Evaluation of Novel Diaza Cage Compounds as MRP Modulators in Cancer Cells.

Aim: Novel MRP modulators are needed to combat MRP-mediated multidrug resistance (MDR) in cancer cells.

Background: Anticancer drug resistance is the main problem in cancer therapy. Causative multidrug efflux pumps are attractive target structures for the development of inhibitors of their activity.

Drug administration via feeding tubes-a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients.

Purpose: Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients.

Methods: Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit.

Investigation of real-life drug intake behaviour in older adults and geriatric patients in Northern Germany - A biopharmaceutical perspective.

Dosing conditions (type and amount of accompanying fluid, the type of food, the time of administration, and dosage form modifications such as crushing tablets) are critical and affect the performance of oral dosage forms in the gastrointestinal tract and thus bioavailability. Because older adults are the primary users of medications and are more susceptible to adverse effects, it is important to understand how they take their medications in order to reduce risks and increase benefits of the pharmacotherapy. The aim of the study was to investigate the real-life drug intake behaviour in geriatric patients and older adults and discuss their influence on drug absorption after oral administration.

Initiation of acute pancreatitis in mice is independent of fusion between lysosomes and zymogen granules.

The co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two different experimental approaches.

Solitary fibrous tumours of the pleura: do we need a different perspective on malignancy?

Objectives: Solitary fibrous tumours of the pleura (SFTP) are historically considered to be benign soft tissue neoplasms. However, a clinical relevant number of these neoplasms have malignant histological features. The objective of this study was to evaluate the percentage of SFTP presenting unfavourable clinical behaviour in order to predict negative long-term outcome.

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis.

Neoplasias pose a significant threat to aging society, underscoring the urgent need to overcome the limitations of traditional chemotherapy through pioneering strategies. Targeted drug delivery is an evolving frontier in cancer therapy, aiming to enhance treatment efficacy while mitigating undesirable side effects. One promising avenue utilizes cell membrane receptors like the folate receptor to guide drug transporters precisely to malignant cells.

Missing prognostic value of soluble PD-1, PD-L1 and PD-L2 in lung cancer patients undergoing chemotherapy - A CEPAC-TDM biomarker substudy.

Background: Programmed cell death receptors and ligands in cancer tissue samples are established companion diagnostics for immune checkpoint inhibitor (ICI) therapies.

Objective: To investigate the relevance of soluble PD-1, PD-L1 and PD-L2 for estimating therapy response and prognosis in non-small cell lung cancer patients (NSCLC) undergoing platin-based combination chemotherapies.

Methods: In a biomarker substudy of a prospective, multicentric clinical trial (CEPAC-TDM) on advanced NSCLC patients, soluble PD-1, PD-L1 and PD-L2 were assessed in serial serum samples by highly sensitive enzyme-linked immunosorbent assays and correlated with radiological response after two cycles of chemotherapy and with overall survival (OS).

Vaccination Training for Pharmacy Undergraduates as a Compulsory Part of the Curriculum?-A Multicentric Observation.

In order to increase vaccination rates, the Government of Germany introduced vaccination against influenza and COVID-19 into the regular care administered by pharmacists. However, vaccination training is yet not integrated into the German pharmacy curriculum. Therefore, the Institute for Clinical Pharmacy and Pharmacotherapy in Duesseldorf had developed an innovative vaccination course using high-fidelity simulation for students.

Loss of Key EMT-Regulating miRNAs Highlight the Role of ZEB1 in EGFR Tyrosine Kinase Inhibitor-Resistant NSCLC.

Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), acquired drug resistance to targeted therapy remains a major obstacle. Epithelial-mesenchymal transition (EMT) has been identified as a key resistance mechanism in NSCLC. Here, we investigated the mechanistic role of key EMT-regulating small non-coding microRNAs (miRNAs) in sublines of the NSCLC cell line HCC4006 adapted to afatinib, erlotinib, gefitinib, or osimertinib.

Spatio-temporal evolution of long-range transported mineral desert dust properties over rural and urban sites in Central Europe.

An exceptionally strong and very fast (120h) mineral dust inflow from North Africa to Poland was predicted by NMMB/BSC-Dust and NAAPS models on 10-11 June 2019. Simultaneous measurements with two complex lidar systems at the EARLINET-ACTRIS urban site in Warsaw (Central Poland) and the PolWET peatland site in Rzecin (Western Poland) captured the evolution of this dust event. The advected air masses had different source areas in North Africa, they were reaching each station via independent pathways, and thus, were unlikely mixed with each other.

