bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity-Based Anorexia Induces Browning of Adipose Tissue Independent of Hypothalamic AMPK
Authors: Fraga Angela , Rial-Pensado Eva , Nogueiras Rubén , Fernø Johan , Diéguez Carlos , Gutierrez Emilio , López Miguel
Published: June 2021

Anorexia nervosa (AN) is an eating disorder leading to malnutrition and, ultimately, to energy wasting and cachexia. Rodents develop activity-based anorexia (ABA) when simultaneously exposed to a restricted feeding schedule and allowed free access to running wheels. These conditions lead to a life-threatening reduction in body weight, resembling AN in human patients. Here, we investigate the effect of ABA on whole body energy homeostasis at different housing temperatures. Our data show that ABA rats develop hyperactivity and hypophagia, which account for a massive body weight loss and muscle cachexia, as well as reduced uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but increased browning of white adipose tissue (WAT). Increased housing temperature reverses not only the hyperactivity and weight loss of animals exposed to the ABA model, but also hypothermia and loss of body and muscle mass. Notably, despite the major metabolic impact of ABA, none of the changes observed are associated to changes in key hypothalamic pathways modulating energy metabolism, such as AMP-activated protein kinase (AMPK) or endoplasmic reticulum (ER) stress. Overall, this evidence indicates that although temperature control may account for an improvement of AN, key hypothalamic pathways regulating thermogenesis, such as AMPK and ER stress, are unlikely involved in later stages of the pathophysiology of this devastating disease.
Assessing the Efficiency and CO2 Reduction Performance of China’s Regional Wind Power Industry Using an Epsilon-Based Measure Model
Authors: Tian Ze , Xiao Qin-Wen , Ren Fang-Rong
Published: June 2021

China has become the largest wind power installation market in the world, and on such a large scale its wind power industry contributes to the sustainability of electricity generation and reduction of carbon emissions, yet has problems such as wind curtailment, insufficient wind power consumption, and regional disparities. Thus, this research uses an epsilon-based measure (EBM) data envelopment analysis (DEA) model to evaluate and compare wind power electricity generation efficiency and CO2 emission reduction efficiency in the eastern, central, western, and northeastern regions of China for the period 2013–2017. The empirical results show that the nation’s overall wind power efficiency presents a significant upward trend, in which the western and northeastern regions have increased the most, while the east region has increased the least. Technical inefficiency is mainly due to diseconomies of scale in China’s wind power industry. Moreover, CO2 emission reduction in the four regions exhibits high efficiency, and the regions’ efficiencies are very consistent with that of installed capacity efficiency. Finally, this study’s policy implications are that industry development plans should be made according to local conditions as well as cross-regional trade of wind power electricity and that the upgrading of wind power generation capacity should be encouraged.
Study on the Calculation Method of Molten Pool Decay Heat Distribution under IVR Condition
Authors: Hao Yisheng , Chen Junyi , Luo Hao , Guo Xiaoyu , Liu Minyun , Huang Shanfang , Wang Kan , Gong Houjun , Li Yang , Hu Yuwen , Lu Chuan
Published: June 2021

As an important strategy to mitigate severe accidents, the in-vessel retention (IVR) technique has been applied to the new generation of pressurized water reactor (PWR). However, under IVR conditions, the decay heat distribution in the molten pool is very uncertain because of the complexity of the molten pool and the calculation method limitations. To explore the calculation method and distribution of the decay heat of lower head molten pool under IVR conditions, the decay heat calculation method is developed based on Reactor Monte Carlo Code (RMC). The verification results show that the relative error of calculation result is generally within ± 0.25%. In addition, geometric modeling for lower head molten pools has been carried out, and distribution of the decay heat in two-layer and three-layer structures has also been accurately calculated. The calculation results indicate that the decay heat power spatial distribution is relatively uniform in the two-layer molten pool structure. The decay heat power at the center of the lower head decreases from 0.71°W/cm3 to 0.023°W/cm3 within 1d-5d. In the three-layer molten pool structure, the spatial distribution of the decay heat power is severely uneven due to the precipitation of heavy metal uranium. Besides, in actual engineering calculations, it should lay emphasis on the heat transfer characteristics and design margin of the upper part of the heavy metal layer and the lower part of the oxide layer because the maximum decay heat power appears at these two positions.
Unpacking Stakeholder Perceptions of the Benefits and Challenges Associated With Urban Greenspaces in Sub-Saharan Africa
Authors: Guenat Solène , Porras Lopez Gabriel , Mkwambisi David D , Dallimer Martin
Published: June 2021

Urban greenspaces underpin ecosystem service provision in cities and are therefore indispensable for human well-being. Nevertheless, they are increasingly disappearing from cities in Sub-Saharan Africa. Understanding how the stakeholders influencing urban greenspace management perceive the benefits provided by urban greenspaces and the challenges to its conservation and management is critical for reversing this trend. Using Malawi’s capital city, Lilongwe, as a case study, we conducted 44 semi-structured interviews to explore the profiles and perceptions of stakeholders who currently hold influence over greenspace planning, conservation and management. Stakeholders with influence over urban greenspace management described the main focus of their organisation as relating to urban planning, natural resources protection and management, development work, or the hospitality business sector. Critically, only a third of all stakeholders focused on natural resources protection and management. Stakeholders had nuanced and varied appreciations of the benefits that greenspaces provide. Regulation and maintenance ecosystem services, as well as cultural services were frequently mentioned. However, provisioning services were mostly mentioned by those in development work. Stakeholders also identified an additional suite of societal benefits that do not directly map onto ecosystem service frameworks, such as the generation of financial income and the provision of employment opportunities. Challenges identified as hampering the planning, conservation and management of greenspaces included inappropriate urbanisation, lack of coordination and participation, and population growth. Lack of coordination was however not widely acknowledged among those focusing on natural resources protection, who conversely identified population growth more often than any other groups. Highlighting how stakeholders with varying priorities perceive ecosystem services a first step towards improving greenspaces management both for their better acceptation and for improving their potential for biodiversity conservation. Specifically, we bring attention to need for stakeholders working with natural resources protection to recognise more the need for collaborations and engagement. Additional research is also necessary to understand how those different perspectives might be integrated into ongoing processes and procedures to manage greenspaces in Sub-Saharan Africa.
Transcriptomic Analysis of the Effect of GAT-2 Deficiency on Differentiation of Mice Naïve T Cells Into Th1 Cells In Vitro
Authors: Ding Xueyan , Chang Yajie , Wang Siquan , Yan Dong , Yao Jiakui , Zhu Guoqiang
Published: June 2021

The neurotransmitter γ-aminobutyric acid (GABA) is known to affect the activation and function of immune cells. This study investigated the role of GABA transporter (GAT)-2 in the differentiation of type 1 helper T (Th1) cells. Naïve CD4+ T cells isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice were cultured; Th1 cell differentiation was induced and transcriptome and bioinformatics analyses were carried out. We found that GAT-2 deficiency promoted the differentiation of naïve T cells into Th1 cells. RNA sequencing revealed 2984 differentially expressed genes including 1616 that were up-regulated and 1368 that were down-regulated in GAT-2 KO cells compared to WT cells, which were associated with 950 enriched Gene Ontology terms and 33 enriched Kyoto Encyclopedia of Genes and Genomes pathways. Notably, 4 signal transduction pathways (hypoxia-inducible factor [HIF]-1, Hippo, phospholipase D, and Janus kinase [JAK]/signal transducer and activator of transcription [STAT]) and one metabolic pathway (glycolysis/gluconeogenesis) were significantly enriched by GAT-2 deficiency, suggesting that these pathways mediate the effect of GABA on T cell differentiation. Our results provide evidence for the immunomodulatory function of GABA signaling in T cell-mediated immunity and can guide future studies on the etiology and management of autoimmune diseases.
High Value Phycotoxins From the Dinoflagellate Prorocentrum
Authors: Camacho-Muñoz Dolores , Praptiwi Radisti A. , Lawton Linda A. , Edwards Christine
Published: June 2021

Marine dinoflagellates produce chemically diverse compounds, with a wide range of biological activity (antimicrobial, anticancer, treatment of neurodegenerative disease along with use as biomedical research tools). Chemical diversity is highlighted by their production of molecules such as the saxitoxin family of alkaloids (C10H17N7O4– 299 g/mol) to the amphipathic maitotoxin (C164H256O68S2Na2– 3,422 g/mol), representing one of the largest and most complex secondary metabolites characterized. Dinoflagellates, are most well-known for the production of red tides which are frequently toxic, including okadaic acid and related dinophysistoxins, which are tumor promoters. The mode of action for these phycotoxins, is by specific inhibition of protein phosphatases, enzymes essential in regulation of many cellular processes. Hence, these compounds are being used for vital cell regulation studies. However, the availability of useful amounts of these compounds has restricted research. Chemical synthesis of some compounds such as okadaic acid has been investigated, but the complexity of the molecule resulted in many lengthy steps and achieved only a poor yield. The use of naturally occurring phytoplankton has been investigated as a potential source of these compounds, but it has been shown to be unreliable and impractical. The most practical option is large scale culture with down-stream processing/purification which requires specialist facilities and expertise. This review, describes the biotechnological potential of these organisms and the challenges to achieve useful yields of high quality phycotoxins usingProrocentrumspp. as an example to produce okadaic acid.
Threatened Mangroves in the Anthropocene: Habitat Fragmentation in Urban Coastalscapes of Pelliciera spp. (Tetrameristaceae) in Northern South America
Authors: Blanco-Libreros Juan F. , Ramírez-Ruiz Karla
Published: June 2021

Mangroves are fragmented habitats thriving in human-dominated coastalscapes worldwide. They provide refuge to threatened plant species, such as the NeotropicalPiñueloMangrove (formerly the monotypicPellicieragenus, recently split into two species:P. rhizophoraeandP. benthamii). However, little is known about the relationship between urbanization and the spatial configuration of mangrove habitat and how it would drive ecological and evolutionary changes in the small populations ofPellicieraspp. We used open data (e.g., land cover, mangrove cover) for 107 locations ofPellicieraspp. in Colombia (extant populations) to assess coastalscape structure and urbanization. We described coastalscape composition dynamics (for 2000 and 2010) and mangrove habitat configuration along a human-domination gradient, using landscape metrics. We computed an urban index to compare urbanization intensity among the study areas along the Caribbean coast and compared coastalscape structure and mangrove spatial metrics between basins (Caribbean and Pacific). The proportion of artificial surfaces was greater in the Caribbean than in the Pacific, but no temporal difference was found. The Caribbean basin exhibited a greater Urban Index, particularly in Cartagena and Urabá. Mangrove fragmentation was also greater in the Caribbean and it was influenced by the degree of urbanization. Mangrove area and core area were smaller in the Caribbean than in the Pacific, while cohesion was significantly lower in Cartagena than in other urban areas of the Caribbean. We propose a conceptual eco-evolutionary framework for linking mangrove patch reduction and isolation to demographic variables ofPellicieraspp. Edge effects are expected to affect birth and mortality rates in small patches. Small patches and small effective populations are expected to be more sensitive to novel biotic interactions, extreme weather, and gradual climate change. Isolation will also influence both emigration and immigration rates of propagules. We propose: (1) Assessing the conservation status of the two species, (2) setting monitoring programs of their populations ofPellicieraspp. and their surrounding coastalscapes (particularly in the Caribbean, (3) declaring protected areas, in wild and urban settings, to reduce mangrove fragmentation and urbanization.
Natural Infection of Covert Mortality Nodavirus in Small Yellow Croaker in Coastal Water
Authors: Xu Tingting , Li Yingxia , Shan Xiujuan , Hao Jingwei , Wu Qiang , Tang Kathy F. J. , Zhang Qingli , Yao Cuiluan
Published: June 2021

Covert mortality nodavirus (CMNV) is an alphanodavirus mainly infecting marine shrimp and co-inhabiting organisms in aquaculture ponds. To evaluate the possibility of CMNV prevalence in the wild fish species, epidemiological survey of CMNV infection in Larimichthys polyactis, the dominant species in the Yellow Sea and East China Sea, were conducted in the present study. We performed CMNV RT-LAMP assay in samples of L. polyactis collected in August 2018 and 2019 and found that CMNV prevalence was 18% and 7%, respectively. The nucleotide sequences of both RdRp and capsid protein genes of CMNV from L. polyactis were 99% similar to those of CMNV isolated from shrimp. CMNV-positive L. polyactis exhibited necrosis of cardiac muscle, oocytes loosely arranging, severe cytoplasmic vacuolation of hepatocytes, moderate pyknosis of brain pyramidal cells, degenerate renal tubular cells with ill-defined margins, and declined spleen cells in the histological examination. Moreover, CMNV-positive signals were further observed in pyramidal cells of the brain, the cortical area of the kidney, oocyte growth rings, and in necrotic tissues of cardiac muscle, liver, and spleen in the in situ hybridization assay. The results revealed that CMNV had colonized in the wild populations of L. polyactis and the ecological risk of CMNV spread and epidemic in wild fish in the coastal water was non-negligible.
Mechanical Behavior of the Novel Gradient Concrete Tower of a Cable-Stayed Bridge
Authors: Wang Zuo-Cai , Duan Da-You , Wang Shu-Hang , Mo Ye , Yin Yong-Gao
Published: June 2021

In this paper, the novel gradient concrete is innovatively applied to the bridge towers of Chizhou Yangtze River Bridge to solve the cracking and insufficient durability problems of concrete towers. Fiber-reinforced concrete is used in the outer functional area of the bridge tower, to significantly improve its crack resistance during construction and service. Moreover, the integrated design of anti-cracking and mechanical properties of tower materials is achieved. To study the performance of the novel functional gradient concrete (FGC) tower, the mechanical properties of the FGC tower material are tested, and the overall finite element stress is analyzed. Based on the material properties, the mechanical behavior of the cable-stayed bridge tower is studied. The temperature and stress of the FGC tower during the generation of the hydration heat are compared with that of the ordinary concrete tower. The crack resistance of the FGC tower is analyzed by the finite element method. The results show that the FGC tower has good mechanical properties and durability for the cable-stayed bridge towers.
Metal and Metal Oxide Based Advanced Ceramics for Electrochemical Biosensors-A Short Review
Authors: Subbaiah G. Bala , Ratnam K. Venkata , Janardhan S. , Shiprath K. , Manjunatha H. , Ramesha M. , Prasad N. V. Krishna , Ramesh S. , Babu T. Anil
Published: June 2021

Identifying and quantifying the biological concentrations of certain biomolecules such as dopamine, glucose, tyrosine, and cholesterol, etc. has become the basis for medical diagnosis in the treatment of a number of related diseases. In most cases, the concentrations of these biomolecules in biofluids like blood acts as a biomarker and becomes crucial in the treatment of diseases. On the other hand, advanced ceramics refers to oxides (alumina, zirconia), non-oxides: (carbides, borides, nitrides, silicides), Composites (particulate reinforced combinations of oxides and non-oxides), etc. This review article discusses recent developments in the field of electrochemical sensors developed using metal and metal oxide based advanced ceramics with an emphasis on developments in the field over the past five years. The article presents the key results, important findings, and interesting chemistry of biosensing advanced ceramic based electrochemical biosensors for some important biomolecules such as acetaminophen, glucose, and dopamine, etc.
The Impact of Endometriosis on Embryo Quality in in-vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-Analysis
Authors: Dongye Houjin , Ji Xiaofeng , Ma Xiaopei , Song Jialun , Yan Lei
Published: June 2021

Background: The association between endometriosis and embryological outcomes remains uncertain. The meta-analysis aimed to evaluate the impact of endometriosis on embryo quality.

Methods: A systematic review and meta-analysis was conducted to investigate the association between the endometriosis and embryo quality. Searches were performed on the three electronic databases: PubMed, EMBASE, and Web of Science. The detailed characteristics and data of the included studies were extracted. The risk ratio with 95% confidence intervals were calculated using the random and fixed effects model. The main outcome measures were high-quality embryo rate, cleavage rate, and embryo formation rate.

Results: A total of 22 studies included were analyzed. Compared with the control group, women with endometriosis had a similar high-quality embryo rate (RR = 1.00; 95% CI, 0.94–1.06), a comparable cleavage rate (RR = 1.00; 95% CI, 0.97–1.02), and a similar embryo formation rate (RR = 1.10; 95% CI, 0.97–1.24). In women with stage III-IV endometriosis, there was no statistically significantly difference in high-quality embryo rate (RR = 1.02; 95% CI, 0.94–1.10), cleavage rate (RR = 1.00; 95% CI, 0.98–1.02), and embryo formation rate (RR = 1.05; 95% CI, 0.97–1.14), compared with those without endometriosis. For women with unilateral endometrioma, pooling of results from the affected ovaries did not show a statistically significantly difference in high-quality embryo rate (RR = 0.99; 95% CI, 0.60–1.63) in comparison to the normal contralateral ovaries.

Conclusions: Our results seem to indicate that endometriosis does not compromise embryo quality from the perspective of morphology.
Functional Status After Pulmonary Rehabilitation as a Predictor of Weaning Success and Survival in Patients Requiring Prolonged Mechanical Ventilation
Authors: Keng Li-Ta , Liang Sheng-Kai , Tseng Chi-Ping , Wen Yueh-Feng , Tsou Ping-Hsien , Chang Chia-Hao , Chang Lih-Yu , Yu Kai-Lun , Lee Meng-Rui , Ko Jen-Chung
Published: June 2021

Background: Comprehensive rehabilitation programs are recommended for patients with prolonged mechanical ventilation (PMV) to facilitate functional recovery and ventilator weaning, but whether the functional status after rehabilitation influences outcome has not been clearly evaluated. This study aimed to investigate the association between post-rehabilitation functional status and weaning and survival outcome in PMV patients.

Methods: We retrospectively enrolled PMV patients admitted to the respiratory care center (RCC), a post-ICU weaning facility with protocolized rehabilitation program, from January 2016 through December 2017. Functional status was measured by the de Morton Mobility Index (DEMMI), with a cut-off value set at 20 points. The primary outcomes were the weaning status at RCC discharge and hospital survival. The secondary outcomes were overall survival and survival at 3 months after RCC discharge. We followed patients until 3 months after RCC discharge or death. Logistic and Cox regressions were performed to identify significant parameters associated with weaning success and survival.

Results: In total, 320 patients were enrolled. The weaning success rate was 71.6%. The survival rate at RCC discharge, hospital discharge, and 3 months after RCC discharge was 89.1, 77.5, and 66.6%, respectively. Post-rehabilitation DEMMI ≥ 20 (odds ratio [OR], 3.514; 95% confidence interval [CI], 1.436–8.598; P = 0.006) was the most significantly associated with weaning success. The weaning success and higher post-rehabilitation DEMMI were the two most significant independent factors associated with both hospital survival (weaning success, OR, 12.272; 95% CI, 5.281–28.517; P < 0.001; post-rehabilitation DEMMI ≥ 20, OR, 6.298; 95% CI, 1.302–30.477; P = 0.022) and survival at 3 months after RCC discharge (weaning success, OR, 38.788; 95% CI, 11.505–130.762; P < 0.001; post-rehabilitation DEMMI ≥ 20, OR, 4.830; 95% CI, 1.072–21.756; P = 0.040). Post-rehabilitation DEMMI ≥ 20 remained significantly association with overall survival at 3 months after RCC discharge (hazard ratio, 0.237; 95% CI, 0.072–0.785; P = 0.018).

Conclusions: Post-rehabilitation functional status of PMV patients was independently associated with weaning success, as well as hospital and 3-month overall survival after RCC discharge. Post-rehabilitation, but not pre-rehabilitation, functional status was a significant parameter associated with weaning success and survival in patients requiring PMV.
Gut Bacterial Diversity in Different Life Cycle Stages of Adelphocoris suturalis (Hemiptera: Miridae)
Authors: Xue Hui , Zhu Xiangzhen , Wang Li , Zhang Kaixin , Li Dongyang , Ji Jichao , Niu Lin , Wu Changcai , Gao Xueke , Luo Junyu , Cui Jinjie
Published: June 2021

Bacteria and insects have a mutually beneficial symbiotic relationship. Bacteria participate in several physiological processes such as reproduction, metabolism, and detoxification of the host. Adelphocoris suturalis is considered a pest by the agricultural industry and is now a major pest in cotton, posing a serious threat to agricultural production. As with many insects, various microbes live inside A. suturalis. However, the microbial composition and diversity of its life cycle have not been well-studied. To identify the species and community structure of symbiotic bacteria in A. suturalis, we used the HiSeq platform to perform high-throughput sequencing of the V3–V4 region in the 16S rRNA of symbiotic bacteria found in A. suturalis throughout its life stages. Our results demonstrated that younger nymphs (1st and 2nd instar nymphs) have higher species richness. Proteobacteria (87.06%) and Firmicutes (9.43%) were the dominant phyla of A. suturalis. At the genus level, Erwinia (28.98%), Staphylococcus (5.69%), and Acinetobacter (4.54%) were the dominant bacteria. We found that the relative abundance of Erwinia was very stable during the whole developmental stage. On the contrary, the relative abundance of Staphylococcus, Acinetobacter, Pseudomonas, and Corynebacterium showed significant dynamic changes at different developmental stages. Functional prediction of symbiotic bacteria mainly focuses on metabolic pathways. Our findings document symbiotic bacteria across the life cycle of A. suturalis, as well as differences in both the composition and richness in nymph and adult symbiotic bacteria. Our analysis of the bacteria in A. suturalis provides important information for the development of novel biological control strategies.
Antimicrobial Resistance and the Spectrum of Pathogens in Dental and Oral-Maxillofacial Infections in Hospitals and Dental Practices in Germany
Authors: Meinen Annika , Reuss Annicka , Willrich Niklas , Feig Marcel , Noll Ines , Eckmanns Tim , Al-Nawas Bilal , Markwart Robby
Published: June 2021

Data on microbiological profiles in odontogenic infections are scarce. This study aimed to analyze the spectrum of pathogens and antimicrobial resistance in clinical isolates from dental and oral-maxillofacial clinical settings in Germany. We analyzed 20,645 clinical isolates (dental practices: n = 5,733; hospitals: n = 14,912) from patients with odontogenic infections using data (2012–2019) from the German Antimicrobial-Resistance-Surveillance (ARS) system. A total of 224 different species from 73 genera were found in clinical isolates from dental practices, and 329 different species from 97 genera were identified in isolates from hospital patients. In both hospitals and dental practices Streptococcus spp. (33 and 36%, respectively) and Staphylococcus spp. (21 and 12%, respectively) were the most frequently isolated microorganisms. In Streptococcus spp. isolates from hospitals, penicillin and aminopenicillin resistance proportions were 8.0% (95%CI 4.7–14.9%) and 6.9% (95%CI 4.7–9.9%), respectively. Substantially lower resistance proportions of penicillin and aminopenicillin were observed in dental practices [2.6% (95%CI 1.4–4.7%) and 2.1% (95%CI 1.1–4.0%), respectively]. Among Staphylococcus aureus isolates from hospital patients methicillin resistance proportions were 12.0% (95%CI 9.7–14.8%), which was higher than in isolates from dental practices (5.8% (95%CI 4.1–8.1%)]. High clindamycin and macrolide resistance proportions (>17%) were observed in Streptococcus spp. and Staphylococcus aureus isolates. In Klebsiella spp. isolates carbapenem resistance proportions were <1%. In sum, substantial antibiotic resistance was observed in isolates from odontogenic infections, which calls for strengthened efforts in antibiotic stewardship and infection prevention and control measures in both hospitals and dental practices.
Inactivation Effect of Thymoquinone on Alicyclobacillus acidoterrestris Vegetative Cells, Spores, and Biofilms
Authors: Fan Qiuxia , Liu Cheng , Gao Zhenpeng , Hu Zhongqiu , Wang Zhouli , Xiao Jianbo , Yuan Yahong , Yue Tianli
Published: June 2021

Alicyclobacillus acidoterrestris (A. acidoterrestris), a spore-forming bacterium, has become a main challenge and concern for the juices and acid beverage industry across the world due to its thermo-acidophilic characteristic. Thymoquinone (TQ) is one of the active components derived from Nigella sativa seeds. The objective of this study was to investigate antibacterial activity and associated molecular mechanism of TQ against A. acidoterrestris vegetative cells, and to evaluate effects of TQ on A. acidoterrestris spores and biofilms formed on polystyrene and stainless steel surfaces. Minimum inhibitory concentrations of TQ against five tested A. acidoterrestris strains ranged from 32 to 64 μg/mL. TQ could destroy bacterial cell morphology and membrane integrity in a concentration-dependent manner. Field-emission scanning electron microscopy observation showed that TQ caused abnormal morphology of spores and thus exerted a killing effect on spores. Moreover, TQ was effective in inactivating and removing A. acidoterrestris mature biofilms. These findings indicated that TQ is promising as a new alternative to control A. acidoterrestris and thereby reduce associated contamination and deterioration in the juice and acid beverage industry.
Protein Predictive Modeling and Simulation of Mutations of Presenilin-1 Familial Alzheimer’s Disease on the Orthosteric Site
Authors: Soto-Ospina Alejandro , Araque Marín Pedronel , Bedoya Gabriel , Sepulveda-Falla Diego , Villegas Lanau Andrés
Published: June 2021

Alzheimer’s disease pathology is characterized by β-amyloid plaques and neurofibrillary tangles. Amyloid precursor protein is processed by β and γ secretase, resulting in the production of β-amyloid peptides with a length ranging from 38 to 43 amino acids. Presenilin 1 (PS1) is the catalytic unit of γ-secretase, and more than 200 PS1 pathogenic mutations have been identified as causative for Alzheimer’s disease. A complete monocrystal structure of PS1 has not been determined so far due to the presence of two flexible domains. We have developed a complete structural model of PS1 using a computational approach with structure prediction software. Missing fragments Met1-Glut72 and Ser290-Glu375 were modeled and validated by their energetic and stereochemical characteristics. Then, with the complete structure of PS1, we defined that these fragments do not have a direct effect in the structure of the pore. Next, we used our hypothetical model for the analysis of the functional effects of PS1 mutations Ala246GLu, Leu248Pro, Leu248Arg, Leu250Val, Tyr256Ser, Ala260Val, and Val261Phe, localized in the catalytic pore. For this, we used a quantum mechanics/molecular mechanics (QM/MM) hybrid method, evaluating modifications in the topology, potential surface density, and electrostatic potential map of mutated PS1 proteins. We found that each mutation exerts changes resulting in structural modifications of the active site and in the shape of the pore. We suggest this as a valid approach for functional studies of PS1 in view of the possible impact in substrate processing and for the design of targeted therapeutic strategies.
Rich Club Characteristics of Alcohol-Naïve Functional Brain Networks Predict Future Drinking Phenotypes in Rhesus Macaques
Authors: Rowland Jared A. , Stapleton-Kotloski Jennifer R. , Alberto Greg E. , Davenport April T. , Epperly Phillip M. , Godwin Dwayne W. , Daunais James B.
Published: June 2021

Purpose: A fundamental question for Alcohol use disorder (AUD) is how and when naïve brain networks are reorganized in response to alcohol consumption. The current study aimed to determine the progression of alcohol’s effect on functional brain networks during transition from the naïve state to chronic consumption.

Procedures: Resting-state brain networks of six female rhesus macaque (Macaca mulatta) monkeys were acquired using magnetoencephalography (MEG) prior to alcohol exposure and after free-access to alcohol using a well-established model of chronic heavy alcohol consumption. Functional brain network metrics were derived at each time point.

Results: The average connection frequency (p < 0.024) and membership of the Rich Club (p < 0.022) changed significantly over time. Metrics describing network topology remained relatively stable from baseline to free-access drinking. The minimum degree of the Rich Club prior to alcohol exposure was significantly predictive of future free-access drinking (r = −0.88, p < 0.001).

Conclusions: Results suggest naïve brain network characteristics may be used to predict future alcohol consumption, and that alcohol consumption alters functional brain networks, shifting hubs and Rich Club membership away from previous regions in a non-systematic manner. Further work to refine these relationships may lead to the identification of a high-risk drinking phenotype.
Socio-Demographic and Knowledge-Related Determinants of Vitamin D Supplementation in the Context of the COVID-19 Pandemic: Assessment of an Educational Intervention
Authors: Žmitek Katja , Hribar Maša , Lavriša Živa , Hristov Hristo , Kušar Anita , Pravst Igor
Published: June 2021

Vitamin D is a pro-hormone, essential for musculo-skeletal health, normal immune system, and numerous other body functions. Vitamin D deficiency is considered as a risk factor in many conditions, and there is growing evidence of its potential role in the severity of COVID-19 outcomes. However, an alarmingly high prevalence of vitamin D deficiency is reported in many regions, and vitamin D supplementation is commonly recommended, particularly during wintertime. To reduce the risk for vitamin D deficiency in the Slovenian population during the COVID-19 pandemic, we conducted mass media intervention with an educational campaign. The objective of this study was to investigate vitamin D supplementation practices in Slovenia before and during the COVID-19 pandemic, and to determine the effects of the educational intervention on supplementation practices. Two data collections were conducted using an online panel with quota sampling for age, sex, and geographical location. A pre-intervention (N= 602, April 2020) and post-intervention (N= 606, December 2020) sampling were done during the first and second COVID-19 lockdown, respectively. We also focused on the identification of different factors connected to vitamin D supplementation, with a particular emphasis on vitamin D-related knowledge. Study results showed significant increase in vitamin D supplementation in the population. Penetration of the supplementation increased from 33% in April to 56% in December 2020. The median daily vitamin D intake in supplement users was 25 μg, with about 95% of supplement users taking safe vitamin D levels below 100 μg/daily. Vitamin D-related knowledge (particularly about dietary sources of vitamin D, the health-related impact of vitamin D, and the prevalence of deficiency) was identified as a key independent predictor of vitamin D supplementation. Based on the study findings, we prepared recommendations to support the development of effective awareness campaigns for increasing supplementation of vitamin D.
Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19
Authors: Alberca Ricardo Wesley , Rigato Paula Ordonhez , Ramos Yasmim Álefe Leuzzi , Teixeira Franciane Mouradian Emidio , Branco Anna Cláudia Calvielli , Fernandes Iara Grigoletto , Pietrobon Anna Julia , Duarte Alberto Jose da Silva , Aoki Valeria , Orfali Raquel Leão , Sato Maria Notomi
Published: June 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease–2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.
Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia
Authors: Fang Qiuyun , Song Yang , Gong Xiaoyuan , Wang Jun , Li Qinghua , Liu Kaiqi , Feng Yahui , Hao Qishan , Li Yan , Wei Hui , Zhang Guangji , Liu Yuntao , Gong Benfa , Wang Ying , Zhou Chunlin , Lin Dong , Liu Bingcheng , Wei Shuning , Gu Runxia , Mi Yingchang , Wang Jianxiang
Published: June 2021

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.
Identification of NAA40 as a Potential Prognostic Marker for Aggressive Liver Cancer Subtypes
Authors: Koufaris Costas , Kirmizis Antonis
Published: June 2021

Liver hepatocellular carcinoma (LIHC) is a leading cause of cancer-related mortality. In this study we initially interrogated the Cancer Genome Atlas (TCGA) dataset to determine the implication of N-terminal acetyltransferases (NATs), a family of enzymes that modify the N-terminus of the majority of eukaryotic proteins, in LIHC. This examination unveiled NAA40 as the NAT family member with the most prominent upregulation and significant disease prognosis for this cancer. Focusing on this enzyme, which selectively targets histone proteins, we show that its upregulation occurs from early stages of LIHC and is not specifically correlated with any established risk factors such as viral infection, obesity or alcoholic disease. Notably, in silico analysis of TCGA and other LIHC datasets found that expression of this epigenetic enzyme is associated with high proliferating, poorly differentiating and more aggressive LIHC subtypes. In particular, NAA40 upregulation was preferentially linked to mutational or non-mutational P53 functional inactivation. Accordingly, we observed that high NAA40 expression was associated with worse survival specifically in liver cancer patients with inactivated P53. These findings define NAA40 as a NAT with potentially oncogenic functions in LIHC and uncover its prognostic value for aggressive LIHC subtypes.
Effects of Brief Mindfulness Interventions on the Interference Induced by Experimental Heat Pain on Cognition in Healthy Individuals
Authors: Gill Louis-Nascan , Tabry Vanessa , Taylor Véronique , Lussier Maxime , Martinu Kristina , Bherer Louis , Roy Mathieu , Rainville Pierre
Published: June 2021

Background:Pain captures attention and interferes with competing tasks demanding cognitive effort. Brief mindfulness interventions involving both conceptual learning and meditation exercises have been shown to improve attention and reduce pain sensitivity, and could potentially reduce pain interference. This study assesses the effect of a 5-day mindfulness intervention (20 min/day) on the interference produced by thermal pain on working memory performance using a 2-back task.

Methods:Healthy participants were randomized into three groups exposed to mindfulness meditation training (n= 15), an active educational control intervention comprising only conceptual information on mindfulness (n= 15), or no intervention (n= 15). The two active interventions were administered in a dual-blind fashion and outcomes were assessed by research personnel blind to this allocation. Evaluation sessions were conducted before and after the interventions to assess the effect of pain on 2-back performance (pain interference). Importantly, both pain stimuli and the 2-back task were calibrated individually and in each session before assessing pain interference, thereby controlling for possible changes in baseline pain sensitivity and cognitive performance. Secondary outcomes included heat pain sensitivity, cold pain tolerance, cognitive inhibition, cognitive flexibility, and divided attention.

Results:Manipulation checks confirmed that heat pain interferes with the performance of the working-memory task. Compared to the no-intervention control group, pain interference was significantly reduced following the conceptual intervention but not the meditation intervention, although a corollary analysis suggests the effect might be due to regression toward the mean caused by baseline imbalance in pain interference. Secondary outcomes also suggested an increase in pain tolerance in the conceptual learning group only.

Discussion:A short mindfulness meditation intervention was insufficient to reduce pain interference but conceptual learning about mindfulness produced some unexpected benefits. Although the generalization of experimental findings to clinical pain conditions may be premature, these results highlight the importance of distinguishing the contribution of mindfulness education and meditation training in future studies. Understanding the effects of mindfulness training on pain regulation and management must take into consideration the multiple factors underlying this complex intervention.
Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study
Authors: Tuan Ta Anh , Ha Nguyen Thi Thu , Xoay Tran Dang , My Tran Thi Kieu , Nghiem Luong Thi , Dien Tran Minh
Published: June 2021

Objective: To identify whether coagulation profiles using thromboelastometry are associated with outcomes in pediatric septic shock. The primary outcomes were the development of disseminated intravascular coagulation (DIC) and the severity of the pediatric intensive care unit (PICU) existing scoring systems, while the secondary outcome was hospital mortality. This study aimed to contribute to current findings of the limitations of conventional tests in determining the optimal timing of anticoagulation in sepsis.

Design: A prospective, observational study conducted between August 2019 and August 2020.

Setting: PICU at a pediatric tertiary hospital in Hanoi, Vietnam.

Patients: Fifty-five pediatric patients who met the septic shock criteria were enrolled.

Measurements and Main Results: Fifty-five patients with septic shock were recruited. At the time of diagnosis, thromboelastometry revealed normocoagulability, hypercoagulability, and hypocoagulability in 29, 29, and 42% of the patients, respectively (p > 0.05); however, most patients in the overt DIC and non-survival groups progressed to hypocoagulability (82 and 64%, respectively). The overt DIC, PELOD-2 > 8, PRISM-III > 11, and non-survival group had a significant hypocoagulable tendency according to thromboelastometry parameters [prolonged clotting time (CT) and clot formation time (CFT); and reduced α-angle (α), maximum clot firmness (MCF), thrombodynamic potential index (TPI)] compared to the non-overt DIC, PELOD-2 ≤ 8, PRISM-III score ≤ 11 and survival group (p < 0.05). Conventional parameters between the normocoagulable and hypercoagulable groups were not different (p > 0.05). Hypocoagulability was characterized by lower platelet count and fibrinogen level, higher prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), and higher D-dimer level than in hypercoagulability (p < 0.05). Hypocoagulable tendency on thromboelastometry had a higher hazard at a PT > 16.1 s [area under the curve (AUC) = 0.747, odds ratio (OR) = 10.5, p = 0.002], INR > 1.4 (AUC = 0.754, OR = 6.9, p = 0.001), fibrinogen <3.3 g/L (AUC = 0.728, OR = 9.9, p = 0.004), and D-dimer > 3,863 ng/mL (AUC = 0.728, OR = 6.7, p = 0.004).

Conclusions: Hypocoagulable tendency using thromboelastometry is associated with the severity of septic shock. Conventional coagulation tests may fail to detect hypercoagulability, which is crucial in determining anticoagulation timing.
Puerarin Ameliorates Caerulein-Induced Chronic Pancreatitis via Inhibition of MAPK Signaling Pathway
Authors: Zeng Xiang-Peng , Zeng Jing-Hui , Lin Xia , Ni Yan-Hong , Jiang Chuan-Shen , Li Da-Zhou , He Xiao-Jian , Wang Rong , Wang Wen
Published: June 2021

Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP), and pancreatic stellate cells (PSCs) are considered to be the key cells. Puerarin is the most important flavonoid active component in Chinese herb Radix Puerariae, and it exhibited anti-fibrotic effect in various fibrous diseases recently. However, the impact and molecular mechanism of puerarin on CP and pancreatic fibrosis remain unknown. This study systematically investigated the effect of puerarin on CP and pancreatic fibrosis in vivo and in vitro. H&E staining, Sirius Red staining, qRT-PCR and Western blotting analysis of fibrosis and inflammation related genes of pancreatic tissues showed that puerarin notably ameliorated pancreatic atrophy, inflammation and fibrosis in a model of caerulein-induced murine CP. Western blotting analysis of pancreatic tissues showed the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) significantly increased after modeling of cerulein, while puerarin could inhibit their phosphorylation levels to a certain extent. We found that puerarin exerted a marked inhibition on the proliferation, migration and activation of PSCs, determined by CCK-8 assay, transwell migration assay, scratch wound-healing assay and expression levels of α-SMA, Fibronectin, Col1α1 and GFAP. Western blotting result demonstrated that puerarin markedly inhibited the phosphorylation of MAPK family proteins (JNK1/2, ERK1/2 and p38 MAPK) of PSCs in a dose-dependent manner whether or not stimulated by platelet-activating factor. In conclusion, the present study showed that puerarin could be a potential therapeutic candidate in the treatment of CP, and the MAPK pathway might be its important target.
Field-Deployable Computer Vision Wood Identification of Peruvian Timbers
Authors: Ravindran Prabu , Owens Frank C. , Wade Adam C. , Vega Patricia , Montenegro Rolando , Shmulsky Rubin , Wiedenhoeft Alex C.
Published: June 2021

Illegal logging is a major threat to forests in Peru, in the Amazon more broadly, and in the tropics globally. In Peru alone, more than two thirds of logging concessions showed unauthorized tree harvesting in natural protected areas and indigenous territories, and in 2016 more than half of exported lumber was of illegal origin. To help combat illegal logging and support legal timber trade in Peru we trained a convolutional neural network using transfer learning on images obtained from specimens in six xylaria using the open source, field-deployable XyloTron platform, for the classification of 228 Peruvian species into 24 anatomically informed and contextually relevant classes. The trained models achieved accuracies of 97% for five-fold cross validation, and 86.5 and 92.4% for top-1 and top-2 classification, respectively, on unique independent specimens from a xylarium that did not contribute training data. These results are the first multi-site, multi-user, multi-system-instantiation study for a national scale, computer vision wood identification system evaluated on independent scientific wood specimens. We demonstrate system readiness for evaluation in real-world field screening scenarios using this accurate, affordable, and scalable technology for monitoring, incentivizing, and monetizing legal and sustainable wood value chains.