bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Evaluate Digital Leadership: A Cross-sectional Study
Authors: Claassen Kevin , Anjos Dominique Rodil Dos , Kettschau Jan , Broding Horst Christoph
Published: April 2021

Background: With the increasing digitalization of the working environment, the demands on managers are changing fundamentally to the point of an emerging field of research in digital leadership. Municipal administrations are particularly affected by the digital transformation processes. Therefore, a score to measure the construct of digital leadership competence in the context of virtual-based workstation was developed and tested.Methods: Based of an online survey with n = 546 employees at virtual-based workstations in municipal administrations in 2020, the instrument is tested regarding selectivity (coefficients), dimensionality (principal component analysis), homogeneity (inter-product-moment correlations), reliability (Cronbach's α) and construct validity (correlation with general leadership skills).Results: The instrument can be considered selective, one-dimensional, homogeneous, reliable and constructively valid in the sense of the formulated hypotheses. By integrating the employees‘ perspective, the instrument aims to be one of the first of its kind to initiate a scientific further discourse. Among other things, the categorization of the co-determination component as either traditional or digital leadership can be discussed.Conclusions: The developed instrument for measuring digital leadership performs well concerning the aspects of discriminatory power, one-dimensionality, homogeneity, reliability as well as construct validity. It aims to induce further research and a scientific discourse on the topic of health-oriented leadership within the world of work 4.0.
Effect of Fungal Endophytes on Plant Growth and Nutrient Uptake in Trifolium Subterraneum and Poa Pratensis as Affected by Plant Host Specificity
Authors: García-Latorre Carlos , Rodrigo Sara M. , SANTAMARIA OSCAR
Published: April 2021

The introduction of well-adapted species, such as Trifolium subterraneum and Poa pratensis, might enhance the forage yield and quality of dehesas pastures for feeding livestock. However, the climatic hardness and poor soils in these agrosystems may limit plant establishment and development. Since fungal endophytes have been found to alleviate the environmental stresses of their host, the aim of this study was to assess the effect of five isolates on forage yield, nutritive value and plant mineral uptake after their inoculation in the two above-mentioned plant species. Two experiments were established (under greenhouse and field conditions) using plants inoculated with two isolates in 2012/2013 (Epicoccum nigrum, Sporormiella intermedia) and three isolates in 2013/2014 (Mucor hiemalis, Fusarium equiseti, Byssochlamys spectabilis). Thus, F. equiseti (E346) increased the herbage yield of T. subterraneum under greenhouse conditions, B. spectabilis was found to improve the forage quality of T. subterraneum by reducing fibre content and of P. pratensis by increasing crude protein. Also, S. intermedia increased the mineral uptake of Ca, Cu, Mn, Pb, Tl and Zn in subclover and M. hiemalis, the uptake of K and Sr in Kentucky bluegrass. These results evidenced the potential of the studied fungal endophytes to enhance herbage yield and the forage nutritional value, although further studies should include all of the intended forage species as certain host specificity in the effect was observed.
Lag Between COVID-19 Cases and Subsequent Deaths
Authors: Donovan Sara , Brett-Major David , Lawler James V.
Published: April 2021

Background: Observed COVID-19 cases and deaths are frequently used as independent factors to justify the use or de-escalation of non-pharmaceutical interventions. To investigate and describe the temporal relationship between changes in epidemic curves for COVID-19 cases and deaths, a longitudinal analysis of these metrics was performed for 16 states in the United States and three countries.Results: The analysis performed demonstrates a considerable, consistent lag between a surge in COVID-19 cases and the subsequent rise in attributable deaths, with approximately a month-long lag observed.Conclusions: The time lag identified must be incorporated in health emergency decision making in order to avoid the pre-mature de-escalation of disease mitigation measures.
Role of Jasmonic and Salicylic Acid on Enzymatic Changes in The Root of Two Alyssum Inflatum Náyr. Populations Exposed to Nickel Toxicity
Authors: Kakavand Shiva Najafi , Karimi Naser , Ghasempour Hamid-Reza , Raza Ali , Chaichi Mehrdad , Modarresi Masoud
Published: April 2021

