bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectively Improve the Astaxanthin Production by Combined Additives Regulating Different Metabolic Nodes in Phaffia rhodozyma
Authors: Li Zhipeng , Yang Haoyi , Zheng Chenhua , Du Xiping , Ni Hui , He Ning , Yang Liang , You Li , Zhu Yanbing , Li Lijun
Published: January 2022

Astaxanthin is an important natural resource that is widely found in marine environments. Metabolic regulation is an effective method for improving astaxanthin production in Phaffia rhodozyma. Most studies have focused on single regulators, which have limited effects. In this study, 16 metabolic regulators were screened to improve astaxanthin production in high-yield and wild-type strains. Fluconazol and glutamic acid increased astaxanthin volumetric yield in MVP14 by 25.8 and 30.9%, respectively, while ethanol increased astaxanthin volumetric yield in DSM626, 29.3%. Furthermore, six additives that inhibit the competing pathways and promote the main pathway for astaxanthin synthesis were selected for combination treatment. We found that the optimal combination was penicillin, ethanol, triclosan, and fluconazol, which increased astaxanthin cell yield by 51%. Therefore, we suggest that simultaneously promoting the master pathways (mevalonate) and inhibiting competing pathways (fatty acid synthesis and ergosterol) is the best strategy to improve astaxanthin cell yield. Moreover, regulators of the biomass pathway should be avoided to improve cell yield. This study provides a technical basis for the utilisation of astaxanthin in P. rhodozyma.
Improvement of the Stability and Activity of an LPMO Through Rational Disulfide Bonds Design
Authors: Zhou Xiaoli , Xu Zhiqiang , Li Yueqiu , He Jia , Zhu Honghui
Published: January 2022

Lytic polysaccharide monooxygenases (LPMOs) oxidatively break down the glycosidic bonds of crystalline polysaccharides, significantly improving the saccharification efficiency of recalcitrant biomass, and have broad application prospects in industry. To meet the needs of industrial applications, enzyme engineering is needed to improve the catalytic performance of LPMOs such as enzyme activity and stability. In this study, we engineered the chitin-active CjLPMO10A from Cellvibrio japonicus through a rational disulfide bonds design. Compared with the wild-type, the variant M1 (N78C/H116C) exhibited a 3-fold increase in half-life at 60°C, a 3.5°C higher T5015, and a 7°C rise in the apparent Tm. Furthermore, the resistance of M1 to chemical denaturation was significantly improved. Most importantly, the introduction of the disulfide bond improved the thermal and chemical stability of the enzyme without causing damage to catalytic activity, and M1 showed 1.5 times the specific activity of the wild-type. Our study shows that the stability and activity of LPMOs could be improved simultaneously by selecting suitable engineering sites reasonably, thereby improving the industrial adaptability of the enzymes, which is of great significance for applications.
Comprehensive Review on the Dynamic and Seismic Behavior of Flat-Bottom Cylindrical Silos Filled With Granular Material
Authors: Mansour Sulyman , Pieraccini Luca , Palermo Michele , Foti Dora , Gasparini Giada , Trombetti Tomaso , Silvestri Stefano
Published: January 2022

The seismic design of industrial flat-bottom ground-supported silos filled with granular material still presents several challenges to be addressed. They are related to the main aspects which differentiate silo structures containing granular material from other civil structural typologies: 1) the relatively low silo structure mass as compared to the ensiled content mass; 2) the granular nature of the ensiled material. Indeed, the internal actions in the structural members are governed by the complex dynamic interactions along the interfaces between granular content and silo wall or base, or even the internal interaction between particles. More in detail, even though the scientific interest in such complex interactions dates back to the middle of the 19th century, several issues are still unclear such as the dependency of the fundamental dynamic properties (period of vibration and damping ratio) on the characteristics of the dynamic excitation (intensity, frequency content, duration) or the amount of ensiled material mass activated during a seismic excitation and provoking extra pressures on the wall (effective mass). Therefore, most of current seismic code provisions for silos are grounded on rather approximate and simplified assumptions leading to often over-conservative evaluations. The present paper intends to provide a comprehensive summary of the mainly acknowledged experimental and theoretical advances in the dynamic and seismic behavior of silos, supporting the potential researcher in the field to understand the real differences between the code assumptions and recommendations and the actual conditions, as well as illustrating the open issues to be still further investigated.
NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype
Authors: Jia Wen , Jolly Mohit Kumar , Levine Herbert
Published: January 2022

The epithelial-mesenchymal transition (EMT) is a cellular process critical for wound healing, cancer metastasis and embryonic development. Recent efforts have identified the role of hybrid epithelial/mesenchymal states, having both epithelial and mesehncymal traits, in enabling cancer metastasis and resistance to various therapies. Also, previous work has suggested that NRF2 can act as phenotypic stability factor to help stablize such hybrid states. Here, we incorporate a phenomenological epigenetic feedback effect into our previous computational model for EMT signaling. We show that this type of feedback can stabilize the hybrid state as compared to the fully mesenchymal phenotype if NRF2 can influence SNAIL at an epigenetic level, as this link makes transitions out of hybrid state more difficult. However, epigenetic regulation on other NRF2-related links do not significantly change the EMT dynamics. Finally, we considered possible cell division effects in our epigenetic regulation model, and our results indicate that the degree of epigenetic inheritance does not appear to be a critical factor for the hybrid E/M state stabilizing behavior of NRF2.
An Efficient and Sustainable Approach to Decarboxylative Cross-Coupling Using Silica Coated Magnetic Copper Nanocatalyst for the Synthesis of Internal Alkynes
Authors: Yadav Manavi , Srivastava Anju , Gaur Rashmi , Gupta Radhika , Arora Gunjan , Sharma Rakesh Kumar
Published: January 2022

A highly efficient magnetically separable copper nanocatalyst has been developed for decarboxylative cross-coupling reaction for the alkynylation of haloarenes using alkynoic acid as a reaction partner. The chemical nature, morphology, size, and magnetic properties of the prepared nanocatalyst were studied by SEM, TEM, EDS, FT-IR, VSM, and ICP techniques. Remarkably, this catalyst represents the first successful copper based heterogeneous system for this type of coupling that provides a low-cost, stable, and environmentally friendly magnetically recoverable entity that can be re-used for seven consecutive runs without appreciable loss in its catalytic performance.
Remedial Boundary Work and Gatekeeper Centrality in a Virtual Entrepreneur Community
Authors: Santana Jessica J.
Published: January 2022

Virtual communities of practice invoke novel forms of boundary work that are newly visible via publicly recorded discourse and failure narratives. This boundary work has critical implications for occupational knowledge, membership, and stratification. Building on social exchange theorization of network gatekeeping, the author tests the assumption that centralized peers are more competitive gatekeepers, in that they react more negatively to remedial narratives. The author tests this theory using empirical data from a virtual entrepreneur community on Reddit. The author finds that a peer’s tenure in the community network is directly related to exclusive, competitive boundary work of remedial members. However, by looking beyond the network structure to the content of the tie, the author finds that exclusive boundary work is not as impactful as inclusive, collaborative boundary work in this open network setting. The author builds on relational cohesion and exchange commitment theory to explain how remedial practitioners circumvent central community gatekeepers through failure narratives that provoke empathy from peripheral peers who experience higher uncertainty than core peers. Understanding these dynamics is critical to promoting recovery from failure and vitality of the community of practice.
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5
Authors: Ercan Huriye , Schrottmaier Waltraud Cornelia , Pirabe Anita , Schmuckenschlager Anna , Pereyra David , Santol Jonas , Pawelka Erich , Traugott Marianna T. , Schörgenhofer Christian , Seitz Tamara , Karolyi Mario , Yang Jae-Won , Jilma Bernd , Zoufaly Alexander , Assinger Alice , Zellner Maria
Published: January 2022

Graphical Abstract
The Role of Cardiac Magnetic Resonance in Myocardial Infarction and Non-obstructive Coronary Arteries
Authors: Liang Kate , Nakou Eleni , Del Buono Marco Giuseppe , Montone Rocco Antonio , D'Amario Domenico , Bucciarelli-Ducci Chiara
Published: January 2022

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) accounts for 5–15% of all presentations of acute myocardial infarction. The absence of obstructive coronary disease may present a diagnostic dilemma and identifying the underlying etiology ensures appropriate management improving clinical outcomes. Cardiac magnetic resonance (CMR) imaging is a valuable, non-invasive diagnostic tool that can aide clinicians to build a differential diagnosis in patients with MINOCA, as well as identifying non-ischemic etiologies of myocardial injury (acute myocarditis, Takotsubo Syndrome, and other conditions). The role of CMR in suspected MINOCA is increasingly recognized as emphasized in both European and American clinical guidelines. In this paper we review the indications for CMR, the clinical value in the differential diagnosis of patients with suspected MINOCA, as well as its current limitations and future perspectives.
Optimal PID Tuning of PLL for PV Inverter Based on Aquila Optimizer
Authors: Guo Zhengxun , Yang Bo , Han Yiming , He Tingyi , He Peng , Meng Xian , He Xin
Published: January 2022

Phase-locked loop (PLL) is a fundamental and crucial component of a photovoltaic (PV) connected inverter, which plays a significant role in high-quality grid connection by fast and precise phase detection and lock. Several novel critical structure improvements and proportional-integral (PI) parameter optimization techniques of PLL were proposed to reduce shock current and promote the quality of grid connection at present. However, the present techniques ignored the differential element of PLL and did not acquire ideal results. Thus, this paper adopts Aquila optimizer algorithm to regulate the proportional-integral-differential (PID) parameters of PLL for smoothing power fluctuation and improving grid connection quality. Three regulation strategies (i.e., PLL regulation, global regulation, and step regulation) are carefully designed to systematically and comprehensively evaluate the performance of the proposed method based on a simulation model in MATLAB/Simulink, namely, “250-kW Grid-Connected PV Array”. Simulation results indicate that PLL regulation strategy can effectively decrease power fluctuation and overshoot with a short response time, low complexity, and time cost. Particularly, the Error(P) and the maximum deviation of output power under optimal parameters obtained by PLL strategy are decreased by 418 W and 12.5 kW compared with those under initial parameters, respectively.
Series Arc Fault Identification Method Based on Multi-Feature Fusion
Authors: Gong Quanyi , Peng Ke , Wang Wei , Xu Bingyin , Zhang Xinhui , Chen Yu
Published: January 2022

With the increase of various loads connected to the low-voltage distribution system, the difficulty of identifying low-voltage series fault arcs has greatly increased, which seriously threatens the electricity safety. Aiming at such problems, a neural network algorithm based on multi-feature fusion is proposed. The fault current has the characteristics of randomness, high frequency noise, and singularity. A GA-BP neural network model is built, and the wavelet analysis method (based on singularity), Fourier transform method (based on high frequency noise), current cycle difference method (based on randomness), and current cycle similarity derivation method (based on randomness) are used for feature extraction and can more comprehensively reflect the characteristics of arc faults. Simulation results show that the multi-feature fusion algorithm has a higher recognition rate than other algorithms. Moreover, compared with the support vector machine model, logistic regression model, and AlexNet model, the GA-BP neural network model has a higher recognition accuracy than the other three models, which can reach 99%.
Soil Surface Micro-Topography by Structure-from-Motion Photogrammetry for Monitoring Density and Erosion Dynamics
Authors: Ehrhardt Annelie , Deumlich Detlef , Gerke Horst H.
Published: January 2022

Soil erosion is a major threat to soil fertility, food security and water resources. Besides a quantitative assessment of soil loss, the dynamics of erosion-affected arable soil surfaces still poses challenges regarding field methods and predictions because of scale-dependent and soil management-related complex soil-crop-atmosphere processes. The objective was to test a photogrammetric Structure-from-Motion (SfM) technique for the mm-scale mapping of the soil surface micro-topography that allows the monitoring without special equipment and with widely available cameras. The test was carried out in May 2018 on three plots of 1.5 m2 (upper-, middle-, and footslope) covering surface structural features (tractor wheel lane, seed rows) along a Maize-cultivated hillslope with a coarse-textured topsoil and a runoff monitoring station. The changes in mm-scaled surface micro-topography were derived from repeatedly photographed images of the same surface area during a 2-weeks period with two rain events. A freely available SfM-program (VisualSfM) and the QGIS software were used to generate 3D-models of the surface topography. Soil cores (100 cm3) were sampled to gravimetrically determine the topsoil bulk density. The micro-topographical changes resulting from rainfall–induced soil mass redistribution within the plots were determined from the differences in SfM maps before and after rain. The largest decrease in mean soil surface elevation and roughness was observed after rain for the middle slope plot and primarily in initially less compacted regions. The spatially-distributed intra-plot changes in soil mass at the mm-scale derived from the digital micro-topography models indicated that local depressions were filled with sediments from surrounding knolls during rainfall. The estimated mass loss determined with the SfM technique decreased, if core sample-based soil settlement was considered. The effect of changes in the soil bulk density could be described after calibration also with an empirical model suggested in the Root-Zone-Water-Quality-Model. Uncertainties in the presented plot-scale SfM-technique were due to geo-referencing and the numerical limitations in the freely available SfM-software. The photogrammetric technique provided valuable information on soil surface structure parameters such as surface roughness. The successful application of SfM with widely available cameras and freely available software might stimulate the monitoring of erosion in regions with limited accessibility.
Seasonal Variations of the Mercury Multiple Isotopic Compositions of Subrural and Urban Aerosols Highlight an Additional Atmospheric Hg0 Oxidation Pathway
Authors: AuYang David , Chen Jiubin , Zheng Wang , Lang Yunchao , Wang Yina , Wang Zhongwei , Zhang Yuanyuan , Liu Yulong , Zhang Ke , Cai Hongming , Yuan Wei , Widory David
Published: January 2022

The mechanisms triggering the large variations in the mercury (Hg) multiple isotopic compositions of atmospheric particle-bound Hg worldwide still remain unclear. The comparison of Hg isotopic compositions in aerosols collected in urban and rural areas may help distinguish the effects of natural processes from those of anthropogenic inputs. We thus investigated the Hg isotopic compositions of PM10 aerosols collected seasonally during 2015 at two monitoring stations on Montreal Island, one located downtown and the other in its westernmost subrural part, barely impacted by the city anthropogenic emissions. Our results show that, while Hg isotopic compositions present no seasonality at the urban station, possibly due to constant anthropogenic emissions, the subrural samples display clear seasonal variations, with higher Δ199Hg and Δ200Hg values (up to 0.77 and 0.12‰, respectively) during summer and close to 0‰ during the rest of the year, that cannot solely be explained by anthropogenic primary emissions. Besides, Δ200Hg measured in the subrural aerosols display a positive correlation with O3 suggesting the implication of secondary processes involving ozone. We propose that the significant summer shift in the multiple Hg isotopic compositions may reflect a transition in the corresponding Hg0 oxidation pathway, from halogens-triggered to ozone-dominated reactions. Still, this hypothesis needs to be further tested. Nevertheless, it demonstrates that Hg isotopes are effective at characterizing secondary processes that control its atmospheric budget, even at a local scale (i.e., urban vs subrural) and could thus be used to better constrain its atmospheric chemistry in various environments.
Urban Catchment-Scale Blue-Green-Gray Infrastructure Classification with Unmanned Aerial Vehicle Images and Machine Learning Algorithms
Authors: Jia Jinlin , Cui Wenhui , Liu Junguo
Published: January 2022

Green infrastructure (GI), such as green roofs, is now widely used in sustainable urban development. An accurate mapping of GI is important to provide surface parameterization for model development. However, the accuracy and precision of mapping GI is still a challenge in identifying GI at the small catchment scale. We proposed a framework for blue-green-gray infrastructure classification using machine learning algorithms and unmanned aerial vehicle (UAV) images that contained digital surface model (DSM) information. We used the campus of the Southern University of Science and Technology in Shenzhen, China, as a study case for our classification method. The UAV was a DJI Phantom 4 Multispectral, which measures the blue, green, red, red-edge, and near-infrared bands and DSM information. Six machine learning algorithms, i.e., fuzzy classifier, k-nearest neighbor classifier, Bayes classifier, classification and regression tree, support vector machine (SVM), and random forest (RF), were used to classify blue (including water), green (including green roofs, grass, trees (shrubs), bare land), and gray (including buildings, roads) infrastructure. The highest kappa coefficient was observed for RF and the lowest was observed for SVM, with coefficients of 0.807 and 0.381, respectively. We optimized the sampling method based on a chessboard grid and got the optimal sampling interval of 11.6 m to increase the classification efficiency. We also analyzed the effects of weather conditions, seasons, and different image layers, and found that images in overcast days or winter days could improve the classification accuracy. In particular, the DSM layer was crucial for distinguishing green roofs and grass, and buildings and roads. Our study demonstrates the feasibility of using UAV images in urban blue-green-gray infrastructure classification, and our infrastructure classification framework based on machine learning algorithms is effective. Our results could provide the basis for the future urban stormwater management model development and aid sustainable urban planning.
Developing a System Framework for China’s Natural Resources Balance Sheet From the Perspective of Sustainable Development
Authors: Chen Pinghua , Xu Huiru , Chen Shuiguang , Shang Yuping , Zhang Baoying , Zhao Xin
Published: January 2022

Exploring and compiling a natural resource balance sheet is of great significance for improving both natural resource and environmental management and for realizing sustainable social and economic development. Based on a literature review of previous studies, in this study, we analyzed the composition, measurement methods, and methods used to acquire data of the major elements used in a natural resource balance sheet, as well as determined that the balance formula for the sheet should comprise natural resource assets, natural resource liabilities, and the benefits of natural resources. A basic report format for the natural resource balance sheet was compiled on this basis.
Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response
Authors: Pesce Elisa , Manfrini Nicola , Cordiglieri Chiara , Santi Spartaco , Bandera Alessandra , Gobbini Andrea , Gruarin Paola , Favalli Andrea , Bombaci Mauro , Cuomo Alessandro , Collino Federica , Cricrì Giulia , Ungaro Riccardo , Lombardi Andrea , Mangioni Davide , Muscatello Antonio , Aliberti Stefano , Blasi Francesco , Gori Andrea , Abrignani Sergio , De Francesco Raffaele , Biffo Stefano , Grifantini Renata
Published: January 2022

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.
Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome
Authors: Dietz Stefanie , Schwarz Julian , Velic Ana , González-Menéndez Irene , Quintanilla-Martinez Leticia , Casadei Nicolas , Marmé Alexander , Poets Christian F. , Gille Christian , Köstlin-Gille Natascha
Published: January 2022

During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced Treg numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications.
Seagrass in a Changing Estuary, the Indian River Lagoon, Florida, United States
Authors: Morris Lori J. , Hall Lauren M. , Jacoby Charles A. , Chamberlain Robert H. , Hanisak M. Dennis , Miller Janice D. , Virnstein Robert W.
Published: January 2022

Seagrass is a major structural habitat in the Indian River Lagoon. Maps documented locations and areal extents of beds periodically since the 1940s, and surveys of fixed transects yielded changes in percent cover and depths at the end of the canopy since 1994. Areal extent increased by ∼7,000 ha from 1994 to 2009, mean percent cover within beds decreased from ∼40 to 20%, and mean percent cover standardized to maximum transect length remained near 20%. Thus, conditions supported a consistent biomass because cover decreased as areal extent increased. Between 2011 and 2019, ∼19,000 ha or ∼58% of seagrasses were lost, with offshore ends of canopies moving shoreward and shallower, and standardized mean percent cover decreased to ∼4%. These changes coincided with blooms of phytoplankton, and ≤ 27% of incident subsurface irradiance at 0.9 m was stressful. Decreases in mean percent cover per month of stress became larger when initial mean cover per transect was < 20%, which suggested that the ratio of aboveground to belowground tissues in the expanded and sparser beds led to respiratory demand that was not met by photosynthesis. Despite intermittent improvements in light penetration, widespread recovery of seagrasses has not occurred potentially due to detrimental feedbacks. For example, loss of seagrass exposed sediments to waves, and the resulting disturbance may have hampered recruitment of new shoots. The same decreases also made 58–88% of the carbon, nitrogen, and phosphorus in seagrass tissue available to other primary producers. These nutrients did not enhance growth of epiphytes, whose biomass decreased by ∼42%, but they apparently fueled blooms of phytoplankton, with mean chlorophyll-a concentrations increasing by > 900%. Such intense blooms increased shading and loss of seagrasses. Fortunately, data showed that patches of seagrasses at depths of 0.5–0.9 m persisted for 22–24 years, which suggested that this depth zone could hold the key to recovery. Nevertheless, optimistic estimates predict recovery could take 12–17 years. Such a long-term, widespread loss of a key structural habitat may generate multiple adverse effects in the system, and mitigating such effects may entail planting seagrasses to accelerate recovery.
Case Report: Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium falciparum Malaria
Authors: Louvois Marion , Simon Loïc , Pomares Christelle , Jeandel Pierre-Yves , Demonchy Elisa , Carles Michel , Delaunay Pascal , Courjon Johan
Published: January 2022

Malaria is still an endemic disease in Africa, with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described, and guidelines recommend biological monitoring until 1 month after the end of the treatment. A link with an autoimmune process is still unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only few cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. We report the case of a 42-year-old man returning from Togo. He was treated with dihydroartemisinin/piperaquine combination for uncomplicated Plasmodium falciparum malaria, with low parasitemia. Nine days after the end of the treatment, the patient developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. After excluding common causes of autoimmune hemolytic anemia, we considered that dihydroartemisinin/piperaquine treatment was involved in this side effect.
Evaluation of the Time Spent by Anesthetist on Clinical Tasks in the Operating Room
Authors: Compère Vincent , Besnier Emmanuel , Clavier Thomas , Byhet Nicolas , Lefranc Florent , Jegou Frederic , Sturzenegger Nicolas , Hardy Jean Baptiste , Dureuil Bertrand , Elie Thomas
Published: January 2022

Background

Changes in the health system in Western countries have increased the scope of the daily tasks assigned to physicians', anesthetists included. As already shown in other specialties, increased non-clinical burden reduces the clinical time spent with patients.

Methods

This was a multicenter, prospective, observational study conducted in 6 public and private hospitals in France. The primary endpoint was the evaluation by an external observer of the time spent per day (in minutes) by anesthetists on clinical tasks in the operating room. Secondary endpoints were the time spent per day (in minutes) on non-clinical organizational tasks and the number of task interruptions per hour of work.

Results

Between October 2017 and April 2018, 54 anesthetists from six hospitals (1 public university hospital, two public general hospitals and three private hospitals) were included. They were followed for 96 days corresponding to 550 hours of work. The proportion of overall clinical time was 62% (58% 95%CI [53; 63] for direct care. The proportion of organizational time was higher in public hospitals (11% in the university hospital (p < 0.001) and 4% in general hospitals (p < 0.01)) compared to private hospitals (1%). The number of task interruptions (1.5/h ± 1.4 in all hospitals) was 4 times higher in the university hospital (2.2/h ± 1.6) compared to private hospitals (0.5/h ± 0.3) (p < 0.05).

Conclusions

Most time in the operating room was spent on clinical care with a significant contrast between public and private hospitals for organizational time.
Association Between Hormone Replacement Therapy and Development of Endometrial Cancer: Results From a Prospective US Cohort Study
Authors: Liang Ying , Jiao Haoyan , Qu Lingbo , Liu Hao
Published: January 2022

Although hormone replacement therapy (HRT) use is associated with elevated endometrial cancer(EC) risk, little evidence assesses potential effect-modifiers on HRT-related EC in a long-term follow-up. In this large-scale longitudinal cohort study, we tried to evaluate the association between different HRT types/methods use and risk of EC, and reveal this risk within different body mass index (BMI) groups. In whole cohort, 677 EC occurred during mean 11.6 years follow-up. Cox proportional hazards regression was used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs) with HRT status (never, former, or current) for risk of EC incidence. Current HRT use was not significantly associated with EC risk (HR for current vs. never HRT use: 1.13; 95% CI: 0.92, 1.38) in the whole cohort, but presented a dose-response effect on increased EC risk (HR for >10-year use vs. never HRT use: 1.73; 95% CI: 1.35, 2.21). Moreover, EC risk differed in distinct regimens or subsets (all Pinteraction < 0.05). Estrogen-only use was associated with elevated EC risk (HR for current vs. never HRT use: 1.51; 95% CI: 1.12, 2.04), but women with high BMI (> 30 kg/m2) who currently use estrogen-only harbored decreased EC risk (HR: 0.56; 95% CI: 0.38, 0.82) compared to counterparts without HRT use. Estrogen-only use is associated with increased EC risk, and precise monitoring of EC development for postmenopausal women with long-term HRT use are urgently needed. BMI could serve as an important surrogate to assess this risk.
Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
Authors: Greenlee John E. , Carlson Noel G. , Abbatemarco Justin R. , Herdlevær Ida , Clardy Stacey L. , Vedeler Christian A.
Published: January 2022

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.
A High Neutrophil-to-Lymphocyte Ratio Predicts Higher Risk of Poststroke Cognitive Impairment: Development and Validation of a Clinical Prediction Model
Authors: Zha Fei , Zhao Jingjing , Chen Cheng , Ji Xiaoqi , Li Meng , Wu Yinyin , Yao Li
Published: January 2022

Objective

Poststroke cognitive impairment (PSCI) is a serious complication of stroke. The neutrophil-to-lymphocyte ratio (NLR) is a marker of peripheral inflammation. The relationship between the NLR and PSCI is far from well studied, and the thesis of this study was to assess the predictive value of the NLR in patients with PSCI, and establish and verify the corresponding prediction model based on this relationship.

Methods

A total of 367 stroke patients were included in this study. Neutrophils, lymphocytes, and NLRs were measured at baseline, and clinical and neuropsychological assessments were conducted 3 months after stroke. The National Institutes of Health Scale (NIHSS) was used to assess the severity of stroke. A Chinese version of the Mini Mental State Examination (MMSE) was used for the assessment of cognitive function.

Results

After three months of follow-up, 87 (23.7%) patients were diagnosed with PSCI. The NLR was significantly higher in PSCI patients than in non-PSCI patients (P < 0.001). Patient age, sex, body mass index, NIHSS scores, and high-density lipoprotein levels also differed in the univariate analysis. In the logistic regression analysis, the NLR was an independent risk factor associated with the patients with PSCI after adjustment for potential confounders (OR = 1.67, 95%CI: 1.21–2.29, P = 0.002). The nomogram based on patient sex, age, NIHSS score, and NLR had good predictive power with an AUC of 0.807. In the validation group, the AUC was 0.816.

Conclusion

An increased NLR at admission is associated with PSCI, and the model built with NLR as one of the predictors can increase prognostic information for the early detection of PSCI.
Estimating Risk of Multiple Sclerosis Disease Reactivation in Pregnancy and Postpartum: The VIPRiMS Score
Authors: Bsteh Gabriel , Hegen Harald , Riedl Katharina , Altmann Patrick , Di Pauli Franziska , Ehling Rainer , Zulehner Gudrun , Rommer Paulus , Leutmezer Fritz , Deisenhammer Florian , Berger Thomas
Published: January 2022

Background:

Evidence guiding personalized decision-making with respect to disease-modifying therapy (DMT) around pregnancy in relapsing multiple sclerosis (RMS) is lacking.

Objective:

To generate and validate a risk score for disease reactivation intrapartum and postpartum in RMS.

Methods:

From the Vienna Innsbruck MS database (VIMSD), we included 343 pregnancies in patients with RMS. Primary endpoint was disease reactivation. Patients were randomly assigned 2:1 in a generation and validation dataset. A predictive score was calculated using the Cox regression and validated.

Results:

In the generation dataset, occurrence of relapse and type of DMT in the year before conception, DMT washout duration, the Expanded Disability Status Scale (EDSS) at conception, and time until DMT restart postpartum were identified as independent predictors of disease reactivation (p < 0.001). The resulting 10-point risk score robustly predicted reactivation (explaining 75% of variance, p < 0.001) identifying patients at high [≥6 points; mean risk 65%; range 50–100%; hazard ratio (HR) 14.5], intermediate (3–5 points; mean risk 24%; range 15–35%; HR 4.3), and low risk (≤2 points; mean risk 6%; range 0–8%) of disease reactivation in pregnancy and up to 6 months postpartum.

Conclusion:

The composite Vienna Innsbruck Pregnancy Risk in Multiple Sclerosis (VIPRiMS) score is a valuable clinical tool to support patients and neurologists in anticipating risk and, thus, individualizing treatment decision-making around pregnancy.
In-Depth Characterization of Somatic and Orofacial Sensitive Dysfunctions and Interfering-Symptoms in a Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mouse Model
Authors: Démosthènes Amélie , Sion Benoît , Giraudet Fabrice , Moisset Xavier , Daulhac Laurence , Eschalier Alain , Bégou Mélina
Published: January 2022

Among the many symptoms (motor, sensory, and cognitive) associated with multiple sclerosis (MS), chronic pain is a common disabling condition. In particular, neuropathic pain symptoms are very prevalent and debilitating, even in early stages of the disease. Unfortunately, chronic pain still lacks efficient therapeutic agents. Progress is needed (i) clinically by better characterizing pain symptoms in MS and understanding the underlying mechanisms, and (ii) preclinically by developing a more closely dedicated model to identify new therapeutic targets and evaluate new drugs. In this setting, new variants of experimental autoimmune encephalomyelitis (EAE) are currently developed in mice to exhibit less severe motor impairments, thereby avoiding confounding factors in assessing pain behaviors over the disease course. Among these, the optimized relapsing-remitting EAE (QuilA-EAE) mouse model, induced using myelin oligodendrocyte glycoprotein peptide fragment (35–55), pertussis toxin, and quillaja bark saponin, seems very promising. Our study sought (i) to better define sensitive dysfunctions and (ii) to extend behavioral characterization to interfering symptoms often associated with pain during MS, such as mood disturbances, fatigue, and cognitive impairment, in this optimized QuilA-EAE model. We made an in-depth characterization of this optimized QuilA-EAE model, describing for the first time somatic thermal hyperalgesia associated with mechanical and cold allodynia. Evaluation of orofacial pain sensitivity showed no mechanical or thermal allodynia. Detailed evaluation of motor behaviors highlighted slight defects in fine motor coordination in the QuilA-EAE mice but without impact on pain evaluation. Finally, no anxiety-related or cognitive impairment was observed during the peak of sensitive symptoms. Pharmacologically, as previously described, we found that pregabalin, a treatment commonly used in neuropathic pain patients, induced an analgesic effect on mechanical allodynia. In addition, we showed an anti-hyperalgesic thermal effect on this model. Our results demonstrate that this QuilA-EAE model is clearly of interest for studying pain symptom development and so could be used to identify and evaluate new therapeutic targets. The presence of interfering symptoms still needs to be further characterized.
Rhythm and Music-Based Interventions in Motor Rehabilitation: Current Evidence and Future Perspectives
Authors: Braun Janzen Thenille , Koshimori Yuko , Richard Nicole M. , Thaut Michael H.
Published: January 2022

Research in basic and clinical neuroscience of music conducted over the past decades has begun to uncover music’s high potential as a tool for rehabilitation. Advances in our understanding of how music engages parallel brain networks underpinning sensory and motor processes, arousal, reward, and affective regulation, have laid a sound neuroscientific foundation for the development of theory-driven music interventions that have been systematically tested in clinical settings. Of particular significance in the context of motor rehabilitation is the notion that musical rhythms can entrain movement patterns in patients with movement-related disorders, serving as a continuous time reference that can help regulate movement timing and pace. To date, a significant number of clinical and experimental studies have tested the application of rhythm- and music-based interventions to improve motor functions following central nervous injury and/or degeneration. The goal of this review is to appraise the current state of knowledge on the effectiveness of music and rhythm to modulate movement spatiotemporal patterns and restore motor function. By organizing and providing a critical appraisal of a large body of research, we hope to provide a revised framework for future research on the effectiveness of rhythm- and music-based interventions to restore and (re)train motor function.
Impending Mental Health Issues During Coronavirus Disease 2019 – Time for Personalized Nutrition Based on the Gut Microbiota to Tide Over the Crisis?
Authors: Dhar Debojyoti
Published: January 2022

Coronavirus disease 2019 (COVID-19) is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our mental health as well. The uncertain future, fear of job loss, lockdown and negative news all around have taken a heavy toll on the mental health of individuals from across the world. Stress and anxiety can affect the COVID-19 patients even more. Recent study suggests COVID-19 infection may lead to post-traumatic stress disorder (PTSD). Certain prebiotics and probiotics have been shown to have anxiolytic effect through gut microbiota modulation. Incidentally, preliminary report also suggests a differential microbial profile in COVID-19 patients as compared to healthy individuals. Gut microbiota’s role in anxiety and depression is well studied. The importance of the “gut-brain” axis has been implicated in overall mental health. It is known that diet, environmental factors and genetics play an important role in shaping gut microbiota. Trials may be initiated to study if personalized diet and supplementation based on individual’s gut microbiome profile may improve the general mental well-being of people prone to anxiety during this pandemic. Also, COVID-19 patients may be provided personalized nutritional therapy based on their gut microbiota profile to see if PTSD and anxiety symptoms can be alleviated.
Effects of Vitamin D and K on Interleukin-6 in COVID-19
Authors: Visser Margot P. J. , Dofferhoff Anton S. M. , van den Ouweland Jody M. W. , van Daal Henny , Kramers Cornelis , Schurgers Leon J. , Janssen Rob , Walk Jona
Published: January 2022

Background

Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.

Methods

We assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.

Results

Comparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.

Conclusions

Dp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.
Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease
Authors: Zambon Azevedo Vittoria , Silaghi Cristina Alina , Maurel Thomas , Silaghi Horatiu , Ratziu Vlad , Pais Raluca
Published: January 2022

An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the “sarcopenic NAFLD phenotype.” This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.