The SWIB domain-containing DNA topoisomerase I of mediates DNA relaxation.

The obligate intracellular bacterial pathogen, (Ct), has a distinct DNA topoisomerase I (TopA) with a C-terminal domain (CTD) homologous to eukaryotic SWIB domains. Despite the lack of sequence similarity at the CTDs between TopA (CtTopA) and TopA (EcTopA), full-length CtTopA removed negative DNA supercoils and complemented the growth defect of an mutant. We demonstrated that CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies.

Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies.

Intracellular bacterial pathogens are distinctive tools for fighting cancer, as they can proliferate in tumors and deliver therapeutic payloads to the eukaryotic cytosol. Cytosol-dwelling bacteria have undergone extensive preclinical and clinical testing, yet the mechanisms of activating innate immunity in tumors are unclear. We report that phylogenetically distinct cytosolic pathogens, including , , and species, elicited anti-tumor responses in poorly immunogenic melanoma and lymphoma in mice.

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.

In recent years, pathogenic variants in ARS genes, encoding aminoacyl-tRNA synthetases (aaRSs), have been associated with human disease. Patients harbouring pathogenic variants in ARS genes have clinical signs partly unique to certain aaRSs defects, partly overlapping between the different aaRSs defects. Diagnosis relies mostly on genetics and remains challenging, often requiring functional validation of new ARS variants.

Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study.

Background: Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested.

Inference-Based Cognitive Behavioral Therapy versus Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: A Multisite Randomized Controlled Non-Inferiority Trial.

Introduction: Although cognitive behavioral therapy (CBT) effectively treats obsessive-compulsive disorder (OCD), many patients refuse CBT or drop out prematurely, partly because of anxiety regarding exposure and response prevention (ERP) exercises. Inference-based cognitive behavioral therapy (I-CBT) focuses on correcting distorted inferential thinking patterns, enhancing reality-based reasoning, and addressing obsessional doubt by targeting underlying dysfunctional reasoning, without incorporating an ERP component. We hypothesized that I-CBT would be non-inferior to CBT.

Pathohistological Findings after Bilateral Ovariectomy in Mares with Behavioral Problems.

Behavioral problems in reproductively healthy mares are a challenging issue that is successfully treated with bilateral ovariectomy (BO). This laparoscopic procedure represents an alternative to conservative treatment for mares not intended for breeding and results in high owner satisfaction regarding behavioral improvement. However, a pathohistological explanation to justify surgical ovarian removal regarding animal welfare is lacking.

POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic-atonic seizures and ataxia.

Objective: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy.

MRI pattern recognition in white matter disease.

Magnetic resonance imaging (MRI) pattern recognition is a powerful tool for quick diagnosis of genetic and acquired white matter disorders. In many cases, distribution and character of white matter abnormalities directly point to a specific diagnosis and guide confirmatory testing. Knowledge of normal brain development is essential to interpret white matter changes in young children.

Amino-acyl tRNA synthetases associated with leukodystrophy.

Amino-acyl tRNA synthetases (ARSs) are enzymes that catalyze the amino-acylation reaction of a specific amino acid and its cognate tRNA and are divided into type 1 (cytosolic) and type 2 (mitochondrial). In this chapter leukodystrophies caused by tRNA synthetase deficiencies are reviewed.

Quantitative MRI distinguishes different leukodystrophies and correlates with clinical measures.

Objectives: The leukodystrophy "vanishing white matter" (VWM) and "metachromatic leukodystrophy" (MLD) affect the brain's white matter, but have very different underlying pathology. We aim to determine whether quantitative MRI reflects known neuropathological differences and correlates with clinical scores in these leukodystrophies.

Methods: VWM and MLD patients and controls were prospectively included between 2020 and 2023.

Analysis of PFAS and further VOC from fluoropolymer-coated cookware by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS).

Per- and polyfluoroalkyl substances (PFAS) are used in the production of PTFE based coatings for cookware. In this study, emission of PFAS and further volatile organic compounds (VOC) from kitchenware articles were investigated. First, method development for thermal extraction of baking trays, frying pans and baking mats at 250 °C was done by testing three different extraction devices.

Bose-Einstein Condensation of Photons in a Four-Site Quantum Ring.

