Geographic Atrophy in Age-Related Macular Degeneration.

Background: Age-related macular degeneration (AMD), a condition of multifactorial origin, is a major cause of irreversible vision loss in industrialized countries. The dry late stage of the disease, known as geographic atrophy (GA), is characterized by progressive loss of photoreceptor cells and retinal pigment epithelial cells in the central retina. An estimated 300 000 to 550 000 people in Germany suffer from GA.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Fundus Autofluorescence Variation in Geographic Atrophy of Age-Related Macular Degeneration: A Clinicopathologic Correlation.

Purpose: The purpose of this study was to develop ground-truth histology about contributors to variable fundus autofluorescence (FAF) signal and thus inform patient selection for treating geographic atrophy (GA) in age-related macular degeneration (AMD).

Methods: One woman with bilateral multifocal GA, foveal sparing, and thick choroids underwent 535 to 580 nm excitation FAF in 6 clinic visits (11 to 6 years before death). The left eye was preserved 5 hours after death.

Controlled Introduction of sp3 Quantum Defects in Fluorescent Carbon Nanotubes by Mechanochemistry.

Precise control over low-dimensional materials holds an immense potential for their applications in sensing, imaging and information processing. The controlled introduction of sp3 quantum defects (color centers) can be used to tailor the optoelectronic properties of single-walled carbon nanotubes (SWCNTs) in the tissue transparency (> 800 nm) and the telecommunication window. However, an uncontrolled functionalization of SWCNTs with defects leads to a loss of the NIR fluorescence.

Tolerance to land-use changes through natural modulations of the plant microbiome.

Land-use changes threaten ecosystems and are a major driver of species loss. Plants may adapt or migrate to resist global change, but this can lag behind rapid anthropogenic changes to the environment. Our data show that natural modulations of the microbiome of grassland plants in response to experimental land-use change in a common garden directly affect plant phenotype and performance, thus increasing plant tolerance.

Anterior segment optical coherence tomography (AS-OCT) assisted analysis of characteristics of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty.

Purpose: To analyse anterior segment optical coherence tomography (AS-OCT) parameters of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for graft failure post penetrating keratoplasty (PK).

Methods: Retrospective evaluation of AS-OCT images of 142 dehiscences post-DMEK in 75 eyes. Dehiscences' size, depth, location, correlation with graft-host interface (GHI) override and step at GHI were assessed.

MAPK pathway activating alteration and immunotherapy efficacy in squamous cell lung carcinoma: results from the randomized, prospective SQUINT trial.

Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.

Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.

Real-World-Evidence of Digital Health Applications (DiGAs) in Rheumatology: Insights from the DiGAReal Registry.

Introduction: Prescribable digital health applications (DiGAs) present scalable solutions to improve patient self-management in rheumatology, however real-world evidence is scarce. Therefore, we aimed to assess the effectiveness, usage, and usability of DiGAs prescribed by rheumatologists, as well as patient satisfaction.

Methods: The DiGAReal registry includes adult patients with rheumatic conditions who received a DiGA prescription.

High risk of drug-resistant tuberculosis in IGRA-negative contacts: should preventive treatment be considered?

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M.

Synergistic activity of Pitstop-2 and 1,6-hexanediol in aggressive human lung cancer cells.

Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.

Continuous goal representations: Distance in representational space affects goal switching.

Theorists across all fields of psychology consider goals crucial for human action control. Still, the question of how precisely goals are represented in the cognitive system is rarely addressed. Here, we explore the idea that goals are represented as distributed patterns of activation that coexist within continuous mental spaces.

Loneliness, social isolation, and living alone: a comprehensive systematic review, meta-analysis, and meta-regression of mortality risks in older adults.

Loneliness, social isolation, and living alone are significant risk factors for mortality, particularly in older adults. This systematic review and meta-analysis aimed to quantify their associations with all-cause and cause-specific mortality in older adults, broadening previous research by including more social factors. Comprehensive searches were conducted in PubMed, APA PsycINFO, and CINAHL until December 31, 2023, following PRISMA 2020 and MOOSE guidelines.

