PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.

Our study explores the complex dynamics of the integrated stress response (ISR) axis, highlighting PIM2 kinase's critical role and its interaction with the BCL2 protein family, uncovering key mechanisms of cell survival and tumor progression. Elevated PIM2 expression, a marker of various cancers, often correlates with disease aggressiveness. Using a model of normal and malignant plasma cells, we show that inhibiting PIM2 kinase inhibits phosphorylated BAD production and activates ISR-mediated NOXA expression.

Fluorescent labelling as a tool for identifying and quantifying nanoplastics.

Advancements in microplastic research are progressing rapidly, yet detecting and identifying nanoplastics remain challenging, especially in natural samples. In this study, we addressed these challenges by employing fluorescent labeling on nanoparticles of six prevalent plastic types (PP, LDPE, HDPE, PS, PET, and PVC) to enable their specific detection the analysis of 3D fluorescence spectra post-staining. Four fluorescent molecules were tested: cyanine-3 phosphoramidite, rhodamine-6G, fluorescein sodium salt, and Vat Red 15.

Southern Madagascar, polycrisis and project failures: A scoping review.

The southern region of Madagascar experiences a series of crises related to agro-climatic, nutritional, security, institutional, and political conditions despite the presence of numerous development aid projects over several decades. To understand this apparent paradox, this scoping review examines 63 peer-reviewed and grey literature studies in both French and English from 1990 to 2023, focusing on project failures in the southern region of Madagascar. The article makes two main contributions.

Integrated surveillance systems for antibiotic resistance in a One Health context: a scoping review.

Background: Antibiotic resistance (ABR) has emerged as a major threat to health. Properly informed decisions to mitigate this threat require surveillance systems that integrate information on resistant bacteria and antibiotic use in humans, animals, and the environment, in line with the One Health concept. Despite a strong call for the implementation of such integrated surveillance systems, we still lack a comprehensive overview of existing organizational models for integrated surveillance of ABR.

Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

Results from a Joined Prospective Study to Evaluate the Sensitivity of the In Vivo Dog QT Assay in Line with the ICH E14/S7B Q&A Best Practices.

The ICH E14/S7B Q&As highlighted the need for best practices concerning the design, execution, analysis, interpretation, and reporting of the in vivo non-rodent QT assay as a component of the integrated risk assessment to potentially support a TQT waiver or substitute. We conducted a dog telemetry study to assess the effects on QTc of six reference compounds (five positive and one negative) previously evaluated by Darpo et al. (2015) in humans.

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model.

The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the robustness and translational value of methods employed during drug development. Electroencephalography (EEG)-based measures like evoked and spontaneous gamma oscillations are considered robust translational biomarkers as they can be recorded in both patients and animal models to probe a key mechanism underlying all SZ symptoms: the excitation/inhibition imbalance mediated by N-methyl-D-aspartate receptor (NMDAr) hypofunction.

Nanoplastic production procedure for scientific purposes: PP, PVC, PE-LD, PE-HD, and PS.

Studies on the environmental impact of nanoplastics face challenges in plastic analysis and a scarcity of nanoplastic materials necessary for the development of analytical techniques and experiments on biota impact. Here we provide detailed procedures for obtaining nanoparticles suspended in water for the most commonly used polymers: Polypropylene (PP), Polyvinylchloride (PVC), Low- and High-Density Polyethylene (PE-LD, PE-HD), and Polystyrene (PS). We dissolved larger size material to reprecipitate nanoparticles.

Pressure injury prevention in the operating unit of a Swiss university hospital: a best practice implementation project.

Objectives: The aim of this project was to promote best practice in pressure injury prevention for patients during the intraoperative period in the main operating unit of a Swiss tertiary hospital, through improving risk assessment, safe positioning and documentation.

Introduction: Pressure injury is a common and serious complication of surgery patients. Despite pressure injuries being mostly preventable, they are not a top priority of operating room professionals.

Evaluation of the Effectiveness of Endovascular Treatment of Type 2 Endoleaks.

