Contact Lens Wear Alters Transcriptional Responses to in Both the Corneal Epithelium and the Bacteria.

Purpose: Healthy corneas resist colonization by virtually all microbes yet contact lens wear can predispose the cornea to sight-threatening infection with . Here, we explored how lens wear changes corneal epithelium transcriptional responses to and its impact on bacterial gene expression.

Methods: Male and female C57BL/6J mice were fitted with a contact lens on one eye for 24 h.

A MRSA mystery: how PBP4 and cyclic-di-AMP join forces against β-lactam antibiotics.

The high-level resistance to next-generation β-lactams frequently found in isolates lacking , which encodes the transpeptidase PBP2a traditionally associated with methicillin-resistant (MRSA), has remained incompletely understood for decades. A new study by Lai et al. found that the co-occurrence of mutations in and , which respectively cause increased PBP4-mediated cell wall crosslinking and elevated cyclic-di-AMP levels, produces synergistic β-lactam resistance rivaling that of PBP2a-producing MRSA (L.

Fe/S proteins in microbial sulfur oxidation.

Iron-sulfur clusters serve as indispensable cofactors within proteins across all three domains of life. Fe/S clusters emerged early during the evolution of life on our planet and the biogeochemical cycle of sulfur is one of the most ancient and important element cycles. It is therefore no surprise that Fe/S proteins have crucial roles in the multiple steps of microbial sulfur metabolism.

The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: Robust gene signature correlates with radiotherapy outcome in patients and xenografts.

Purpose: To assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets.

Materials And Methods: Mice bearing xenografts (n = 59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n = 242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C).

PD-L1 mRNA Detection in Immunohistochemically Negative Patients: A Complementary Method for a Better Treatment Selection?

Background/aim: PD-L1 inhibitors have been approved for cisplatin-ineligible urothelial cancer patients relapsing after radical cystectomy. A prerequisite for therapy is a positive PD-L1 expression in the tumor tissue, whereas no options are available for patients with negative PD-L1 status. However, studies revealed that many PD-L1-negative patients also responded to PD-L1 therapy.

Identification of a novel lipoic acid biosynthesis pathway reveals the complex evolution of lipoate assembly in prokaryotes.

Lipoic acid is an essential biomolecule found in all domains of life and is involved in central carbon metabolism and dissimilatory sulfur oxidation. The machineries for lipoate assembly in mitochondria and chloroplasts of higher eukaryotes, as well as in the apicoplasts of some protozoa, are all of prokaryotic origin. Here, we provide experimental evidence for a novel lipoate assembly pathway in bacteria based on a sLpl(AB) lipoate:protein ligase, which attaches octanoate or lipoate to apo-proteins, and 2 radical SAM proteins, LipS1 and LipS2, which work together as lipoyl synthase and insert 2 sulfur atoms.

Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways.

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors.

Transforming Industrial Manipulators via Kinesthetic Guidance for Automated Inspection of Complex Geometries.

The increased demand for cost-efficient manufacturing and metrology inspection solutions for complex-shaped components in High-Value Manufacturing (HVM) sectors requires increased production throughput and precision. This drives the integration of automated robotic solutions. However, the current manipulators utilizing traditional programming approaches demand specialized robotic programming knowledge and make it challenging to generate complex paths and adapt easily to unique specifications per component, resulting in an inflexible and cumbersome teaching process.

Plant mitochondrial introns as genetic markers - conservation and variation.

Plant genomes are comprised of nuclear, plastid and mitochondrial components characterized by different patterns of inheritance and evolution. Genetic markers from the three genomes provide complementary tools for investigations of inheritance, genetic relationships and phenotypic contributions. Plant mitochondrial genomes are challenging for universal marker development because they are highly variable in terms of size, gene order and intergenic sequences and highly conserved with respect to protein-coding sequences.

Elevating the Standard of Care for Patients with Psoriasis: 'Calls to Action' from Epicensus, a Multistakeholder Pan-European Initiative.

Introduction: Despite advances in treatment options and the management of patients with psoriasis, considerable unmet needs remain. Our objective was to identify ways to elevate the standard of care for patients with psoriasis by combining the perspectives of three important stakeholders: patients, clinicians and payors, and define 'Calls to Action' designed to achieve the identified changes.

Methods: Eight themes relevant to elevating the standard of care were identified from an insights-gathering questionnaire completed by all three stakeholder groups.

Pseudomonas aeruginosa Can Diversify after Host Cell Invasion to Establish Multiple Intracellular Niches.

Within epithelial cells, Pseudomonas aeruginosa depends on its type III secretion system (T3SS) to escape vacuoles and replicate rapidly in the cytosol. Previously, it was assumed that intracellular subpopulations remaining T3SS-negative (and therefore in vacuoles) were destined for degradation in lysosomes, supported by data showing vacuole acidification. Here, we report in both corneal and bronchial human epithelial cells that vacuole-associated bacteria can persist, sometimes in the same cells as cytosolic bacteria.

Design and evaluation of poly-nitrogenous adjuvants capable of potentiating antibiotics in Gram-negative bacteria.

Antibiotic resistance has been a growing public health crisis since the 1980s. Therefore, it is essential not only to continue to develop novel antibiotics but also to develop new methods for overcoming resistance mechanisms in pathogenic bacteria so antibiotics can be reactivated towards these resistant strains. One common cause of antibiotic resistance in Gram-negative bacteria is reduced permeability of the tightly packed, negatively charged lipopolysaccharide outer membrane (OM), which dramatically reduces or even prevents antibiotic accumulation within the cell.

Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) may benefit from personalised treatment, requiring biomarkers that characterize the tumour and predict treatment response. We integrate pre-treatment CT radiomics and whole-transcriptome data from a multicentre retrospective cohort of 206 patients with locally advanced HNSCC treated with primary radiochemotherapy to classify tumour molecular subtypes based on radiomics, develop surrogate radiomics signatures for gene-based signatures related to different biological tumour characteristics and evaluate the potential of combining radiomics features with full-transcriptome data for the prediction of loco-regional control (LRC). Using end-to-end machine-learning, we developed and validated a model to classify tumours of the atypical subtype (AUC [95% confidence interval] 0.

Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: a sensitive imaging biomarker.

Purpose: Grey matter (GM) atrophy due to neuronal loss is a striking feature of patients with CLN3 disease. A precise and quantitative description of disease progression is needed in order to establish an evaluation tool for current and future experimental treatments. In order to develop a quantitative marker to measure brain volume outcome, we analysed the longitudinal volumetric development of GM, white matter (WM) and lateral ventricles and correlated those with the clinical course.

Development and validation of a 6-gene signature for the prognosis of loco-regional control in patients with HPV-negative locally advanced HNSCC treated by postoperative radio(chemo)therapy.

Purpose: The aim of this study was to develop and validate a novel gene signature from full-transcriptome data using machine-learning approaches to predict loco-regional control (LRC) of patients with human papilloma virus (HPV)-negative locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radio(chemo)therapy (PORT-C).

Materials And Methods: Gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective training cohort of 128 patients and an independent validation cohort of 114 patients from the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG).

A bibliometric review of peripartum cardiomyopathy compared to other cardiomyopathies using artificial intelligence and machine learning.

As developments in artificial intelligence and machine learning become more widespread in healthcare, their potential to transform clinical outcomes also increases. Peripartum cardiomyopathy is a rare and poorly-characterised condition that presents as heart failure in the last trimester prior to delivery or within 5-6 months postpartum. The lack of a definitive understanding of the molecular causes and clinical progress of this condition suggests that bibliometrics will be well-suited to creating new insights into this serious clinical problem.

Peripartum cardiomyopathy: a global effort to find the cause and cure for the rare and little understood disease.

In this review, we present our current understanding of peripartum cardiomyopathy (PPCM) based on reports of the incidence, diagnosis and current treatment options. We summarise opinions on whether PPCM is triggered by vascular and/or hormonal causes and examine the influence of comorbidities such as preeclampsia. Two articles published in 2021 strongly support the hypothesis that PPCM may be a familial disease.

Enabling Self-Directed Academic and Personal Wellbeing Through Cognitive Education.

Background: The international crisis of declining learner wellbeing exacerbated by the COVID-19 pandemic with its devastating effects on physical health and wellbeing, impels the prioritization of initiatives for specifically enabling academic and personal wellbeing among school learners to ensure autonomous functioning and flourishing in academic and daily life. Research emphasizes the role of self-directed action in fostering wellbeing. However, there is limited research evidence of how self-directed action among school learners could be advanced.

Fat Quantification in Dual-Layer Detector Spectral Computed Tomography: Experimental Development and First In-Patient Validation.

Objectives: Fat quantification by dual-energy computed tomography (DECT) provides contrast-independent objective results, for example, on hepatic steatosis or muscle quality as parameters of prognostic relevance. To date, fat quantification has only been developed and used for source-based DECT techniques as fast kVp-switching CT or dual-source CT, which require a prospective selection of the dual-energy imaging mode.It was the purpose of this study to develop a material decomposition algorithm for fat quantification in phantoms and validate it in vivo for patient liver and skeletal muscle using a dual-layer detector-based spectral CT (dlsCT), which automatically generates spectral information with every scan.

Analyses of molecular subtypes and their association to mechanisms of radioresistance in patients with HPV-negative HNSCC treated by postoperative radiochemotherapy.

Purpose: To assess the relation of the previously reported classification of molecular subtypes to the outcome of patients with HNSCC treated with postoperative radio(chemo)therapy (PORT-C), and to assess the association of these subtypes with gene expressions reflecting known mechanisms of radioresistance.

Material And Methods: Gene expression analyses were performed using the GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective patient cohort (N = 128) of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) with locally advanced HNSCC treated with PORT-C.

The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium.

During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion to the endothelium and transendothelial migration, play a crucial role in extravasation. Here we have studied the role of vascular endothelial (VE)-cadherin which is expressed aberrantly by breast cancer cells and might promote such interactions.

Efficient Joint Estimation of Tracer Distribution and Background Signals in Magnetic Particle Imaging Using a Dictionary Approach.

Background signals are a primary source of artifacts in magnetic particle imaging and limit the sensitivity of the method since background signals are often not precisely known and vary over time. The state-of-the art method for handling background signals uses one or several background calibration measurements with an empty scanner bore and subtracts a linear combination of these background measurements from the actual particle measurement. This approach yields satisfying results in case that the background measurements are taken in close proximity to the particle measurement and when the background signal drifts linearly.