A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer.

Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells.

CpG island methylator phenotype classification improves risk assessment in pediatric T-cell Acute Lymphoblastic Leukemia.

Current intensive treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has substantial side-effects, highlighting a need for novel biomarkers to improve risk stratification. Canonical biomarkers such as genetics and immunophenotype are largely not used in pediatric T-ALL stratification. This study aimed to validate the prognostic relevance of DNA methylation CpG island methylator phenotype (CIMP) risk stratification in two pediatric T-ALL patient cohorts: the Nordic NOPHO ALL2008 T-ALL study cohort (n=192) and the Dutch DCOG ALL-10/ALL-11 validation cohorts (n=156).

Synthesis of a Transient Cationic Phosphaborene and its Trapping by Facile Aliphatic C-H Bond Activation.

The synthesis of a transient cationic phosphaborene [(Mes*)P=B(CAAC)]+ (Mes* = 2,4,6,-trit-tert-butylphenyl, CAAC = cyclic alkylamino carbene) by halide abstraction from the B-brominated analogue is reported. This species was found to undergo rapid and selective intramolecular aliphatic C-H bond activation to yield a phosphinoborenium cation, which undergoes facile deprotonation to give a cyclic base-stabilized phosphaborene. Computational investigation of the mechanism of C-H activation indicates a boron-centred activation route with an exceptionally low barrier of 8 kJ mol-1, followed by a nearly barrierless hydride migration from boron to phosphorus.

Molecular cytogenetic study of the fetal genome in idiopathic recurrent pregnancy loss.

Objective: Despite numerous studies on the causes of recurrent pregnancy loss (RPL), nearly half of cases remain unidentified, which determines the research relevance. This study aims to investigate microchromosomal variations in the fetal genome associated with the development of idiopathic RPL.

Methods: The research was supported by the Centre for Molecular Medicine and the Research Institute of Obstetrics, Gynecology and Perinatology and conducted over a period of 2 years.

Ascending aortic replacement versus aortic root replacement in patients with type A aortic dissection involving the aortic root.

Background: Extensive surgical resection of the thoracic aorta in patients with type A aortic dissection (TAAD) is thought to reduce the risk of late aortic wall degeneration and the need for repeat aortic operations.

Objectives: We evaluated the early and late outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root.

Design: Retrospective, multicenter cohort study.

Amplifying Women's Voices in Menopause Research: The Importance of Inclusive Perspectives.

Menopause, a significant life transition for half the global population, intersects biological, cultural and social dimensions. Despite its universal occurrence, menopause research has historically been dominated by biomedical perspectives, often neglecting women's voices and diverse experiences. This article highlights the importance of including women's perspectives in menopause research to ensure relevance, accuracy and equity.

Association of prostate-specific antigen density with prostate cancer mortality after a benign systematic prostate biopsy result.

Objective: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy.

Patients And Methods: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.

Luteinizing hormone receptor knockout mouse: What has it taught us?

Luteinizing hormone (LH), along with its agonist choriongonadotropin (hCG) in humans, is the key hormone responsible for the tropic regulation of the gonadal function. LH and hCG act through their cognate receptor, the luteinizing hormone/choriongonadotropin receptor (LHCGR; more appropriately LHR in rodents lacking CG), located in the testis in Leydig cells and in the ovary in theca, luteal, and luteinizing granulosa cells. Low levels in LHCGR are also expressed in numerous extragonadal sites.

Microcystin shapes the phycosphere through community filtering and by influencing cross-feeding interactions.

The cyanobacterium causes harmful algal blooms that pose a major threat to human health and ecosystem services, particularly due to the prevalence of the potent hepatotoxin microcystin (MC). With their pronounced EPS layer, colonies also serve as a hub for heterotrophic phycosphere bacteria. Here, we tested the hypothesis that the genotypic plasticity in its ability to produce MC influences the composition and assembly of the phycosphere microbiome.

Ambiguous Genitalia Due to 3β-Hydroxysteroid Dehydrogenase Type 2 Deficiency: Clinical, Genetic, and Functional Characterization of Two Novel Variants.

3β-Hydroxysteroid dehydrogenase 2 deficiency (3βHSD2D) is a rare form of congenital adrenal hyperplasia (CAH) with variable clinical presentation. We describe a 46, XY child with ambiguous genitalia and CAH without apparent adrenal insufficiency due to 2 novel heterozygous variants in the gene (c.779C > T/p.

Towards a sustainable set of European Core Health Indicators (ECHI).

Background: The European Core Health Indicators (ECHI) are a set of 88 indicators that provide a compact overview of the extensive field of European public health and healthcare. The ECHI set adds value to European Union health information systems (HIS) for both Member States and EU-associated countries and the European Commission by providing a solid, comparable information base on national public health and healthcare trends and developments. The indicators allow for learning by comparison and the list supports the organisation of national health information systems.

