Characteristics of “Tip-DCs and MDSCs” and Their Potential Role in Leishmaniasis

Since the first description of dendritic cells (DCs) by Steinman and Cohn (1973), the myeloid lineage of leukocytes was investigated intensively. Nowadays it is obvious that myeloid cells, especially DCs, are crucial for the adaptive and innate immune response against intracellular pathogens such as Leishmania major parasites. Based on the overlapping expression of molecules that were commonly used to classify myeloid cells, it becomes difficult to denominate those cell types precisely. Of note, most of these markers used for myeloid cell identification are expressed on a broad range of myeloid cells, and should therefore be handled with care if used for subtyping of myeloid cells. In this mini-review we aim to discuss the relative impact of DCs that release TNF and nitric oxide (Tip-DCs) and myeloid cells with suppressive capacities (myeloid-derived suppressor cells, MDSCs) in infectious diseases such as experimental leishmaniasis. In our point of view it cannot be excluded that the novel subsets that were denominated as “Tip-DCs” and “MDSCs” might not be classical “subsets” but rather represent myeloid cells in a transient maturation stage expressing different genes, in response to the surrounding environment

Intrasession and Intersession Reproducibility of Artificial Scotoma pRF Mapping Results at Ultra- High Fields

Published online September 6, 2022.Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the pRF center position (Spearman correlation coefficients for x, y: .0.95; eccentricity: .0.87; polar angle: .0.98), but only modest reproducibility for pRF size (Spearman correlation coefficients around 0.4). We further examined the scotoma detection performance using an automated method based on a reference dataset acquired with full-field stimulation. For the 2° artificial scotoma, the group-averaged scotoma sizes were estimated at between 1.92° and 2.19° for different sessions. We conclude that pRF mapping of visual field losses yields robust, reproducible measures of retinal function and suggest the use of pRF mapping as an objective method for monitoring visual deficits during therapeutic interventions or disease progression.Austrian Science Fund (FWF) P35583; P33180; KLI670 Eusko Jaurlaritza (Gobierno Vasco) BERC 2022-2025 Spanish State Research Agency CEX2020-001010-S Spanish Ministry of Science and Innovation IJC2020-042887-

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease

Published: March 13, 2023Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage. Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD)were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC). Results: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained fromwedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar 2.5 degrees: 0.88±0.11;wedge/ring<2.5 degrees: 0.89 ± 0.12 wedge/ring; >2.5 degrees: 0.86 ± 0.10) for the peripheral visual field. Conclusions: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.Supported by the Austrian Science Fund (FWF); KLI 670-B3

Characterization and implications of the initial estimated glomerular filtration rate 'dip' upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial

Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3-5 ml/min/1.73 m(2) decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin and largely reversible, this 'eGFR dip' may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with eGFR available at baseline and week four were categorized by initial eGFR change into three groups; over 10% decline ('eGFR dipper'), over 0 and up to 10% decline ('eGFR intermediate'), no eGFR decline ('eGFR non-dipper'). Baseline characteristics of 'eGFR intermediate' and 'eGFR non-dipper' were generally comparable. An initial 'eGFR dip' was observed in 28.3% of empagliflozin versus 13.4% of placebo-treated participants; odds ratio 2.7 [95% Confidence Interval 2.3-3.0]. In multivariate logistic regression, diuretic use and higher KDIGO risk category at baseline were independently predictive of an 'eGFR dip' in empagliflozin versus placebo. Safety and beneficial treatment effects with empagliflozin on cardiovascular and kidney outcomes were consistent across subgroups based on these predictive factors. The initial 'eGFR dip' did not have a major impact on the treatment effect of empagliflozin on subsequent cardiovascular death, hospitalization for heart failure, and incident or worsening kidney disease. Thus, patients with type 2 diabetes with more advanced kidney disease and/or on diuretic therapy were more likely to experience an 'eGFR dip' of over 10% with empagliflozin, but reduction in cardiovascular and kidney outcomes was not relevantly modified by such 'eGFR dip.

Sustainable wood electronics by iron-catalyzed laser-induced graphitization for large-scale applications

Ecologically friendly wood electronics will help alleviating the shortcomings of state-of-art cellulose-based “green electronics”. Here we introduce iron-catalyzed laser-induced graphitization (IC-LIG) as an innovative approach for engraving large-scale electrically conductive structures on wood with very high quality and efficiency, overcoming the limitations of conventional LIG including high ablation, thermal damages, need for multiple lasing steps, use of fire retardants and inert atmospheres. An aqueous bio-based coating, inspired by historical iron-gall ink, protects wood from laser ablation and thermal damage while promoting efficient graphitization and smoothening substrate irregularities. Large-scale (100 cm2), highly conductive (≥2500 S m−1) and homogeneous surface areas are engraved single-step in ambient atmosphere with a conventional CO2 laser, even on very thin (∼450 µm) wood veneers. We demonstrate the validity of our approach by turning wood into highly durable strain sensors, flexible electrodes, capacitive touch panels and an electroluminescent LIG-based device

A Tunable Transition Metal Dichalcogenide Entangled Photon-Pair Source

Entangled photon-pair sources are at the core of quantum applications like quantum key distribution, sensing, and imaging. Operation in space-limited and adverse environments such as in satellite-based and mobile communication requires robust entanglement sources with minimal size and weight requirements. Here, we meet this challenge by realizing a cubic micrometer scale entangled photon-pair source in a 3R-stacked transition metal dichalcogenide crystal. Its crystal symmetry enables the generation of polarization-entangled Bell states without additional components and provides tunability by simple control of the pump polarization. Remarkably, generation rate and state tuning are decoupled, leading to equal generation efficiency and no loss of entanglement. Combining transition metal dichalcogenides with monolithic cavities and integrated photonic circuitry or using quasi-phasematching opens the gate towards ultrasmall and scalable quantum devices

ChatGPT’s performance in German OB/GYN exams – paving the way for AI-enhanced medical education and clinical practice

BackgroundChat Generative Pre-Trained Transformer (ChatGPT) is an artificial learning and large language model tool developed by OpenAI in 2022. It utilizes deep learning algorithms to process natural language and generate responses, which renders it suitable for conversational interfaces. ChatGPT’s potential to transform medical education and clinical practice is currently being explored, but its capabilities and limitations in this domain remain incompletely investigated. The present study aimed to assess ChatGPT’s performance in medical knowledge competency for problem assessment in obstetrics and gynecology (OB/GYN).MethodsTwo datasets were established for analysis: questions (1) from OB/GYN course exams at a German university hospital and (2) from the German medical state licensing exams. In order to assess ChatGPT’s performance, questions were entered into the chat interface, and responses were documented. A quantitative analysis compared ChatGPT’s accuracy with that of medical students for different levels of difficulty and types of questions. Additionally, a qualitative analysis assessed the quality of ChatGPT’s responses regarding ease of understanding, conciseness, accuracy, completeness, and relevance. Non-obvious insights generated by ChatGPT were evaluated, and a density index of insights was established in order to quantify the tool’s ability to provide students with relevant and concise medical knowledge.ResultsChatGPT demonstrated consistent and comparable performance across both datasets. It provided correct responses at a rate comparable with that of medical students, thereby indicating its ability to handle a diverse spectrum of questions ranging from general knowledge to complex clinical case presentations. The tool’s accuracy was partly affected by question difficulty in the medical state exam dataset. Our qualitative assessment revealed that ChatGPT provided mostly accurate, complete, and relevant answers. ChatGPT additionally provided many non-obvious insights, especially in correctly answered questions, which indicates its potential for enhancing autonomous medical learning.ConclusionChatGPT has promise as a supplementary tool in medical education and clinical practice. Its ability to provide accurate and insightful responses showcases its adaptability to complex clinical scenarios. As AI technologies continue to evolve, ChatGPT and similar tools may contribute to more efficient and personalized learning experiences and assistance for health care providers

Translational evaluation of gait behavior in rodent models of arthritic disorders with the CatWalk device – a narrative review

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201

Ectopic callose deposition into woody biomass modulates the nano-architecture of macrofibrils

Plant biomass plays an increasingly important role in the circular bioeconomy, replacing non-renewable fossil resources. Genetic engineering of this lignocellulosic biomass could benefit biorefinery transformation chains by lowering economic and technological barriers to industrial processing. However, previous efforts have mostly targeted the major constituents of woody biomass: cellulose, hemicellulose and lignin. Here we report the engineering of wood structure through the introduction of callose, a polysaccharide novel to most secondary cell walls. Our multiscale analysis of genetically engineered poplar trees shows that callose deposition modulates cell wall porosity, water and lignin contents and increases the lignin-cellulose distance, ultimately resulting in substantially decreased biomass recalcitrance. We provide a model of the wood cell wall nano-architecture engineered to accommodate the hydrated callose inclusions. Ectopic polymer introduction into biomass manifests in new physico-chemical properties and offers new avenues when considering lignocellulose engineering.Bourdon et al. demonstrate the possibility to ectopically synthesize callose, a polymer restricted to primary cell walls, into Arabidopsis and aspen secondary cell walls to manipulate their ultrastructure and ultimately reduce their recalcitrance