bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparins enhance C1 esterase inhibitor activity: a promising remedy for acute hereditary angioedema
Authors: Zhou Yingyan , Majluf-Cruz Abraham , Dennis Jaclyn , Woroch Eric , Hor Lilian , Hellbusch Brandon , Archuleta Erin , Fornis Lorelenn , Garcia Cindy , Aerts Shanae L. , Bai Xiyuan , Bevers Shaun , Schmidt Eric P. , Bates Melanie , Fugit Randolph V. , Nieto-Martinez Sandra , Galvan Manuel , Giclas Patricia , Frazer-Abel Ashley , Chan Edward D. 
Published: February 2022

ABSTRACTRationaleHereditary angioedema (HAE) is a potentially life-threatening illness most commonly due to deficiency or dysfunction of C1-esterase inhibitor (C1-INH). While specific treatments are available to thwart acute exacerbations, they are extremely costly and some can be associated with rare but serious side effects. The heparins are long known to augment C1-INH activity and case reports / series have documented their efficacy in treating HAE.Objectiveto determine if unfractionated heparin and two low-molecular weight heparins (enoxaparin and nadroparin) can augment C1-INH activityex vivoin the sera of patients with HAE and in anin vitrobiochemical assay.MethodsC1-INH activity in the absence or presence of the heparin formulations were analyzed by two different methods. To measure C1-INH activityex vivo, a commercially available assay was utilized with patient sera, excess amounts of C1s, and a substrate of C1s which, upon cleavage by C1s, produces a chromogenic product. To determine biochemically the C1-INH activityin vitro, a pharmacologic grade C1-INH, recombinant C1s (C1s-CCP12SP), and a peptide substrate of C1s were employed. Microscale thermophoresis was used to determine whether C1-INH binds to heparin.Main resultsin patient sera, nadroparin was superior to enoxaparin and unfractionated heparin in augmenting C1-INH activity, followed by enoxaparin and then unfractionated heparin. In thein vitrobiochemical assay, all three heparins augmented C1-INH-C1s binding linearly in a dose-dependent fashion. Microscale thermophoresis assay demonstrated that nadroparin binds to C1-INH, providing a mechanism by which heparin facilitates the interaction between C1-INH and the proteases known to produce bradykinin, the mediator of HAE.Conclusionlow-molecular weight heparin augments C1-INH activity and should be studied as a potential treatment for acute HAE.
Modulating neutrophils leads to changes in CNS output
Authors: Coulibaly A.P. , Salken I. , Provencio J.J. 
Published: February 2022

AbstractIt has become increasingly evident that immune cells play a role in modulating brain function. Neutrophils are the most abundant innate immune cell in mammals. Until recently, our understanding of the physiological role of these cells was limited to infection and cancer. Recently, it has emerged that neutrophils play critical roles in modulating tissue health and physiology. There has been evidence that neutrophils populate the rodent meninges. As such, we hypothesized that like other meningeal immune cells, neutrophils play a neuromodulatory role. Using a depletion paradigm, anti-Ly6G antibody injection, we demonstrate that the loss of neutrophils leads to changes in cognitive flexibility and social interactions in mice. Furthermore, the depletion paradigm led to a 50% decrease in the number of neutrophils in the meninges, which in turn led to the proliferation of resident immature neutrophils within the meninges. Finally, our data show that this immature population reenters the cell cycle only in response to specific physiological stimuli (neutrophil depletion, and stress). In conclusion, this study demonstrates that there are resident neutrophils within the meninges and that elucidating their function in the nervous system will deepen our understanding of immune regulation of brain function.
Spatially Resolved and Highly Complexed Protein and RNA in situ Detection by Combining CODEX with RNAscope In Situ Hybridization
Authors: Cheng Yilun , Burrack Rachel M. , Li Qingsheng 
Published: February 2022

ABSTRACTHighly multiplexed protein and RNA in situ concurrent detection on a single tissue section is highly desirable for both basic and applied biomedical research. CODEX is a new and powerful platform to visualize up to 60 protein biomarkers in situ and RNAscope in situ hybridization (RNAscope) is a novel RNA detection system with single-copy sensitivity and unprecedent specificity at a single cell level. Nevertheless, to our knowledge, the combination CODEX and RNAscope remained unreported until this study. Here we report a simple and reproducible combination of CODEX and RNAscope (Comb-CODEX-RNAscope). We also determined the cross-reactivities of CODEX anti-human antibodies to rhesus macaques, a widely used animal model of human disease.
Inactivation of Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse
Authors: Li Yuanyuan , Xu Wenyan , Makova Svetlana , Brueckner Martina , Sun Zhaoxia 
Published: February 2022

