bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice
Authors: Saadane Aicha , Veenstra Alexander A. , Minns Martin S. , Tang Jie , Du Yunpeng , Abubakr Elghazali Fatima , Lessieur Emma M. , Pearlman Eric , Kern Timothy S. 
Published: January 2023

Abstract
Aims/hypothesis
Accumulating evidence suggests that leucocytes play a critical role in diabetes-induced vascular lesions and other abnormalities that characterise the early stages of diabetic retinopathy. However, the role of monocytes has yet to be fully investigated; therefore, we used Ccr2−/− mice to study the role of CCR2+ inflammatory monocytes in the pathogenesis of diabetes-induced degeneration of retinal capillaries.

Methods
Experimental diabetes was induced in wild-type and Ccr2−/− mice using streptozotocin. After 2 months, superoxide levels, expression of inflammatory genes, leucostasis, leucocyte- and monocyte-mediated cytotoxicity against retinal endothelial cell death, retinal thickness and visual function were evaluated. Retinal capillary degeneration was determined after 8 months of diabetes. Flow cytometry of peripheral blood for differential expression of CCR2 in monocytes was assessed.

Results
In nondiabetic mice, CCR2 was highly expressed on monocytes, and Ccr2−/− mice lack CCR2+ monocytes in the peripheral blood. Diabetes-induced retinal superoxide, expression of proinflammatory genes Inos and Icam1, leucostasis and leucocyte-mediated cytotoxicity against retinal endothelial cells were inhibited in diabetic Ccr2-deficient mice and in chimeric mice lacking Ccr2 only from myeloid cells. In order to focus on monocytes, these cells were immuno-isolated after 2 months of diabetes, and they significantly increased monocyte-mediated endothelial cell cytotoxicity ex vivo. Monocytes from Ccr2-deficient mice caused significantly less endothelial cell death. The diabetes-induced retinal capillary degeneration was inhibited in Ccr2−/− mice and in chimeric mice lacking Ccr2 only from myeloid cells.

Conclusions/interpretation
CCR2+ inflammatory monocytes contribute to the pathogenesis of early lesions of diabetic retinopathy.

Graphical abstract
In-depth characterization of protein N-glycosylation for a COVID-19 variant-design vaccine spike protein
Authors: Huang Jiangming , Hou Shouzeng , An Jiao , Zhou Chenliang 
Published: January 2023

AbstractCOVID-19 is caused by SARS-CoV-2 infection and remains one of the biggest pandemics around the world since 2019. Vaccination has proved to be an effective way of preventing SARS-CoV-2 infection and alleviating the hospitalization burden. Among different forms of COVID-19 vaccine design, the spike protein of SARS-CoV-2 virus is widely used as a candidate vaccine antigen. As a surface protein on the virus envelop, the spike was reported to be heavily N-glycosylated and glycosylation had a great impact on its immunogenicity and efficacy. Besides, N-glycosylation might vary greatly on different expression systems and sequence variant designs. Therefore, comprehensive analysis of spike N-glycosylation is of great significance for better vaccine understanding and quality control. In this study, full characterization of N-glycosylation was performed for a Chinese Hamster Ovary (CHO) cell expressed variant-designed spike protein. The spike protein featured the latest six-proline substitution design together with the incorporation of a combination of mutation sites. Trypsin and Glu-C digestion coupled with PNGase F strategies were adopted, and effective LC–MS/MS methods were applied to analyze samples. As a result, a total of 19 N-glycosites were identified in the recombinant pike protein at intact N-glycopeptide level. Quantitative analysis of released glycan by LC–MS/MS was also performed, and 31 high-abundance N-glycans were identified. Sequencing analysis of glycan was further provided to assist glycan structure confirmation. Moreover, all of the analyses were performed on three consecutive manufactured batches and the glycosylation results on both glycosite and glycans showed good batch-to-batch consistency. Thus, the reported analytical strategy and N-glycosylation information may well facilitate studies on SARS-CoV-2 spike protein analysis and quality studies.
Graphical Abstract
Pediatric whole-body magnetic resonance imaging: comparison of STIR and T2 Dixon sequences in the detection and grading of high signal bone marrow changes
Authors: Zadig P. , von Brandis E. , Ording Müller L. S. , Tanturri de Horatio L. , Rosendahl K. , Avenarius D. F. M. 
Published: January 2023

Abstract
Objectives
To compare short time inversion recovery (STIR) and T2 Dixon in the detection and grading of high signal intensity areas in bone marrow on whole-body MRI in healthy children.

Methods
Prospective study, including whole-body 1.5-T MRIs from 77 healthy children. Two experienced radiologists in consensus identified and graded areas of high bone marrow signal on STIR and T2-weighted (T2W) turbo spin echo (TSE) Dixon images (presence, extension) in two different sessions at an interval of at least 3 weeks. In a third session, a third observer joined the two readers for an additional consensus reading with all sequences available (substitute gold standard).

Results
Four hundred ninety of 545 (89.9%) high signal areas were visible on both sequences, while 27 (5.0%) were visible on STIR only and 28 (5.1%) on T2W Dixon only. Twenty-four of 27 (89%) lesions seen on STIR only, and 25/28 (89%) seen on T2W Dixon only, were graded as mildly increased signal intensity. The proportion of true positive high signal lesions was higher for the T2W Dixon images as compared to STIR (74.2% vs. 68.2%) (p = 0.029), while the proportion of false negatives was lower (25.9% vs. 31.7% (p = 0.035) for T2W Dixon and STIR, respectively). There was a moderate agreement between the T2W Dixon and STIR-based extension scores on a 0–4 scale, with a kappa of 0.45 (95% CI = 0.34–0.56).

Conclusions
Most high signal bone marrow changes identified on a 1.5-T whole-body MRI were seen on both STIR and water-only T2W Dixon, underscoring the importance of using identical protocols when following bone-marrow signal changes over time.

Key Points
• Whole-body MRI is increasingly being used to diagnose and monitor diseases in children, such as chronic non-bacterial osteomyelitis, malignant/metastatic disease, and histiocytosis.
• Standardized and validated imaging protocols, as well as reference standards by age for the growing skeleton are lacking.
• Prospective single-center study showed that 90% of high signal bone marrow areas identified on a 1.5-T whole-body MRI in healthy children is seen on both STIR and water-only T2W Dixon, while 5% is seen on STIR only and 5% on T2W Dixon only.
Impact of sea ice transport on Beaufort Gyre liquid freshwater content
Authors: Cornish Sam B. , Muilwijk Morven , Scott Jeffery R. , Marson Juliana M. , Myers Paul G. , Zhang Wenhao , Wang Qiang , Kostov Yavor , Johnson Helen L. , Marshall John 
Published: January 2023

AbstractThe Arctic Ocean’s Beaufort Gyre (BG) is a wind-driven reservoir of relatively fresh seawater, situated beneath time-mean anticyclonic atmospheric circulation, and is covered by mobile pack ice for most of the year. Liquid freshwater accumulation in and expulsion from this gyre is of critical interest due to its potential to affect the Atlantic meridional overturning circulation and due to the importance of freshwater in modulating vertical fluxes of heat, nutrients and carbon in the ocean, and exchanges of heat and moisture with the atmosphere. Here, we investigate the hypothesis that wind-driven sea ice transport into/from the BG region influences the freshwater content of the gyre and its variability. To test this hypothesis, we use the results of a coordinated climate response function experiment with four ice-ocean models, in combination with targeted experiments using a regional setup of the MITgcm, in which we rotate the surface wind forcing vectors (thereby changing the ageostrophic component of these winds). Our results show that, via an effect on the net thermodynamic growth rate, anomalies in sea ice transport into the BG affect liquid freshwater adjustment. Specifically, increased ice import increases freshwater retention in the gyre, whereas ice export decreases freshwater in the gyre. Our results demonstrate that uncertainty in the ageostrophic component of surface winds, and in the dynamic sea ice response to these winds, has important implications for ice thermodynamics and freshwater. This sensitivity may explain some of the observed inter-model spread in simulations of Beaufort Gyre freshwater and its adjustment in response to wind forcing.
Mouth rinsing and ingesting salty or bitter solutions does not influence corticomotor excitability or neuromuscular function
Authors: Gray Edward , Cavaleri Rocco , Siegler Jason 
Published: January 2023

Abstract
Purpose
To explore the effect of tasting unpleasant salty or bitter solutions on lower limb corticomotor excitability and neuromuscular function.

