HDBSCAN) to quantitatively characterize prevalent coordination environments of chemical species within MD data.

The bio-adsorption competence of tailor made lemon grass adsorbents on oils: An in-vitro approach.

The oil contamination in aquatic system is considered as most serious environmental issues and identifying a suitable ecofriendly solution for this oil pollution management is critical. Hence, this research was designed to evaluate the oils (petrol, diesel, engine oil, and crude oil) adsorptive features through raw lemon grass adsorbent, physically/chemically treated adsorbents. Initially, such raw and treated adsorbents were characterized by Scanning Electron Microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and Energy-Dispersive X-ray Spectroscopy (EDS) analysis.

Synthesis and characterization of barium doped CaO heterogeneous nanocatalyst for the production of biodiesel from Catharanthus roseus seeds: Kinetics, optimization and performance evaluation.

The exploitation of petroleum derivatives to meet the energy demands of the cutting edge is thought of as impractical because of asset shortage. The current necessitates that the world community improves future energy sources by developing sustainable, ecofriendly alternatives. In this work, biodiesel is produced through the transesterification of Catharanthus roseus seed oil with a barium-doped CaO heterogeneous nanocatalyst.

MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer.

KRAS-LKB1 (KL) mutant lung cancers silence STING owing to intrinsic mitochondrial dysfunction, resulting in T cell exclusion and resistance to programmed cell death (ligand) 1 (PD-[L]1) blockade. Here we discover that KL cells also minimize intracellular accumulation of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) to further avoid downstream STING and STAT1 activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition (MPS1i) potently re-engages this pathway in KL cells via micronuclei generation.

MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer.

Unlabelled: Immunotherapy has shown limited efficacy in patients with EGFR-mutated lung cancer. Efforts to enhance the immunogenicity of EGFR-mutated lung cancer have been unsuccessful to date. Here, we discover that MET amplification, the most common mechanism of resistance to third-generation EGFR tyrosine kinase inhibitors (TKI), activates tumor cell STING, an emerging determinant of cancer immunogenicity (1).

Prevention of malaria in pregnancy: The threat of sulfadoxine-pyrimethamine resistance.

Malaria infection in pregnancy can lead to adverse outcomes for both the pregnant person and fetus. The administration of intermittent preventative therapy (IPTp) with sulfadoxine-pyrimethamine (SP) during pregnancy (IPTp-SP) improves outcomes, including severe maternal anemia, placental malaria infection, and low infant birth weight. The WHO recommends IPTp-SP for pregnant individuals living in areas of moderate or high malaria transmission in Africa.

Adenosine sulfamates: Next generation of antimalarials.

Tackling the ancient infectious foe of malaria, Xie et al. (2022) uncover a novel class of nucleoside analogs that selectively hijack and inhibit the tyrosine tRNA synthase of the parasite. With high potency, good oral bioavailability, and minimal host cell toxicity, these inhibitors show promise as next-generation antimalarials.

Panobinostat in combination with bortezomib and dexamethasone in multiply relapsed and refractory myeloma; UK routine care cohort.

The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules.

Emerging pharma residue contaminants: Occurrence, monitoring, risk and fate assessment - A challenge to water resource management.

Water is one of the important gifts to mankind. In recent days the accessibility of pharmaceuticals in the environment is progressively a worldwide concern. The significant wellspring of these contaminations in water assets is drugs for human use or veterinary medications.

PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo.

Proprotein convertase subtilin/kexin type 9 (PCSK9) is a protease secreted mainly by hepatocytes and in lesser quantities by intestines, pancreas, and vascular cells. Over the years, this protease has gained importance in the field of cardiovascular biology due to its regulatory action on the low-density lipoprotein receptor (LDLR). However, recently, it has also been shown that PCSK9 acts independent of LDLR to cause vascular inflammation and increase the severity of several cardiovascular disorders.

PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology.

Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is secreted mostly by hepatocytes and to a lesser extent by the intestine, pancreas, kidney, adipose tissue, and vascular cells. PCSK9 has been known to interact with the low-density lipoprotein receptor (LDLR) and chaperones the receptor to its degradation. In this manner, targeting PCSK9 is a novel attractive approach to reduce hyperlipidaemia and the risk for cardiovascular diseases.

A robust vasculogenic microfluidic model using human immortalized endothelial cells and Thy1 positive fibroblasts.

Human umbilical vein endothelial cells (HUVECs) and stromal cells, such as human lung fibroblasts (FBs), have been widely used to generate functional microvascular networks (μVNs) in vitro. However, primary cells derived from different donors have batch-to-batch variations and limited lifespans when cultured in vitro, which hampers the reproducibility of μVN formation. Here, we immortalize HUVECs and FBs by exogenously expressing human telomerase reverse transcriptase (hTERT) to obtain stable endothelial cell and FB sources for μVN formation in vitro.