ABSTRACTBackgroundNephronophthisis (NPHP) is a ciliopathy characterized by renal fibrosis and cyst formation, and accounts for a significant portion of end stage renal disease in children and young adults. Currently no targeted therapy is available for this disease. NPHP2 is one of the 25 NPHP genes identified to date. In mouse, global knockout of Nphp2 leads to renal fibrosis and cysts. However, the precise contribution of different cell types and the relationship between epithelial cysts and interstitial fibrosis remains undefined.MethodsHere, we generated cell-type specific knockout mouse models of Nphp2 and characterized kidney morphology and phenotype. We additionally investigated the impact of removing cilia via deletion of the cilia biogenesis gene Ift88 on phenotype severity in Nphp2 mutants.ResultsEpithelial specific knockout of Nphp2 in Nphp2flox/flox; Ksp-Cre mutant mice resulted in renal cyst formation and severe fibrosis, while Nphp2flox/flox; Foxd1-Cre mice, where Nphp2 is deleted in stromal cells, displayed no observable phenotypes. Further, myofibroblast activation occurred early during disease progression and preceded detectable cyst formation in the Nphp2flox/flox; Ksp-Cre kidney. Moreover, concomitant removal of cilia partially suppressed the phenotypes of the Nphp2flox/flox; Ksp-Cre mutant kidney, supporting a significant role of cilia in Nphp2 function in vivo.ConclusionsOur results highlight the critical role of renal epithelial cilia and epithelial-stromal communication in NPHP.Significance statementNephronophthisis (NPHP) is a ciliopathy characterized by interstitial fibrosis and epithelial cysts in the kidney. A significant portion of end stage renal disease occurring before age 30 results from NPHP. However, the molecular etiology of NPHP remains to be elucidated. By generating and analyzing tissue specific knockout mouse models of Nphp2/Inversin, authors pinpoint defective epithelial cells as the driver for both epithelial cysts and interstitial fibrosis. Moreover, the profibrotic response is triggered before cyst formation in the epithelial-specific Nphp2 knockout model. Mechanistically, authors provide evidence that Nphp2 may function to inhibit a cilia-dependent pro-fibrotic and pro-cystic pathway.
Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment
Authors: Kumar Suresh , Karuppanan Kalimuthu , Subramaniam Gunasekaran 
Published: February 2022

ABSTRACTThe Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron’s receptor-binding domain and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterising, in the receptor-binding domain (RBD), we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and electronegative human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild type. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N and Y505H.
Phosphorylation by casein kinase 2 ensures ER-phagy receptor TEX264 binding to ATG8 proteins
Authors: Chino Haruka , Yamasaki Akinori , Ode Koji L , Ueda Hiroki R , Noda Nobuo N , Mizushima Noboru 
Published: February 2022

AbstractSelective autophagy cargos are recruited to autophagosomes primarily by interacting with autophagosomal ATG8 family proteins via the LC3-interacting region (LIR). The upstream sequence of most LIRs contains negatively charged residues such as Asp, Glu, and phosphorylated Ser and Thr. However, the significance of LIR phosphorylation (compared with having acidic amino acids) and the structural basis of phosphorylated LIR–ATG8 binding are not entirely understood. Here, we show that the serine residues upstream of the core LIR of the endoplasmic reticulum (ER)-phagy receptor TEX264 are phosphorylated by casein kinase 2, which is critical for its interaction with ATG8s, autophagosomal localization, and ER-phagy. Structural analysis showed that phosphorylation of these serine residues increased binding affinity by producing multiple hydrogen bonds with ATG8s that cannot be mimicked by acidic residues. This binding mode is different from those of other ER-phagy receptors that utilize a downstream helix, which is absent from TEX264, to increase affinity. These results suggest that phosphorylation of the LIR is critically important for strong LIR–ATG8 interactions, even in the absence of auxiliary interactions.
Bird-strike damage analysis of composite panels with different stiffeners
Authors: Zhang Yile , Zhou Yadong , Sun Youchao 
Published: February 2022

Purpose
The purpose of this paper is to analyze the bird impact damage of fuselage composite stiffened structures by numerical method and to evaluate the damage and the bird impact resistance of different structures.

Design/methodology/approach
The deformation and damage of composite stiffened plates during bird impact are numerically analyzed by the explicit finite element software LS-DYNA. A comparative study on the numerical calculation results was conducted by using SPH (Smoothed Particle Hydrodynamics)-FEM (Finite Element Method) modeling and simulation. First, the I-shaped, T-shaped, straight stiffened plates and unstiffened plate were designed. Second, the accuracy of the bird model was verified and further used to evaluate bird strikes on composite stiffened plate. Third, the results of damage modes as well as displacements of the stiffened plates were compared.

Findings
The stiffeners can increase the local stiffness of the composite panel, which can effectively inhibit the bird’s movement along the impact direction. Adding stiffeners can change the panel matrix tension damage from global distribution to local distribution mode; however, the impact damage distribution and the ability to inhibit damage propagation can differ for different stiffened panels. Especially, the I-stiffened panel exhibits a better anti-bird strike performance.

Originality/value
The analysis of geometric parameters of structural components by numerical methods can reduce the cost of the design phase and has been widely used in aircraft design. The present study evaluated the bird impact damage of composite stiffened plates with different structures, which provides a guideline for selecting the stiffened plate structure in the fuselage skin.
Thermal behavior of grain-oriented electrical steel wound core solid-state transformer
Authors: Ichou Houssam , Roger Daniel , Rossi Mathieu 
Published: February 2022

Purpose
This paper aims to propose a new design for high-power compact solid-state transformers (SSTs) made with grain-oriented electrical steel (GOES) wound cores that benefit from the natural reduction of iron losses at high temperatures.

Design/methodology/approach
An experimental approach, coupled with numerical and analytical investigations, is widely used for proving the validity of the proposed concept.

Findings
With cores much hotter than coils, the new design of medium frequency transformers can be used for building compact SSTs that rated powers and common-mode insulation voltages much higher than existing ones with similar efficiencies.

Research limitations/implications
The thermal design must provide a large difference between core and coil temperatures in a reasonable volume.

Practical implications
The increasing number of intermittent renewable sources place electric grid stability at risk. Smart nodes, made of SSTs, improve the global grid stability because they are able to provide real-time control of energy fluxes at critical points. In railway applications, high-power SST cells can be distributed along the train providing a larger volume for passengers.

Social implications
The increasing part of electricity in a flexible grid requires performant and high-power SSTs made with components that have an environmental footprint as low as possible.

Originality/value
This paper proves that the design of high-power transformers with GOES wound cores much hotter than coils is possible. It proposes also a thermal equivalent circuit that helps the design.
Maritime resilience during the COVID-19 pandemic: impacts and solutions
Authors: Chua Jie Ying , Foo Ryan , Tan Kim Hock , Yuen Kum Fai 
Published: February 2022

PurposeThis study aims to study the resilience of the maritime industry by analyzing the impacts of COVID-19 on the maritime industry, in particular, on the shipping management aspect and offshore sector, investigate the effectiveness of current solutions and recommend future solutions for the industry to reduce or mitigate the negative impacts.Design/methodology/approachIn order to better appreciate resilience in the maritime industry, the study conducted secondary research and semi-structured online interviews to (1) identify the impacts of COVID-19 on the shipping management and offshore sector, (2) analyze the effectiveness of current solutions and (3) provide some strategies to enhance the effectiveness of the current measures.Findingshe results are congruent with existing literature which indicate that the pandemic has negatively affected the global economy, changed the global trade network and contributed to the sharp decline in demand for oil. In response to the pandemic, governments have implemented safety and health-related measures such as lockdown, safe-distancing and travel restrictions. Often, measures differ from countries to countries and these non-standardized and changing regulations further increase the challenges faced by the industry. From the shipping management perspective, the industry experienced issues such as crew changing, trade contraction and the expiration of shipping certificates, which supported and validated current research. Meanwhile, the offshore industry is challenged by the increasing market volatility and uncertainty, increasing need to source for alternative fuels and the declining oil exploration activities. Current strategies adopted by shipping management companies include crew change management, capacity management and the extension of ship certificates, whereas offshore industry chose to collaborate with oil majors.Research limitations/implicationsBy identifying the impacts and challenges and studying the effectiveness of solutions adopted by the maritime industry, this paper allows maritime industry stakeholders and policymakers to develop strategies to mitigate the effects of the global health crisis and strengthen the resilience of the industry. However, as the pandemic continues to develop and evolve, strategies need to be reviewed continuously in response to the changing situations.Originality/valueThis research analyses the impacts and solutions in response to the COVID-19 pandemic, which contributes to the development and formulation of strategies to strengthen the resilience of maritime transport.
Research that sparked attention on the social Web in 2020: an Altmetric analysis of “top 100” articles
Authors: Rehman Ikhlaq ur , Ganaie Shabir Ahmad , Wani Javaid Ahmad 
Published: February 2022

Purpose
The study aims to analyse the “Top 100” articles that were most discussed on social media in 2020.

Design/methodology/approach
This study is based on the data retrieved from the Altmetric database. The data were tabulated in Microsoft Excel for further analysis. Moreover, articles were examined at an individual level to retrieve author affiliations for research collaboration analysis.

Findings
The most discussed article on social media for the year 2020 has an Article Attention Score (AAS) of 34775. COVID-19 related studies have dominated the list and it comes as no surprise since COVID-19 became the focal point of many researchers and publishers ever since the pandemic started. These articles have been published across 63 journals with the highest contributions from reputed journals such as Nature, PLoS ONE and Science. The majority (46%) of articles has been published in open access. Finally, the majority of publications are a result of research collaboration.

Originality/value
This study reflects the societal impact of research that could be used as an indicator of research performance.
Winery diversification options for Native American tribal enterprises
Authors: Hutchens Randi , Way Kelly , Becnel Jennifer N. 
Published: February 2022

PurposeThis study examined the perceptions of tribal members regarding the strengths, challenges and opportunities presented by tribal winery operation. Issues of business diversification, marketing, perceived barriers to success, potential benefits to the tribe and the role of agriculture in the preservation of tribal heritage were considered.Design/methodology/approachA modified mixed-methods exploratory sequential research model was used to collect and organize data in two studies. In Study 1 quantitative data was used to inform the development of Study 2 which included a qualitative interview protocol. Qualitative interviews followed to elaborate on the various aspects of each of these areas of consideration.FindingsResults indicate that there is neutral to positive opinion on tribal wineries and that any venture would have to be carefully thought out in terms of marketing and preserving tribal heritage.Practical implicationsThis research examined the potential strengths, challenges and opportunities provided by tribal winery operation that can be used to inform future business practices.Originality/valueThe results of this research provide a framework for consideration of the potential strengths and opportunities provided by tribal winery operation.
Mental toughness for employees: towards conceptual clarity and scale development
Authors: Ruparel Namita , Choubisa Rajneesh , Seth Himanshu , Dubey Shubha 
Published: February 2022

PurposeTime and again, scholars have emphasized the vitality of mental toughness for success in performance-oriented contexts. Despite the awareness about the significance of mental toughness, there is ambiguity in the conceptual consensus of the factors that comprise of the construct in an organizational setup. Second, there is a dearth of a psychometrically sound measure that assesses mental toughness among employees.Design/methodology/approachThe study follows a multi-method approach to develop a mental toughness questionnaire. First, to arrive at a consensus of the factors that construe mental toughness, a meta-ethnography was done. Subsequently, a measure of mental toughness was developed and tested following scale development norms.FindingsDrawing from the results of qualitative inquiry, four factors of mental toughness were derived, namely, perseverance, control, challenge and commitment. Then, the scale development process was followed. Results of psychometric testing using three samples were above the acceptable range, justifying the use of developed scale for academic and professional purposes.Originality/valueThis study is a novel attempt in the literature to extract factors of mental toughness through meta-ethnography and consequently develop a scale.
Contribution of Internet of things in water supply chain management: A bibliometric and content analysis
Authors: Velani Arman Firoz , Narwane Vaibhav S. , Gardas Bhaskar B. 
Published: February 2022

Purpose
This paper aims to identify the role of internet of things (IoT) in water supply chain management and helps to understand its future path from the junction of computer science and resource management.

Design/methodology/approach
The current research was studied through bibliometric review and content analysis, and various contributors and linkages were found. Also, the possible directions and implications of the field were analyzed.

Findings
The paper’s key findings include the role of modern computer science in water resource management through sensor technology, big data analytics, IoT, machine learning and cloud computing. This, in turn, helps in understanding future implications of IoT resource management.

Research limitations/implications
A more extensive database can add up to more combinations of linkages and ideas about the future direction. The implications and understanding gained by the research can be used by governments and firms dealing with water management of smart cities. It can also help find ways for optimizing water resources using IoT and modern-day computer science.

Originality/value
This study is one of the very few investigations that highlighted IoT’s role in water supply management. Thus, this study helps to assess the scope and the trend of the case area.