bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative mass spectrometry imaging of drugs and metabolites: a multiplatform comparison
Authors: Lamont Lieke , Hadavi Darya , Viehmann Brent , Flinders Bryn , Heeren Ron M. A. , Vreeken Rob J. , Porta Siegel Tiffany 
Published: March 2021

AbstractMass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 μg/g tissue, R2 0.97 and 0.98 linearity, relative standard deviation QC <13.6%, and 97–112% accuracy. Other MS modes resulted in LOD 6.7–569.4 and 2.6–119.1 μg/g tissue, R2 0.86–0.98 and 0.86–0.98 linearity, relative standard deviation QC < 19.4 and < 37.5%, and 70–356% and 64–398% accuracy for drug candidates A and B, respectively. In addition, we propose an optimized 3D printed mimetic tissue model to increase the overall analytical throughput of our approach for large animal studies. The MRM imaging platform was applied as proof-of-principle for quantitative detection of drug candidates A and B in four dog livers and compared to LC-MS. The Q-MSI concentrations differed <3.5 times with the concentrations observed by LC-MS. Our presented MRM-based Q-MSI approach provides a more selective and high-throughput analytical platform due to MRM specificity combined with an optimized 3D printed mimetic tissue model.
Graphical abstract
Impact of exogenous maltogenic α-amylase and maltotetraogenic amylase on sugar release in wheat bread
Authors: Rebholz Gerold Felix , Sebald Karin , Dirndorfer Sebastian , Dawid Corinna , Hofmann Thomas , Scherf Katharina Anne 
Published: March 2021

AbstractThe use of exogenous maltogenic α-amylases or maltotetraogenic amylases of bacterial origin is common in wheat bread production, mainly as antistaling agents to retard crumb firming. To study the impact of maltogenic α-amylase and maltotetraogenic amylase on straight dough wheat bread, we performed a discovery-driven proteomics approach with commercial enzyme preparations and identified the maltotetraogenic amylase P22963 from Pelomonas saccharophila and the maltogenic α-amylase P19531 from Geobacillus stearothermophilus, respectively, as being responsible for the amylolytic activity. Quantitation of mono-, di- and oligosaccharides and residual amylase activity in bread crumb during storage for up to 96 h clarified the different effects of residual amylase activity on the sugar composition. Compared to the control, the application of maltogenic α-amylase led to an increased content of maltose and especially higher maltooligosaccharides during storage. Residual amylase activity was detectable in the breads containing maltogenic α-amylase, whereas maltotetraogenic amylase only had a very low residual activity. Despite the residual amylase activities and changes in sugar composition detected in bread crumb, our results do not allow a definite evaluation of a potential technological function in the final product. Rather, our study contributes to a fundamental understanding of the relation between the specific amylases applied, their residual activity and the resulting changes in the saccharide composition of wheat bread during storage.
Complete integrability of the Benjamin–Ono equation on the multi-soliton manifolds
Authors: Sun Ruoci 
Published: March 2021

AbstractThis paper is dedicated to proving the complete integrability of the Benjamin–Ono (BO) equation on the line when restricted to everyN-soliton manifold, denoted by$$\mathcal {U}_N$$UN. We construct generalized action–angle coordinates which establish a real analytic symplectomorphism from$$\mathcal {U}_N$$UNonto some open convex subset of$${\mathbb {R}}^{2N}$$R2Nand allow to solve the equation by quadrature for any such initial datum. As a consequence,$$\mathcal {U}_N$$UNis the universal covering of the manifold ofN-gap potentials for the BO equation on the torus as described by Gérard–Kappeler (Commun Pure Appl Math, 2020.10.1002/cpa.21896.arXiv:1905.01849). The global well-posedness of the BO equation on$$\mathcal {U}_N$$UNis given by a polynomial characterization and a spectral characterization of the manifold$$\mathcal {U}_N$$UN. Besides the spectral analysis of the Lax operator of the BO equation and the shift semigroup acting on some Hardy spaces, the construction of such coordinates also relies on the use of a generating functional, which encodes the entire BO hierarchy. The inverse spectral formula of anN-soliton provides a spectral connection between the Lax operator and the infinitesimal generator of the very shift semigroup.
A quantitative approach for measuring laterality in clinical fMRI for preoperative language mapping
Authors: Olaru Maria , Nillo Ryan M. , Mukherjee Pratik , Sugrue Leo P. 
Published: March 2021

Abstract
Purpose
fMRI is increasingly used for presurgical language mapping, but lack of standard methodology has made it difficult to combine/compare data across institutions or determine the relative efficacy of different approaches. Here, we describe a quantitative analytic framework for determining language laterality in clinical fMRI that addresses these concerns.

Methods
We retrospectively analyzed fMRI data from 59 patients who underwent presurgical language mapping at our institution with identical imaging and behavioral protocols. First, we compared the efficacy of different regional masks in capturing language activations. Then, we systematically explored how laterality indices (LIs) computed from these masks vary as a function of task and activation threshold. Finally, we determined the percentile threshold that maximized the correlation between the results of our LI approach and the laterality assessments from the original clinical radiology reports.

Results
First, we found that a regional mask derived from a meta-analysis of the fMRI literature better captured language task activations than masks based on anatomically defined language areas. Then, we showed that an LI approach based on this functional mask and percentile thresholding of subject activation can quantify the relative ability of different language tasks to lateralize language function at the population level. Finally, we determined that the 92nd percentile of subject-level activation provides the optimal LI threshold with which to reproduce the original clinical reports.

Conclusion
A quantitative framework for determining language laterality that uses a functionally-derived language mask and percentile thresholding of subject activation can combine/compare results across tasks and patients and reproduce clinical assessments of language laterality.
Are Surgeons Working Smarter or Harder? A Systematic Review Comparing the Physical and Mental Demands of Robotic and Laparoscopic or Open Surgery
Authors: Park Laura Seohyun , Pan Feiyang , Steffens Daniel , Young Jane , Hong Jonathan 
Published: March 2021

AbstractBackgroundMinimally invasive surgical techniques such as robotic surgical platforms have provided favourable outcomes for patients, but the impact on surgeons is not well described. This systematic review aims to synthesize and evaluate the physical and mental impact of robotic surgery on surgeons compared to standard laparoscopic or open surgery.MethodsA search strategy was developed to identify peer‐reviewed English articles published from inception to end of December 2019 on the following databases: MEDLINE, PubMed, PsycINFO and Embase. The articles were assessed using a modified Newcastle–Ottawa tool.ResultsOf the 6563 papers identified, 30 studies were included in the qualitative synthesis of this review. Most of the included studies presented a high risk of bias. A total of 13 and 21 different physical and mental tools, respectively, were used to examine the impact on surgeons. The most common tool used to measure physical and mental demand were surface electromyography (N = 9) and the NASA Task Load Index (NASA‐TLX; N = 8), respectively. Majority of studies showed mixed results for physical (N = 10) and mental impact (N = 7). This was followed by eight and six studies favouring RS over other surgical modalities for physical and mental impact, respectively.ConclusionMost studies showed mixed physical and mental outcomes between the three surgical modalities. There was a high risk of bias and methodological heterogeneity. Future studies need to correlate mental and physical stress with long‐term impact on the surgeons.
Application of Real‐Time Augmented Reality Laparoscopic Navigation in Splenectomy for Massive Splenomegaly
Authors: Tao Hai‐Su , Lin Jin‐Yu , Luo Wang , Chen Rui , Zhu Wen , Fang Chi‐Hua , Yang Jian 
Published: March 2021

AbstractObjectivesTo evaluate the clinical impact and technical feasibility of augmented reality laparoscopic navigation (ARLN) system in laparoscopic splenectomy for massive splenomegaly.MethodsThe clinical data of 17 consecutive patients who underwent laparoscopic splenectomy using ARLN (ARLN group) and 26 patients without ARLN guidance (Non‐ARLN group) between January 2018 and April 2020 were enrolled. Propensity score matching (PSM) analysis was performed between the patients with and without ARLN guidance at a ratio of 1:1.ResultsMean intraoperative blood loss was significantly lower in the ARLN‐group than in the Non‐ARLN group (306.6 ml vs. 462.6 ml, p = 0.047). All the patients in the ARLN‐group achieved successful splenic artery dissection, while surgical success was achieved in 12 patients in the Non‐ARLN group (p = 0.044). Postoperative hospital stay was significantly longer in the Non‐ARLN group (3.8 days vs. 4.5 days, p = 0.040).ConclusionsARLN can provide feasible and accurate intraoperative image guidance, and it could be helpful in the performance of laparoscopic splenectomy for massive splenomegaly.
Cytokines as therapeutic targets for cardio- and cerebrovascular diseases
Authors: Liberale Luca , Ministrini Stefano , Carbone Federico , Camici Giovanni G. , Montecucco Fabrizio 
Published: March 2021

AbstractDespite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.
Early germline differentiation in bivalves: TDRD7 as a candidate investigational unit for Ruditapes philippinarum germ granule assembly
Authors: Filanti Beatrice , Piccinini Giovanni , Bettini Simone , Lazzari Maurizio , Franceschini Valeria , Maurizii Maria Gabriella , Milani Liliana 
Published: March 2021

AbstractThe germline is a key feature of sexual animals and the ways in which it separates from the soma differ widely across Metazoa. However, at least at some point during germline differentiation, some cytoplasmic supramolecular structures (collectively called germ plasm-related structures) are present and involved in its specification and/or differentiation. The factors involved in the assembly of these granular structures are various and non-ubiquitous among animals, even if some functional patterns and the presence of certain domains appear to be shared among some. For instance, the LOTUS domain is shared by Oskar, the Holometabola germ plasm master regulator, and some Tudor-family proteins assessed as being involved in the proper assembly of germ granules of different animals. Here, we looked for the presence of LOTUS-containing proteins in the transcriptome of Ruditapes philippinarum (Bivalvia). Such species is of particular interest because it displays annual renewal of gonads, sided by the renewal of germline differentiation pathways. Moreover, previous works have identified in its early germ cells cytoplasmic granules containing germline determinants. We selected the orthologue of TDRD7 as a candidate involved in the early steps of germline differentiation through bioinformatic predictions and immunohistological patterning (immunohistochemistry and immunofluorescence). We observed the expression of the protein in putative precursors of germline cells, upstream to the germline marker Vasa. This, added to the fact that orthologues of this protein are involved in the assembly of germ granules in mouse, zebrafish, and fly, makes it a worthy study unit for investigations on the formation of such structures in bivalves.
A single nucleotide substitution in the coding region of Ogura male sterile gene, orf138, determines effectiveness of a fertility restorer gene, Rfo, in radish
Authors: Yamagishi Hiroshi , Jikuya Megumi , Okushiro Kanako , Hashimoto Ayako , Fukunaga Asumi , Takenaka Mizuki , Terachi Toru 
Published: March 2021

AbstractCytoplasmic male sterility (CMS) observed in many plants leads defect in the production of functional pollen, while the expression of CMS is suppressed by a fertility restorer gene in the nuclear genome. Ogura CMS of radish is induced by a mitochondrial orf138, and a fertility restorer gene, Rfo, encodes a P-type PPR protein, ORF687, acting at the translational level. But, the exact function of ORF687 is still unclear. We found a Japanese variety showing male sterility even in the presence of Rfo. We examined the pollen fertility, Rfo expression, and orf138 mRNA in progenies of this variety. The progeny with Type H orf138 and Rfo showed male sterility when their orf138 mRNA was unprocessed within the coding region. By contrast, all progeny with Type A orf138 were fertile though orf138 mRNA remained unprocessed in the coding region, demonstrating that ORF687 functions on Type A but not on Type H. In silico analysis suggested a specific binding site of ORF687 in the coding region, not the 5′ untranslated region estimated previously, of Type A. A single nucleotide substitution in the putative binding site diminishes affinity of ORF687 in Type H and is most likely the cause of the ineffectiveness of ORF687. Furthermore, fertility restoration by RNA processing at a novel site in some progeny plants indicated a new and the third fertility restorer gene, Rfs, for orf138. This study clarified that direct ORF687 binding to the coding region of orf138 is essential for fertility restoration by Rfo.
Evaluation on the Effect of Pressure Transients on Rock Joints in Unlined Hydropower Tunnels Using Numerical Simulation
Authors: Neupane Bibek , Panthi Krishna Kanta 
Published: March 2021

AbstractFrequent pressure transients are identified as the cause of block failures in many unlined hydropower tunnels. The primary design objective of such tunnels is to prevent hydraulic jacking at design static pressure and mass oscillation but neglects the effect of short transients, i.e., water hammer. The issue has not been studied from the perspective of hydro-mechanical interactions due to frequent pore pressure changes in the rock mass. This article mainly focuses on the effect of pressure transients at different static heads, or different effective normal stresses across the joints and the effect of time period of pressure transient. Further, the change in such behaviour due to different mechanical properties of rock joints, such as stiffness, friction angle and dilation, is investigated. Numerical simulations of observed pore pressure response in the rock mass during a pressure transient are carried out using distinct element code 3DEC. The results show that relative joint deformation due to short pressure transients are the highest when joint normal stresses are 1.5–2.5 times higher than static water pressure in the tunnel and thus the vulnerability to weakening of such joints by hydraulic fatigue is higher. Further, results show that water hammers can travel up to 4 m into the rock mass even in stiff joint conditions and sufficiently high normal stresses. Results further indicate that the hydraulic impact due to water hammer is smaller as compared to mass oscillation. It is concluded that water hammers, wherever applicable along the waterway, can still contribute to hydraulic fatigue of rock joints in addition to the effect of mass oscillation and cannot be neglected when pressure transients occur frequently. Tunnel filling/dewatering and mass oscillations cause macroscopic joint displacements or block movements over long-term operation which is the major cause of block falls in unlined pressure tunnels.
RETRACTED ARTICLE: Forecasting major impacts of COVID-19 pandemic on country-driven sectors: challenges, lessons, and future roadmap
Authors: Kumar Saket , Viral Rajkumar , Deep Vikas , Sharma Purushottam , Kumar Manoj , Mahmud Mufti , Stephan Thompson 
Published: March 2021

AbstractThe pandemic caused by the coronavirus disease 2019 (COVID-19) has produced a global health calamity that has a profound impact on the way of perceiving the world and everyday lives. This has appeared as the greatest threat of the time for the entire world in terms of its impact on human mortality rate and many other societal fronts or driving forces whose estimations are yet to be known. Therefore, this study focuses on the most crucial sectors that are severely impacted due to the COVID-19 pandemic, in particular reference to India. Considered based on their direct link to a country’s overall economy, these sectors include economic and financial, educational, healthcare, industrial, power and energy, oil market, employment, and environment. Based on available data about the pandemic and the above-mentioned sectors, as well as forecasted data about COVID-19 spreading, four inclusive mathematical models, namely—exponential smoothing, linear regression, Holt, and Winters, are used to analyse the gravity of the impacts due to this COVID-19 outbreak which is also graphically visualized. All the models are tested using data such as COVID-19 infection rate, number of daily cases and deaths, GDP of India, and unemployment. Comparing the obtained results, the best prediction model is presented. This study aims to evaluate the impact of this pandemic on country-driven sectors and recommends some strategies to lessen these impacts on a country’s economy.
The impact of school closure and social isolation on children in vulnerable families during COVID-19: a focus on children’s reactions
Authors: Larsen Linda , Helland Maren Sand , Holt Tonje 
Published: March 2021

AbstractFor children the consequences of the COVID-19 public health measures may have long-term effects into adulthood. By exploring children’s reactions more broadly, we are better placed to understanding the breadth of implications of home school and social isolation under COVID-19. The present study explored how COVID-19 related variables, namely, home school experience, child perceived family stress and instability, screen time use, missing friends and worry about virus infection are associated with children’s emotional, somatic/cognitive and worry reactions, respectively. A total of 442 children (M = 11.43 years, SD = 2.59) from the longitudinal FamilieForSK-study participated and a series of hierarchical linear regression models were applied controlling for background variables including children’s psychological vulnerability. Results showed significant associations between all COVID-19 related predictors, except screen time use, and the three outcomes. Family stress and instability had the strongest effects with standardised betas ranging from .356 to .555 and collectively, predictors explained between 20.7 and 44.1% of variance in outcomes. Furthermore, several associations were moderated by age and older children were more negatively impacted (i.e., higher level of reported reactions). The present study provides more conclusive evidence of the effects of home school and social isolation under COVID-19 on children. It also exemplifies the importance of focusing on children’s reactions more broadly, as there was evidence that children on average had fewer emotional reactions compared to before the pandemic.
Simulative investigation of wind turbine gearbox loads during power converter fault
Authors: Röder Julian , Jacobs Georg , Duda Tobias , Bosse Dennis , Herzog Fabian 
Published: March 2021

AbstractThree phase short circuit power converter faults in wind turbines (WT) result in highly dynamic generator torque reversals, which lead to load reversals within the drivetrain. Dynamic load reversals in combination with changing rotational speeds are, for example, critical for smearing within roller bearings. Therefore, an investigation of the correlation between three phase short circuit converter faults and drivetrain component failures is necessary.Due to the risk of damage and the resulting costs, it is not economically feasible to extensively investigate three phase short circuit converter faults on test benches. Valid WT drivetrain models can be used instead. A WT drivetrain model, which has been developed and validated in a national project at the CWD, is used and a three phase short circuit converter fault is implemented. In this paper, the resulting torque load on the drivetrain for a three phase short circuit converter fault in rated power production is presented. This converter fault leads to a highly dynamic reversing electromagnetic torque which exceeds the rated torque by a factor of three. As a result the load on the rotor side high speed shaft (HSS) bearing oscillates and increases by around 15 per cent compared to rated power production. Simultaneously the rotational velocity of the HSS oscillates with an amplitude of 10 rpm. Therefore an increase in the risk of smearing is expected.