Clinical validation of a biopsy-based six-gene signature prognostic for aggressive prostate cancer.

Objectives: This study aimed to clinically validate the six-gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue.

Methods: MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cancer (UPCA,  = 100). The primary outcome of adverse pathology and secondary outcomes of high primary Gleason (≥G4) and high pathological T-stage (≥T3) were assessed by likelihood ratio statistics and area under the receiver operating characteristic curves from logistic regression models; time to biochemical recurrence was assessed by likelihood ratio statistics and C-indexes from Cox proportional hazard regression models.

Specific modulation of 28S_Um2402 rRNA 2'--ribose methylation as a novel epitranscriptomic marker of ZEB1-induced epithelial-mesenchymal transition in different mammary cell contexts.

The epithelial-mesenchymal transition (EMT) is a dynamic transdifferentiation of epithelial cells into mesenchymal cells. EMT programs exhibit great diversity, based primarily on the distinct impact of molecular activities of the EMT transcription factors. Using a panel of cancer cell lines and a series of 71 triple-negative primary breast tumors, we report that the EMT transcription factor ZEB1 modulates site-specific chemical modifications of ribosomal RNA (rRNA).

Parental Drinking Patterns and Adolescent Alcohol Consumption: Considering the Role of Sex and Developmental Stage.

Introduction: Research indicates that parental behaviors shape adolescents' alcohol consumption, but it is unclear whether mothers or fathers have a more significant impact and how this relationship varies by sex and developmental stage. This study examines the effects of parental alcohol consumption patterns on adolescents in Russia using a large representative sample.

Methods: The study employs pooled data from the Russia Longitudinal Monitoring Survey-Higher School of Economics (RLMS-HSE) from 2006 to 2019.

Rationale and design of the HOVON 170 DLBCL-ANTICIPATE trial: preventing anthracycline-induced cardiac dysfunction with dexrazoxane.

Background: Dexrazoxane has been studied for its ability to prevent anthracycline-induced cardiac dysfunction (AICD) in several trials but its use in clinical practice remains limited. This is related to the low to moderate quality of the generated evidence, safety concerns and restricted prescribing indications. Additional randomized trials are needed before this drug can be routinely integrated into cardio-oncology clinical practice.

Exploring the luminescent and thermometric potentials of samarium(III) diketonate complexes with extended fluoroalkyl chains.

We synthesized and investigated a new series of Sm 1,3-diketonate complexes with CF-homologous thiophene-containing ligands. A clear correlation was found between the number of fluorine atoms in the 1,3-diketone's carbon chain and the luminescent properties of the samarium(III) complexes. The ligand modification method employed facilitates targeted and significant enhancements in the photoluminescence quantum yield (PLQY).

Effect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.

Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination.

Biosimilars: A Critical Review of Development, Regulatory Landscape, and Clinical Implications.

The biopharmaceutical industry has witnessed significant growth in the development and approval of biosimilars. These biosimilars aim to provide cost-effective alternatives to expensive originator biosimilars, alleviating financial pressures within healthcare. The manufacturing of biosimilars is a highly complex process that involves several stages, each of which must meet strict regulatory standards to ensure that the final product is highly similar to the reference biologic.

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population.

The Thorny Skate (Amblyraja radiata) is a vulnerable species displaying a discrete size-polymorphism in the northwest Atlantic Ocean (NWA). We conducted whole genome sequencing of samples collected across its range. Genetic diversity was similar at all sampled sites, but we discovered a ~ 31 megabase bi-allelic supergene associated with the size polymorphism, with the larger size allele having introgressed in the last ~160,000 years B.

Early palliative care in metastatic uveal melanoma (early together): protocol of a prospective randomized Phase III trial.

Metastatic uveal melanoma (UM) patients often initially present with limited symptoms despite a poor prognosis, complicating communication with patients and caregivers. Early Together (NCT04728113) is a randomized Phase III trial that integrates early palliative care through systematic joint visits involving the palliative care team and the medical oncologist, compared with standard oncological care, in 162 metastatic UM patients beginning systemic treatment. This collaboration aims to enhance patient functioning, improve quality of life and facilitate coping mechanisms.

Finite Element Analysis (FEA) for Influence of Variation in Dental Implant Dimensions (Length and Diameter) on Peri-implant Bone Stress/Strain Distribution: A Systematic Review.

Background & Objective: Currently, there are many implants in clinical use, making it hard to choose the right one for the patient. The success rate of an implant depends on its diameter, length, and direction of insertion in bone. In implant dentistry, Finite Element Analysis (FEA) simulates intraoral conditions in vitro and analyzes the effects of implant material, diameter, size, and other components related to oral structure on the implant and peri-implant tissues.

Negative gas adsorption transitions and pressure amplification phenomena in porous frameworks.

Nanoporous solids offer a wide range of functionalities for industrial, environmental, and energy applications. However, only a limited number of porous materials are responsive, the nanopore dynamically alters its size and shape in response to external stimuli such as temperature, pressure, light or the presence of specific molecular stimuli adsorbed inside the voids deforming the framework. Adsorption-induced structural deformation of porous solids can result in unique counterintuitive phenomena.

Nuclear calcium signaling in D1 receptor-expressing neurons of the nucleus accumbens regulates molecular, cellular and behavioral adaptations to cocaine.

Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).

Diverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment.

Alzheimer's disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the APP and secretase location relative to ordered or disordered membrane microdomains. We used high-resolution NMR to probe the interactions of the cholesterol analog with APP transmembrane domain in two membrane-mimicking systems resembling ordered or perturbed lipid environments (bicelles/micelles).

Cr-Doped Nanocrystalline TiO-CrO Nanocomposites with p-p Heterojunction as a Stable Gas-Sensitive Material.

Nanocrystalline TiO is a perspective semiconductor gas-sensing material due to its long-term stability of performance, but it is limited in application because of high electrical resistance. In this paper, a gas-sensing nanocomposite material with p-p heterojunction is introduced based on p-conducting Cr-doped TiO in combination with p-conducting CrO. Materials were synthesized via a single-step flame spray pyrolysis (FSP) technique and comprehensively studied by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) specific surface area analysis, transition electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and Raman spectroscopy.

Biodegradation of Phenol at High Initial Concentration by 3D Strain: Biochemical and Genetic Aspects.

Phenolic compounds are an extensive group of natural and anthropogenic organic substances of the aromatic series containing one or more hydroxyl groups. The main sources of phenols entering the environment are waste from metallurgy and coke plants, enterprises of the leather, furniture, and pulp and paper industries, as well as wastewater from the production of phenol-formaldehyde resins, adhesives, plastics, and pesticides. Among this group of compounds, phenol is the most common environmental pollutant.

Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by RNA-Seq.

Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3.

Modeling of historical and future changes in temperature and precipitation in the Panj River Basin in Central Asia under the CMIP5 RCP and CMIP6 SSP scenarios.

This study examines the complexities of climate modeling, specifically in the Panj River Basin (PRB) in Central Asia, to evaluate the transition from CMIP5 to CMIP6 models. The research aimed to identify differences in historical simulations and future predictions of rainfall and temperature, examining the accuracy of eight General Circulation Models (GCMs) used in both CMIP5 (RCP4.5 and 8.

Astrocyte-to-neuron HO signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer's disease model.

Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron HO signalling cascade in Drosophila that is essential for long-term memory formation.

The role of mitochondrial dysfunction in Huntington's disease: Implications for therapeutic targeting.

Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by cognitive decline, motor dysfunction, and psychiatric disturbances. A common feature of neurodegenerative disorders is mitochondrial dysfunction, which affects the brain's sensitivity to oxidative damage and its high oxygen demand. This dysfunction may plays a significant role in the pathogenesis of Huntington's disease.

SMARCB1-deficient malignant melanocytic uveal tumours: a new neural crest-derived tumour entity with SMARCB1-related germline predisposition.

Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.

Single-Cell RNA Sequencing Reveals LEF1-Driven Wnt Pathway Activation as a Shared Oncogenic Program in Hepatoblastoma and Medulloblastoma.

(1) Background: Hepatoblastoma and medulloblastoma are two types of pediatric tumors with embryonic origins. Both tumor types can exhibit genetic alterations that affect the β-catenin and Wnt pathways; (2) Materials and Methods: This study used bioinformatics and integrative analysis of multi-omics data at both the tumor and single-cell levels to investigate two distinct pediatric tumors: medulloblastoma and hepatoblastoma; (3) Results: The cross-transcriptome analysis revealed a commonly regulated expression signature between hepatoblastoma and medulloblastoma tumors. Among the commonly upregulated genes, the transcription factor LEF1 was significantly expressed in both tumor types.

QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite.

The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption.

Bone sarcomas and cancer predisposition syndromes.

Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GROUPOS and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists.