bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative assessment of myelin density using [11C]MeDAS PET in patients with multiple sclerosis: a first-in-human study
Authors: van der Weijden Chris W. J. , Meilof Jan F. , van der Hoorn Anouk , Zhu Junqing , Wu Chunying , Wang Yanming , Willemsen Antoon T. M. , Dierckx Rudi A. J. O. , Lammertsma Adriaan A. , de Vries Erik F. J. 
Published: April 2022

Abstract

Purpose
Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [11C]MeDAS as a PET tracer for myelin imaging in humans.

Methods
Six healthy controls and 11 MS patients underwent MRI and dynamic [11C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [11C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [11C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model.

Results
Visual analysis of the fits of [11C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (Ki), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived Ki, but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities.

Conclusion
[11C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification.
Trial registration.
NL7262. Registered 18 September 2018.
Livestock Use on Public Lands in the Western USA Exacerbates Climate Change: Implications for Climate Change Mitigation and Adaptation
Authors: Kauffman J. Boone , Beschta Robert L. , Lacy Peter M. , Liverman Marc 
Published: April 2022

AbstractPublic lands of the USA can play an important role in addressing the climate crisis. About 85% of public lands in the western USA are grazed by domestic livestock, and they influence climate change in three profound ways: (1) they are significant sources of greenhouse gases through enteric fermentation and manure deposition; (2) they defoliate native plants, trample vegetation and soils, and accelerate the spread of exotic species resulting in a shift in landscape function from carbon sinks to sources of greenhouse gases; and (3) they exacerbate the effects of climate change on ecosystems by creating warmer and drier conditions. On public lands one cow-calf pair grazing for one month (an “animal unit month” or “AUM”) produces 875 kg CO2e through enteric fermentation and manure deposition with a social carbon cost of nearly $36 per AUM. Over 14 million AUMs of cattle graze public lands of the western USA each year resulting in greenhouse gas emissions of 12.4 Tg CO2e year−1. The social costs of carbon are > $500 million year−1or approximately 26 times greater than annual grazing fees collected by managing federal agencies. These emissions and social costs do not include the likely greater ecosystems costs from grazing impacts and associated livestock management activities that reduce biodiversity, carbon stocks and rates of carbon sequestration. Cessation of grazing would decrease greenhouse gas emissions, improve soil and water resources, and would enhance/sustain native species biodiversity thus representing an important and cost-effective adaptive approach to climate change.
Automated artifact detection in abbreviated dynamic contrast-enhanced (DCE) MRI-derived maximum intensity projections (MIPs) of the breast
Authors: Kapsner Lorenz A. , Ohlmeyer Sabine , Folle Lukas , Laun Frederik B. , Nagel Armin M. , Liebert Andrzej , Schreiter Hannes , Beckmann Matthias W. , Uder Michael , Wenkel Evelyn , Bickelhaupt Sebastian 
Published: April 2022

Abstract
Objectives
To automatically detect MRI artifacts on dynamic contrast-enhanced (DCE) maximum intensity projections (MIPs) of the breast using deep learning.

Methods
Women who underwent clinically indicated breast MRI between October 2015 and December 2019 were included in this IRB-approved retrospective study. We employed two convolutional neural network architectures (ResNet and DenseNet) to detect the presence of artifacts on DCE MIPs of the left and right breasts. Networks were trained on images acquired up to and including the year 2018 using a 5-fold cross-validation (CV). Ensemble classifiers were built with the resulting CV models and applied to an independent holdout test dataset, which was formed by images acquired in 2019.

Results
Our study sample contained 2265 examinations from 1794 patients (median age at first acquisition: 50 years [IQR: 17 years]), corresponding to 1827 examinations of 1378 individuals in the training dataset and 438 examinations of 416 individuals in the holdout test dataset with a prevalence of image-level artifacts of 53% (1951/3654 images) and 43% (381/876 images), respectively. On the holdout test dataset, the ResNet and DenseNet ensembles demonstrated an area under the ROC curve of 0.92 and 0.94, respectively.

