ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging.

Importance: The phase 3 randomized EMBARK trial evaluated enzalutamide with or without leuprolide in high-risk nonmetastatic hormone-sensitive prostate cancer. Eligibility relied on conventional imaging, which underdetects metastatic disease compared with prostate-specific membrane antigen-positron emission tomography (PSMA-PET).

Objective: To describe the staging information obtained by PSMA-PET/computed tomography (PSMA-PET/CT) in a patient cohort eligible for the EMBARK trial.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

A multi-omics approach to unravel the interaction between heat and drought stress in the holobiont.

The impact of combined heat and drought stress was investigated in and compared to individual stresses to reveal additive effects and interactions. A combination of plant metabolomics and root and rhizosphere bacterial metabarcoding were used to unravel effects at the plant holobiont level. Hierarchical cluster analysis of metabolomics signatures pointed out two main clusters, one including heat and combined heat and drought, and the second cluster that included the control and drought treatments.

Chemical Probes for Investigating the Endocannabinoid System.

Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.

ESAIC focused guidelines for the management of the failing epidural during labour epidural analgesia.

Background: Labour epidural analgesia reportedly fails in up to 10 to 25% of cases. A joint taskforce of European Society of Anaesthesiology and Intensive Care (ESAIC) experts was created to develop this focused guideline on the management of failing epidural analgesia in a previously well functioning epidural catheter.

Design: Six clinical questions were defined using a PICO (Population/Intervention/Comparison/Outcome) strategy to conduct a systematic literature search.

Developing Gingerol-Based Analogs against Infections.

(), a Gram-negative opportunistic pathogen, produces virulent factors and forms biofilms through a quorum sensing (QS) mechanism. Modulating QS networks is considered an effective strategy for treating infections. Particularly, the system, one of the QS networks, can be a potential target in treating patients with chronic infections.

Glyphosate binding and speciation at the water-goethite interface: A surface complexation model consistent with IR spectroscopy and MO/DFT.

Binding of glyphosate (PMG) to metal (hydr)oxides controls its availability and mobility in natural waters and soils, and these minerals are often suggested for the removal of PMG from wastewaters. However, a solid mechanistic and quantitative description of the adsorption behavior and surface speciation on these surfaces is still lacking, while it is essential for understanding PMG behavior in aquatic and terrestrial systems. This study gives new insights through advanced surface complexation modeling of new and previously published adsorption data, supplemented with MO/DFT calculations of the geometry, thermochemistry and theoretical infrared (IR) spectra of the surface complexes.

Bullet characterization using Photon-Counting detector CT: A phantom study with intact bullets.

Objectives: Photon-counting detector CT (PCD-CT) is expected to substantially improve and expand CT-imaging applicability due to its intrinsic spectral capabilities, increased spatial resolution, reduced electronic noise, and improved image contrast. The current study aim is to evaluate PCD-CT efficacy in characterizing bullets based on their dimensions, shape, and material composition.

Materials And Methods: This is an observational phantom study examining 11 unfired, intact bullets of various common calibers, placed in ballistic gelatin.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.

Role of amino acid substitutions on proteolytic stability of histatin 5 in the presence of secreted aspartyl proteases and salivary proteases.

Histatin 5 (Hst5) is a 24-amino-acid peptide naturally present in human saliva that has been proposed as a potential antifungal therapeutic. However, Hst5 is susceptible to degradation by secreted aspartyl proteases (Saps) produced by Candida albicans, which could limit its efficacy as a therapeutic. To better understand the role of the lysine residues of Hst5 in proteolysis by C.

Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.

Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development.

Transforming Households with Refraction and Innovative Financial Technology (THRIFT): study protocol for a randomised controlled trial of vision interventions and online banking among the elderly in Kurigram.

Introduction: Presbyopia, difficulty in seeing close-ups, affects a billion people globally. Mobile financial services (MFS) have been mandated since January 2021 for Bangladesh government social safety net payments, including old age allowance (OAA) and widow allowance (WA). We report the protocol for the Transforming Households with Refraction and Innovative Financial Technology randomised trial assessing the impact on the use of online banking of providing presbyopic safety net beneficiaries with reading glasses, and brief smartphone and mobile banking app training.

Zweifel olefination for C-glycosylation.

C-glycosides are significant in medicinal chemistry due to their resistance to enzymatic hydrolysis, making them more stable and bioavailable compared to O-glycosides. Their unique structure also offers potential for developing drugs with improved therapeutic properties, particularly in treating diseases like diabetes and cancer. The main challenge in synthesizing C-glycosides lies in forming the carbon-carbon bond between the sugar and aglycone efficiently, while controlling the stereochemistry and minimizing side reactions.

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.

Background: Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking.

Methods: We used cross-sectional data from the Rhineland Study (N = 5812, 55.2 ± 13.

Enrichment of putative plant growth promoting microorganisms in biodynamic compared with organic agriculture soils.

The potential of soils to maintain biological productivity, defined as soil health, is strongly influenced by human activity, such as agriculture. Therefore, soil management has always been a concern for sustainable agriculture and new methods that account for both soil health and crop yield must be found. Biofertilization using microbial inoculants emerges as a promising alternative to conventional interventions such as excessive mineral fertilization and herbicide use.

Platelet characteristics in extremely preterm infants after fatty acid supplementation: a randomized controlled trial.

Background: Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.

Method: Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal enteral AA/DHA supplementation or standard care (controls).

Degradable starch microspheres transarterial chemoembolization (DSM-TACE) in patients with unresectable hepatocellular carcinoma: results from the Prospective Multicenter Observational HepaStar Trial.

Objectives: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study.

Materials And Methods: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled.

A cellulose synthase-like protein governs the biosynthesis of alkaloids.

Decades of research on the infamous antinutritional steroidal glycoalkaloids (SGAs) in Solanaceae plants have provided deep insights into their metabolism and roles. However, engineering SGAs in heterologous hosts has remained a challenge. We discovered that a protein evolved from the machinery involved in building plant cell walls is the crucial link in the biosynthesis of SGAs.