Seven new species in (, ) from the Northern Hemisphere recovered through morphological and molecular methods.

The ectomycorrhizal genus (, ) is studied using morphological and molecular methods. Seven new species are identified and described, , and , bringing the total number of accepted species to 13. All new species are supported by ITS sequences from basidiomata and from environmental soil and root-tip sequences available in public databases.

Which clinical trial designs and statistical approaches have been used in assessments of orphan maintenance by the European Medicines Agency between 2012 and 2022? A cross-sectional study.

Objectives: In the European Union, a new orphan medicinal product must demonstrate 'significant benefit' over approved medicinal products targeting the same indication. To demonstrate a significant benefit, comparisons between the new product and the already approved medicinal products-either directly by a head-to-head comparison within a clinical trial or indirectly as a cross-trial comparison-are necessary. In this study, we investigate the types of trial designs and statistical approaches used for demonstrating a significant benefit of a new orphan medicinal product against approved comparators used between 2012 and 2022.

Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements.

Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD).

Deep learning estimation of proton stopping power with photon-counting computed tomography: a virtual study.

Purpose: Proton radiation therapy may achieve precise dose delivery to the tumor while sparing non-cancerous surrounding tissue, owing to the distinct Bragg peaks of protons. Aligning the high-dose region with the tumor requires accurate estimates of the proton stopping power ratio (SPR) of patient tissues, commonly derived from computed tomography (CT) image data. Photon-counting detectors for CT have demonstrated advantages over their energy-integrating counterparts, such as improved quantitative imaging, higher spatial resolution, and filtering of electronic noise.

Recurrent discharges of non-petroleum substances from chemical tankers in Swedish marine Natura 2000 sites are against the aims of EU Directives.

The transport of non-petroleum substances such as vegetable oils, other bio-based oils and their refined products by chemical tankers is increasing worldwide. The majority of the non-petroleum substances carried by chemical tankers will have detrimental effects on the marine environment if accidentally spilled or discharged during tank washing procedures. Swedish Coast Guard aircrafts detected 233 discharges of floating non-petroleum substances in the Swedish territorial sea and Swedish Exclusive Economic Zone (EEZ) between 2020 and 2023.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer - A Swedish cohort study.

Introduction: Perfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited.

Early vascular aging in chronic kidney disease: focus on microvascular maintenance, senescence signature and potential therapeutics.

Chronic kidney disease (CKD) is a strong risk factor for cardiovascular mortality and morbidity. We hypothesized that a senescent phenotype instigated by uremic toxins could account for early vascular aging (EVA) and vascular dysfunctions of microvasculature in end stage kidney disease (ESKD) patients which ultimately lead to increased cardiovascular complication. To test this hypothesis, we utilized both in vivo, and ex vivo approaches to study endothelial and smooth muscle function and structure, and characterized markers related to EVA in 82 ESKD patients (eGFR <15 ml/min) and 70 non-CKD controls.

Navigating the orphan medicinal product designation: Evidence requirements for gene therapies in Europe.

To provide insight into regulatory decision-making at the time of granting initial orphan designation by the Committee for Orphan Medicinal Products, we have conducted a retrospective analysis for viral vector-mediated gene therapies in rare non-oncological conditions with respect to the data provided to support the criteria to be met in successful applications. We found that a high proportion of non-clinical in vivo data was used for gene therapies, indicating earlier submissions of products that are at the stage of preclinical research and not in clinical development. Clinical data were submitted in only 13% of the applications, containing preliminary results derived from early-stage clinical trials in few patients.

Metronomic chemotherapy using capecitabine and cyclophosphamide in metastatic breast cancer - efficacy, tolerability and quality of life results from the phase II METRO trial.

Background: Chemotherapy is commonly used in metastatic breast cancer (MBC) to prolong life and improve quality of life (QoL). The optimal dosing and sequencing beyond the second line of treatment are unknown and pose a risk of overtreatment. Continuous low oral doses of metronomic chemotherapy using capecitabine 500 mg three times daily and cyclophosphamide 50 mg once daily (MCT-CX) may be an effective and tolerable treatment option for patients with MBC.

Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators of low-density lipoprotein receptor (LDLR). Information on role and regulation of PCSK9 in lung is very limited. Our study focuses on understanding the role and regulation of PCSK9 in the lung.

Introducing waterbirth in a university hospital setting in Sweden: A qualitative study of midwives' experiences.

Introduction: Waterbirth is a popular and increasing care option in several countries but is still debated. In Sweden, there are challenges in the process of reintroducing waterbirth after decades of interruption invoked by a dissuasion. The aim of this study was to explore factors affecting midwives' provision of waterbirth at a university birthing clinic in Sweden.

Men's views on causes and consequences of erectile dysfunction or premature ejaculation in a primary care population: a qualitative study.

Objective: To explore men's views on the causes and consequences of two common sexual dysfunctions - erectile dysfunction and premature ejaculation - and how this affects physical and mental health as well as social life and intimate or close relations.

Design: A qualitative design with semi-structured interviews using open-ended questions was employed. Individual interviews were conducted, audio recorded and transcribed, and a qualitative content analysis of the text was performed.

Inherited retinal dystrophies and orphan designations in the European Union.

Inherited Retinal Dystrophies (IRD) are diverse rare diseases that affect the retina and lead to visual impairment or blindness. Research in this field is ongoing, with over 60 EU orphan medicinal products designated in this therapeutic area by the Committee for Orphan Medicinal Products (COMP) at the European Medicines Agency (EMA). Up to now, COMP has used traditional disease terms, like retinitis pigmentosa, for orphan designation regardless of the product's mechanism of action.

Advancing rare disease treatment: EMA's decade-long insights into engineered adoptive cell therapy for rare cancers and orphan designation.

Adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has emerged as a promising approach for targeting and treating rare oncological conditions. The orphan medicinal product designation by the European Union (EU) plays a crucial role in promoting development of medicines for rare conditions according to the EU Orphan Regulation.This regulatory landscape analysis examines the evolution, regulatory challenges, and clinical outcomes of genetically engineered ACT, with a focus on CAR-T cell therapies, based on the European Medicines Agency's Committee for Orphan Medicinal Products review of applications evaluated for orphan designation and maintenance of the status over a 10-year period.

A revised genus-level classification for ().

is a small family of polypores and hydnoid fungi in the order (). The family consists of white-rot fungi, some of which are serious tree pathogens. Combining morphological evidence with a phylogenetic dataset of six genetic markers, we revise generic concepts in the family and propose a seven-genus classification system for the family.

The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered.

UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes.

A First Step Toward a Family of Morphed Human Body Models Enabling Prediction of Population Injury Outcomes.

The injury risk in a vehicle crash can depend on occupant specific factors. Virtual crash testing using finite element human body models (HBMs) to represent occupant variability can enable the development of vehicles with improved safety for all occupants. In this study, it was investigated how many HBMs of different sizes that are needed to represent a population crash outcome through a metamodel.

The European landscape for gene therapies in orphan diseases: 6-year experience with the EMA Committee for Orphan Medicinal Products.

In 2000, the European Union (EU) introduced the orphan pharmaceutical legislation to incentivize the development of medicinal products for rare diseases. The Committee for Orphan Medicinal Products (COMP), the European Medicines Agency committee responsible for evaluation of applications for orphan designation (OD), received an increasing flow of applications in the field of gene therapies over the last years. Here, the COMP has conducted a descriptive analysis of applications regarding gene therapies in non-oncological rare diseases, with respect to (a) targeted conditions and their rarity, (b) characteristics of the gene therapy products proposed for OD, with a focus on the type of vector used, and (c) regulatory aspects pertaining to the type of sponsor and development, by examining the use of available frameworks offered in the EU such as protocol assistance and PRIME.

The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment.

Neuroblastoma is the most common extracranial solid tumor in childhood and arises from neural crest cells of the developing sympathetic nervous system. Prostaglandin E (PGE) has been identified as a key pro-inflammatory mediator of the tumor microenvironment (TME) that promotes neuroblastoma progression. We report that the interaction between the microRNA miR-574-5p and CUG-binding protein 1 (CUGBP1) induces the expression of microsomal prostaglandin E synthase 1 (mPGES-1) in neuroblastoma cells, which contributes to PGE biosynthesis.

High-content screening of drug combinations of an mPGES-1 inhibitor in multicellular tumor spheroids leads to mechanistic insights into neuroblastoma chemoresistance.

High-throughput drug screening enables the discovery of new anticancer drugs. Although monolayer cell cultures are commonly used for screening, their limited complexity and translational efficiency require alternative models. Three-dimensional cell cultures, such as multicellular tumor spheroids (MCTS), mimic tumor architecture and offer promising opportunities for drug discovery.