Conclusion
Neural networks are able to reliably detect artifacts that may impede the diagnostic assessment of MIPs derived from DCE subtraction series in breast MRI. Future studies need to further explore the potential of such neural networks to complement quality assurance and improve the application of DCE MIPs in a clinical setting, such as abbreviated protocols.

Key Points
• Deep learning classifiers are able to reliably detect MRI artifacts in dynamic contrast-enhanced protocol-derived maximum intensity projections of the breast.
• Automated quality assurance of maximum intensity projections of the breast may be of special relevance for abbreviated breast MRI, e.g., in high-throughput settings, such as cancer screening programs.
Screen-detected and interval breast cancer after concordant and discordant interpretations in a population based screening program using independent double reading
Authors: Martiniussen Marit A. , Sagstad Silje , Larsen Marthe , Larsen Anne Sofie F. , Hovda Tone , Lee Christoph I. , Hofvind Solveig 
Published: April 2022

Abstract
Objectives
To analyze rates, odds ratios (OR), and characteristics of screen-detected and interval cancers after concordant and discordant initial interpretations and consensus in a population-based screening program.

Methods
Data were extracted from the Cancer Registry of Norway for 487,118 women who participated in BreastScreen Norway, 2006–2017, with 2 years of follow-up. All mammograms were independently interpreted by two radiologists, using a score from 1 (negative) to 5 (high suspicion of cancer). A score of 2+ by one of the two radiologists was defined as discordant and 2+ by both radiologists as concordant positive. Consensus was performed on all discordant and concordant positive, with decisions of recall for further assessment or dismiss. OR was estimated with logistic regression with 95% confidence interval (CI), and histopathological tumor characteristics were analyzed for screen-detected and interval cancer.

Results
Among screen-detected cancers, 23.0% (697/3024) had discordant scores, while 12.8% (117/911) of the interval cancers were dismissed at index screening. Adjusted OR was 2.4 (95% CI: 1.9–2.9) for interval cancer and 2.8 (95% CI: 2.5–3.2) for subsequent screen-detected cancer for women dismissed at consensus compared to women with concordant negative scores. We found 3.4% (4/117) of the interval cancers diagnosed after being dismissed to be DCIS, compared to 20.3% (12/59) of those with false-positive result after index screening.

Conclusion
Twenty-three percent of the screen-detected cancers was scored negative by one of the two radiologists. A higher odds of interval and subsequent screen-detected cancer was observed among women dismissed at consensus compared to concordant negative scores. Our findings indicate a benefit of personalized follow-up.

Key Points
• In this study of 487,118 women participating in a screening program using independent double reading with consensus, 23% screen-detected cancers were detected by only one of the two radiologists.
• The adjusted odds ratio for interval cancer was 2.4 (95% confidence interval: 1.9, 2.9) for cases dismissed at consensus using concordant negative interpretations as the reference.
• Interval cancers diagnosed after being dismissed at consensus or after concordant negative scores had clinically less favorable prognostic tumor characteristics compared to those diagnosed after false-positive results.
The learning curve in bladder MRI using VI-RADS assessment score during an interactive dedicated training program
Authors: da Silva Miguel Correia , Pecoraro Martina , Pisciotti Martina Lucia , Dehghanpour Ailin , Forookhi Ali , Lucciola Sara , Bicchetti Marco , Messina Emanuele , Catalano Carlo , Panebianco Valeria 
Published: April 2022

Abstract
Objective
The purpose of the study was to evaluate the effect of an interactive training program on the learning curve of radiology residents for bladder MRI interpretation using the VI-RADS score.

Methods
Three radiology residents with minimal experience in bladder MRI served as readers. They blindly evaluated 200 studies divided into 4 subsets of 50 cases over a 3-month period. After 2 months, the first subset was reassessed, resulting in a total of 250 evaluations. An interactive training program was provided and included educational lessons and case-based practice. The learning curve was constructed by plotting mean agreement as the ratio of correct evaluations per batch. Inter-reader agreement and diagnostic performance analysis were performed with kappa statistics and ROC analysis.

Results
As for the VI-RADS scoring agreement, the kappa differences between pre-training and post-training evaluation of the same group of cases were 0.555 to 0.852 for reader 1, 0.522 to 0.695 for reader 2, and 0.481 to 0.794 for reader 3. Using VI-RADS ≥ 3 as cut-off for muscle invasion, sensitivity ranged from 84 to 89% and specificity from 91 to 94%, while the AUCs from 0.89 (95% CI:0.84, 0.94) to 0.90 (95% CI:0.86, 0.95). Mean evaluation time decreased from 5.21 ± 1.12 to 3.52 ± 0.69 min in subsets 1 and 5. Mean grade of confidence improved from 3.31 ± 0.93 to 4.21 ± 0.69, in subsets 1 and 5.

Conclusion
An interactive dedicated education program on bladder MRI and the VI-RADS score led to a significant increase in readers’ diagnostic performance over time, with a general improvement observed after 100–150 cases.

Key Points
• After the first educational lesson and 100 cases were interpreted, the concordance on VI-RADS scoring between the residents and the experienced radiologist was significantly higher.
• An increase in the grade of confidence was experienced after 100 cases.
• We found a decrease in the evaluation time after 150 cases.
Characterization of low levels of turbulence generated by grids in the settling chamber of a laminar wind tunnel
Authors: Romblad Jonas , Greiner Michael , Guissart Amandine , Würz Werner 
Published: April 2022

AbstractWind tunnel investigations of how Natural Laminar Flow (NLF) airfoils respond to atmospheric turbulence require the generation of turbulence, whose relevant characteristics resemble those in the atmosphere. The lower, convective part of the atmospheric boundary layer is characterized by low to medium levels of turbulence. The current study focuses on the small scales of this turbulence. Detailed hot-wire measurements have been performed to characterize the properties of the turbulence generated by grids mounted in the settling chamber of the Laminar Wind Tunnel (LWT). In the test section, the very low base turbulence level of Tuu ≅ 0.02% (10 ≤ f ≤ 5000 Hz) is incrementally increased by the grids up to Tuu ≅ 0.5%. The turbulence spectrum in the u-direction shows the typical suppression of larger scales due to the contraction between grids and test section. Still, the generated turbulence provides a good mapping of the spectrum measured in flight for most of the frequency range 500 ≤ f ≤ 3000 Hz, where Tollmien-Schlichting (TS)-amplification occurs for typical NLF airfoils. The spectra in v and w-direction exhibit distinct inertial subranges with slopes being less steep compared to the − 5/3 slope of the Kolmogorov spectrum. The normalized spectra in u-direction collapse together well for all grids, whereas in v- and w-directions the inertial- and dissipative subranges are more clearly distinguished for the coarser grids. It is demonstrated that the dissipation rate ε is a suitable parameter for comparing the wind tunnel turbulence with the atmospheric turbulence in the frequency range of interest. By employing the grids, turbulence in the range 4.4 × 10–7 ≤ ε ≤ 0.40 m2/s3 at free-stream velocity U∞ = 40 m/s can be generated in the LWT, which covers representative dissipation rates of free flight NLF applications. In the x-direction, the spectra of the v and w-components develop progressively more pronounced inertial- and dissipative subranges, and the energy below f ≈ 400 Hz decreases. In contrast, the spectral energy of the u-component increases across the whole frequency range, when moving downstream. This behavior can be explained by the combination of energy transport along the Kolmogorov cascade and the incipient return to an isotropic state.
Graphic Abstract
Effect of caffeine on muscle oxygen saturation during short-term all-out exercise: a double-blind randomized crossover study
Authors: Ruiz-Moreno Carlos , Gutiérrez-Hellín Jorge , Lara Beatriz , Del Coso Juan 
Published: April 2022

Abstract
Purpose
The ergogenic effect of oral caffeine administration on short-term all-out exercise performance is well established. However, the potential mechanisms associated with caffeine’s ergogenicity in this type of exercise are poorly understood. The aim of this study was to investigate whether caffeine intake modifies muscle oxygen saturation during the 15-s Wingate Anaerobic Test.

Methods
Fifteen moderately trained individuals (body mass = 67.4 ± 12.3 kg; height 171.3 ± 6.9 cm; age 31 ± 6 years) took part in two identical experimental trials after the ingestion of (a) 3 mg/kg of caffeine or (b) 3 mg/kg of cellulose (placebo). After 60 min for substances absorption, participants performed a 15-s Wingate test on a cycle ergometer against a load representing 7.5% of participant’s body mass. Muscle oxygen saturation was continuously measured during exercise with near-infrared spectroscopy and blood lactate concentration was measured 1 min after exercise.

Results
In comparison to the placebo, the oral administration of caffeine increased peak power by 2.9 ± 4.5% (from 9.65 ± 1.38 to. 9.92 ± 1.40 W/kg, P = 0.038; effect size (ES), 95% confidence intervals = 0.28, 0.05–0.51), mean power by 3.5 ± 6.2% (from 8.30 ± 1.08 to 8.57 ± 1.12 W/kg, P = 0.044; ES = 0.36, 0.01–0.71) and blood lactate concentration by 20.9 ± 24.7% (from 12.4 ± 2.6 to 14.8 ± 4.0 mmol/L, P = 0.005; ES = 0.59, 0.16–1.02). However, caffeine did not modify the curve of muscle oxygen desaturation during exercise (lowest value was 23.1 ± 14.1 and 23.4 ± 14.1%, P = 0.940).

Conclusion
Caffeine’s ergogenic effect during short-term all-out exercise seems to be associated with an increased glycolytic metabolism with no influence of enhanced muscle oxygen saturation.
Patterns of amygdala region pathology in LATE-NC: subtypes that differ with regard to TDP-43 histopathology, genetic risk factors, and comorbid pathologies
Authors: Cykowski Matthew D. , Arumanayagam Anithachristy S. , Powell Suzanne Z. , Rivera Andreana L. , Abner Erin L. , Roman Gustavo C. , Masdeu Joseph C. , Nelson Peter T. 
Published: April 2022

AbstractTransactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology is a hallmark of limbic-predominant age-related TDP-43 encephalopathy (LATE). The amygdala is affected early in the evolution of LATE neuropathologic change (LATE-NC), and heterogeneity of LATE-NC in amygdala has previously been observed. However, much remains to be learned about how LATE-NC originates and progresses in the brain. To address this, we assessed TDP-43 and other pathologies in the amygdala region of 184 autopsied subjects (median age = 85 years), blinded to clinical diagnoses, other neuropathologic diagnoses, and risk genotype information. As previously described, LATE-NC was associated with older age at death, cognitive impairment, and the TMEM106B risk allele. Pathologically, LATE-NC was associated with comorbid hippocampal sclerosis (HS), myelin loss, and vascular disease in white matter (WM). Unbiased hierarchical clustering of TDP-43 inclusion morphologies revealed discernable subtypes of LATE-NC with distinct clinical, genetic, and pathologic associations. The most common patterns were: Pattern 1, with lamina II TDP-43 + processes and preinclusion pathology in cortices of the amygdala region, and frequent LATE-NC Stage 3 with HS; Pattern 2, previously described as type-β, with neurofibrillary tangle-like TDP-43 neuronal cytoplasmic inclusions (NCIs), high Alzheimer’s disease neuropathologic change (ADNC), frequent APOE ε4, and usually LATE-NC Stage 2; Pattern 3, with round NCIs and thick neurites in amygdala, younger age at death, and often comorbid Lewy body disease; and Pattern 4 (the most common pattern), with tortuous TDP-43 processes in subpial and WM regions, low ADNC, rare HS, and lower dementia probability. TDP-43 pathology with features of patterns 1 and 2 were often comorbid in the same brains. Early and mild TDP-43 pathology was often best described to be localized in the “amygdala region” rather than the amygdala proper. There were also important shared attributes across patterns. For example, all four patterns were associated with the TMEM106B risk allele. Each pattern also demonstrated the potential to progress to higher LATE-NC stages with confluent anatomical and pathological patterns, and to contribute to dementia. Although LATE-NC showed distinct patterns of initiation in amygdala region, there was also apparent shared genetic risk and convergent pathways of clinico-pathological evolution.
Post-enucleation socket syndrome—a novel pathophysiological definition
Authors: Rokohl Alexander C. , Kopecky Adam , Trester Marc , Wawer Matos Philomena A. , Pine Keith R. , Heindl Ludwig M. 
Published: April 2022

Abstract
Background
The last definition of the post-enucleation socket syndrome (PESS) by Tyers and Collin—formulated almost 40 years ago in 1982—is predominantly based on the clinical characteristics and does not include the insights of newer studies into the pathophysiological mechanism of the PESS.

Methods
A systematic PubMed literature review regarding the pathophysiological mechanism of the PESS was performed, and results were comprised to give an overview of the current knowledge of the PESS including the exact pathophysiological mechanism.

Results
The primarily postulated pathophysiological mechanism of the PESS was the atrophy of orbital tissues, especially of fat, resulting in variable clinical findings. Newer studies using high-resolution computed tomography and magnetic resonance imaging or performing histopathological analyses found no orbital fat atrophy but rather a rotatory displacement of the orbital tissues from superior to posterior and from posterior to inferior together with the retraction of the extraocular muscles and a possible volume loss of the orbital implant by resorption if it is manufactured from hydroxyapatite. PESS results in a backward tilt of the superior fornix, a deep superior sulcus, a pseudo-ptosis, a lower eyelid elongation and laxity, a shallower inferior fornix, as well as enophthalmos and may lead to an inability of wearing ocular prostheses.

Conclusions
A novel and comprehensive definition of the PESS is proposed: PESS is a multifactorial and variable syndrome caused by a rotatory displacement of orbital contents together with the retraction of the extraocular muscles and possible resorption of the orbital implant if it is manufactured from hydroxyapatite.
Interferon antagonists encoded by SARS-CoV-2 at a glance
Authors: Lee Jung-Hyun , Koepke Lennart , Kirchhoff Frank , Sparrer Konstantin M. J. 
Published: April 2022

AbstractThe innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.
Programmed death receptor ligand-2 (PD-L2) bearing extracellular vesicles as a new biomarker to identify early triple-negative breast cancer patients at high risk for relapse
Authors: Hoffmann Oliver , Wormland Sebastian , Bittner Ann-Kathrin , Collenburg Monika , Horn Peter A. , Kimmig Rainer , Kasimir-Bauer Sabine , Rebmann Vera 
Published: April 2022

Abstract
Purpose
Based on the tumor-promoting features of extracellular vesicles (EV) and PD-L1/2-bearing EV subpopulations (PD-L1/2EV), we evaluated their potential as surrogate markers for disease progression or eligibility criteria for PD-1 immune checkpoint inhibition (ICI) approaches in early triple-negative breast cancer (TNBC).

Methods
After enrichment of EV from plasma samples of 56 patients before and 50 after chemotherapy (CT), we determined levels of EV particle number and PD-L1/2EV by nanoparticle tracking analysis or ELISA and associated the results with clinical status/outcome and the presence of distinct circulating tumor cells (CTC) subpopulations.

Results
Compared to healthy controls, patients had a tenfold higher EV concentration and significantly elevated PD L2EV but not PD L1EV levels. The most important clinical implications were found for PD-L2EV. High PD-L2EV levels were associated with a significantly reduced 3-year progression-free and overall survival (PFS and OS). A loss of PD-L2EV after CT was significantly more prominent in patients achieving pathological complete response (pCR). Increased pre-CT PD-L2EV levels were found in patients having NOTCH1-positive or ERBB3-positive CTC. The presence of ERBB3-positive CTC combined with high pre-CT PD-L2EV resulted in a shorter PFS.

Conclusion
This study highlights PD L2EV as a promising biomarker for risk assessment of TNBC patients and represents the basic for additional studies introducing PD-L2EV as an eligibility criterion for PD-1 ICI approaches.