bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of Spike Infectivity, Processing and Neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2
Authors: Pastorio Chiara , Zech Fabian , Noettger Sabrina , Jung Christoph , Jacob Timo , Sparrer Konstantin M.J. , Kirchhoff Frank 
Published: April 2022

ABSTRACTThe SARS-CoV-2 Omicron variant rapidly outcompeted other variants and currently dominates the COVID-19 pandemic. Its enhanced transmission, immune evasion and pathogenicity is thought to be driven by numerous mutations in the Omicron Spike protein. Here, we examined the impact of amino acid changes that are characteristic for the BA.1 and/or BA.2 Omicron lineages on Spike function, processing and susceptibility to neutralization. Individual mutations of S371F/L, S375F and T376A in the ACE2 receptor-binding domain as well as Q954H and N969K in the hinge region 1 impaired infectivity, while changes of G339D, D614G, N764K and L981F moderately enhanced it. Most mutations in the N-terminal region and the receptor binding domain reduced sensitivity of the Spike protein to neutralization by sera from individuals vaccinated with the BNT162b2 vaccine or therapeutic antibodies. Our results represent a systematic functional analysis of Omicron Spike adaptations that allowed this SARS-CoV-2 variant to overtake the current pandemic.HIGHLIGHTSS371F/L, S373P and S375F impair Spike function and revert in some BA. 1 isolatesChanges of Q954H and N969K in HR1 reduce while L981F enhances S-mediated infectionOmicron-specific mutations in the NTD and RBD of Spike reduce neutralizationN440K, G446S, E484A and Q493K confer resistance to bamlanivimab or imdevimab
3’ RNA sequencing does not increase power or reduce costs for gene expression analysis
Authors: Crow Taylor M , Gill JA , Whitehead Andrew , Runcie Daniel E 
Published: April 2022

AbstractBackgroundSequencing RNA transcripts for gene expression profiling is a popular and important technique with broad utility in biological sciences. We set out to comprehensively compare the two most popular methods for generating sequencing libraries for differential gene expression analysis: 3-end sequencing, which generates libraries from the 3’ end of an RNA transcript; and traditional RNA sequencing, which generates libraries from whole RNA transcripts. We include three species in our experiment to test whether our findings replicate across genomes and genome assemblies.ResultsWe found similar levels of precision and power to detect differentially expressed genes between the two methods. Notably, whole transcript RNA-seq performed better in the non-traditional model species included in our study.ConclusionOverall, we recommended whole transcript RNA sequencing for the added benefits of alternative splicing detection, and gene-body variant detection.
Schizophrenia-derived hiPSC brain microvascular endothelial cells show impairments in angiogenesis and blood-brain barrier function
Authors: Casas Bárbara S. , Vitória Gabriela , Prieto Catalina P. , Casas Mariana , Chacón Carlos , Uhrig Markus , Ezquer Fernando , Ezquer Marcelo , Rehen Stevens K. , Palma Verónica 
Published: April 2022

AbstractSchizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed out a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ.As SZ is a neurodevelopmental disease, the use of human induced pluripotent stem cells (hiPSC) allows disease biology modeling retaining the patient’s unique genetic signature. Previously, we reported a VEGF-A signaling impairment in SZ-hiPSC derived neural lineages leading to a decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective Blood-Brain Barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC’s secretome reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis that traces schizophrenia origins to brain development and BBB dysfunction.
The impact of gamification on the patient's engagement in the online health community
Authors: Ouyang Peng , Wang Jian-Jun , Ali Usman 
Published: April 2022

PurposeGamification has been widely implemented to improve user engagement in the online health community (OHC). While its effect on the physicians' engagement has recently been documented, whether and how gamification influences the patients' engagement in the OHC remains an untapped research area. The purpose of this study is to fill this dearth by encompassing the gamification strategy of Haodf.com, which awards the “Annual Physician” badges to the physicians, to analyze how this gamification approach motivates patients’ engagement in the OHC.Design/methodology/approachReal-world data are leveraged from the OHC. The Tobit model is employed for modeling the gamification-patient's engagement nexus in an OHC. Robust findings are obtained by incorporating different measures of a dependent variable, a set of control variables about the physician's characteristics and hospital's features, and alternative estimation techniques.FindingsThe results reveal that a patient's engagement in the OHC in the form of appointments and review-posting behavior is enhanced by the gamification strategy. Besides, the positive influence of gamification on the patient's engagement is further strengthened by the physician's professional capital. It is basically obtained that the gamification is an efficacious tool to accelerate not only the physicians' engagement but also of the patients in the OHC platform.Originality/valueThe study provides both theoretical and empirical discussion to enrich the understanding on how OHCs enhance patients' engagement by developing gamification techniques. The findings guide the practitioners of OHC to better understand the implications of their gamification design to optimize user engagement.
Robust stability analysis of switched grey neural network models with distributed delays over C
Authors: Zhang Lei , Xue Huanbin , Li Zeying , Wei Yong 
Published: April 2022

PurposeThe purpose of this paper is to study the dynamic behavior of complex-valued switched grey neural network models (SGNMs) with distributed delays when the system parameters and external input are grey numbers.Design/methodology/approachFirstly, by using the properties of grey matrix, M-matrix theory and Homeomorphic mapping, the existence and uniqueness of equilibrium point of the SGNMs were discussed. Secondly, by constructing a proper Lyapunov functional and using the average dwell time approach and inequality technique, the robust exponential stability of the SGNMs under restricted switching was studied. Finally, a numerical example is given to verify the effectiveness of the proposed results.FindingsSufficient conditions for the existence and uniqueness of equilibrium point of the SGNMs have been established; sufficient conditions for guaranteeing the robust stability of the SGNMs under restricted switching have been obtained.Originality/value(1) Different from asymptotic stability, the exponential stability of SGNMs which include grey parameters and distributed time delays will be investigated in this paper, and the exponential convergence rate of the SGNMs can also be obtained; (2) the activation functions, self-feedback coefficients and interconnected matrices are with different forms in different subnetworks; and (3) the results obtained by LMIs approach are complicated, while the proposed sufficient conditions are straightforward, which are conducive to practical applications.
How health consciousness and social consciousness affect young consumers purchase intention towards organic foods
Authors: Su Yuandong , Khaskheli Asadullah , Raza Syed Ali , Yousufi Sara Qamar 
Published: April 2022

PurposeThis current research investigates antecedents affecting young consumers' purchasing intention of organic foods in a developing nation’s (Pakistan) context utilizing Theory of Planned Behavior. For this purpose, theoretical framework comprising characteristics of a product, concerns of consumers and consciousness were proposed.Design/methodology/approachResponses were collected from a sample comprising 418 young consumers through the convenience sampling technique. The data has been evaluated through Structural Equation Modeling.FindingsFindings demonstrate that characteristics of products and concerns of consumers significantly affect young consumer's health and social consciousness. However, such health and social consciousness were found to have an insignificant effect on young consumers' attitudes. Moreover, findings also show that attitude is positively linked with young consumers' purchase frequency towards organic foods. Outcomes also approve moderation of environmental awareness between attitude and organic food purchasing intention.Practical implicationsThe present study offers numerous implications for marketers, policymakers and socio-ecological organizations regarding development of intervention strategies to promote the purchase of organic foods. The study provides implications regarding making organic foods more accessible to all consumers in order to increase organic food consumption in developing countries.Originality/valueAlthough young consumers are aware of organic food products, their knowledge about the concept is limited. Therefore, this study provides an understanding of consumer's perspective regarding their purchase intention of organic foods, which will help marketers, researchers and food producers to achieve marketing strategies for the development of these products.
Authentic leadership: boosting organisational learning capability and innovation success
Authors: Domínguez-Escrig Emilio , Mallén Broch Francisco Fermín , Chiva Ricardo , Lapiedra Alcamí Rafael 
Published: April 2022

Purpose
Despite the growing interest in the study of authentic leadership, there is little empirical evidence of the consequences of this type of leadership for companies. On the other hand, the mediating variables that may explain these results have not been explored in depth either. Although the academic literature suggests, from a theoretical point of view, that these leaders could favour innovation, little has been studied from an empirical perspective. This study aims to try to cover these gaps.

Design/methodology/approach
The main goal of this study is to analyse the mediating effect of organisational learning capability in the relationship between authentic leadership and innovation success. Considering a sample frame of 263 Spanish companies, this study tested the proposed hypotheses through structural equations.

Findings
The results provide empirical evidence of the positive effect of authentic leaders to promote organisational learning capability. In addition, this study confirms the positive effect of organisational learning capability on innovation success. Finally, organisational learning capability mediates the relationship between authentic leadership and innovation success.

Originality/value
To the best of the authors’ knowledge, this is the first attempt to empirically study the effects of authentic leadership on organisational learning capability and innovation success.
Integrin β2 and β3: Two plasmatocyte markers deepen our understanding of the development of plasmatocytes in the silkworm Bombyx mori
Authors: Zhang Kui , Su Jingjing , Hu Xin , Yan Xiaomin , Chen Siyuan , Li Chongyang , Pan Guangzhao , Chang Hongbo , Tian Wenli , Abbas Muhammad Nadeem , Cui Hongjuan 
Published: April 2022

AbstractInsect hemocytes play important biological roles at developmental stages, metamorphosis, and innate immunity. As one of the most abundant cell types, plasmatocytes can participate in various innate immune responses, especially in encapsulation and node formation. Here, 2 molecular markers of plasmatocytes, consisting of integrin β2 and β3, were identified and used to understand the development of plasmatocytes. Plasmatocytes are widely distributed in the hematopoietic system, including circulating hemolymph and hematopoietic organs (HPOs). HPOs constantly release plasmatocytes with high proliferative activity in vitro; removal of HPOs leads to a dramatic reduction in the circulating plasmatocytes, and the remaining plasmatocytes gradually lose their ability to proliferate in vivo. Our results demonstrated that the release of plasmatocytes from HPOs is regulated by insulin‐mediated signals and their downstream pathways, including PI3K/Akt and MAPK/Erk signals. The insulin/PI3K/Akt signaling pathway can significantly irritate the hematopoiesis, and its inhibitor LY294002 could inhibit the hemocytes discharged from HPOs. While the insulin/MAPK/Erk signaling pathway plays a negative regulatory role, inhibiting its activity with U0126 can markedly promote the discharge of plasmatocytes from HPOs. Our results indicate that the circulating plasmatocytes are mainly generated and discharged by HPOs. This process is co‐regulated by the PI3K/Akt and MAPK/Erk signals in an antagonistic manner to adjust the dynamic balance of the hemocytes. These findings can enhance our understanding of insect hematopoiesis.
Cardiopulmonary exercise testing to observe subclinical abnormalities in cardiopulmonary function in patients undergoing peritoneal dialysis
Authors: Wu Xin , Zhang Ying , Wang FengLi , Xiang Jie 
Published: April 2022

AbstractBackgroundDecreased cardiorespiratory fitness (CRF) related to cardiopulmonary function increases the risk of cardiovascular disease in patients with end‐stage kidney disease. Thus, early detection of the cause of impaired cardiopulmonary function in patients undergoing peritoneal dialysis (PD) is of important clinical significance.MethodsIn this cross‐sectional study, symptom‐restricted cardiopulmonary exercise testing (CPET) was performed in 30 patients undergoing PD and in 23 age‐ and sex‐matched healthy control subjects. A fixed workload was added every minute until fatigue, and breath‐by‐breath respiratory gas was analysed with an automated gas analyzer at 10‐s intervals.ResultsThe peak oxygen uptake (16.39 ± 0.83 vs. 25.77 ± 1.33 ml/kg/min p < 0.001) and the oxygen uptake at the anerobic threshold of patients undergoing PD (9.61 ± 0.34 vs. 14.55 ± 0.64 ml/kg/min; p < 0.001) were lower than in healthy control subjects, and both of these parameters correlated with body mass index and left atrial dimension. A steeper minute ventilation/carbon dioxide production slope (27.20 ± 0.68 vs. 24.29 ± 0.69；p < 0.01) and a lower end‐tidal carbon dioxide partial pressure (37.93 ± 0.54 vs. 41.27 ± 0.83 mmHg；p < 0.05) were observed in patients undergoing PD. The oxygen pulse and oxygen uptake efficiency slope was smaller in patients undergoing PD. The Maximum heart rate (126.07 ± 4.01 vs. 149.96 ± 5.29 bpm；p < 0.01) and 1‐min heart rate recovery (13.93 ± 1.52 vs. 24.39 ± 1.61 bpm；p < 0.01) were also lower in patients undergoing PD.ConclusionSubclinical cardiopulmonary dysfunction may exist in patients with PD, and a reduction in CRF in patients undergoing PD is affected by both central and peripheral functions. CPET has potential value in revealing the mechanism of impaired CRF and in discovering subclinical abnormalities in cardiopulmonary function.
The contribution of canopy samples to assessments of forestry effects on native bees
Authors: Milam Joan , Cunningham‐Minnick Michael , Roberts Henry Patrick , Buelow Christopher , King David I. 
Published: April 2022

AbstractForest management is often practiced to enhance conditions for wildlife, including native bees. Evaluations of the effects of forest management on bees have shown that abundance and diversity are higher in newly created early‐successional conditions. To date, studies have restricted sampling to the forest understory; however, recent research finds that bee abundance is as high or higher in forest canopies than in understories, suggesting that previous observations of substantially greater bee abundance and diversity in recently managed areas could be an artifact of incomplete sampling of the vertical gradient within forests. To examine the potential implications of sampling biases associated with the failure of previous studies to include canopy samples in comparisons of managed and unmanaged forests, we sampled bees within a recently harvested forest as well as the understory and canopy of adjacent unmanaged forest. Bee abundance and diversity were an order of magnitude higher in managed areas compared to the unmanaged forest, even when understory and canopy samples were combined. These results suggest that not sampling the canopy is inconsequential with respect to the broadly reported conclusion that managed areas support more abundant and diverse bee communities than surrounding forest cover.
Conservation potentials and limitations of large carnivores in protected areas: A case study in Northeast China
Authors: Wen Dusu , Qi Jinzhe , Long Zexu , Gu Jiayin , Tian Yumiao , Roberts Nathan James , Yang Eryan , Kong Weiyao , Zhao Yan , Sun Quan , Jiang Guangshun 
Published: April 2022

AbstractProtected areas are considered the cornerstone of endangered wildlife conservation. However, quantified conservation potentials and limitations of large carnivores in protected areas are lacking. In the Northeast Tiger and Leopard National Park (NTLNP) in China, our camera trap survey in 2019 found 26–27 adult Amur tigers and 49–59 adult Amur leopards occurring in the park. Based on spatial area, current prey populations, and environmental carrying capacity of prey, we estimated the supportable number of tigers to be 55, 90, and 101 individuals, respectively. For leopard, these values were 95, 356, and 572, respectively. Further simulations indicated that human land use change scenarios did not contribute much to increasing the potential prey‐supportable populations of Amur tiger and leopard. Our results showed that the number of tigers and leopards in NTLNP is currently low and has a high recovery potential. However, even the highest supportable population is not enough to support the sustainable existence of an Amur tiger population. Therefore, we suggest that, in addition to further restoration and improvement of the prey population and habitat quality in NTLNP, managers should strengthen the connectivity between NTLNP and other habitat patches to form a well‐connected network of protected areas. Promoting the spread of tigers and leopards outwards from this source population in NTLNP through ecological corridor construction would enlarge the area of habitat and is a crucial measure for realizing the sustainable survival of an Amur tiger population in Northeast China.
Physiologically‐based pharmacokinetic model‐based translation of OATP1B‐mediated drug–drug interactions from coproporphyrin I to probe drugs
Authors: Mochizuki Tatsuki , Aoki Yasunori , Yoshikado Takashi , Yoshida Kenta , Lai Yurong , Hirabayashi Hideki , Yamaura Yoshiyuki , Rockich Kevin , Taskar Kunal , Takashima Tadayuki , Chu Xiaoyan , Zamek‐Gliszczynski Maciej J. , Mao Jialin , Maeda Kazuya , Furihata Kenichi , Sugiyama Yuichi , Kusuhara Hiroyuki 
Published: April 2022

AbstractThe accurate prediction of OATP1B‐mediated drug–drug interactions (DDIs) is challenging for drug development. Here, we report a physiologically‐based pharmacokinetic (PBPK) model analysis for clinical DDI data generated in heathy subjects who received oral doses of cyclosporin A (CysA; 20 and 75 mg) as an OATP1B inhibitor, and the probe drugs (pitavastatin, rosuvastatin, and valsartan). PBPK models of CysA and probe compounds were combined assuming inhibition of hepatic uptake of endogenous coproporphyrin I (CP‐I) by CysA. In vivo Ki of unbound CysA for OATP1B (Ki,OATP1B), and the overall intrinsic hepatic clearance per body weight of CP‐I (CLint,all,unit) were optimized to account for the CP‐I data (Ki,OATP1B, 0.536 ± 0.041 nM; CLint,all,unit, 41.9 ± 4.3 L/h/kg). DDI simulation using Ki,OATP1B reproduced the dose‐dependent effect of CysA (20 and 75 mg) and the dosing interval (1 and 3 h) on the time profiles of blood concentrations of pitavastatin and rosuvastatin, but DDI simulation using in vitro Ki,OATP1B failed. The Cluster Gauss–Newton method was used to conduct parameter optimization using 1000 initial parameter sets for the seven pharmacokinetic parameters of CP‐I (β, CLint, all, FaFg, Rdif, fbile, fsyn, and vsyn), and Ki,OATP1B and Ki,MRP2 of CysA. Based on the accepted 546 parameter sets, the range of CLint, all and Ki,OATP1B was narrowed, with coefficients of variation of 12.4% and 11.5%, respectively, indicating that these parameters were practically identifiable. These results suggest that PBPK model analysis of CP‐I is a promising translational approach to predict OATP1B‐mediated DDIs in drug development.
Classification of patients with embolic stroke of undetermined source into cardioembolic and non‐cardioembolic profile subgroups
Authors: Martin Max Christian , Sichtermann Thorsten , Schürmann Kolja , Habib Pardes , Wiesmann Martin , Schulz Jörg B. , Nikoubashman Omid , Pinho João , Reich Arno 
Published: April 2022

AbstractBackground and purposeIt is currently thought that embolic stroke of undetermined source (ESUS) has diverse underlying hidden etiologies, of which cardioembolism is one of the most important. The subgroup of patients with this etiology could theoretically benefit from oral anticoagulation, but it remains unclear if these patients can be correctly identified from other ESUS subgroups and which markers should be used. We aimed to determine whether a machine‐learning (ML) model could discriminate between ESUS patients with cardioembolic and those with non‐cardioembolic profiles using baseline demographic and laboratory variables.MethodsBased on a prospective registry of consecutive ischemic stroke patients submitted to acute revascularization therapies, an ML model was trained using the age, sex and 11 selected baseline laboratory parameters of patients with known stroke etiology, with the aim of correctly identifying patients with cardioembolic and non‐cardioembolic etiologies. The resulting model was used to classify ESUS patients into those with cardioembolic and those with non‐cardioembolic profiles.ResultsThe ML model was able to distinguish patients with known stroke etiology into cardioembolic or non‐cardioembolic profile groups with excellent accuracy (area under the curve = 0.82). When applied to ESUS patients, the model classified 40.3% as having cardioembolic profiles. ESUS patients with cardioembolic profiles were older, more frequently female, more frequently had hypertension, less frequently were active smokers, had higher CHA2DS2‐VASc (Congestive heart failure or left ventricular systolic dysfunction, Hypertension, Age ≥ 75 [doubled], Diabetes, Stroke/transient ischemic attack [doubled], Vascular disease, Age 65–74, and Sex category) scores, and had more premature atrial complexes per hour.ConclusionsAn ML model based on baseline demographic and laboratory variables was able to classify ESUS patients into cardioembolic or non‐cardioembolic profile groups and predicted that 40% of the ESUS patients had a cardioembolic profile.