A Pattern-Based OCT Metric for Glaucoma Detection.

Purpose: To develop and test a novel optical coherence tomography (OCT) metric for the detection of glaucoma based on a logistic regression model (LRM) and known patterns of glaucomatous damage.

Methods: The six variables of the LRM were based on characteristic patterns of damage seen on the OCT thickness maps of the ganglion cell layer plus inner plexiform layer (GCL+) and retinal nerve fiber layer (RNFL). Two cohorts were used to develop the LRM.

The state of hand rub dispensers in healthcare settings - a multicenter assessment in 19 German healthcare facilities.

Background: Hand hygiene is one of the most important hygiene measures to prevent healthcare-associated infections. Well-functioning hand rub dispensers are the foundation of hand hygiene but are often overlooked in research. As the point of origin for hand hygiene, dispensers not only promote compliance through ease of use, but also strongly influence the amount of hand rub used per disinfection.

Acclimation of mature spruce and beech to five years of repeated summer drought - The role of stomatal conductance and leaf area adjustment for water use.

Forests globally are experiencing severe droughts, leading to significant reductions in growth, crown dieback and even tree mortality. The ability of forest ecosystems to acclimate to prolonged and repeated droughts is critical for their survival with ongoing climate change. In a five-year throughfall exclusion experiment, we investigated the long-term physiological and morphological acclimation of mature Norway spruce (Picea abies [L.

MeDaX: A Knowledge Graph on FHIR.

In Germany, the standard format for exchange of clinical care data for research is HL7 FHIR. Graph databases (GDBs), well suited for integrating complex and heterogeneous data from diverse sources, are currently gaining traction in the medical field. They provide a versatile framework for data analysis which is generally challenging for raw FHIR-formatted data.

Workflows and locations matter - insights from electronic hand hygiene monitoring into the use of hand rub dispensers across diverse hospital wards.

Background: While healthcare-associated infections (HAIs) affect approximately 3.2-6.5% of hospitalised patients in the US and Europe, improving hand hygiene (HH) could reduce HAI rates.

GPR41 and GPR43 regulate CD8 T cell priming during herpes simplex virus type 1 infection.

Naïve CD8 T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8 T cells into long-lived and protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8 T cell differentiation.

CD4 T cell immunity against cutaneous melanoma encompasses multifaceted MHC II-dependent responses.

Whereas CD4 T cells conventionally mediate antitumor immunity by providing help to CD8 T cells, recent clinical studies have implied an important role for cytotoxic CD4 T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4 T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4 T cells with tumor debris-laden MHC II host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II melanoma cells alone could also promote CD4 T cell control.

Stem-like exhausted and memory CD8 T cells in cancer.

T cells can acquire a broad spectrum of differentiation states following activation. At the extreme ends of this continuum are short-lived cells equipped with effector machinery and more quiescent, long-lived cells with heightened proliferative potential and stem cell-like developmental plasticity. The latter encompass stem-like exhausted T cells and memory T cells, both of which have recently emerged as key determinants of cancer immunity and response to immunotherapy.

Exploiting Unique Features of Microneedles to Modulate Immunity.

Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses-often more protective or therapeutic-compared to conventional needle delivery.

The multifaceted roles of CD4 T cells and MHC class II in cancer surveillance.

CD4 T cells exhibit diverse functions in cancer surveillance. Concordantly, single-cell transcriptional analyses have revealed several distinct CD4 T-cell differentiation states in tumours, including cytotoxic and regulatory subsets associated with favourable or unfavourable outcomes, respectively. These transcriptional states are determined and further shaped by dynamic interactions of CD4 T cells with different types of immune cells, stromal cells and cancer cells.

CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity.

Antiviral CD8 T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4 T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone.

CD8 T Cells Promote Pathological Angiogenesis in Ocular Neovascular Disease.

Background: CD4 (cluster of differentation) and CD8 T cells are increased in the ocular fluids of patients with neovascular retinopathy, yet their role in the disease process is unknown.

Methods: We describe how CD8 T cells migrate into the retina and contribute to pathological angiogenesis by releasing cytokines and cytotoxic factors.

Results: In oxygen-induced retinopathy, flow cytometry revealed the numbers of CD4 and CD8 T cells were increased in blood, lymphoid organs, and retina throughout the development of neovascular retinopathy.

An interactive feedback system for increasing hand antisepsis adherence in stationary intensive care.

Background: Pathogens causing infections are in many cases transmitted via the hands of personnel. Thus, hand antisepsis has strong epidemiological evidence of infection prevention. Depending on various factors, hand antisepsis adherence ranges between 9.

Physiological recovery of tree water relations upon drought release-response of mature beech and spruce after five years of recurrent summer drought.

As climate change progresses, the frequency and duration of drought stress events are increasing. While the mechanisms of drought acclimation of trees has received considerable attention in recent years, the recovery processes remain critically understudied. We used a unique throughfall exclusion experiment in a mature temperate mixed forest consisting of the more isohydric Norway spruce and more anisohydric European beech, to study the recovery and resilience after drought release.

Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.

Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self-assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll-like receptor agonists (TLRas).

Dynamics of initial carbon allocation after drought release in mature Norway spruce-Increased belowground allocation of current photoassimilates covers only half of the carbon used for fine-root growth.

After drought events, tree recovery depends on sufficient carbon (C) allocation to the sink organs. The present study aimed to elucidate dynamics of tree-level C sink activity and allocation of recent photoassimilates (C ) and stored C in c. 70-year-old Norway spruce (Picea abies) trees during a 4-week period after drought release.

Recovery after long-term summer drought: Hydraulic measurements reveal legacy effects in trunks of Picea abies but not in Fagus sylvatica.

Climate change is expected to increase the frequency and intensity of summer droughts. Sufficient drought resistance, the ability to acclimate to and/or recover after drought, is thus crucial for forest tree species. However, studies on the hydraulics of mature trees during and after drought in natura are scarce.

Exploring the evolution of biochemical models at the network level.

The evolution of biochemical models is difficult to track. At present, it is not possible to inspect the differences between model versions at the network level. Biochemical models are often constructed in a distributed, non-linear process: collaborators create model versions on different branches from novel information, model extensions, during curation and adaption.

Computational Models for Clinical Applications in Personalized Medicine-Guidelines and Recommendations for Data Integration and Model Validation.

The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes and pathways that characterize human biology, but they also lead to a more profound understanding of the mechanisms and factors that drive diseases; hence, they allow personalized treatment strategies that are guided by central clinical questions. However, despite the growing popularity of computational-modelling approaches in different stakeholder communities, there are still many hurdles to overcome for their clinical routine implementation in the future.

CRISPitope: A generic platform to model target antigens for adoptive T cell transfer therapy in mouse tumor models.

This protocol details the procedure for CRISPR-assisted insertion of epitopes (CRISPitope), a flexible approach for generating tumor cells expressing model CD8 T cell epitopes fused to endogenously encoded gene products of choice. CRISPitope-engineered tumor cells can be recognized by T cell receptor-transgenic (TCRtg) CD8 T cells that are widely used in immunology research. Using mice inoculated with CRISPitope-engineered tumor cells, researchers can investigate how the choice of the target antigen for T cell immunotherapies influences treatment efficacy and resistance mechanisms.

CD4+ T cell immunity to Salmonella is transient in the circulation.

While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently.

Tumor reactivity of CD8 T cells favors acquisition of dysfunctional states in human melanoma.

A recent study by Oliveira et al. provides, in unprecedented detail, novel insights into the relationship between tumorreactivity and functional states of CD8 T cells in metastatic melanoma.