Salicylic acid (SA) and jasmonic acid (JA) as plant growth regulators (PGRs) have the potential to ameliorate plant development and tolerance to deleterious effects of toxic metals like nickel (Ni). Therefore, the current study was carried out to evaluate SA and JA's interactive effect on the root antioxidative response of two Alyssum inflatum Nyár. populations against Ni-toxicity. Two A. inflatum species under Ni-stress conditions (0, 100, 200, and 400 µM) were exposed to alone or combined levels of SA (0, 50, and 200 µM) and JA (0, 5, and 10 µM) treatments. Results showed that high Ni doses reduced the roots fresh weight (FW) in two populations than control; however, the use of external PGRs had ameliorated roots biomass by mitigated Ni-toxicity. Under Ni toxicity, SA and JA, especially their combination, induced high Ni accumulation in plants' roots. Moreover, the application of SA and JA alone, as well as combined SA + JA, was found to be effective in the scavenging of hydrogen peroxide (H2O2) by improving the activity of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in both populations under Ni-toxicity. Overall, our results manifest that SA and JA's external use, especially combined SA + JA treatments, ameliorate root biomass and plant tolerance by restricting translocation Ni to the shoot, accumulating in roots, and also enhancing antioxidant defense systems.
Potential Threats of Nanoplastic Accumulation in Human Induced Pluripotent Stem Cells
Authors: Jeong Hyejoong , Kim Wijin , Choi Daheui , Heo Jiwoong , Han Uiyoung , Jung Se Yong , Park Hee Ho , Hong Sung-Tae , Park Ju Hyun , Hong Jinkee
Published: April 2021

Background: Micro- and nanoplastics (NPs) produced from the bulk fragmentation are rampant in the world by enormous plastic trash everyday life. NPs can be exposed to humans through a variety of routes, including inhalation and intake. The threat to humans from NPs is increasing invisibly. Nowadays, many people are concerned about human safety and health, but few are reported about the effects of NP on humans. To overcome the limitations in human studies, human induced pluripotent stem cells (hiPSCs) were used as an optimal in vitro platform to investigate developmental toxicology and subtle changes on cellular functions in terms of differentiation potential throughout a long-term culture. Results: Negatively charged polystyrene nanoplastics (PS NPs) were used to exclude acute toxic issues of surface charge and investigate the impact of the NP's size and nature during bioaccumulation. Intracellular observations revealed that NPs up to 1000 nm were over-internalized into single cells within 48 h, and smaller NPs demonstrated greater potency at decreasing number of viable cells by a strong correlation with the number of NPs on an equal mass basis. Also, PS NPs caused a significant reduction in self-renewal capacity of hiPSCs for 48 h. After the cells were exposed to PS NPs for 48 to 96 h at the beginning of the differentiation process, NPs accumulated in hiPSC did not render cellular functions vulnerable or adversely affect EB formation, EB-mediated differentiation, and neural lineage differentiation for up to 14 days.Conclusion: This study confirmed that hiPSC exposure to polystyrene nanoplastics results in acute toxicity and non-significant long-term effects on cellular functions. This report is important for understanding the developmental toxicology of nanoplastics and the origin of disease.
The Top 100 Cited Articles in Osteonecrosis of the Femoral Head: a Bibliometric Analysis
Authors: Zhang Yumin , Wang Yakang , Chen Juan , Cheng Qianyue , Zhang Binfei , Hao Linjie , Ma Tao , Qin Siqing , Song Wei , Wen Pengfei
Published: April 2021

Background: The number of articles of clinical and basic research for osteonecrosis of the femoral head (ONFH) is increasing, to our knowledge, there is still a lack of bibliometric analysis on ONFH articles. The purpose of this study was to identify the top 100 cited (T100) articles related to ONFH research and analyze the characteristics and qualities of these articles.Methods: The T100 articles on ONFH were retrieved from the Web of Science database. The information about each article including citations, titles, authors, journals, countries, institutions, and keywords, was recorded for bibliometric analysis. Results: The T100 articles related to ONFH were mainly published from 1991 to 2010 (n=70), and originated from 24 countries. The USA, China, and Japan were the most productive countries in this regard. The most prolific institution was the University of Pennsylvania from the USA with 6 publications and 742 citations. The most-cited article was published in 1995 by Professor Steinberg ME. The five most frequently occurring keywords were “femoral head”, “osteonecrosis”, “core decompression”, “total hip arthroplasty” and “follow up”. The keywords like "bone tissue engineering" and "extracorporeal shock wave" have emerged in recent years.Conclusions: The USA, China, and Japan contributed greatly in terms of the T100 articles. The outcomes of core decompression and total hip arthroplasty gathered most research interests. In recent years, bone tissue engineering and extracorporeal shock wave have become new trends. However, the mechanism of ONFH is still unclear.
Neuronal induction of BNIP3-mediated mitophagy slows systemic aging in Drosophila
Authors: Schmid Edward , Pyo Jung-Hoon , Walker David
Published: April 2021

The effects of aging on the brain are widespread and present at both the cellular and functional level. Mitochondrial dysfunction is a hallmark of brain aging, but, the interplay between mitochondrial quality control, neuronal aging, and organismal health is not well understood. Here, we show that aging leads to a decline in mitochondrial autophagy (mitophagy) in the Drosophila brain and a concomitant increase in mitochondrial content. We find that induction of BCL2-interacting protein 3 (BNIP3), a mitochondrial outer membrane protein, in the adult nervous system induces mitophagy and prevents the accumulation of dysfunctional mitochondria in the aged brain. Importantly, neuronal induction of BNIP3-mediated mitophagy increases organismal longevity and healthspan. Furthermore, neuronal BNIP3-mediated mitophagy improves mitochondrial homeostasis and proteostasis in aged muscle, indicating cell non-autonomous effects. In addition, neuronal BNIP3-mediated mitophagy improves intestinal homeostasis in aged flies. Our findings identify BNIP3 as a novel therapeutic target to counteract brain aging and prolong overall organismal health with age.
Association of Gait With Global and Domain-specific Cognitive Function Among Community-dwelling Older Adults: A Cross-sectional Study
Authors: HAO WEN , Zhao Wenjing , Kimura Takashi , Ukawa Shigekazu , Kadoya Ken , Kondo Katsunori , Tamakoshi Akiko
Published: April 2021

Background: Gait is associated with cognitive function and is a trait marker of dementia; however, research on gait and cognitive function usually concentrates on several individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and domain-specific cognitive function.Methods: The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70–81 years. Gait was measured by asking participants to walk a 6-meter course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and domain-specific cognitive function adjusted for several confounding factors.Results: Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β=-0.565, [-0.967, -0.163]), executive function (P=0.012), and memory (P=0.045); initial contact was associated with executive function (P=0.019).Conclusion: Better gait was related to better cognitive function, especially the general cycle, which was correlated with both global and domain-specific cognitive function. The predictive value should be examined in future cohort studies.
An Open-Label Prospective Pilot Trial of Nucleus Accumbens Deep Brain Stimulation for Children with Autism Spectrum Disorder and Severe, Refractory Self-Injurious Behaviour: Study Protocol
Authors: Yan Han , Siegel Lauren , Breitbart Sara , Gorodetsky Carolina , Fasano Alfonso , Rahim Aliya , Loh Alvin , Kulkarni Abhaya V. , Ibrahim George M.
Published: April 2021

Background
Children and youth with Autism Spectrum Disorder (ASD) may manifest self-injurious behaviours (SIB) that may become severe and refractory with limited pharmacologic or behavioural treatment options. Here, we present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc) for children and youth with ASD and severe, refractory SIB.
Methods
This is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioural clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Treatment efficacy will be assessed by changes in the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), the Behaviour Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behaviour Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.
Discussion
This study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioural, neuro-imaging and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.
Trial Registration
Registration on ClinicalTrials.gov was completed on June 12 of 2019 with the Identifier: NCT03982888. https://clinicaltrials.gov/ct2/show/NCT03982888
Elevated thyroid hormone caused by high concentrate diet participates in hepatic metabolic disorders in dairy cows
Authors: Chen Qu , Wu Chen , Yao Zhihao , Cai Liuping , Ni Yingdong , Mao Shengyong
Published: April 2021

Background
Feeding a high concentrate diet is widely used to satisfy high milk yields, however, if used over a longer term it can cause metabolic disorders. Abnormal secretion of hormones is one of the important causes of metabolic disorders caused by high concentrate diet, however, the related research is still limited. In total, 12 mid-lactating dairy cows were randomly assigned to HC group (60% concentrate of dry matter, n = 6) or LC group (40% concentrate of dry matter, n = 6). All cows were slaughtered at the 21st day, and blood and liver samples were collected.
Results
Compared with LC group, HC group showed reduced serum triglyceride (TG), free fatty acid (FFA), total cholesterol (TC), low density lipoprotein (LDL-C), and increased liver glycogen and glucose (P < 0.05). Real-time PCR results showed that genes related to gluconeogenesis, namely, glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) were significantly upregulated and accompanied greater gluconeogenic protein expression in HC group (P < 0.05). The expression of hepatic genes and proteins related to lipogensis, including sterol regulatory element-binding protein 1 (SREBP1), long-chain acyl-CoA synthetase 1 (ACSL1), and fatty acid synthase (FAS) were downregulated in HC group (P < 0.05). However, the expression of genes and proteins related to β-oxidation, including carnitine palmitoyltransferase 1α (CPT1α) and peroxisome proliferator activated receptor α (PPARα) were significantly increased in HC group (P < 0.05). The levels of serum cortisol, thyroxin (T4), triiodothyronine (T3), free triiodothyronine (FT3) and liver FT3 elevated significantly in HC group (P < 0.05). Moreover, the expression of thyroid hormone receptor (THR) upregulated at gene and protein levels (P < 0.05).
Conclusions
Taken together, this study first reports that abnormal secretion of TH induced by high concentrate diet participates in metabolic disorders, and it regulates glycometabolism and lipid metabolism through its actions on the liver in lactating dairy cows.
Evaluation of Subcooled MQL in cBN Hard Turning of powder-based Cr-Mo-V Tool Steel Using Simulations and Experiments
Authors: Laakso Sampsa Vili Antero , Mallipeddi Dinesh , Krajnik Peter
Published: April 2021

Metal cutting fluids for improved cooling and lubrication are an environmental risk and a health risk for workers. Minimizing water consumption in industry is also a goal for a more sustainable production. Therefore, metal cutting emulsions that contain hazardous additives and consume considerable amounts of water are being replaced with more sustainable metal cutting fluids and delivery systems, like vegetable oils that are delivered in small aerosol droplets, i.e. via minimum quantity lubrication (MQL). Since the volume of the cutting fluid in MQL is small, the cooling capacity of MQL is not optimal. In order to improve the cooling capacity of the MQL, the spray can be subcooled using liquid nitrogen. This paper investigates subcooled MQL with machining simulations and experiments. The simulations provide complementary information to the experiments, which would be otherwise difficult to obtain, e.g. thermal behavior in the tool-chip contact and residual strains on the workpiece surface. The cBN hard turning simulations and experiments are done for powder-based Cr-Mo-V tools steel, Uddeholm Vanadis 8 using MQL subcooled to -10 °C and regular MQL at room temperature. The cutting forces and tool wear are measured from the experiments, that are used as the calibration factor for the simulations. After calibration, the simulations are used to evaluate the thermal effects of the subcooled MQL, and the surface residual strains on the workpiece. The simulations are in good agreement with the experiments in terms of chip morphology and cutting forces. The cutting experiments and simulations show that there is only a small difference between the subcooled MQL and regular MQL regarding the wear behavior, cutting forces or process temperatures. The simulations predict substantial residual plastic strain on the workpiece surface after machining. The surface deformations are shown to have significant effect on the simulated cutting forces after the initial tool pass, an outcome that has major implications for inverse material modelling.
Numerical Analysis of Friction Conditions on Temperature and Phases Within Forged Ti-6Al-4V Aeroengine Drum
Authors: Luo Shiyuan , Jiang Yongxin , Zhang Po , Yu Fengping , Liu Siwen
Published: April 2021

Friction conditions significantly impact the temperature and phases of titanium forged parts, further directly affecting the microstructures and mechanical properties of final parts. In this paper, a 2D simplified FE model combined with phase transition equations is developed to simulate Ti-6Al-4V drum forging procedure. Then, friction effects on the temperature and phases of the forged drum are numerically analyzed and verified by experiments. Results indicate that unlike little influence on α+β phase, improving friction obviously decreases the general levels of temperature and β phase and increases the homogeneities of α and β phases within the forged drum, which are associated with cooling rates and the heating effects of friction and deformation.
Molecular Characterization, Expression and Functional Analysis of Yak IFITM3 Gene
Authors: Wang Haipeng , Wang Li , Li Juan , Fu Fang , Zheng Yao , Zhang Ling
Published: April 2021

Background IFITM3 is interferon-induced transmembrane 3, which plays an extremely key role in anti-proliferation, anti-virus and anti-tumor diseases. To expand our understanding of the role of IFITM3 in yak, this experiment studied its function. Results Firstly, the yak ( Bos grunniens ) IFITM3 ( BgIFITM3 ) gene contained a 5’-untranslated region (UTR) (25 bp), a coding region (441 bp), and a 3’-UTR (115 bp). The expression of BgIFITM3 gene in liver was significantly higher than that in heart, spleen, lung and kidney ( P <0.01). BgIFITM3 protein was localized on the yak hepatocyte membrane, and its expression level was increased first and then stabilized from 1 day to 5 years of age. Moreover, the prokaryotic expression vector of BgIFITM3 protein was constructed and expressed successfully, with a molecular weight of 19.5 kDa. Besides, the activity of yak hepatocyte was significantly inhibited after treating with BgIFITM3 protein (10 and 20 μg/mL) ( P <0.01). The expression levels of ERBB-2, IRS-1, PI3KR-1, AKT-1 and MAPK-3 were significantly lower after treating with 20 μg/mL BgIFITM3 protein ( P <0.05). Finally, the activity of HepG2 cells was significantly inhibited after treating with BgIFITM3 protein (1, 10 and 20 μg/mL) ( P <0.05). While the cloning ability and migration ability of HepG2 cells were significantly inhibited after treating with 10 μg/mL BgIFITM3 protein ( P <0.05). The mitochondria of HepG2 cells were concentrated, cristae widened, and the double film density of mitochondria was increased after treating with 10 μg/mL BgIFITM3 protein. After 10 μg/mL BgIFITM3 protein treating, the expression levels of VDAC-2, VDAC-3 , p53 genes were significantly increased, but the expression level of GPX-4 gene was significantly decreased ( P <0.01). Conclusion Taken together, the BgIFITM3 protein could inhibit the proliferations of yak hepatocyte and HepG2 cells by regulating the PI3K/Akt pathway or ferroptosis-related genes, respectively. These results benefit for further study of the function of BgIFITM3 protein.
Implementation of a Community-Based Low-Calorie Dietary Intervention for the Induction of Type-2 Diabetes and Pre-Diabetes Remission: A Feasibility Study Utilising a Type-2 Hybrid Design
Authors: Quimby Kim , Sobers Natasha , George Colette , Greaves Natalie , Browman-Jones Francine , Samuels T Alafia
Published: April 2021

Objectives

The aims of this feasibility study were to (1) examine the implementation of a community-based health advocate (CHA) training program to develop the clinical skills needed to support a diabetes remission protocol based on a low-calorie diet (LCD) and (2) investigate if participant weight loss can be achieved and diabetes remission induced under these conditions.
Methods

This tripartite study followed a type-2 implementation-effectiveness design. Three faith-based organizations (FBOs) were purposively selected as study sites. Implementation outcomes were guided by the Consolidated Framework for Implementation Research. During the pre-implementation phase, site ‘readiness’ to facilitate the intervention was determined from a site visit and an interview with the FBOs’ leadership. During the implementation phase, congregants could volunteer for the 10-week CHA training which included practical exercises in weight, glucose and blood pressure (BP) measurement, and a summative practical assessment. Acceptability and implementation effectiveness were assessed via survey. During the intervention phase, other congregants and community members with T2DM or pre-diabetes and overweight were invited to participate in the 12-week LCD. Anti-diabetic medication was discontinued on day-1 of the intervention. Clinical effectiveness was determined from the change in weight, fasting blood glucose (FBG) and BP which were monitored weekly at the FBO by the CHA. HbA1C was performed at week 1 and 12.
Results

The FBOs were found to be ready as determined by their adequate resources and engagement in health-related matters. Twenty-nine CHAs completed the training; all attained a passing grade at ≥ 1 clinical station, indicating implementation effectiveness. CHA feedback indicated that the program structure was acceptable and provided sufficient access to intervention-related material. Thirty-one persons participated in the LCD (11 T2DM:20 pre-diabetes). Mean (95%CI) weight loss was 6.8kgs (5.4–8.2) p < 0.00001; 7.9kgs in males vs 6.6kgs in females; A1C decreased from 6.6–6.2%, p = 0.003 and FBG from 6.4-6.0mmol/L; p = 0.004. T2DM remission rates were 60% and 90% by A1C < 6.5% and FBG < 7mmol/L respectively. Pre-diabetes remission was 18% and 40% by A1C < 5.7% and FBG < 5.6 respectively.
Conclusion

Implementation of a community-based diabetes remission protocol is both feasible and clinically effective. Its sustainability is to be determined. Adaptability to other disorders or other settings should be investigated.
Trial Registration
: NCT03536377 registered 24th May 2018 at https://clinicaltrials.gov/ct2/show/NCT03536377
Classification of Facial Images to Assist in the Diagnosis of Autism Spectrum Disorder
Authors: Michelassi Gabriel C. , Bortoletti Henrique S. , Pinheiro Tuany D. , Nobayashi Thiago , Barros Fabio R. D. , Testa Rafael L. , Silva Andréia F. , Revers Mirian C. , Portolese Joana , Pedrini Helio , Brentani Helena , Nunes Fatima L. S. , Machado-Lima Ariane
Published: April 2021

Autism Spectrum Disorder (ASD) is a developmental disorder that persistently impairs communication and social interaction, with a high degree of clinical heterogeneity. The fact that the diagnosis is based on clinical observation which requires therapy expertise, interviews with parents and application of questionnaires, it contributes to delaying the diagnosis until school age. The study of anthropometric measures in individuals with ASD and individuals in typical development (TD) showed there are some differences between the two groups. However, there is a lack of computational tools to assist in the acquisition and analysis process of these measures. This paper proposes a computer-aided medical decision support system that, given a child’s facial image captured by a digital camera, can discriminate between the two groups, ASD and TD, thus helping in the diagnosis. We defined a protocol for image acquisition and preprocessing, tested and compared methods for dataset balancing, dimension reduction and classification. The best results were obtained by a SVM classifier with 86.2% accuracy. Once the proposed model is based on facial images, it has the potential to facilitate early diagnosis of ASD.
Integration of Enzyme Constraints in a Genome-scale Metabolic Model of Aspergillus Niger Improves Phenotype Predictions
Authors: Zhou Jingru , Zhuang Yingping , Xia Jianye
Published: April 2021