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients.

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB.

Accurate machine learning prediction of sexual orientation based on brain morphology and intrinsic functional connectivity.

Background: Sexual orientation in humans represents a multilevel construct that is grounded in both neurobiological and environmental factors.

Objective: Here, we bring to bear a machine learning approach to predict sexual orientation from gray matter volumes (GMVs) or resting-state functional connectivity (RSFC) in a cohort of 45 heterosexual and 41 homosexual participants.

Methods: In both brain assessments, we used penalized logistic regression models and nonparametric permutation.

Correction: Döring et al. Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy. 2021, , 18.

The authors would like to correct an error made through no fault of their own in the title paper [...

Hippocampus mediates nocebo impairment of opioid analgesia through changes in functional connectivity.

The neural mechanisms underlying placebo analgesia have attracted considerable attention over the recent years. In contrast, little is known about the neural underpinnings of a nocebo-induced increase in pain. We previously showed that nocebo-induced hyperalgesia is accompanied by increased activity in the hippocampus that scaled with the perceived level of anxiety.

Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue.

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies.

Respiratory function modulated during execution, observation, and imagination of walking via SII.

The Mirror Neurons System (MNS) consists of brain areas active during actions execution, as well as observation-imagination of the same actions. MNS represents a potential mechanism by which we understand other's action goals. We investigated MNS activation for legs actions, and its interaction with the autonomic nervous system.

Novel Symmetrical Cage Compounds as Inhibitors of the Symmetrical MRP4-Efflux Pump for Anticancer Therapy.

Within the last decades cancer treatment improved by the availability of more specifically acting drugs that address molecular target structures in cancer cells. However, those target-sensitive drugs suffer from ongoing resistances resulting from mutations and moreover they are affected by the cancer phenomenon of multidrug resistance. A multidrug resistant cancer can hardly be treated with the common drugs, so that there have been long efforts to develop drugs to combat that resistance.

An extended lidar-based cirrus cloud retrieval scheme: first application over an Arctic site.

Accurate and precise characterization of cirrus cloud geometrical and optical properties is essential for better constraining their radiative footprint. A lidar-based retrieval scheme is proposed here, with its performance assessed on fine spatio-temporal observations over the Arctic site of Ny-Ålesund, Svalbard. Two contributions related to cirrus geometrical (dynamic Wavelet Covariance Transform (WCT)) and optical properties (constrained Klett) are reported.

Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy.

Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing.

Water vapor satellite products in the European Arctic: An inter-comparison against GNSS data.

The European Arctic is a region of high interest for climate change. Water vapor plays a fundamental role in global warming; therefore, high-quality water vapor monitoring is essential for assimilation in forecast simulations. The seven analyzed instruments on-board satellite platforms are: Atmospheric Infrared Sounder (AIRS), Global Ozone Monitoring Instrument 2 (GOME-2), Moderate-Resolution Imaging Spectroradiometer (MODIS), Ozone Monitoring Instrument (OMI), SCanning Imaging Absorption Spectrometer for Atmospheric Carthography (SCIAMACHY) and Polarization and Directionality of the Earth's Reflectances (POLDER).

Novel Nonsymmetrical 1,4-Dihydropyridines as Inhibitors of Nonsymmetrical MRP-Efflux Pumps for Anticancer Therapy.

Cancer is a strong global burden with increasing numbers of diseases and ongoing anticancer drug resistance. The number of structurally novel anticancer drugs is strongly limited. They cause high costs for the social health systems.

KOKON: A Germany-Wide Collaborative Research Project to Identify Needs, Provide Information, Foster Communication and Support Decision-Making about Complementary and Alternative Medicine in Oncology.

Background: The German Cancer Aid set up a priority research programme with the intention to generate high-quality information based on evidence and to make this information easily accessible for health-care professionals and advisors, researchers, patients, and the general public.

Summary: The Kompetenznetz Komplementärmedizin in der Onkologie (KOKON) received 2 funding periods within this programme. During the first funding period, KOKON assessed patients' and health-care professionals' informational needs, developed a consulting manual for physicians, developed an education programme for self-help groups, set up a knowledge database, and developed a pilot information website for patients.

The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm.

Prediction errors are thought to drive associative fear learning. Surprisingly little is known about the possible contribution of the cerebellum. To address this question, healthy participants underwent a differential fear conditioning paradigm during 7T magnetic resonance imaging.