ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn's Disease.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected.

Development of a Large-Scale Pathogen Screening Test for the Biosafety Evaluation of Canine Mesenchymal Stem Cells.

Background: The action of mesenchymal stem cells (MSCs) is the subject of intense research in the field of regenerative medicine, including their potential use in companion animals, such as dogs. To ensure the safety of canine MSC batches for their application in regenerative medicine, a quality control test must be conducted in accordance with Good Manufacturing Practices (GMP). Based on guidance provided by the European Medicines Agency, this study aimed to develop and validate a highly sensitive and robust, nucleic acid-based test panel for the detection of various canine pathogens.

from brown bear: A comprehensive analysis reveals novel genotypes and distribution of all detected variants in domestic and wild animals.

(phylum , class ) is a zoophilic opportunistic pathogen with recognized potential for invasive infections in humans. Although this pathogenic yeast is widespread in nature, it has been primarily studied in domestic animals, so available data on its genotypes in the wild are limited. In this study, 80 yeast isolates recovered from 42 brown bears () were identified as by a culture-based approach.

Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy.

DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the c and systems-the only DNA transposons currently employed in clinical trials-during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems.

A Comprehensive Evaluation of the Performance of Prediction Algorithms on Clinically Relevant Missense Variants.

The rapid integration of genomic technologies in clinical diagnostics has resulted in the detection of a multitude of missense variants whose clinical significance is often unknown. As a result, a plethora of computational tools have been developed to facilitate variant interpretation. However, choosing an appropriate software from such a broad range of tools can be challenging; therefore, systematic benchmarking with high-quality, independent datasets is critical.

The Rad5 Helicase and RING Domains Contribute to Genome Stability through their Independent Catalytic Activities.

Genomic stability is compromised by DNA damage that obstructs replication. Rad5 plays a prominent role in DNA damage bypass processes that evolved to ensure the continuation of stalled replication. Like its human orthologs, the HLTF and SHPRH tumor suppressors, yeast Rad5 has a RING domain that supports ubiquitin ligase activity promoting PCNA polyubiquitylation and a helicase domain that in the case of HLTF and Rad5 was shown to exhibit an ATPase-linked replication fork reversal activity.

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases.

The Combination of Single-Cell and Next-Generation Sequencing Can Reveal Mosaicism for Mutations and the Fine Molecular Details of Tumorigenesis.

Germline mutations in the and genes are responsible for hereditary breast and ovarian cancer syndrome. Germline and somatic mutations may define therapeutic targets and refine cancer treatment options. However, routine BRCA diagnostic approaches cannot reveal the exact time and origin of mutation formation, and thus, the fine details of their contribution to tumor progression remain less clear.

Children's comprehension of prosodically marked focus in Hungarian: How mandatory syntactic focus-marking affects the trajectory of acquisition.

This study investigates children's identification of prosodic focus in Hungarian, a language in which syntactic focus-marking is mandatory. Assuming that regular syntactic focus-marking diminishes the disambiguating role of prosodic marking in acquisition, we expected that in sentences in which focus is only disambiguated by prosody, adult-like comprehension of prosodic focus-marking should be delayed in comparison to the Germanic and Romance languages investigated previously using the same experimental method that we adopted. Our results, confirming this prediction, suggest that the developmental trajectory of the comprehension of prosodic focus-marking may be substantially affected by cross-linguistic grammatical variation in the marking of focus.

Robust high-throughput assays to assess discrete steps in ubiquitination and related cascades.

Background: Ubiquitination and ubiquitin-like protein post-translational modifications play an enormous number of roles in cellular processes. These modifications are constituted of multistep reaction cascades. Readily implementable and robust methods to evaluate each step of the overall process, while presently limited, are critical to the understanding and modulation of the reaction sequence at any desired level, both in terms of basic research and potential therapeutic drug discovery and development.

Primary Open Versus Closed Implantation Strategy for Totally Implantable Venous Access Ports: The Multicentre Randomized Controlled PORTAS-3 Trial (DRKS 00004900).

Objectives: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation.

Background Data: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear.

Methods: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial.

Gd/Sm-Pr Co-Doped Ceria: A First Report of the Precipitation Method Effect on Flash Sintering.

In this work, ceria-based ceramics with the composition GdPrCeO and SmPrCeO, were synthesized by a simple co-precipitation process using either ammonium carbonate or ammonia solution as a precipitating agent. After the calcination, all of the produced samples were constituted by fluorite-structured ceria only, thus showing that both dopant and co-dopant cations were dissolved in the fluorite lattice. The ceria-based nanopowders were uniaxially compacted and consequently flash-sintered using different electrical cycles (including current-ramps).

Investigation of Electrochemical, Optical and Thermal Effects during Flash Sintering of 8YSZ.

This paper reports the electrochemical, optical and thermal effects occurring during flash sintering of 8 mol % yttria-stabilized zirconia (8YSZ). In-situ observations of polycrystalline and single crystal specimens revealed electrochemical blackening/darkening during an incubation period prior to flash sintering. The phenomenon is induced by cathodic partial reduction under DC fields.

Modelling regional cropping patterns under scenarios of climate and socio-economic change in Hungary.

Impacts of socio-economic, political and climatic change on agricultural land systems are inherently uncertain. The role of regional and local-level actors is critical in developing effective policy responses that accommodate such uncertainty in a flexible and informed way across governance levels. This study identified potential regional challenges in arable land use systems, which may arise from climate and socio-economic change for two counties in western Hungary: Veszprém and Tolna.

Lifestyle, habitat and farmers' risk of exposure to tick bites in an endemic area of tick-borne diseases in Hungary.

Controlling tick bites on farmers is important to the management of tick-borne diseases and occupational health risks in agriculture. Based on an extensive household survey conducted between June and August 2015 with 219 farmers from western Hungary where tick-borne diseases are endemic, we analysed the pattern of farmers' self-reported contacts with ticks and investigated the potential interactions between farmers, landscape and the risk of exposure to tick bites. We developed a lifestyle typology based on farmers' socioeconomic profiles, farming objectives and time use patterns, and a habitat typology describing different configurations of tick habitats and agricultural areas in place of farming.

Transcarotid Artery Revascularization With Flow Reversal.

Purpose: To report a study evaluating the safety and efficacy of stenting via direct carotid access with flow reversal using the ENROUTE Transcarotid Neuroprotection System.

Methods: Between March 2009 and June 2012, 75 patients (mean age 72.6 years; 45 men) underwent carotid artery stenting with the ENROUTE System; the majority of patients (63, 84%) were asymptomatic.

DNA-dependent protease activity of human Spartan facilitates replication of DNA-protein crosslink-containing DNA.

Mutations in SPARTAN are associated with early onset hepatocellular carcinoma and progeroid features. A regulatory function of Spartan has been implicated in DNA damage tolerance pathways such as translesion synthesis, but the exact function of the protein remained unclear. Here, we reveal the role of human Spartan in facilitating replication of DNA-protein crosslink-containing DNA.

Relating farmer's perceptions of climate change risk to adaptation behaviour in Hungary.

Understanding how farmers perceive climate change risks and how this affects their willingness to adopt adaptation practices is critical for developing effective climate change response strategies for the agricultural sector. This study examines (i) the perceptual relationships between farmers' awareness of climate change phenomena, beliefs in climate change risks and actual adaptation behaviour, and (ii) how these relationships may be modified by farm-level antecedents related to human, social, financial capitals and farm characteristics. An extensive household survey was designed to investigate the current pattern of adaptation strategies and collect data on these perceptual variables and their potential antecedents from private landowners in Veszprém and Tolna counties, Hungary.

Simultaneous detection of BRCA mutations and large genomic rearrangements in germline DNA and FFPE tumor samples.

The development of breast and ovarian cancer is strongly connected to the inactivation of the BRCA1 and BRCA2 genes by different germline and somatic alterations, and their diagnosis has great significance in targeted tumor therapy, since recently approved PARP inhibitors show high efficiency in the treatment of BRCA-deficient tumors. This raises the need for new diagnostic methods that are capable of performing an integrative mutation analysis of the BRCA genes not only from germline DNA but also from formalin-fixed and paraffin-embedded (FFPE) tumor samples. Here we describe the development of such a methodology based on next-generation sequencing and a new bioinformatics software for data analysis.

A randomised comparison of transradial and transfemoral approach for carotid artery stenting: RADCAR (RADial access for CARotid artery stenting) study.

Aims: Limited data exist on radial access in carotid artery stenting. This multicentre prospective randomised study was performed to compare the outcome and complication rates of transradial and transfemoral carotid artery stenting.

Methods And Results: The clinical and angiographic data of 260 consecutive patients with high risk for carotid endarterectomy, treated between 2010 and 2012 by carotid stenting with cerebral protection, were evaluated.

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis.

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR).

Retrograde transpedal stenting of the tibioperoneal trunk in critical limb ischemia.

Management of critical limb ischemia (CLI) requires a combined treatment approach: optimal medical therapy and revascularization procedures are both essential for favorable outcome. With the development of endovascular interventions these new modalities took the primary role in limb revascularization, especially in CLI patients, where the culprit lesion is often located below the knee (BTK) level, making the surgical procedure unfeasible. In our present case report, we demonstrate a successful percutaneous recanalization of a surgically non-treatable tibioperoneal trunk occlusion.

First clinical use of a novel neurovascular access and neuroprotection system demonstrates complete absence of emboli by transcranial Doppler during carotid artery stenting.

This article focuses on the first use of the MICHI™ Neuroprotection System in a transcervical carotid artery stenting procedure. The patient presented with an asymptomatic, 80% stenosis of the right internal carotid artery extending into the common carotid artery. The lesion was successfully treated with transcervical carotid access and reverse flow embolic protection and the successful placement of a carotid stent followed by balloon post-dilatation.

Safety and feasibility of a novel transcervical access neuroprotection system for carotid artery stenting in the PROOF Study.

Background: Randomized controlled trials have shown that periprocedural rates of stroke and death are higher with carotid artery stenting (CAS) than with carotid endarterectomy (CEA) in the treatment of carotid artery stenosis. Diffusion-weighted magnetic resonance imaging (DW-MRI) has shown higher rates of clinically silent new ischemic brain lesions when CAS is performed as compared with CEA. The Silk Road Medical Embolic PROtectiOn System: First-In-Man (PROOF) Study is a single-arm first-in-man study using the MICHI Neuroprotection System (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcervical access and cerebral embolic protection system.