High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p.

DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.

The neural basis of the insight memory advantage.

Creative problem solving and memory are inherently intertwined: memory accesses existing knowledge while creativity enhances it. Recent studies show that insights often accompanying creative solutions enhance long-term memory. This insight memory advantage (IMA) is explained by the 'insight as prediction error (PE)' hypothesis which states that insights arise from PEs updating predictive solution models and thereby enhancing memory.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Revealing microRNA regulation in single cells.

MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation.

Influence of frailty status on the incidence of intraoperative hypotensive events in elective surgery: Hypo-Frail, a single-centre retrospective cohort study.

Background: Frailty is a predictor of morbidity and mortality in older patients. This study aimed to investigate the influence of frailty status on likelihood, rate, duration, and severity of intraoperative hypotension (IOH), which can lead to severe organ dysfunction.

Methods: Surgical patients (≥70 yr old) with preoperative frailty assessment were analysed retrospectively.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al.

Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.

Background: Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.

Objectives: To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.

Trends in work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs): Data from the German National Database (2010-2022).

Objective: To analyse work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs), namely rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ANCA-associated vasculitis (AAV).

Methods: A cross-sectional sample of 16 421 patients from the National Database of the German Collaborative Arthritis Centers, aged <65 years were analysed. For each diagnosis, yearly rates of absenteeism, employment and disability pensions were analysed from 2010 to 2022.

Ex Vivo Fluorescence Confocal Microscopy for intraoperative evaluations of staple lines and surgical margins in specimens of the lung - a proof-of-concept study.

Intraoperative consultation is frequently used during the surgical treatment of lung tumors for the diagnosis of malignancy and the assessment of surgical margins. The latter is often problematic given the nature of the applied staple lines, which cannot be readily examined in frozen sections. Seventy-nine samples of surgical margins (71 staple lines and 8 open margins) from 52 lung specimens were examined using an ex vivo fluorescence confocal microscope (FCM).

Classification of Fibro-osseous Tumors in the Craniofacial Bones using DNA Methylation and Copy Number Alterations.

Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS.

Characterization of the putative yeast mitochondrial triacylglycerol lipase Tgl2.

Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are the main components of mitochondrial membranes. In the cell, neutral lipids like triacylglycerides (TAGs) are stored in lipid droplets, playing an important role in maintaining cellular health.

Dengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.

Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation.

First evidence of human infection by the kinetoplastid flagellate Dimastigella trypaniformis in a patient with urinary tract infection.

We present a case of an 88-year-old man with symptoms consistent with a urinary tract infection, whose diagnostic workup uncovered a previously unrecognized motile flagellated protozoan. Molecular identification confirmed the organism as Dimastigella trypaniformis, a free-living kinetoplastid from the Rhynchomonadidae family. Known only from soil samples in Scotland and termite gut contents in Australia and Germany, Dimastigella trypaniformis has not been previously reported to infect vertebrate hosts.

Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab.

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

Exploring and increased acetate biosynthesis in Synechocystis PCC 6803 through insertion of a heterologous phosphoketolase and overexpressing phosphotransacetylase.

Acetate is a biological anion with many applications in the chemical and food industries. In addition to being a common microbial fermentative end-product, acetate can be produced by photosynthetic cyanobacteria from CO using solar energy. Using wild-type cells of the unicellular model cyanobacterium Synechocystis PCC 6803 only low levels of acetate are observed outside the cells.

Long Term Results of a Comparative Study of Percutaneous and Surgically Created Proximal Forearm Arteriovenous Fistulae.

Objective: This retrospective, single centre, comparative effectiveness study aimed to compare the long term outcomes of percutaneous arteriovenous fistulae (pAVF) and surgically created arteriovenous fistulae (sAVF) created in the proximal forearm for haemodialysis access.

Methods: Data were reviewed from a prospectively maintained database on patients who underwent pAVF or sAVF creation from September 2017 to September 2023. A total of 217 pAVFs (61 WavelinQ and 156 Ellipsys) and 158 sAVFs were analysed.

Rationale and Design of the Prevail Global Trial Program Evaluating the Prevail Drug-Coated Balloon in Patients with In-stent Restenosis and De Novo Small Vessel Disease.

Background And Rationale: In-stent restenosis (ISR) remains the leading cause of treatment failure following percutaneous coronary intervention (PCI) with contemporary drug-eluting stents. Especially in small caliber coronary arteries, restenosis is common following PCI and represents a treatment challenge. Drug-coated balloons (DCB) are an attractive alternative to stents for treatment of both ISR and small vessel disease.

Improving MRI turbulence quantification by addressing the measurement errors caused by the derivatives of the turbulent velocity field - Sequence development and in-vitro validation.

Purpose: To improve the current method for MRI turbulence quantification which is the intravoxel phase dispersion (IVPD) method. Turbulence is commonly characterized by the Reynolds stress tensor (RST) which describes the velocity covariance matrix. A major source for systematic errors in MRI is the sequence's sensitivity to the variance of the derivatives of velocity, such as the acceleration variance, which can lead to a substantial measurement bias.