BackgroundGenome-scale Metabolic Model (GSMM) is a powerful tool for the study of cellular metabolic characteristics. With the development of multi-omics measurement techniques in recent years, new methods that integrating multi-omics data into the GSMM show promising effects on the predicted results. It does not only improve the accuracy of phenotype prediction but also enhances the reliability of the model for simulating complex biochemical phenomena, which can promote theoretical breakthroughs for specific gene target identification or better understanding the cell metabolism on the system level.ResultsBased on the basic GSMM model iHL1210 of Aspergillus niger, we integrated large-scale enzyme kinetics and proteomics data to establish a GSMM based on enzyme constraints, termed a GEM with Enzymatic Constraints using Kinetic and Omics data (GECKO). The results show that enzyme constraints effectively improve the model’s phenotype prediction ability, and extended the model’s potential to guide target gene identification through predicting metabolic phenotype changes of A. niger by simulating gene knockout. In addition, enzyme constraints significantly reduced the solution space of the model, i.e., flux variability over 40.10% metabolic reactions were significantly reduced. The new model showed also versatility in other aspects, like estimating large-scale B values, predicting the differential expression of enzymes under different growth conditions. ConclusionsThis study shows that incorporating enzymes’ abundance information into GSMM is very effective for improving model performance with A. niger. Enzyme-constrained model can be used as a powerful tool for predicting the metabolic phenotype of Aspergillus niger by incorporating proteome data. In the foreseeable future, with the fast development of measurement techniques, and more precise and rich proteomics quantitative data being obtained for A. niger, the enzyme-constrained GSMM model will show greater application space on the system level.
Identification of RRM2 as a Potential Biomarker for the Diagnosis and Prognosis of Rheumatoid Arthritis
Authors: Biao Wu , Chen Yufeng , Zhong Junlong , Zhong Shuping , Wang Bin , Li Xuegang , Jiang Ning , Shang Jie , Xu Xianghe , Lu Huading
Published: April 2021

Background: Rheumatoid arthritis (RA) is a common autoimmune disease that can occur at any age. If treatment is delayed, RA can seriously affect the patients’ quality of life. However, there is no diagnostic criteria for RA and the positive predictive value of the current biomarkers is moderate. Objective: to identify RA-associated susceptibility genes and explore their potential as a novel biomarker for diagnosis and evaluation of the prognosis of RA.Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy human donors and RA patients. RNA-seq analyses were performed to identify the differentially expressed genes (DEGs) between RA and control samples. The PBMCs-mRNA in DEGs were further subjected to enrichment analysis. Furthermore, the hub genes and key modules associated with RA were screened by bioinformatics analyses. Then, the expression of hub genes in RA were assessed in mRNA expression profiles. Next, real time-quantitative PCR (RT-qPCR) analyses were performed to further confirm the expression of the hub genes from the PBMCs that collected from 47 patients with RA and 40 healthy controls. Finally, we evaluated the clinical characters for the candidate mRNAs.Results: RNA-seq analyses revealed the expression of 178 mRNAs from PBMCs were disregulated between the healthy controls and the RA patients. Bioinformatics analyses revealed 10 hub mRNAs. The top 3 significant functional modules screened from PPI network functionally were involved in DNA replication origin binding, chemokine activity, etc. After validating the 10 hub mRNAs in GSE93272 dataset and clinical samples, we identified 3 candidate mRNAs, including ASPM, DTL and RRM2. Among which, RRM2 showed great capacity in discriminating between remissive RA and active RA. Significant correlations were observed between DTL and IL-8, TNF-α, between RRM2 and CDAI, DAS-28, tender joints and swollen joints, respectively. The AUC values of ASPM, DTL and RRM2 were 0.654, 0.995 and 0.990, respectively.Conclusion: We successfully identified multiple candidate mRNAs associated with RA. RRM2 showed high diagnosis efficiency with the AUC of 0.990 (sensitivity=100%, specificity=97.5%). And RRM2 severed as an additional biomarker for evaluating disease activity. The findings provided a novel candidate biomarker for diagnosis and evaluation of the prognosis of RA.
Increasing Medicinal and Phytochemical Compounds of Coneflower (Echinacea Purpurea L.) Medicinal Plant using New Hydroponic Culture Media and Nutrition Pattern
Authors: Ahmadi Fatemeh , Samadi Abbas , Sepehr Ebrahim , Rahimi Amir , Shabala Sergey
Published: April 2021

Medicinal plants are considered as one of the most important sources of chemical compounds, so preparing a suitable culture media for medicinal plant growth is a critical factor. The present study is aimed to improve the caffeic acid derivatives and alkylamides percentages of Echinacea purpurea root extract by optimizing the NO3-/NH4 + ratio in new hydroponic culture media. Perlite particle size in the growing media was varied as very coarse perlite (more than 2 mm), coarse perlite (1.5-2 mm), medium perlite (1-1.5 mm), fine perlite (0.5-1 mm), and very fine perlite (less than 0.5 mm) with a mixture of peat moss at 50:50 v/v and 30:70 v/v peat moss to perlite ratios. Two NO3-/NH4 + ratios (90:10 and 70:30) were tested in each growing media. All phytochemical analyses were performed according to standard methods using high performance liquid chromatography (HPLC). It was found that the E. purpurea grown in the medium containing very fine-grade perlite with 50:50 v/v perlite to peat moss ratio had the maximum caffeic acid derivatives, including chicoric acid (17 mg/g DW), caftaric acid (6.3 mg/g DW), chlorogenic acid (0.93 mg/g DW), cynarin (0.84 mg/g DW), and echinacoside (0.73 mg/g DW), as well as, alkylamides (54.21%). The percentages of these phytochemical compounds increased by decreasing perlite particle size and increasing of NO3-/NH4 + ratio. The major alkylamide in the E. purpurea root extract was dodeca-2E, 4E, 8Z-10 (E/Z)-tetraenoic acid isobutylamide in all treatments, ranging from 31.12% to 54.21% of total dry weight. It can be concluded that optimizing hydroponic culture media and nutrient solution has significant effects on E. purpurea chemical compounds.
TPGen: Prescription Generation Using Knowledge-guided Translator
Authors: Ruan Chunyang , Luo Hua , Wu Yingpei , Yang Yun
Published: April 2021

Background: Prescriptions contain a lot of clinical information and play a pivotal role in the clinical diagnosis of Traditional Chinese Medicine (TCM), which is a combination of herb to treat the symptoms of a patient from decision-making of doctors. In the process of clinical decision-making, a large number of prescriptions have been invented and accumulated based on TCM theories. Mining complex and the regular relationships between symptoms and herbs in the prescriptions are important for both clinical practice and novel prescription development. Previous work used several machine learning methods to discover regularities and generate prescriptions but rarely used TCM knowledge to guide prescription generation and described why each herb is predicted for treating a symptom. Methods: In this work, we employ a machine translation mechanism and propose a novel sequence-to-sequence (seq2seq) architecture termed TPGen to generate prescriptions. TPGen consisting of an encoder and a decoder is a well-known framework for resolving the machine translation problem in the natural language processing (NLP) domain. We use the lite transformer and Bi-directional Gate Recurrent Units(Bi-GRUS) as a fundamental model in TPGen, and integrate TCM clinical knowledge to guide the model improvement termed TPGen+. Results: We conduct extensive experiments on a public TCM dataset and clinical data. The experimental results demonstrate that our proposed model is effective and outperforms other state-of-the-art methods in TCM expert evaluation. The approach will be beneficial for clinical prescription discovery and diagnosis
Using Machine Learning for Early Prediction of Cardiogenic Shock in Patients with Acute Heart Failure
Authors: Rahman Faisal , Finkelstein Noam , Alyakin Anton , Gilotra Nisha , Trost Jeff , Schulman Steven , Saria Suchi
Published: April 2021

Objective: Despite technological and treatment advancements over the past two decades, cardiogenic shock (CS) mortality has remained between 40-60%. A number of factors can lead to delayed diagnosis of CS, including gradual onset and nonspecific symptoms. Our objective was to develop an algorithm that can continuously monitor heart failure patients, and partition them into cohorts of high- and low-risk for CS.Methods: We retrospectively studied 24,461 patients hospitalized with acute decompensated heart failure, 265 of whom developed CS, in the Johns Hopkins Healthcare system. Our cohort identification approach is based on logistic regression, and makes use of vital signs, lab values, and medication administrations recorded during the normal course of care. Results: Our algorithm identified patients at high-risk of CS. Patients in the high-risk cohort had 10.2 times (95% confidence interval 6.1-17.2) higher prevalence of CS than those in the low-risk cohort. Patients who experienced cardiogenic shock while in the high-risk cohort were first deemed high-risk a median of 1.7 days (interquartile range 0.8 to 4.6) before cardiogenic shock diagnosis was made by their clinical team. Conclusions: This risk model was able to predict patients at higher risk of CS in a time frame that allowed a change in clinical care. Future studies need to evaluate if CS analysis of high-risk cohort identification may affect outcomes.
Identification and documentation of Ethno-veterinary remedies used by Afar Pastoralists for the treatment of Camel diseases in Ethiopia
Authors: Gutema Fikadu , G.Aregawi Weldegebrial , Bekele Juhar Tesfaye , Geletu Abel sorsa
Published: April 2021