Thermalization of radiation by contact to matter is a well-known concept, but the application of thermodynamic methods to complex quantum states of light remains a challenge. Here, we observe Bose-Einstein condensation of photons into the hybridized ground state of a coupled four-site ring potential. In our experiment, the periodically closed ring lattice superimposed by a weak harmonic trap for photons is realized inside a spatially structured dye-filled microcavity.

Complete genomes of two cluster AK phages isolated from soil samples in Newburgh, NY, United States.

Two phages belonging to phage cluster AK were isolated from soil samples collected in Newburgh, NY in 2021. Both are lytic with a genome organization typical of siphoviruses except for two genes encoding minor tail proteins with pyocin-knob domains found early in the genome, before the terminase gene.

Heterozygous missense CSF1R variants hamper in vitro CD34+-derived dendritic cell generation but not in vivo dendritic cell development.

Colony stimulating factor 1 receptor (CSF1R) is an essential receptor for both colony stimulating factor 1 (CSF1) and interleukin (IL) 34 signaling expressed on monocyte precursors and myeloid cells, including monocytes, dendritic cells (DC), and microglia. In humans, dominant heterozygous pathogenic variants in CSF1R cause a neurological condition known as CSF1R-related disorder (CSF1R-RD), typically with late onset, previously referred to as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). CSF1R-RD is characterized by microglia reduction and altered monocyte function; however, the impact of pathogenic CSF1R variants on the human DC lineage remains largely unknown.

Clinical Usage and Potential Benefits of a Continuous Glucose Monitoring Predict App.

Continuous glucose monitoring (CGM) has become an increasingly important tool for self-management in people with diabetes mellitus (DM). In this paper, we discuss recommendations on how to implement predictive features provided by the Accu-Chek SmartGuide Predict app in clinical practice. The Predict app's features are aimed at ultimately reducing diabetes stress and fear of hypoglycemia in people with DM.

[Ga]Ga-PSMA-11 PET and Prostate Cancer Bone Metastases: Diagnostic Performance of Available Standardized Criteria.

In up to two thirds of prostate-specific membrane antigen (PSMA) PET scans, unspecific bone uptake has been described. The aim of this study was to estimate the diagnostic accuracy of [Ga]Ga-PSMA-11 PET/CT for bone metastases and the occurrence of equivocal lesions. We analyzed retrospectively 118 patients who underwent a [Ga]Ga-PSMA-11 PET/CT for initial staging or recurrence evaluation.

Age-appropriate or delayed myelination? Scoring myelination in routine clinical MRI.

Background: Assessment of myelination is a core issue in paediatric neuroimaging and can be challenging, particularly in settings without dedicated paediatric neuroradiologists. Deep learning models have recently been shown to be able to estimate myelination age in children with normal MRI, but currently lack validation for patients with myelination delay and implementation including pre-processing suitable for local imaging is not trivial. Standardized myelination scores, which have been successfully used as biomarkers for myelination in hypomyelinating diseases, rely on visual, semiquantitative scoring of myelination on routine clinical MRI and may offer an easy-to-use alternative for assessment of myelination.

Typical and atypical MRI patterns of rare brain disorders: The challenge of low numbers.

This commentary is on the original article by Oikarainen et al. on pages 186–194 of this issue.

Thermal desorption - gas chromatography - mass spectrometry (TD-GC-MS) analysis of PFAS used in food contact materials.

Per- and polyfluoroalkyl substances (PFAS) are used in food contact materials (FCMs), e.g. as production aids in the fabrication of PTFE based coatings for kitchenware or as additives in paper and board.

The role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized Y glass microspheres SIRT: a preliminary machine learning study.

Background: Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing Y selective internal radiation therapy (SIRT).

Materials/methods: This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with Y SIRT.

Riboflavin transporter deficiency in young adults unmasked by dietary changes.

Riboflavin transporter deficiency (RTD) is a genetic disorder of reduced riboflavin (vitamin B2) uptake that causes progressive, multifocal neurological dysfunction. Most patients present in early childhood; if patients present later in life, symptoms usually develop more gradually. We report three previously healthy young adults, who developed rapidly progressive neurological symptoms after decreasing dietary intake of meat and dairy.