Microwave-assisted synthesis and and studies of pyrano[3,2-]quinoline-3-carboxylates as dual acting anti-cancer and anti-microbial agents and potential topoisomerase II and DNA-gyrase inhibitors.

A microwave-assisted method was utilized to synthesize novel pyranoquinolone derivatives as dual acting topoisomerase II/DNA gyrase inhibitors with apoptosis induction ability for halting lung cancer and staphylococcal infection. Herein, the designed rationale was directed toward mimicking the structural features of both topoisomerase II and DNA gyrase inhibitors as well as endowing them with apoptosis induction potential. The absolute configuration of the series was assigned using X-ray diffraction analysis.

Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

Values of Life: 40 years of The Value of Life.

This special section brings together international scholars celebrating the 40 anniversary of John Harris' book, (1985), and John Harris and his contributions to the field of bioethics more generally.

The chemistry of halide-based solid electrolytes: unlocking advances in solid-state Li-ion batteries.

Solid-state batteries (SSBs) represent a transformative advancement in electrochemical energy storage, offering exceptional energy density, enhanced safety, and broad operational temperature ranges, making them ideal for next-generation applications. While liquid electrolytes dominate conventional lithium-ion batteries (LIBs) due to their high conductivity and efficient electrode interface wetting, their flammability and volatility pose significant safety risks, particularly in electric vehicles and portable electronics. Solid electrolytes, a cornerstone of SSB technology, offer a promising pathway to enhance LIB energy density and safety.

Sand Play and 0- to 8-Year-Old Children's Physical, Cognitive and Socioemotional Outcomes: A Mixed-Methods Systematic Review.

Background: Sand play (SP) is a global phenomenon that may be linked to children's health outcomes, but limited evidence exists. The purpose was to synthesize evidence on the association between SP and 0- to 8-year-old children's physical, cognitive and socioemotional outcomes.

Methods: CINAHL, Academic Search Premier, PsycINFO, SPORTDiscus with Full Text, ERIC, Medline, Scopus and Google Scholar were searched.

Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer.

Introduction: Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.

General practitioners' clinical decision-making in patients that could have cancer: a vignette study comparing the Baltic states with four Nordic countries.

Objective: Relative one-year cancer survival rates in the Baltic states are lower than the European mean; in the Nordic countries they are higher than the mean. This study investigated the likelihood of General Practitioners (GPs) investigating or referring patients with a low but significant risk of cancer in these two regions, and how this was affected by GP demographics.

Design: A survey of GPs using clinical vignettes.

Interactive and unimodal relationships between plant biomass, abiotic factors, and plant diversity in global grasslands.

Grasslands cover approximately a third of the Earth's land surface and account for about a third of terrestrial carbon storage. Yet, we lack strong predictive models of grassland plant biomass, the primary source of carbon in grasslands. This lack of predictive ability may arise from the assumption of linear relationships between plant biomass and the environment and an underestimation of interactions of environmental variables.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

Development of a 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis.

This investigation aimed to develop a radiographic 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis (JIA), and to perform a validation against expert evaluations. Data were collected from a population-based Nordic JIA cohort of 240 patients that received a cone-beam computed tomography (CBCT) scan approximately 17 years after onset of JIA. The cohort was randomized into two groups: A baseline group for establishing the index (n = 210) and a test group (n = 30).

Causal analysis of dietary preferences and the risk of endometriosis using large-scale population data.

Dietary factors have recently been recognized as potentially influential in the pathogenesis of endometriosis (EM), yet studies on the causal relationship between dietary preferences and EM are limited. The present study aimed to explore the causal relationships between 187 dietary preferences and EM using Mendelian randomization (MR) methods. This study utilised genome-wide association study data from over 500,000 European participants for dietary preferences and 64,658 EM patients from Finland.

Predictive value of myositis antibodies: role of semiquantitative classification and positivity for more than one autoantibody.

Objectives: We assessed the positive predictive value (PPV) of 17 myositis antibodies for having a diagnosis of myositis and other myositis-spectrum conditions (interstitial lung disease (ILD), connective tissue diseases (CTD), malignancy) and evaluated the impact of semiquantitative classification and antibody overlap on the PPVs.

Materials And Methods: We retrospectively identified 1068 individuals ≥18 years who tested positive for ≥1 antibody in the EUROLINE myositis line blot assay or positive for anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in an ELISA-based test between 2015 and 2020 in 15 out of the 20 hospital districts in Finland. We extracted clinical diagnoses from the Care Register for Health Care between January 2013 and June 2022.

Retrospective multicenter analysis of the Trenza Embolization Device for endovascular therapy of intracranial aneurysms: initial results and short-term follow-up.

Background: Intrasaccular devices are increasingly used in endovascular therapy of intracranial aneurysms, in particular wide-necked and ruptured aneurysms. The Trenza Embolization Device (TED) is an innovative intrasaccular device for medium- to large-sized aneurysms. Currently, literature about the TED is scarce.