Methods
Nine females and eleven males participated (age: 27 ± 7 years, BMI: 25.3 ± 4.0 kg m−2). Unpleasant salty (1 M) and bitter (2 mM quinine) solutions were compared to water, sweetened water, and no solution, which functioned as control conditions. In a non-blinded randomized cross-over order, each solution was mouth rinsed (10 s) and ingested before perceptual responses, instantaneous heart rate (a marker of autonomic nervous system activation), quadricep corticomotor excitability (motor-evoked potential amplitude) and neuromuscular function during a maximal voluntary contraction (maximum voluntary force, resting twitch force, voluntary activation, 0–50 ms impulse, 0–100 impulse, 100–200 ms impulse) were measured.

Results
Hedonic value (water: 47 ± 8%, sweet: 23 ± 17%, salt: 71 ± 8%, bitter: 80 ± 10%), taste intensity, unpleasantness and increases in heart rate (no solution: 14 ± 5 bpm, water: 18 ± 5 bpm, sweet: 20 ± 5 bpm, salt: 24 ± 7 bpm, bitter: 23 ± 6 bpm) were significantly higher in the salty and bitter conditions compared to control conditions. Nausea was low in all conditions (< 15%) but was significantly higher in salty and bitter conditions compared to water (water: 3 ± 5%, sweet: 6 ± 13%, salt: 7 ± 9%, bitter: 14 ± 16%). There was no significant difference between conditions in neuromuscular function or corticomotor excitability variables.

Conclusion
At rest, unpleasant tastes appear to have no influence on quadricep corticomotor excitability or neuromuscular function. These data question the mechanisms via which unpleasant tastes are proposed to influence exercise performance.
Quantitative perfusion assessment using indocyanine green during surgery — current applications and recommendations for future use
Authors: Van Den Hoven P. , Osterkamp J. , Nerup N. , Svendsen M. B. S. , Vahrmeijer Alexander , Van Der Vorst J. R. , Achiam M. P. 
Published: January 2023

Abstract
Purpose
Incorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a possible solution. However, only through quantification of the fluorescence signal can an objective and reproducible evaluation of tissue perfusion be obtained. This narrative review aims to provide an overview of the available quantification methods for perfusion assessment using ICG NIR fluorescence imaging and to present an overview of current clinically utilized software implementations.

Methods
PubMed was searched for clinical studies on the quantification of ICG NIR fluorescence imaging to assess tissue perfusion. Data on the utilized camera systems and performed methods of quantification were collected.

Results
Eleven software programs for quantifying tissue perfusion using ICG NIR fluorescence imaging were identified. Five of the 11 programs have been described in three or more clinical studies, including Flow® 800, ROIs Software, IC Calc, SPY-Q™, and the Quest Research Framework®. In addition, applying normalization to fluorescence intensity analysis was described for two software programs.

Conclusion
Several systems or software solutions provide a quantification of ICG fluorescence; however, intraoperative applications are scarce and quantification methods vary abundantly. In the widespread search for reliable quantification of perfusion with ICG NIR fluorescence imaging, standardization of quantification methods and data acquisition is essential.
Combined effects of vitamin D and neferine on the progression and metastasis of colorectal cancer
Authors: Yang Jinfeng , Zhang Qinyu , Huang Guanlin , Cong Jiacheng , Wang Ting , Zhai Xiaoya , Zhang Juzheng , Qi Guangying , Zhou Lihua , Jin Jiamin 
Published: January 2023

Abstract
Purpose
To investigate the synergistic effect of vitamin D and neferine on the growth and metastasis of colorectal cancer (CRC).

Methods
The synergistic effect of biologically active form of vitamin D, VD3 and neferine on the treatment of CRC was investigated by bliss analysis. Colony formation and wound healing ability, migration and invasion ability, and epithelial mesenchymal transition of HCT-116 cells, as a response to the combination treatment with VD3 and neferine were evaluated.

