ANCA-associated vasculitis with slowly progressive renal dysfunction: a little-known but treatable disease.

The clinical spectrum of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with renal involvement includes forms with a slowly progressive course. These forms are poorly recognised and, therefore, often associated with misdiagnosis and delayed treatment. We present here a case of slowly progressive AAV with renal involvement.

HPV and p53 status as precision determinants of head and neck cancer response to DNA-PKcs inhibition in combination with irradiation.

Major risk factors of head and neck squamous cell carcinoma (HNSCC) are tobacco use and human papillomavirus (HPV). HPV E6 oncoprotein leads to p53 degradation, whereas HPV-negative cancers are frequently associated with TP53 mutations. Peposertib is a potent and selective, orally administered small-molecule inhibitor of the catalytic subunit of the DNA-dependent kinase (DNA-PKcs), a key regulator of non-homologous end joining (NHEJ).

Synchrotron X-ray imaging of soft biological tissues - principles, applications and future prospects.

Synchrotron-based tomographic phase-contrast X-ray imaging (SRµCT or SRnCT) is a versatile isotropic three-dimensional imaging technique that can be used to study biological samples spanning from single cells to human-sized specimens. SRµCT and SRnCT take advantage of the highly brilliant and coherent X-rays produced by a synchrotron light source. This enables fast data acquisition and enhanced image contrast for soft biological samples owing to the exploitation of phase contrast.

Studies to assess natural resource recovery and evaluate monitoring methods for restored bottomland hardwood forests.

The Natural Resource Damage Assessment and Restoration process assesses natural resource injury due to oil or chemical spills and calculates the damages to compensate the public for those injuries. Ecological restoration provides a means for recovering resources injured or lost due to contamination from oil or chemical spills by restoring the injured site after remediation, or acquiring or reconstructing equivalent resources off site to replace those lost due to the spill. In the case of restored forests, once restoration is implemented, monitoring of forest ecology helps keep recovery on track, with the maturation of forest vegetation, recovered soil conditions, and development of microbial, fungal, and faunal communities, necessary for ecologically functioning forests.

Vegetation community recovery on restored bottomland hardwood forests in northeast Indiana, USA.

Vegetation communities in restored bottomland hardwood forests in northeast Indiana were studied 6-21 years after restoration to assess progress toward restoration objectives. The study focused on four sites that were restored to compensate for resource injuries after contaminant releases. The restored sites were compared with four reference-site conditions, including crops (prerestoration condition), old field communities representing a no-management alternative, locally sampled second-growth mature forests, and forest community types described by the US National Vegetation Classification (USNVC), which represent ideal or defining conditions of recognized vegetation communities.

"Straw in the Clay Soil" Strategy: Anticarbon Corrosive Fluorine-Decorated Graphene Nanoribbons@CNT Composite for Long-Term PEMFC.

Carbon corrosion poses a significant challenge in polymer electrolyte membrane fuel cells (PEMFCs), leading to reduced cell performance due to catalyst layer degradation and catalyst detachment from electrodes. A promising approach to address this issue involves incorporating an anticorrosive carbon material into the oxygen reduction reaction (ORR) electrode, even in small quantities (≈3 wt% in electrode). Herein, the successful synthesis of fluorine-doped graphene nanoribbons (F-GNR) incorporated with graphitic carbon nanotubes (F-GNR@CNT), demonstrating robust resistance to carbon corrosion is reported.

Spurious self-feedback of mean-field predictions inflates infection curves.

The susceptible-infected-recovered (SIR) model and its variants form the foundation of our understanding of the spread of diseases. Here, each agent can be in one of three states (susceptible, infected, or recovered), and transitions between these states follow a stochastic process. The probability of an agent becoming infected depends on the number of its infected neighbors, hence all agents are correlated.

Early life socioeconomic inequalities and type 2 diabetes incidence: Longitudinal analyses in the Maastricht study.

Aim: Type 2 diabetes (T2D) is a common chronic disease that disproportionally affects groups with a low socioeconomic position (SEP). This study aimed to examine associations between childhood SEP and incident T2D, independent of adult SEP.

Methods: Longitudinal data from The Maastricht Study were used (N=6,727, 55.

Do poor psychosocial resources mediate health inequalities in type 2 diabetes mellitus? Findings from the Maastricht study.

Low socioeconomic position (SEP) has been identified as a risk factor for type 2 diabetes mellitus (T2DM), and psychosocial resources might be on the pathway in this association. We examined two poor psychosocial resources, low control beliefs and inferiority beliefs, that might link low SEP with T2DM. 8292 participants aged 40-75 living in Southern Netherlands participated in The Maastricht Study starting from September 2010 to October 2020 and were followed up to 10 years with annual questionnaires.

Greater exposure to PM and PM was associated with lower corneal nerve measures: the Maastricht study - a cross-sectional study.

Background: Epidemiological and toxicological studies indicate that increased exposure to air pollutants can lead to neurodegenerative diseases. To further confirm this relationship, we evaluated the association between exposure to ambient air pollutants and corneal nerve measures as a surrogate for neurodegeneration, using corneal confocal microscopy.

Methods: We used population-based observational cross-sectional data from The Maastricht Study including N = 3635 participants (mean age 59.

How Model Organisms and Model Uncertainty Impact Our Understanding of the Risk of Sublethal Impacts of Toxicants to Survival and Growth of Ecologically Relevant Species.

Understanding how sublethal impacts of toxicants affect population-relevant outcomes for organisms is challenging. We tested the hypotheses that the well-known sublethal impacts of methylmercury (MeHg) and a polychlorinated biphenyl (PCB126) would have meaningful impacts on cohort growth and survival in yellow perch (Perca flavescens) and Atlantic killifish (Fundulus heteroclitus) populations, that inclusion of model uncertainty is important for understanding the sublethal impacts of toxicants, and that a model organism (zebrafish Danio rerio) is an appropriate substitute for ecologically relevant species (yellow perch, killifish). Our simulations showed that MeHg did not have meaningful impacts on growth or survival in a simulated environment except to increase survival and growth in low mercury exposures in yellow perch and killifish.

A column study: Impact of redox, substrate composition and exposure order on toluene and benzene biodegradation and microbial communities.

Aromatic compounds persist as hazardous contaminants in both aquatic and terrestrial environments, needing rapid and effective remediation strategies. This study evaluated toluene and benzene biodegradation under sulfate and nitrate-reducing conditions in column experiments, utilizing aquifer sediments from a contaminated site. Over a period of 36 weeks, four glass columns were operated simultaneously in an alternating flow-batch regime.

A Measure of the Impact on Real-Time Patient Care of Evidence-based Medicine Logs.

Introduction: Evidence-based medicine (EBM) is a critical skill for physicians, and EBM competency has been shown to increase implementation of best medical practices, reduce medical errors, and increase patient-centered care. Like any skill, EBM must be practiced, receiving iterative feedback to improve learners' comprehension. Having residents document patient interactions in logbooks to allow for residency program review, feedback, and documentation of competency has been previously described as a best practice within emergency medicine (EM) to document practice-based learning (PBL) competency.

E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.

Unlabelled: Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage.

Peposertib, a DNA-PK Inhibitor, Enhances the Anti-Tumor Efficacy of Topoisomerase II Inhibitors in Triple-Negative Breast Cancer Models.

Triple-negative breast cancer (TNBC) remains the most lethal subtype of breast cancer, characterized by poor response rates to current chemotherapies and a lack of additional effective treatment options. While approximately 30% of patients respond well to anthracycline- and taxane-based standard-of-care chemotherapy regimens, the majority of patients experience limited improvements in clinical outcomes, highlighting the critical need for strategies to enhance the effectiveness of anthracycline/taxane-based chemotherapy in TNBC. In this study, we report on the potential of a DNA-PK inhibitor, peposertib, to improve the effectiveness of topoisomerase II (TOPO II) inhibitors, particularly anthracyclines, in TNBC.

Multiscale and multimodal imaging for three-dimensional vascular and histomorphological organ structure analysis of the pancreas.

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas.

Per- and Polyfluoroalkyl Substances: Impacts on Morphology, Behavior and Lipid Levels in Zebrafish Embryos.

The presence of per- and polyfluoroalkyl substances (PFASs) in aquatic environments is often persistent and widespread. Understanding the potential adverse effects from this group of chemicals on aquatic communities allows for better hazard characterization. This study examines impacts on zebrafish () embryo physiology, behavior, and lipid levels from exposure to perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and heptadecafluorooctanesulfonic acid (PFOS).

The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.

The one-carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)- and DNA-dependent protein kinase (DNA-PK)-dependent manner.

low-dose phase-contrast CT for quantification of functional and anatomical alterations in lungs of an experimental allergic airway disease mouse model.

Introduction: Synchrotron-based propagation-based imaging (PBI) is ideally suited for lung imaging and has successfully been applied in a variety of small animal studies. Virtually all these experiments were tailored to achieve extremely high spatial resolution close to the alveolar level while delivering high x-ray doses that would not permit longitudinal studies. However, the main rationale for performing lung imaging studies in small animal models is the ability to follow disease progression or monitor treatment response in the same animal over time.

Direct observations of microbial community succession on sinking marine particles.

Microbial community dynamics on sinking particles control the amount of carbon that reaches the deep ocean and the length of time that carbon is stored, with potentially profound impacts on Earth's climate. A mechanistic understanding of the controls on sinking particle distributions has been hindered by limited depth- and time-resolved sampling and methods that cannot distinguish individual particles. Here, we analyze microbial communities on nearly 400 individual sinking particles in conjunction with more conventional composite particle samples to determine how particle colonization and community assembly might control carbon sequestration in the deep ocean.

Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes.

Objective: Diabetic peripheral neuropathy (DPN) is common; however, the features and burden of neuropathic pain (NP) in type 1 diabetes (T1D) are poorly understood. We evaluated the incidence of first occurrence, annual prevalence, remission, and risk factors for NP during long-term follow-up of participants with T1D.

Research Design And Methods: The Michigan Neuropathy Screening Instrument (MNSI) was administered annually (1994-2020) for 1,324 participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

DNA-Dependent Protein Kinase Inhibitor Peposertib Potentiates the Cytotoxicity of Topoisomerase II Inhibitors in Synovial Sarcoma Models.

Synovial sarcoma is a rare and highly aggressive subtype of soft tissue sarcoma. The clinical challenge posed by advanced or metastatic synovial sarcoma, marked by limited treatment options and suboptimal outcomes, necessitates innovative approaches. The topoisomerase II (Topo II) inhibitor doxorubicin has remained the cornerstone systemic treatment for decades, and there is pressing need for improved therapeutic strategies for these patients.