bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-guided steric hindrance engineering of Bacillus badius phenylalanine dehydrogenase for efficient l-homophenylalanine synthesis
Authors: Wu Tao , Mu Xiaoqing , Xue Yuyan , Xu Yan , Nie Yao 
Published: October 2021

Abstract
Background
Direct reductive amination of prochiral 2-oxo-4-phenylbutyric acid (2-OPBA) catalyzed by phenylalanine dehydrogenase (PheDH) is highly attractive in the synthesis of the pharmaceutical chiral building block l-homophenylalanine (l-HPA) given that its sole expense is ammonia and that water is the only byproduct. Current issues in this field include a poor catalytic efficiency and a low substrate loading.

Results
In this study, we report a structure-guided steric hindrance engineering of PheDH from Bacillus badius to create an enhanced biocatalyst for efficient l-HPA synthesis. Mutagenesis libraries based on molecular docking, double-proximity filtering, and a degenerate codon significantly increased catalytic efficiency. Seven superior mutants were acquired, and the optimal triple-site mutant, V309G/L306V/V144G, showed a 12.7-fold higher kcat value, and accordingly a 12.9-fold higher kcat/Km value, than that of the wild type. A paired reaction system comprising V309G/L306V/V144G and glucose dehydrogenase converted 1.08 M 2-OPBA to l-HPA in 210 min, and the specific space–time conversion was 30.9 mmol g−1 L−1 h−1. The substrate loading and specific space–time conversion are the highest values to date. Docking simulation revealed increases in substrate-binding volume and additional degrees of freedom of the substrate 2-OPBA in the pocket. Tunnel analysis suggested the formation of new enzyme tunnels and the expansion of existing ones.

Conclusions
Overall, the results show that the mutant V309G/L306V/V144G has the potential for the industrial synthesis of l-HPA. The modified steric hindrance engineering approach can be a valuable addition to the current enzyme engineering toolbox.
miR-181a regulates the host immune response against Schistosoma japonicum infection through the TLR4 receptor pathway
Authors: Tang Yixiao , Shen Yuanxi , Hong Yang , Zhang Zuhang , Zhai Qi , Fu Zhiqiang , Li Hao , Lu Ke , Lin Jiaojiao 
Published: October 2021

Abstract
Background
Schistosomiasis japonica is a serious zoonotic parasitic disease. Preliminary studies have shown that the expression of microRNA-181a (miR-181a) in the liver, lung and spleen tissues of susceptible host BALB/c mice and resistant host reed vole (Microtus fortis) 10 days post-infection (dpi) with Schistosoma japonicum was significantly different from pre-infection levels. This difference suggests the possibility that miR-181a expression may be related to the regulation of the hosts’ early immune response against S. japonicum infection and thereby affect the development and survival of parasites in their final hosts.

Methods
BALB/c mice, M. fortis, Toll-like receptor 4 (TLR4)-deficient mice and wild-type mice (C57BL/6) were infected with S. japonicum, and differences in miR-181a expression between BALB/c mice and M. fortis over different time points post-infection (0, 3, 7, 10 and 14 dpi) were compared. MiR-181a mimic, miR-181a inhibitor and irrelevant miRNA, as well as lipopolysaccharide (LPS), a TLR4 receptor ligand, were used to transfect mouse RAW264.7 macrophages. The expression levels of the TLR4 pathway-related cytokines interleukin (IL)-1β, tumor necrosis factor α (TNF-α) and IL-6 were detected by quantitative PCR analysis.

Results
The expression of miR-181a was significantly upregulated in the serum and liver of mice infected with S. japonicum and downregulated in the serum and liver of M. fortis. T-helper cell (Th1)-type cytokines, such as TNF-α, IL-6 and IL-1β, and Th2-type cytokines, such as IL-10 and IL-4, were differentially expressed in M. fortis and BALB/c mice in the early stage of infection. The expression level of miR-181a in the serum was threefold higher in TLR4-deficient mice than in wild-type mice 10 dpi with S. japonicum. The expression of IL-1β, TNF-α and IL-6 decreased in RAW264.7 cells transfected with miR-181a mimic and increased in cells transfected with miR-181a inhibitor. miR-181a expression was downregulated and the expressions of TLR4 and three TLR4 pathway-related cytokines (IL-1β, IL-6, and TNF-α) were upregulated in RAW264.7 macrophages stimulated with the TLR4 receptor ligand LPS.

Conclusion
These results suggest the possibility of mutual regulation between miR-181a and the TLR4 signaling pathway during S. japonicum infection. miR-181a may regulate the expression of pro-inflammatory factors through the TLR4 receptor pathway and participate in the immunomodulatory effect of anti-S. japonicum infection.

Graphical abstract
Development of whole-cell catalyst system for sulfide biotreatment based on the engineered haloalkaliphilic bacterium
Authors: Zhang Manqi , Xue Qiong , Zhang Shengjie , Zhou Heng , Xu Tong , Zhou Jian , Zheng Yanning , Li Ming , Kumar Sumit , Zhao Dahe , Xiang Hua 
Published: October 2021

AbstractMicroorganisms play an essential role in sulfide removal. Alkaline absorption solution facilitates the sulfide’s dissolution and oxidative degradation, so haloalkaliphile is a prospective source for environmental-friendly and cost-effective biodesulfurization. In this research, 484 sulfide oxidation genes were identified from the metagenomes of the soda-saline lakes and a haloalkaliphilic heterotrophic bacterium Halomonas salifodinae IM328 (=CGMCC 22183) was isolated from the same habitat as the host for expression of a representative sequence. The genetic manipulation was successfully achieved through the conjugation transformation method, and sulfide: quinone oxidoreductase gene (sqr) was expressed via pBBR1MCS derivative plasmid. Furthermore, a whole-cell catalyst system was developed by using the engineered strain that exhibited a higher rate of sulfide oxidation under the optimal alkaline pH of 9.0. The whole-cell catalyst could be recycled six times to maintain the sulfide oxidation rates from 41.451 to 80.216 µmol·min−1·g−1 dry cell mass. To summarize, a whole-cell catalyst system based on the engineered haloalkaliphilic bacterium is potentiated to be applied in the sulfide treatment at a reduced cost.
Health-related quality of life in critically ill survivors: specific impact of cardiac arrest in non-shockable rhythm
Authors: Geri Guillaume , Aissaoui Nadia , Colin Gwenhael , Cariou Alain , Lascarrou Jean-Baptiste 
Published: October 2021

Abstract
Background
Intensive care has a strong impact on health-related quality of life (HRQOL). The specific impact of cardiac arrest in non-shockable rhythm is poorly known.

Patients and methods
We gathered patients included in two randomized controlled trials (AWARE and HYPERION). The HYPERION trial included ICU-treated non-shockable cardiac arrest patients. The AWARE study included ICU patients requiring mechanical ventilation. We compared the 3-months HRQOL of these patients to those of a large sample of the French general population. Physical and mental dimension were compared. Multivariable linear regression was used to pick up factors associated with HRQOL.

Results
72 and 307 patients of the HYPERION and the AWARE studies were compared to 20,574 French controls. ICU patients evidenced lower scores in all the SF-36 dimensions compared to the controls. Similar scores were observed in both HYPERION and AWARe trials. The physical component score was lower in patients from the HYPERION trial compared to those from the AWARE trials and to controls (38.6 [29.6-47.8], 35.4 [27.5-46.4] vs. 53.0 [46.0-56.7], $$\hbox {p}<0.001$$

p
<
0.001

). After adjustment for age and gender, HYPERION and AWARE trial status were associated wit lower physical component score.

Conclusion
Health-related quality of life of unshockable cardiac arrest survivors evaluated at 3 months was similar to ICU survivors and significantly lower than in individuals from general population, especially in the physical dimensions.
Carbon emission factor decomposition and carbon peak prediction based on multi-objective decision and information fusion processing
Authors: Shi Chunxue , Feng Xiwen 
Published: October 2021

AbstractGlobal warming caused by excessive carbon dioxide emissions has seriously threatened the sustainable development of human society. How to reduce carbon dioxide emissions has become a common problem faced by the international community. This article aims to study the decomposition of carbon emission factors and the prediction of carbon peaks from the perspective of multi-objective decision-making and information fusion processing. The sample collection method and statistical analysis method are used to collect samples and simplify the algorithm. A collection experiment of carbon emission factors based on the industry of City A is designed. The experimental data collection takes into account the conversion of coal and oil products into standard coal and carbon dioxide the resulting emissions impact. The experimental results in this paper show that the simulated and real values of my country’s petroleum carbon emissions have both increased from 2000 to 2015, and the decline will be controlled in 2017. Both the simulated value and the real value of my country's coal carbon emissions have been on the rise from 2000 to 2015, and the decline will be controlled in 2017. The carbon emissions of coal are far greater than those of petroleum. The research on carbon emission factor decomposition and carbon peak prediction based on multi-objective decision-making and information fusion processing has been completed well. The research results can be used for industrial carbon emission factor decomposition and carbon peak prediction in other cities across the country.
Pricing strategies of an oligopolist in federated cloud markets
Authors: Khandelwal Yash , Dogra Arushi , Ganti Karthik , Purini Suresh , Reddy Puduru V. 
Published: October 2021

AbstractIn this paper, we study how an oligopolist influences the coalition structure in federated cloud markets. Specifically, we use cooperative game theory to model the circumstances under which a cloud provider prefers to join a cloud federation vis-a-vis consider taking a price offer made by an oligopolist. We consider two price offering strategies for an oligopolist: non-adaptive and adaptive. In non-adaptive strategy, an oligopolist makes a price offer to all the cloud providers simultaneously. It can be noted that the oligopolist can buy-out all the cloud providers by making a price offer which is equal to a core allocation and the total price offer made by the oligopolist is equal to the value of the grand coalition. In adaptive strategy, the oligopolist approaches the cloud providers one after another in a sequential manner. We show that by using the adaptive strategy, the oligopolist can buy-out all the cloud providers at a total price offer which is less than that of the non-adaptive strategy.
What sub-Saharan African countries can learn from malaria elimination in China
Authors: Badmos Abubakar Olaitan , Alaran Aishat Jumoke , Adebisi Yusuff Adebayo , Bouaddi Oumnia , Onibon Zainab , Dada Adeniyi , Lin Xu , Lucero-Prisno Don Eliseo 
Published: October 2021

AbstractMalaria is one of the most devastating diseases plaguing the sub-Saharan African region since time immemorial. In spite of a global reduction in mortality rates, a significant proportion of deaths due to malaria is still accounted for in the region. China recently joined the 40 countries declared malaria free by the World Health Organization and became the first country in the WHO Western Pacific Region to be awarded the certification. We commented on the strategies employed by China to eliminate malaria, address challenges facing malaria control in sub-Saharan Africa, and derive lessons that could be learned in the sub-Saharan African context.
Comparative study between liver biopsy and non-invasive biomarkers in assessment of hepatic fibrosis in children with chronic liver diseases
Authors: Behairy Ola Galal , El-Shimi Ola Samir , Shalan Naglaa Hamed 
Published: October 2021

Abstract
Background
Liver biopsy is the gold standard for detecting the degree of liver fibrosis; however, invasiveness constitutes its main limiting factor in clinical application, so we aimed to evaluate the non-invasive biomarker formulas (APRI and FIB-4) and their modified forms by BMI z-score (M-APRI, M-FIB-4, and B-AST) compared to liver biopsy in the assessment of liver fibrosis in children with chronic liver diseases. Two hundred children aged 6.3 ± 3.8 years (98 males, 102 females) with chronic liver diseases underwent liver biopsy. The stage of fibrosis was assessed according to the METAVIR system for all children, and the following non-invasive biomarker formulas were calculated: APRI, modified APRI (M-APRI: BMI z-score × APRI), Fibrosis-4 index (FIB-4), modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and B-AST (BMI z-score × AST). The best cutoff value was calculated to detect early fibrosis (F1–F2) from advanced liver fibrosis (F3–F4).