Results
VD3 and neferine showed a synergistic effect on CRC cell growth at a relatively low dose. The wound healing and colony formation capacity, cell migration and invasion abilities were all decreased by combination use of VD3 and neferine, compared to the VD3 or neferine treated single group. Furthermore, VD3 and neferine significantly decreased the expressions of N-cadherin, vimentin, snail, and slug in HCT-116 cells.

Conclusion
These data suggest that neferine enhances the anticancer capability of VD3 and reduces the dose dependency of VD3. The combination of vitamin D with neferine appears to be a potential therapeutic strategy for CRC.
Mental burden and moral distress among oncologists and oncology nurses in Germany during the third wave of the COVID-19 pandemic: a cross-sectional survey
Authors: Sommerlatte Sabine , Lugnier Celine , Schoffer Olaf , Jahn Patrick , Kraeft Anna-Lena , Kourti Eleni , Michl Patrick , Reinacher-Schick Anke , Schmitt Jochen , Birkner Thomas , Schildmann Jan , Herpertz Stephan 
Published: January 2023

Abstract
Purpose
There is evidence for mental burden and moral distress among healthcare workers during the pandemic. However, there is scarcity of analyses regarding possible correlations of mental burden and moral distress in this context. This study provides data to quantify mental burden and possible associations with moral distress among physicians and nurses working in oncology in Germany.

Methods
We conducted a cross-sectional online survey with physicians and nurses working in oncology in Germany between March and July 2021. Next to sociodemographic characteristics and working conditions, mental burden and moral distress were assessed using standardized instruments. Binary multivariate logistic regression using the enter method was performed in order to explore the relationship between mental burden and moral distress.

Results
121 physicians and 125 nurses were included in the study. Prevalence of clinically relevant depressive symptoms, anxiety, somatic symptoms, burnout symptoms and moral distress was 19.2, 14.5, 12.7, 46.0 and 34.7% in physicians and 41.4, 24.0, 46.8, 46.6 and 60.0% in nurses respectively. Mental burden was significantly associated with moral distress, being female/diverse, younger age < 40 and increase in workload. Nurses who felt sufficiently protected from COVID-19 reported significantly less moral distress.

Conclusion
To improve pandemic resilience, there is a need to ensure safe working environment including psychosocial support. Further evidence on risk and protective factors for moral distress is needed to be able to develop and implement strategies to protect healthcare workers within and beyond the pandemic.
CheSS: Chest X-Ray Pre-trained Model via Self-supervised Contrastive Learning
Authors: Cho Kyungjin , Kim Ki Duk , Nam Yujin , Jeong Jiheon , Kim Jeeyoung , Choi Changyong , Lee Soyoung , Lee Jun Soo , Woo Seoyeon , Hong Gil-Sun , Seo Joon Beom , Kim Namkug 
Published: January 2023

AbstractTraining deep learning models on medical images heavily depends on experts’ expensive and laborious manual labels. In addition, these images, labels, and even models themselves are not widely publicly accessible and suffer from various kinds of bias and imbalances. In this paper, chest X-ray pre-trained model via self-supervised contrastive learning (CheSS) was proposed to learn models with various representations in chest radiographs (CXRs). Our contribution is a publicly accessible pretrained model trained with a 4.8-M CXR dataset using self-supervised learning with a contrastive learning and its validation with various kinds of downstream tasks including classification on the 6-class diseases in internal dataset, diseases classification in CheXpert, bone suppression, and nodule generation. When compared to a scratch model, on the 6-class classification test dataset, we achieved 28.5% increase in accuracy. On the CheXpert dataset, we achieved 1.3% increase in mean area under the receiver operating characteristic curve on the full dataset and 11.4% increase only using 1% data in stress test manner. On bone suppression with perceptual loss, we achieved improvement in peak signal to noise ratio from 34.99 to 37.77, structural similarity index measure from 0.976 to 0.977, and root-square-mean error from 4.410 to 3.301 when compared to ImageNet pretrained model. Finally, on nodule generation, we achieved improvement in Fréchet inception distance from 24.06 to 17.07. Our study showed the decent transferability of CheSS weights. CheSS weights can help researchers overcome data imbalance, data shortage, and inaccessibility of medical image datasets. CheSS weight is available at https://github.com/mi2rl/CheSS.
Strategic Conflict Management using Recurrent Multi-agent Reinforcement Learning for Urban Air Mobility Operations Considering Uncertainties
Authors: Huang Cheng , Petrunin Ivan , Tsourdos Antonios 
Published: January 2023

