Pneumatic tube transport of trastuzumab in IV bags-Effect of headspace and surfactant on subvisible particle formation.

In hospitals, IV bags can be prepared in advance for logistical and microbial safety reasons in a compounding unit and then transported to wards. Transport of protein drugs using a pneumatic tube system has been reported to result in high particle levels. In this study, pneumatic tube transport of trastuzumab in saline polyolefin bags was compared to delivery by hospital porters using an electric platform truck in an underground tunnel system.

Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.

The intestinal mucosal barrier is a dynamic system that allows nutrient uptake, stimulates healthy microbe-host interactions, and prevents invasion by pathogens. The mucosa consists of epithelial cells connected by cellular junctions that regulate the passage of nutrients covered by a mucus layer that plays an important role in host-microbiome interactions. Mimicking the intestinal mucosa for assays, particularly the generation of a mucus layer, has proven to be challenging.

A worldwide look into long COVID-19 management: an END-COVID survey.

Background: Long COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide.

Methods: A survey-based study investigating long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID and PATS).

Thermoforming for Small Feature Replication in Melt Electrowritten Membranes to Model Kidney Proximal Tubule.

A novel approach merging melt electrowriting (MEW) with matched die thermoforming to achieve scaffolds with micron-sized curvatures (200 - 800 µm versus 1000 µm of mandrel printing) for in vitro modeling of the kidney proximal tubule (PT) is proposed. Recent advances in this field emphasize the relevance of accurately replicating the intricate tissue microenvironment, particularly the curvature of the nephrons' tubular segments. While MEW offers promising capabilities for fabricating highly and porous precise 3D structures mimicking the PT, challenges persist in approximating the diameter of tubular scaffolds to match the actual PT.

Risk stratification and treatment goals in pulmonary arterial hypertension.

Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions.

3D layered co-culture model enhances Trastuzumab Deruxtecan sensitivity and reveals the combined effect with G007-LK in HER2-positive non-small cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) aberrations are observed in various cancers. In non-small cell lung cancer, genetic alterations activating HER2, mostly exon 20 insertion mutations, occur in approximately 2-4% of cases. Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate has been approved as the first HER2-targeted drug for HER2-mutant lung cancer.

Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping.

Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A.

Sequential, Electrochemical-Photochemical Synthesis of 1,2,4-Triazolo-[4,3-a]pyrazines.

1,2,4-triazolo-[4,3-a]pyrazine was prepared via a two-step electrochemical, photochemical process. First, a 5-substituted tetrazole is electrochemically coupled to 2,6-dimethoxypyrazine to yield 1,5- and 2,5- disubstituted tetrazoles. Subsequent photochemical excitation of the 2,5-disubstituted tetrazole species using an ultraviolet lamp releases nitrogen gas and produces a short-lived nitrilimine intermediate.

Structural bases of inhibitory mechanism of Ca1.2 channel inhibitors.

The voltage-gated calcium channel Ca1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of Ca1.

Remote endpoints for clinical trials in cystic fibrosis: Report from the U.S. CF foundation remote endpoints task force.

The COVID-19 pandemic necessitated a rapid shift in clinical research to perform virtual visits and remote endpoint assessments, providing a key opportunity to optimize the use of remote endpoints for clinical trials in cystic fibrosis. The use of remote endpoints could allow more diverse participation in clinical trials while minimizing participant burden but must be robustly evaluated to ensure adequate performance and feasibility. In response, the Cystic Fibrosis Foundation convened the Remote Endpoint Task Force (Supplemental Table 1), a multidisciplinary group of CF researchers with remote endpoint expertise and community members tasked to better understand the current and future use of remote endpoints for clinical research.

Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN.

About 500,000 patients with rare adult solid cancers (RASC) are diagnosed yearly in Europe. Delays and unequal quality of management impact negatively their survival. Since 2017, European reference networks (ERN) aim to improve the quality of care of patients with rare disease.

Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures.

Introduction: Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents.

Results: In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations.

Angelica acutiloba Kitagawa flower induces A549 cell pyroptosis via the NF-κB/NLRP3 pathway for anti-lung cancer effects.

Angelica acutiloba Kitagawa, a traditional medicinal herb of the Umbelliferae family, has been demonstrated to have anticancer activity. In this study, we investigated the anti-lung cancer effects of two compounds extracted from A. acutiloba flowers: kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE) and platanoside (PLA).

Quantitative prediction of CYP3A-mediated drug-drug interactions by correctly estimating fraction metabolized using human liver chimeric mice.

Background And Purpose: Fraction metabolized (f ) and fraction transported (f ) are important for understanding drug-drug interactions (DDIs) in drug discovery and development. However, current in vitro systems cannot accurately estimate in vivo f due to inability to reflect the f by efflux transporters (f ). This study demonstrates how CYP3A-mediated DDI for CYP3A/P-gp substrates can be predicted using Hu-PXB mice as human liver chimeric mice.

Card9/neutrophil signalling axis promotes IL-17A-mediated ankylosing spondylitis.

Objective: Polymorphisms in the antifungal signalling molecule are associated with ankylosing spondylitis (AS). Here, we investigated the cellular mechanism by which CARD9 controls pathogenic Th17 responses and the onset of disease in both experimental murine AS and patients.

Methods: Experiments in SKG, Card9SKG, neutrophil-deplete SKG mice along with murine, neutrophil and CD4 T cell cocultures examined Card9 function in neutrophil activation, Th17 induction and arthritis in experimental AS.

Rapid and accurate genotyping of human SNP rs671 in aldehyde dehydrogenase 2 gene using one-step CRISPR/Cas12b assay without DNA amplification.

Background: The SNP rs671 of Human aldehyde dehydrogenase (ALDH) is G-A transition at 1510th nucleotides, which is an important clinical indicator of alcoholic liver disease, digestive tract cancer and some drug efficiency. The commonly used genotyping assay of this polymorphism is relatively time-consuming and costly.

Finding: This study develops a rapid and accurate one-step CRISPR/Cas12b assay to distinguish the G1510A polymorphism of human ALDH2 free of DNA amplification.

Neuroprotective Potential of L-Glutamate Transporters in Human Induced Pluripotent Stem Cell-Derived Neural Cells against Excitotoxicity.

Human induced pluripotent stem cell (hiPSC)-derived neural cells have started to be used in safety/toxicity tests at the preclinical stage of drug development. As previously reported, hiPSC-derived neurons exhibit greater tolerance to excitotoxicity than those of primary cultures of rodent neurons; however, the underlying mechanisms remain unknown. We here investigated the functions of L-glutamate (L-Glu) transporters, the most important machinery to maintain low extracellular L-Glu concentrations, in hiPSC-derived neural cells.

CORAL Models for Drug-Induced Nephrotoxicity.

Drug-induced nephrotoxicity is a major cause of kidney dysfunction with potentially fatal consequences. The poor prediction of clinical responses based on preclinical research hampers the development of new pharmaceuticals. This emphasises the need for new methods for earlier and more accurate diagnosis to avoid drug-induced kidney injuries.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence.

Π-Π interactions stabilize PeptoMicelle-based formulations of Pretomanid derivatives leading to promising therapy against tuberculosis in zebrafish and mouse models.

Tuberculosis is the deadliest bacterial disease globally, threatening the lives of millions every year. New antibiotic therapies that can shorten the duration of treatment, improve cure rates, and impede the development of drug resistance are desperately needed. Here, we used polymeric micelles to encapsulate four second-generation derivatives of the antitubercular drug pretomanid that had previously displayed much better in vivo activity against Mycobacterium tuberculosis than pretomanid itself.

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care.

Over 1400 patients using dry powder inhalers (DPIs) to deliver COPD maintenance therapies were recruited across Europe and Australia. Their peak inspiratory flow (PIF) was measured, inhaler technique was observed, and adherence to treatment assessed. From relating the findings with patient health status, and thereby identifying critical errors, key clinical recommendations for primary care clinicians were determined, namely - measure PIF before prescribing a DPI to ensure inhalation manoeuvre ability is well-matched with the device.

Structural basis for Na1.7 inhibition by pore blockers.

Voltage-gated sodium channel Na1.7 plays essential roles in pain and odor perception. Na1.