Background: Endovascular abdominal aortic aneurysm repair (EVAR) is a safe and minimally invasive alternative to open surgical repair for infra renal aortic aneuvrysm. EVAR requires lifelong post-procedural surveillance. Endoleaks represent the main complication.

Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

Background: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors.

PIM2 kinase has a pivotal role in plasmablast generation and plasma cell survival, opening up novel treatment options in myeloma.

The differentiation of B cells into plasmablasts (PBs) and then plasma cells (PCs) is associated with extensive cell reprogramming and new cell functions. By using specific inhibition strategies (including a novel morpholino RNA antisense approach), we found that early, sustained upregulation of the proviral integrations of Moloney virus 2 (PIM2) kinase is a pivotal event during human B-cell in vitro differentiation and then continues in mature normal and malignant PCs in the bone marrow. In particular, PIM2 sustained the G1/S transition by acting on CDC25A and p27Kip1 and hindering caspase 3-driven apoptosis through BAD phosphorylation and cytoplasmic stabilization of p21Cip1.

HEMO life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study.

Background: M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys.

Capitalizing on the G7 Research Compact.

Rules for S&T collaboration should be integrated with trade and investment agreements.

Targeting IgE polyadenylation signal with antisense oligonucleotides decreases IgE secretion and plasma cell viability.

Background: Allergy regroups numerous complex and various diseases classified as IgE-dependent or non-IgE-dependent hypersensitivities. IgEs are expressed as membrane and secreted forms by B cells and plasma cells, respectively. In IgE-mediated hypersensitivity, IgE secretion and binding to the high-affinity IgE receptor FcεRI on effector cells are responsible for the onset of allergic symptoms; in contrast, surface IgE expression as a B-cell receptor is barely detectable.

Overground and Virtual Reality Gait Speed Are Associated With Atypical Symptom Reporting in Active Duty Service Members With a History of Mild to Moderate Traumatic Brain Injury.

Objective: Physical therapy following traumatic brain injury (TBI) can be negatively impacted by psychological symptoms, atypical symptom reporting, and response bias. We examined rates of Symptom Validity Test (SVT) failure in active duty military service members with a history of mild-moderate TBI and its impact on gait speed.

Setting: Intensive Outpatient Program at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center.

ADT2FHIR - A Tool for Converting ADT/GEKID Oncology Data to HL7 FHIR Resources.

Harmonized and interoperable data management is a core requirement for federated infrastructures in clinical research. Institutions participating in such infrastructures often have to invest large degrees of time and resources in implementing necessary data integration processes to convert their local data to the required target structure. If the data is already available in an alternative shared data structure, the transformation from source to the desired target structure can be implemented once and then be distributed to all participants to reduce effort and harmonize results.

A Novel Oxygen Carrier (M101) Attenuates Ischemia-Reperfusion Injuries during Static Cold Storage in Steatotic Livers.

The combined impact of an increasing demand for liver transplantation and a growing incidence of nonalcoholic liver disease has provided the impetus for the development of innovative strategies to preserve steatotic livers. A natural oxygen carrier, HEMO2life, which contains M101 that is extracted from a marine invertebrate, has been used for static cold storage (SCS) and has shown superior results in organ preservation. A total of 36 livers were procured from obese Zucker rats and randomly divided into three groups, i.

Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment.

Currently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.

Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors.

IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety of cancers, including metastatic melanoma and renal cell carcinoma. We recently reported the identification of several novel heme-displacing IDO1 inhibitors, including the clinical molecules linrodostat (BMS-986205) and BMS-986242. Both molecules contain quinolines that, while being present in successful medicines, are known to be potentially susceptible to oxidative metabolism.

Therapeutic Potential of Hemoglobin Derived from the Marine Worm (M101): A Literature Review of a Breakthrough Innovation.

Oxygen (O) is indispensable for aerobic respiration and cellular metabolism. In case of injury, reactive oxygen species are produced, causing oxidative stress, which triggers cell damaging chemical mediators leading to ischemic reperfusion injuries (IRI). Sufficient tissue oxygenation is necessary for optimal wound healing.