Murine neonatal cardiac regeneration depends on Insulin-like growth factor 1 receptor signaling.

Unlike adult mammals, the hearts of neonatal mice possess the ability to completely regenerate from myocardial infarction (MI). This observation has sparked vast interest in deciphering the potentially lifesaving and morbidity-reducing mechanisms involved in neonatal cardiac regeneration. In mice, the regenerative potential is lost within the first week of life and coincides with a reduction of Insulin-like growth factor 1 receptor (Igf1r) expression in the heart.

An IL-1β-driven neutrophil-stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma.

Human bone marrow permanently harbors high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In individuals with multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. We investigated myeloma-associated alterations in human marrow neutrophils and the impact of stromal inflammation on neutrophil function.

Frailty Screening is Associated with Hospitalization and Decline in Quality of Life and Functional Status in Older Patients with Inflammatory Bowel Disease.

Background And Aims: Our goals were to study frailty screening in association with hospitalization and decline in quality of life [QoL] and functional status in older patients with inflammatory bowel diseases [IBD].

Methods: This was a prospective multicentre cohort study in IBD patients ≥65 years old using frailty screening [G8 Questionnaire]. Outcomes were all-cause, acute, and IBD-related hospitalization, any infection, any malignancy, QoL [EQ5D-3L], and functional decline (Instrumental Activities of Daily Living [IADL]) during 18 months of follow-up.

Off-line analysis in the manganese catalysed epoxidation of ethylene-propylene-diene rubber (EPDM) with hydrogen peroxide.

The epoxidation of ethylene-propylene-diene rubber (EPDM) with 5-ethylidene-2-norbornene (ENB) as the diene to epoxidized EPDM (eEPDM) creates additional routes to cross-linking and reactive blending, as well as increasing the polarity and thereby the adhesion to polar materials, , mineral fillers such as silica. The low solubility of apolar, high molecular weight polymers in the polar solvents constrains the catalytic method for epoxidation that can be applied. Here we have applied an prepared catalyst comprising a manganese(ii) salt, sodium picolinate and a ketone to the epoxidation of EPDM rubber with hydrogen peroxide (HO) as the oxidant in a solvent mixture, that balances the need for polymer and catalyst/oxidant miscibility and solubility.

Identification of High-Risk Multiple Myeloma With a Plasma Cell Leukemia-Like Transcriptomic Profile.

Purpose: Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma (NDMM) on the basis of the presence of ≥ 20% circulating tumor cells (CTCs). A molecular marker for pPCL is currently lacking, which could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically.

Methods: A transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by leveraging information on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with NDMM included in the Cassiopeia or HO143 trials and 29 patients with pPCL from the EMN12/HO129 trial.

Molecular Signature of F-FDG PET Biomarkers in Newly Diagnosed Multiple Myeloma Patients: A Genome-Wide Transcriptome Analysis from the CASSIOPET Study.

The International Myeloma Working Group recently fully incorporated F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these F-FDG PET biomarkers could be fully endorsed as risk classifiers by the hematologist community, further characterization of underlying molecular aspects was necessary.

VS38c and CD38-Multiepitope Antibodies Provide Highly Comparable Minimal Residual Disease Data in Patients With Multiple Myeloma.

Objectives: To compare flow cytometric minimal residual disease (MRD) data obtained using the EuroFlow approach, including the CD38-multiepitope (ME) antibody or the VS38c antibody.

Methods: We evaluated 29 bone marrow samples from patients with multiple myeloma (MM), of whom 15 had received daratumumab within the past 6 months. We evaluated MRD data and fluorescence intensities.

Cabergoline Stimulates Human Endometrial Stromal Cell Decidualization and Reverses Effects of Interleukin-1β In Vitro.

Context: Human embryonic implantation is regulated by neuroendocrine hormones, ovarian steroids, growth factors, and cytokines. Sympathetic innervation of the uterus also may play a role.

Objective: We tested the hypothesis that cabergoline (Cb), an agonist of type 2 dopamine receptors (DRD2), could influence endometrial decidualization in vitro.

Women and babies are dying from inertia: a collaborative framework for obstetrical drug development is urgently needed.

Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

Background & Aims: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life).

Methods: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed.

V-Domain Ig Suppressor of T Cell Activation (VISTA) Expression Is an Independent Prognostic Factor in Multiple Myeloma.

Multiple myeloma (MM) is characterized by loss of anti-tumor T cell immunity. Despite moderate success of treatment with anti-PD1 antibodies, effective treatment is still challenged by poor T cell-mediated control of MM. To better enable identification of shortcomings in T-cell immunity that relate to overall survival (OS), we interrogated transcriptomic data of bone marrow samples from eight clinical trials ( = 1654) and one trial-independent patient cohort ( = 718) for multivariate analysis.

The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape.

Progression and persistence of malignancies are influenced by the local tumor microenvironment, and future eradication of currently incurable tumors will, in part, hinge on our understanding of malignant cell biology in the context of their nourishing surroundings. Here, we generated paired single-cell transcriptomic datasets of tumor cells and the bone marrow immune and stromal microenvironment in multiple myeloma. These analyses identified myeloma-specific inflammatory mesenchymal stromal cells, which spatially colocalized with tumor cells and immune cells and transcribed genes involved in tumor survival and immune modulation.

Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial.

The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects.

Recyclability of Photoinduced Cross-Linked EPM Rubber with Anthracene-Grafted Groups: Problems and Their Solutions.

In this paper, we present the formation of reversible covalently cross-linked networks in ethylene propylene rubber with grafted anthracene groups (EPM-g-AN) based on the principles of photoinduced anthracene dimerization. First, an industrial-grade EPM rubber grafted with maleic anhydride functional groups (EPM-g-MA) was modified with 9-anthracenemethanol. By irradiating EPM-g-AN with UV light (365 nm), the anthracene moieties dimerize via [4 + 4]cycloaddition, forming a covalent network.

Analytical Validation of SKY92 for the Identification of High-Risk Multiple Myeloma.

Multiple myeloma (MM) is an incurable plasma cell cancer with a large variability in survival. Patients with MM classified as high risk by the SKY92 gene expression classifier are at high risk of relapse and short survival. Analytical validation of the SKY92 assay was performed with primary bone marrow specimens from 12 patients with MM and 7 reference cell line specimens.

Search for multiple myeloma risk factors using Mendelian randomization.

The etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls.

Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome.

Study Question: Can kisspeptin treatment induce gonadotrophin responses and ovulation in preclinical models and anovulatory women with polycystic ovary syndrome (PCOS)?

Summary Answer: Kisspeptin administration in some anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy.

What Is Known Already: PCOS is a prevalent, heterogeneous endocrine disorder, characterized by ovulatory dysfunction, hyperandrogenism and deregulated gonadotrophin secretion, in need of improved therapeutic options. Kisspeptins (encoded by Kiss1) are master regulators of the reproductive axis, acting mainly at GnRH neurons, with kisspeptins being an essential drive for gonadotrophin-driven ovarian follicular maturation and ovulation.

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.

Background: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).

Results: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression.

An objective and automated method for evaluating abdominal hyperalgesia in a rat model for endometriosis.

Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters.