bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding condensation domain selectivity in non-ribosomal peptide biosynthesis: structural characterization of the acceptor bound state
Authors: Cryle Max , Izore Thierry , Ho Y. T. , Kaczmarski Joe , Gavriilidou Athina , Chow Ka , Steer David , Goode Robert , Schittenhelm Ralf , Tailhades Julien , Tosin Manuela , Challis Gregory , Krenske Elizabeth , Ziemert Nadine , Jackson Colin 
Published: January 2021

Abstract
Non-ribosomal peptide synthetases are important enzymes for the assembly of complex peptide natural products. Within these multi-modular assembly lines, condensation domains perform the central function of chain assembly, typically by forming a peptide bond between two peptidyl carrier protein (PCP)-bound substrates. In this work, we report the first structural snapshots of a condensation domain in complex with an aminoacyl-PCP acceptor substrate. These structures allow the identification of a mechanism that controls access of acceptor substrates to the active site in condensation domains. The structures of this previously uncharacterized complex also allow us to demonstrate that condensation domain active sites do not contain a distinct pocket to select the side chain of the acceptor substrate during peptide assembly but that residues within the active site motif can instead serve to tune the selectivity of these central biosynthetic domains.
Anatomical Consideration of Deep Calf Veins: Application to Catheter-Directed Thrombolysis
Authors: Yi Kyu-Ho , Kim Hee-Jin 
Published: January 2021

Abstract
An antegrade approach is frequently used in catheter-directed thrombolysis to remove deep-vein thrombosis. However, the antegrade approach is difficult when accessing veins with small diameters, therefore, understanding the variation of deep calf vein is important. This study measured the diameters and surface areas of the proximal and distal posterior tibial vein, peroneal vein, and anterior tibial vein in order to determine which are preferable for venous access. This study dissected 132 legs from Korean and Thai cadavers. The proximal and distal posterior tibial vein, peroneal vein, and anterior tibial vein were scanned and measured. The mean diameter and surface area were largest for the proximal tibial vein, at 6.34 mm and 0.312 cm2, respectively, followed by the anterior tibial vein (5.22 mm and 0.213 cm2), distal posterior tibial vein (3.29 mm and 0.091 cm2), and peroneal vein (3.43 mm and 0.081 cm2). The proximal posterior tibial vein and anterior tibial vein have large diameters and surface areas, which make them ideal for applying an antegrade approach in catheter-directed thrombolysis. The distal posterior tibial vein and peroneal vein are not recommended due to their smaller surface areas and also the anatomical variations therein.
Co-Contraction Analyses of the Body Wall Muscles in Caenorhabditis Elegans by Calcium Imaging Assay and Simulation
Authors: Soh Zu , Yamashita Hiroki , Suzuki Michiyo , Sakamoto Kazuma , Tsuji Toshio 
Published: January 2021

Abstract
Caenorhabditis elegans can generate locomotion under various environments with completely different drag levels. Therefore, animals should have strategies for adapting to the changes in the dynamics of locomotion imposed by various environments. We hypothesized that co-contraction between the ventral and dorsal body wall muscles plays such a role and validated the presence of a co-contraction strategy through both experimental and mathematical modeling approaches. To this end, the fluorescence of calcium ion (Ca2+) corresponding to a part of activities of the body wall muscles were measured. The results indicated a significant difference in the co-fluorescence rate between the animals moving in low- and high-drag environments. The contribution of co-contraction to the dynamics of locomotion was then analysed using a body dynamics model. The simulation results suggested that co-contraction allows the dominance of body stiffness over viscous drag so that the phase difference between the local curvature of the body and muscle activities can be maintained under different environmental drag levels. Therefore, co-contraction can be an effective strategy for adapting to environmental drag that changes the dynamics of locomotion.
In Vitro Investigations on Optimizing and Nebulization of IVT-mRNA Formulations for Potential Pulmonary Based Alpha-1-Antitrypsin Deficiency Treatment
Authors: Rosenecker Joseph , Guan Shan , Darmstädter Max , Xu Chuanfei 
Published: January 2021

Abstract

Background: In vitro transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The pulmonary delivery of IVT-mRNA encoding alpha-1-antitrypsin (A1AT) is a promising strategy for protein replacement therapy of alpha-1-antitrypsin deficiency (AATD). The nebulized A1AT-mRNA formulations would be a highly acceptable and tolerable remedy for the AATD patients in the future. Method: we first optimized parameters that were influencing the transfection efficiency of formulations containing IVT-mRNA and Lipofectamine2000 based on human bronchial epithelial cells transfection. Cell viability was evaluated by performing MTT assay after transfection with different IVT-mRNA lipoplexes. Functional analysis was employed to assess the biological function of A1AT proteins produced from optimized formulations using anti-trypsin assay and anti-elastase assay. Results: Lipoplexes prepared by IVT-mRNA encoding A1AT (A1AT-mRNA) in optimum conditions can successfully transfect human bronchial epithelial cells without significant toxicity. A reduction in transfection efficiency was observed for aerosolized lipoplexes that can be partially overcome by increasing the initial amount of components. A1AT produced from cells transfected by nebulized A1AT-mRNA lipoplexes is functional and can successfully inhibit the enzyme activity of trypsin as well as elastase. Conclusion: Aerosolization of A1AT-mRNA therapeutic constitute a potentially powerful means to transfect airway epithelial cells with the purpose of producing functional A1AT while bringing along the unique advantages of IVT-mRNA.
JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblasts Transdifferentiation in Graves' Orbital Fibroblasts
Authors: Hou Tzu-Yu , Wu Shi-Bei , Kau Hui-Chuan , Tsai Chieh-Chih 
Published: January 2021

Abstract
Transforming growth factor-β1 (TGF-β1)-induced myofibroblasts transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathway through which TGF-β1 activates Graves’ orbital fibroblasts is unclear. This study investigated the role of mitogen-activated protein kinase (MAPK) pathways in TGF-β1-induced myofibroblasts transdifferentiation of Graves’ orbital fibroblasts. MAPK pathways were assessed by measuring the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) using Western blot analysis. The expression levels of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), fibronectin, and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-3) representing fibrogenesis processes were analysed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of MAPK pathways. After treating Graves’ orbital fibroblasts with TGF-β1, the phosphorylation levels of p38 and JNK but not ERK were increased. Meanwhile, CTGF, α-SMA and fibronectin were overexpressed. After pre-incubation with p38, JNK and ERK inhibitors respectively, the TGF-β1-induced expression of CTGF, α-SMA, fibronectin, TIMP-1 and TIMP3 was abolished by p38 and JNK inhibitors but not ERK inhibitors. This study confirmed TGF-β1-induced myofibroblasts transdifferentiation in Graves' orbital fibroblasts via p38 and JNK signaling. Thus, MAPK pathways may be potential targets for the management of GO.
Oral Health Status among Older Adults Attending Public Clinics in Khartoum State, Sudan: a cross-sectional study
Authors: Salih Mayson , Ali Raouf , Nasir Elwalid 
Published: January 2021

Abstract
Background

As the number of older adults is growing worldwide, understanding the extension of the oral health problems of the older population is important for the determination of treatment needs and for future planning of dental services. This study assessed the oral health status and prosthetic needs among a group of older adults living in Khartoum State, Sudan.
Methods

A cross sectional study among individuals ≥ 60 years attending Health Care Centers. The clinical examination was based on the WHO oral health examination form for adults, 2013, which includes dentition status, periodontal conditions, oral mucosal lesions, tooth wear, prosthetic status and prosthetic needs.
Results

249 older adults participated in the study, 64.3% were males and the mean age was 68.4 years (SD ± 6.7). The mean (DMFT) was 15.9 (SD ± 9.1), with 85.3%, 94.8%, and 19.3% of the participants had decayed, missed or filled teeth, respectively. Periodontal pockets were present in 41.9% of the participants and attachment loss was in 84.2%. Only 14.9% had mucosal lesions while 46.2% showed signs of tooth wear. Although only 5.2% were completely edentulous, 93.2% of the participants need at least one unit prosthesis while only 10% had removable dentures. The main predicting factors of poor oral health were being female, poor oral hygiene practices, frequency and reason of dental visits, and poor perceived poor oral health.
Conclusion

Despite the low level of edentulism, the oral health of older adults of the studied Sudanese population was poor. They showed high prevalence and severity of missed and decayed teeth, periodontal disease and high prosthetic treatment needs.
A retrospective study of electroencephalogram parameters during general anaesthesia in infants and young children
Authors: Gao Zhengzheng , Zhang Jianmin , Wang Xiaoxue , Yao Mengnan , Sun Lan , Qiu Dongyu , Ren Yi 
Published: January 2021

Abstract
Background

This retrospective study describes electroencephalogram (EEG) parameters in infants and young children under general anaesthesia. The study’s primary objective was to detect determinants of patient state index (PSI) levels.
Methods

We analysed EEG parameters in patients aged 1–36 months who received sevoflurane or propofol as the primary anaesthetic in Beijing Children’s Hospital from September 1, 2019, to April 30, 2020. Patients were stratified into two age groups: 1–12 and 13–36 months. The relationship between EEG parameters and clinical parameters was analysed by multivariable linear regression.
Results

Sixty-two patients were involved in the final analysis, including 35 boys and 27 girls. Average patient age and weight were 14.5 (5.8–24.0) months and 9.9 (8.0–12) kg, respectively. Spectral edge frequency (SEF), PSI and blood pressure were lower (p < 0.001) and burst suppression rate (BSR) and heart rate higher (p < 0.001) at the age of 1–12 months under general anaesthesia. The most significant factor associated with higher levels of PSI was a higher SEF at the age of 1–36 months (1–12 months p = 0.001; 13–26 months p < 0.001); burst suppression occurrence decreased the PSI level (p = 0.031). Older age or higher blood pressure increased PSI levels in children under 1 year old (p = 0.028 and p = 0.002).
Conclusions

SEF was the most significant determinant associated with PSI levels in infants and young children during general anaesthesia, and burst suppression occurrence decreases the PSI level. Moreover, age and blood pressure might affect PSI levels in infants.
Healthcare Providers Experiences of Comprehensive Emergency Obstetric Care in Somaliland: An Explorative Study with Focus on Cesarean Deliveries
Authors: Kiruja Jonah , Essén Birgitta , Erlandsson Kerstin , Klingberg-Allvin Marie , Osman Fatumo 
Published: January 2021

Abstract

Background: Severe obstetric morbidity and mortality remain a serious challenge in developing countries such as Somaliland. Despite the wide implementation of comprehensive emergency obstetric care in Sub-Saharan Africa, including Somaliland, the reduction of severe maternal morbidity and mortality has been slow. Aim: This study aims to explore the experiences of healthcare providers (HCPs) regarding the provision of emergency obstetric care in a referral hospital and four maternal and child health centers in Somaliland. Method: An exploratory qualitative approach using focus group discussions was employed at the main referral and teaching hospital and four maternal and child health centers in Hargeisa, Somaliland. Twenty-eight healthcare providers were divided into groups of 6-8 for 1 to 2-hour discussions. HCPs included in the study had experiences in providing care to women with severe maternal complications. Data were analyzed using thematic analysis. Results: Collectivistic decision making through family ties was identified by HCPs to act as a barrier to provision of life saving obstetric interventions. This tradition of decision making at a group level rather than at the individual level was perceived as time-consuming and delayed HCPs from obtaining informed consent to provide lifesaving obstetric care. Low socioeconomic status, poor knowledge about maternal healthcare among users affected care seeking among women. Suboptimal care affecting provision of emergency obstetric care at the hospital was reported to be due to miscommunication, inadequate interprofessional collaboration and lack of infrastructure. Conclusion: HCPs experiences provided vital insights into the care provided to women with severe obstetric complications in Somaliland. To ensure smooth and timely decision-making processes, the antenatal period can be used to prepare families for potential obstetric emergencies and to obtain signed consents. Key Words: Maternal, Somaliland, Healthcare providers, Family ties, Emergency obstetric care, Cesarean section
Self-Care Behavior Prevention of Covid-19 in the General Population Based on Pender Health Promotion Model
Authors: Pouresmali Asghar , Alizadehgoradel Jaber , Molaei Behnam , Vanderhasselt Marie-Anne , Fathi Davod 
Published: January 2021

Abstract
BackgroundCoronavirus with sudden and widespread outbreak has obviously imposed devastating consequences in various aspects of human life. The purpose of this study was to determine the predictive value of Pender's health promotion model (HPM) structures in self-care preventive behavior against COVID-19 among the general population of Ardabil, Iran. MethodsThe present retrospective descriptive-correlational study was conducted on 200 citizens of Ardabil aged 18 and over in 2020, who were selected by convenience sampling through social media. Data collection tools included demographic profile, perceived self-efficacy scale, perceived emotions questionnaire, perceived social support questionnaire, perceived benefits and barriers questionnaire, researcher-made COVID-19 self-care questionnaire and commitment to action questionnaire based on Pender's HPM structures in an online manner. Data were analyzed by Amos 22 software and using structural equation modeling (SEM). ResultsAccording to the results, direct path analysis to COVID-19 self-care behavior indicated that the variables of perceived self-efficacy, interpersonal effects, positive emotion and perceived benefits are able to significantly predict self-care behaviors. Moreover, the bootstrapping test results in the indirect path analysis demonstrated that the variables of perceived self-efficacy, perceived social support, and perceived barriers and benefits through the mediator variable of commitment to action are able to significantly predict COID-19 self-care behavior.ConclusionsBased on the findings of the present study, it can be claimed that the proposed model of COVID-19 self-care behavior has an acceptable fitness in the general population. It seems that this model can be employed in developing educational programs and intervention techniques to modify people's attitudes and behaviors.
Ethnobotanical Wield Edible Plants and Tradition Used in Vientiane Province, Lao P.D.R
Authors: KHAMPHILAVONG KHAMBAY , Lili Zhang , Yongxiang Kang , Hua Li , Nishantha Muththanthirige D L C , Awais Muhammad 
Published: January 2021

Abstract
Background: Local people harvested wild edible plants to provide food and cash income for indigenous people and are of good importance to guarantee global food security. Individuals also play a significant role in maintaining the productivity and stability of indigenous ecosystems. Vientiane province, the middle part of Laos, is regarded as the biodiversity hotspot. The people who are living there have consolidated traditional knowledge about plants used. Hence, with the developing country, wild edible plants are threatening, and the associated local knowledge is in danger of being lost. However, wild plants surveys were conducted to investigate and documented the wild edible plants indigenous experience used by local people.Methods: Five-teen villages were carried out the field investigation. The information was collected using questionnaires, direct observation, individual discussion, semi-structured interviews, key informant interviews, group discussion, and participatory rural appraisal (PRA).Results: In this research, information about 202 wild edible plant species in 150 genera of 83 families was recorded. Most species were edible fruits (55 species), followed by young leaves (48 species). The wild edible plants are sources or fresh markets for local people, especially those living in remote areas, to procure mineral elements and vitamins. In addition, were 79 species sold as a mixture at the market. Therefore, the utilization of wild edible plants related to knowledge was according swiftly, especially in an area with the livable transportation and booming traveler.Conclusion: Local food, wild plant species are abundant and diverse in Vientiane province. The people provide food and proteins to remote areas people and also be a source of income. Hence, their associated traditional knowledge and wild edible plants are facing a variety of intimidation. So, preservation and sustainable utilization of these wild plants in this region are important. To document of these plant species might provide incipient information for conservation, probably further exploitation and will gather local indigenous knowledge.
Effects of Violent Video Games on Aggressive Behaviors Among Children: The Role of Anger and Trait Aggression in China
Authors: Zhang Qian , Tian JingJin , Chen LunChao , Cao Yi 
Published: January 2021

Abstract
The current study examined the violent video game effect on aggressive behaviors and the potential role of anger and trait aggression among Chinese children (n = 248; Mage = 6.09, SD = 0.21). Half of them were randomly assigned to play a violent or a neutral video game for 20 minutes. Results showed that brief exposure of children to a violent video game produced a small but significant increases in aggressive behaviors. More specifically, males exhibited more aggressive behaviors than females in the violent game condition. Moderation analysis suggested that the violent video game effect on aggression was not moderated by trait aggression, but this effect was mediated by increased anger (especially for males). These findings indicated that males who were exposed to a violent video game might be regarded as the key group to reduce aggression by training to vent their anger. Results are interpreted within and support the framework of the General Aggression Model (GAM).
Increased Carvone Production in Escherichia Coli by Balancing Expression of Limonene Conversion Enzymes Through Targeted QconCAT Proteome Analysis
Authors: Yoshida Erika , Kojima Motoki , Suzuki Munenori , Matsuda Fumio , Onuki Akiko , Nishio Yousuke , Usuda Yoshihiro , Kondo Akihiko , Ishii Jun 
Published: January 2021

Abstract
Background Natural mint flavor is produced by extraction from mint, which is not efficient enough to make it environment friendly process. (−)-Carvone is the monoterpenoid with key flavor of spearmint, and there has been an attempt to produce (−)-carvone by recombinant Escherichia coli. Although all enzymes in (−)-carvone biosynthesis have been functionally expressed in E. coli independently, the yield of (−)-carvone was low in the previous study.ResultsWe have found a by-product formation when cytochrome P450 limonene-6-hydroxylase (P450)/cytochrome P450 reductase (CPR) and carveol dehydrogenase (CDH) were expressed in single cell. These by-products were determined as dihydrocarveol and dihydrocarvone. We hypothesized that the enzymatic kinetics and the expression levels of P450 and CDH are quite different in E. coli. Therefore, two strains independently expressing P450/CPR and CDH were mixed with different mixing ratio, confirming increase in carvone production and decrease in by-product formation when CDH input was reduced. To determine the optimum balance of enzyme expressions, proteome analysis quantification concatemer (QconCAT) method to quantify P450, CPR, and CDH was developed. Using the QconCAT standard protein that was artificially created by concatenating the tryptic peptides, the ratio between P450 and CDH was calculated, and their optimum ratio to maximize (−)-carvone production was shown. Then, a single strain expressing both P450/CPR and CDH was constructed to imitate the superior expression ratio. The upgraded strain showed 15-fold improvement compared to the initial strain, showing 44 ± 6.3 mg/L of (−)-carvone production from 100 mg/L (−)-limonene as a starting substrate.ConclusionsImproved expression balance of P450 and CDH in recombinant E. coli increased the (−)-carvone production using (−)-limonene as the direct substrates by the whole-cell biocatalysis, showing approximately 150 times higher titer than previous report. Our study showed the usefulness of proteome analysis QconCAT method in the strain development for industrial biotechnology field.
Distribution of ABO&nbsp;Blood Groups and Their Association With Low Risk of Severe COVID-19 Infection in Patients
Authors: Peng Minfei , Huang Shigao , Lv Qingqing , Chen Chaochao , Qin Jiajia , He Minmin , Yang Jie , Chen Shiyong , Zhao Qi 
Published: January 2021

Abstract
Background: To date, only few studies have focused on the correlation between ABO blood groups and COVID-19 infection risk, especially gender differences in infection risk. Our study aimed to describe the ABO blood group distribution and its association with risk of severe COVID-19 infection for effective identification of the susceptible population. Method：From January 21 to February 20, 2020, we compared the ABO blood group distribution and gender distribution and performed a correlation analysis in severe, non-severe, and non-COVID-19 patients. Results The results showed that the laboratory indices were significantly different between blood type O and non-blood-type-O COVID-19 patients. This indicated that patients of the type O blood group had a relatively lower risk of severe COVID-19 infection than patients of other blood types; in particular, females with blood type O had a lower risk of severe COVID-19 infection than males. Conclusion: Herein, we report a potentially simple prediction decision system to minimize the risk of severe COVID-19 infection based on blood type. Special attention should be paid to patients with blood types other than type O to minimize their risk of severe COVID-19 infection.