Results
There were positive correlations between all studied non-invasive biomarker models (APRI, FIB-4, M-APRI, M-FIB-4, B-AST) and fibrosis score as an increase in fibrosis score was associated with an increase in mean ± SD of all studied biomarker formulas. The best cutoff values of non-invasive biomarker models in the diagnosis of early fibrosis (F1–F2) were APRI > 0.96, M-APRI > 0.16, FIB-4 > 0.019, M-FIB-4 > 0.005, and B-AST > −8 with an area under the curve above 0.7 each, while the best cutoff values of non-invasive biomarker models (APRI, M-APRI, FIB-4, M-FIB-4, and B-AST) in the diagnosis of advanced liver fibrosis (F3–F4) were >1.96, >2.2, >0.045, and >0.015, >92.1, respectively, with an area under the curve above 0.8 each.

Conclusion
APRI, M-APRI, FIB-4, M-FIB-4, and B-AST are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis in children with chronic liver diseases of different etiologies especially those that include BMI z-scores in their formulas.
COVID-19 in children: an approach for multisystem inflammatory syndrome
Authors: Morsy Haneen K. , Tohamy Noha S. , Abd El Ghaffar Hager M. , Sayed Rana , Sabri Nagwa A. 
Published: October 2021

Abstract
Background and objectives
Children suffering from coronavirus disease (COVID-19) usually present with mild symptoms and show lower mortality rates than adults. However, there have been several recent reports of more severe hyperinflammatory presentation in pediatric COVID-19 patients. This review article aims to summarize the current literature available on the main clinical features and management approaches of multisystem inflammatory syndrome in children (MIS-C).

Methods
The authors searched different indexing databases for observational and interventional studies using search terms including “Coronavirus, COVID-19, pediatric, MIS-C, Kawasaki, and inflammation.” The retrieved publications were further assessed for relevance to the topic. Only relevant articles were included in writing this review article.

Main body
Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome temporally related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in pediatrics. It is characterized by persistent fever, rash, elevated inflammatory markers, and multiorgan failure with increasing rates of cardiovascular and gastrointestinal involvement. The exact pathophysiologic mechanisms of MIS-C are still unknown, but it is postulated to be due to an exaggerated immune response to SARS-CoV-2 infection. Multisystem inflammatory syndrome in children is diagnosed by exclusion of other underlying causes of organ failure. There is a lack of clinical evidence on the management of MIS-C. The current guidelines depend mainly on expert opinion based on the management of other hyper-inflammatory syndromes in children. Patients suffering from MIS-C are treated with intravenous immunoglobulin (IVIg), corticosteroids, infliximab, tocilizumab, and anakinra.

Conclusions
Despite the growing reports on COVID-19 in children, there is still a lot to elucidate on the pathophysiology, diagnosis, and subsequent management of MIS-C. Further trials are needed to investigate new approaches to manage MIS-C. Specific evidence-based guideline for management of MIS-C should be tailored to the current available information on MIS-C.
Early management of patients with aneurysmal subarachnoid hemorrhage in a hospital without neurosurgical/neuroendovascular facilities: a consensus and clinical recommendations of the Italian Society of Anesthesia and Intensive Care (SIAARTI)
Authors: Picetti Edoardo , Berardino Maurizio , Bertuccio Alessandro , Bertuetti Rita , Boccardi Edoardo Pietro , Caricato Anselmo , Castioni Carlo Alberto , Cenzato Marco , Chieregato Arturo , Citerio Giuseppe , Gritti Paolo , Longhi Luca , Martino Costanza , Munari Marina , Rossi Sandra , Stocchetti Nino , Zoerle Tommaso , Rasulo Frank , Robba Chiara 
Published: October 2021

Abstract
Background
The immediate management of subarachnoid hemorrhage (SAH) patients in hospitals without neurosurgical/neurointerventional facilities and their transfer to a specialized center is challenging and not well covered in existing guidelines. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance.

Methods
A multidisciplinary consensus panel composed by 19 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery and interventional neuroradiology) was created. A modified Delphi approach was adopted.

Results
A total of 14 statements have been discussed. Consensus was reached on 11 strong recommendations and 2 weak recommendations. In one case, where consensus could not be agreed upon, no recommendation could be provided.

Conclusions
Management of SAH in a non-specialized setting and early transfer are difficult and may have a critical impact on outcome. Clinical advice, based on multidisciplinary consensus, might be helpful. Our recommendations cover most, but not all, topics of clinical relevance.
Enregisterment eines /r/-Allophons?
Authors: Kehrein Roland 
Published: October 2021

In the study presented in this paper the use of a specific linguistic non-standard feature of German by 100 speakers representing three generations was analysed. The speakers originate from 25 different locations within the Middle Franconian dialect formation covering the middle-western parts of Germany. The feature analysed is the realisation of the Standard German phoneme /r/ as a voiceless velar or uvular fricative [x, χ] when following a short vowel and preceding a coronal obstruent. The comparison of how frequently the speakers use [χ] in different communicative contexts results in the observation of three types of speakers (i. e., [χ] users): The first type are dialect speakers mostly of the older generation (60 years and above) who use the variant in a traditional manner, namely when aiming at producing their best way to pronounce Standard German. According to these speakers [χ] forms part of the Standard German pronunciation norm. The second type is mainly represented by middle aged speakers (45–55 years) who use the feature in nearly all communicative contexts except when they have a dialect competency and are asked to produce their “strongest dialect”. Finally, the third type of speakers are mainly young people (17–23 years) who do not have any dialect competence. These speakers only use [χ] when they are asked to produce their “strongest dialect” and/or when they are talking to friends. On the basis of these results it is argued that, between these types of speakers and the generations they represent, a re-evaluation of the feature has taken place that may be classified as enregisterment, because speakers of the third type seem to use [χ] indexically in order to signal familiarity with their interlocutors on a interpersonal-social level.
Resilience and Hopelessness: Exploring the Mediator Role of Spirituality in the Global Situation of COVID-19
Authors: Maraj Hafza Aroosa , Gülerce Hakan , Rana Shehnaz , Meraj Munazzah 
Published: October 2021

This research aims to describe and to define the importance of spirituality as a mediator in the global pandemic situation of COVID-19 in Pakistan while having positive correlation with resilience and inverse with hopelessness. The correlational research design was used and data was gathered by simple random sampling and there was a use of standardized psychological instruments to measure the variables. The participants were (N=540) Pakistani general population (male and female) with the age range of 18–60. The outcomes revealed that resilience was positively correlated with spirituality (r=0.72; p <0.01) while spiritualty is negatively correlated with hopelessness (r=-0.76; p <0.01) and resilience was negatively correlated with hopelessness (r=-0.78, p <0.01). Mediation analysis shows that spirituality performed a strong intermediating role between resilience and hopelessness the direct effect of hopelessness on resilience was -5.9** whereas the indirect effect through spirituality was -1.7** and the total effect size was – 7.6**. It is revealed that spirituality has a strong impact on the resilience behavior and reduces the hopelessness even in the worldwide disastrous situation. This study enhances the literature related to the psychological research and prompts the role of spiritual coping strategies especially in the state of uncertainty like coronavirus pandemic.
Beethoven jako aktor historyczny. Perspektywa mikrohistoryczna w muzykologii
Authors: Mika Bogumiła 
Published: October 2021

The article focuses on issues of microhistory and the usefulness of this historiographical practice in musicological research. The author begins by presenting the key issues relating to microhistory, referring extensively to the book What Is Microhistory? by István M. Szijártó and Sigurður Gylfi Magnússon. She then quotes and briefly discusses the most significant musicological works which employed microhistorical strategy. These are Mark Everist’s book Music Drama at the Paris Odéon, 1824–1828, Tamara Levitz’s Modernist Mysteries: Perséphone and Peter J. Schmelz’s article “Shostakovich” Fights the Cold War: Reflections from Great to Small. The main part of the text is devoted to Mark Ferraguto’s monograph Beethoven 1806. That publication is wholly based on the microhistorical approach, thus open- ing a new perspective in reflection on the instrumental works by the Master from Bonn. Ferraguto analyses Beethoven’s works from 1806 and early 1807 in the context of the people and the instruments for which they were composed; he also explores the nature of and reasons for the composer’s retreat from the „heroic phase”, analysing various aspects of contemporary musical, social and political life in Vienna. He does so while concentrating on selected, characteristic moments which define the given opus. Unlike the earlier musicological works based on the microhistorical strategy, Ferraguto’s monograph is not overburdened with detail, but makes an excellent job of linking contextual issues with analysis of musical composition. In this way it enriches musicological research by providing it with a new, interesting dimension.