AbstractThe rapidly evolving urban air mobility (UAM) develops the heavy demand for public air transport tasks and poses great challenges to safe and efficient operation in low-altitude urban airspace. In this paper, the operation conflict is managed in the strategic phase with multi-agent reinforcement learning (MARL) in dynamic environments. To enable efficient operation, the aircraft flight performance is integrated into the process of multi-resolution airspace design, trajectory generation, conflict management, and MARL learning. The demand and capacity balancing (DCB) issue, separation conflict, and block unavailability introduced by wind turbulence are resolved by the proposed the multi-agent asynchronous advantage actor-critic (MAA3C) framework, in which the recurrent actor-critic networks allow the automatic action selection between ground delay, speed adjustment, and flight cancellation. The learned parameters in MAA3C are replaced with random values to compare the performance of trained models. Simulated training and test experiments performed on a small urban prototype and various combined use cases suggest the superiority of the MAA3C solution in resolving conflicts with complicated wind fields. And the generalization, scalability, and stability of the model are also demonstrated while applying the model to complex environments.
Fear, Fanaticism, and Fragile Identities
Authors: Tietjen Ruth Rebecca 
Published: January 2023

AbstractIn this article, I provide a philosophical analysis of the nature and role of perceived identity threats in the genesis and maintenance of fanaticism. First, I offer a preliminary definition of fanaticism as the social identity-defining devotion to a sacred value that demands universal recognition and is complemented by a hostile antagonism toward people who dissent from one’s group’s values. The fanatic’s hostility toward dissent thereby takes the threefold form of outgroup hostility, ingroup hostility, and self-hostility. Second, I provide a detailed analysis of the fears of fanaticism, arguing that each of the three aforementioned forms of hostile antagonism corresponds to one form of fear or anxiety: the fanatic’s fear of the outgroup, renegade members of the ingroup, and problematic aspects of themselves. In each of these three forms of fear, the fanatic experiences both their sacred values and their individual and social identity as being threatened. Finally, I turn to a fourth form of fear or anxiety connected to fanaticism, namely the fanatic’s anxiety of and flight from the existential condition of uncertainty itself, which, at least in some cases, ground the fanatic’s fearfulness.
Multiplatform molecular analysis of vestibular schwannoma reveals two robust subgroups with distinct microenvironment
Authors: Landry Alexander P. , Wang Justin Z. , Suppiah Suganth , Zadeh Gelareh 
Published: January 2023

Abstract
Background
Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more aggressive nature and pattern of growth. Predicting who will fall into which category consistently remains uncertain. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease.

Methods
We select all vestibular schwannomas from our tumour bank with both methylation and RNA profiling available. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings, given a paucity of external samples with available multi-omic data.

Results
A total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups (“immunogenic” and “proliferative”) with significant differences in immune, stroma, and tumour cell abundance (p < 0.05). Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial to mesenchymal transition program, suggesting a need for subgroup-specific targeted treatment/trial design in the future.

Conclusions
We leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.
How Hot Can Small Solar Flares Get?
Authors: Harra Louise , Battaglia Andrea F. , Barczynski Krzysztof , Collier Hannah , Krucker Säm , Reeves Katharine K. , Doschek George 
Published: January 2023

AbstractThe temperature reached by solar flares is a key parameter to understanding the physical process that causes the energy release. In this work, we analysed data from a Hinode Observing Programme that focused on high cadence measurement of the flaring plasma. This was carried out when the X-ray imager and spectrometer (STIX) on Solar Orbiter was observing. We analysed 3 small microflares, and determined their evolution and temperature. The temperature of the B2.8 microflare reached 16 MK. There was evidence in the smaller B1.4 flare of Fe xxiv emission, indicating that hot plasma of 15 MK can be reached.