Exploring the influence of medical staffing and birth volume on observed-to-expected cesarean deliveries: a panel data analysis of integrated obstetric and gynecological departments in Germany.

Introduction: Cesarean deliveries account for approximately one-third of all births in Germany, prompting ongoing discussions on cesarean section rates and their connection to medical staffing and birth volume. In Germany, the majority of departments integrate obstetric and gynecological care within a single department.

Methods: The analysis utilized quality reports from German hospitals spanning 2015 to 2019.

Polarized vision in the eyes of the most effective predators: dragonflies and damselflies (Odonata).

Polarization is a property of light that describes the oscillation of the electric field vector. Polarized light can be detected by many invertebrate animals, and this visual channel is widely used in nature. Insects rely on light polarization for various purposes, such as water detection, improving contrast, breaking camouflage, navigation, and signaling during mating.

iForensic, multicentric validation of digital whole slide images (WSI) in forensic histopathology setting according to the College of American Pathologists guidelines.

Pathology has benefited from the rapid progress of image-digitizing technology during the last decade. However, the application of digital whole slide images (WSI) in forensic pathology still needs to be improved. WSI validation is crucial to ensure diagnostic performance, at least equivalent to glass slides and light microscopy.

Left ventricular rigor mortis interferes with postmortem aortic root geometry.

Aortic regurgitation is a common valve disease and can be caused by delineated findings such as fenestrations or hardly discernible alterations of the aortic root geometry. Therefore, aortic regurgitation can be a challenging diagnosis during an autopsy. Cardiac surgeons, however, are confronted with comparable problems during surgery and have developed a refined knowledge of the anatomy of the aortic root including its geometry.

How does an intervention work?-English Version : Development of an effect model for a complex intervention to prevent recurring or persistent pain using the example of PAIN 2.0.

In addition to the usual evaluation approach (usually a clinical randomized trial in the sense of the question: does an intervention work), complex interventions require further systematic investigations to prove their effectiveness. The role of the context in which the intervention is delivered is essential here, as is consideration of the question of why an intervention works (or does not work). Detailed recommendations exist for the planning and implementation of effectiveness studies on complex interventions, to which interdisciplinary multimodal pain therapy undoubtedly belongs.

Highly accurate real-space electron densities with neural networks.

Variational ab initio methods in quantum chemistry stand out among other methods in providing direct access to the wave function. This allows, in principle, straightforward extraction of any other observable of interest, besides the energy, but, in practice, this extraction is often technically difficult and computationally impractical. Here, we consider the electron density as a central observable in quantum chemistry and introduce a novel method to obtain accurate densities from real-space many-electron wave functions by representing the density with a neural network that captures known asymptotic properties and is trained from the wave function by score matching and noise-contrastive estimation.

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.

Voltage-gated sodium channels (VGSCs) in the peripheral nervous system shape action potentials (APs) and thereby support the detection of sensory stimuli. Most of the nine mammalian VGSC subtypes are expressed in nociceptors, but predominantly, three are linked to several human pain syndromes: while Nav1.7 is suggested to be a (sub-)threshold channel, Nav1.

Dynamic photosynthetic labeling and carbon-positional mass spectrometry monitor in vivo Rubisco carbon assimilation rates.

RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE/OXYGENASE (RUBISCO) is the most abundant enzyme and CO2 bio-sequestration system on Earth. Its in vivo activity is usually determined by 14CO2 incorporation into 3-phosphoglycerate (3PGA). However, the radiometric analysis of 3PGA does not distinguish carbon positions.

MOMENT registry: Patients with advanced non-small-cell lung cancer harboring exon 14 skipping treated with systemic therapy.

exon 14 ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with ex14 skipping NSCLC receiving conventional therapies.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.