Background: Ethnoveterinary medicine is a scientific term for traditional animal health care that encompasses knowledge, belief, practice and skill of the community used for curing diseases and maintaining health of animals. A cross-sectional study was conducted using semi-structured questionnaires from September 2016 to August 2017 to gather information on the knowledge, practice and skill of the pastoralists and traditional healers about the importance and application of Ethno-veterinary medicine. Moreover, this study was conducted with the objectives of identification and documentation of major ethno-veterinary medicinal plants commonly used to treat camel aliments in Afar region.Result: A total of 146 traditional healers and pastoralists were interviewed for baseline and reliable information about Ethno-veterinary medicinal practice in Afar region. Accordingly, 99.3% of the respondents were men in which 66.44% of them were in the age range of 45-60. Majorities (76.02%) of the information’s concerning EVM were obtained from the elders among which 84.93% responded that the overall EVM practice and status in pastoral society of Afar is decreasing. A total of 710 plant species supposed to have medicinal property were recommended by pastoralists to be used for the treatment of 49 different animal diseases. Among 64 plants specimen collected, Balanites aegyptia, Cissus rotundifolia (Forssk.) Vahl, Cadaba rotundifolia Forssk, Solanum sp, Acalypha indica L and Tamarix aphylla (L.) Karsts were the commonly used plant species with high fidelity value. Concerned with plant parts used, leaf (20.5%) was the most frequently used plant parts followed by root (19.4%), fruit (14.4%), seed (10.8%) and entire plant (8.8%). These herbal remedies were administered orally, nasally, ocular and topically.Conclusion: pastoralists and traditional healers in Afar region have immense indigenous knowledge and practices of treating sick animals which should be supported by scientific techniques for analyzing the active ingredients contained in each plant species and for evaluating the safety, efficacy and dosage of the commonly used medicinal plants. In addition, on station establishment of commonly used medicinal plant nursery for conservation purpose and to conduct in-depth phytochemical analysis is paramount important.
Prospective intra-individual blinded comparison of [18F]PSMA-1007 and [68Ga]Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer
Authors: Pattison David A , Debowski Maciej , Gulhane Brook , Arnfield Evyn G. , Pelecanos Anita M. , Garcia Peter L. , Latter Melissa J. , Lin Charles Y. , Roberts Matthew J. , Ramsay Stuart C. , Thomas Paul A.
Published: April 2021

Introduction[18F]PSMA-1007 has potential advantages over [68Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [18FPSMA-1007 and [68Ga]Ga-PSMA-11 for TNM with American Joint Committee on Cancer (AJCC) prognostic stage, and assess differences in tracer uptake.MethodsFifty men (mean age 71.8) were imaged with [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader.ResultsScan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7–12.0) and a minority of patients (28%) were currently treated with androgen deprivation therapy. [18F]PSMA-1007 uptake was significantly higher than [68Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases, and most physiologic sites except for urinary bladder which was significantly lower. [18F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [68Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [68Ga]Ga-PSMA-11 (one equivocal local recurrence).ConclusionOverall AJCC prognostic stage was similar (92%) between [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases, and most physiologic sites except urinary bladder which aided [18F]PSMA-1007 local staging of the prostate primary / local recurrence and regional nodal disease adjacent ureters. However [18F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified.
Comprehensive analysis of mutations and clonal evolution patterns in a cohort of patients with cytogenetically normal acute myeloid leukemia
Authors: Yusoff Yuslina Mat , Ahid Fadly , Seman Zahidah Abu , Abdullah Julia , Kamaluddin Nor Rizan , Esa Ezalia , Zakaria Zubaidah
Published: April 2021

Background

Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability driving clonal selection during treatment and evolution of leukemic clones. We performed high throughput exome sequencing of matched presentation and relapsed samples from 6 cytogenetically normal AML (CN-AML) patients treated with standard remission induction chemotherapy in order to investigate the mutational landscape of CN-AML and clonal evolution during AML treatment.
Result

A total of 24 and 32 somatic variants were identified in presentation and relapse samples respectively with an average of 4.0 variants per patient at presentation and 5.3 variants per patient at relapse, with SNVs were more frequent than indels at both disease stages. All patients have somatic variants in at least one gene that frequently mutated in AML at both disease presentation and relapse, with most of these variants are classic AML and recurrent hotspot mutations including NPM1 p.W288fs, FLT3-ITD, NRAS p.G12D and IDH2 p.R140Q. In addition, we found two clonal evolution patterns of relapse: (1) a leukemic clone at disease presentation acquires additional mutations and evolves into the relapse clone after the chemotherapy; (2) a leukemic clone at disease presentation persists at relapse without the addition of novel somatic mutations.
Conclusion

The findings from this study suggest that the relapse-initiating clones may pre-exist before therapy, which harbor or acquire mutations that confer selective advantage during chemotherapy, resulting in clonal expansion and eventually leading to relapse.
Ultra-high bandwidth fiber-optic data transmission with a single chip source
Authors: Tan Mengxi , Xu Xingyuan , Moss David
Published: April 2021

We report world record high data transmission over standard optical fiber from a single optical source. We achieve a line rate of 44.2 Terabits per second (Tb/s) employing only the C-band at 1550nm, resulting in a spectral efficiency of 10.4 bits/s/Hz. We use a new and powerful class of micro-comb called soliton crystals that exhibit robust operation and stable generation as well as a high intrinsic efficiency that, together with an extremely low spacing of 48.9 GHz enables a very high coherent data modulation format of 64 QAM. We achieve error free transmission across 75 km of standard optical fiber in the lab and over a field trial with a metropolitan optical fiber network. This work demonstrates the ability of optical micro-combs to exceed other approaches in performance for the most demanding practical optical communications applications.
Vulnerability Modellers Toolkit, An Open-source Platform for Vulnerability Analysis
Authors: Martins Luis , Silva Vitor , Crowley Helen , Cavalieri Francesco
Published: April 2021

Vulnerability functions describe the expected loss for a given ground shaking intensity level and are an essential component in probabilistic seismic risk assessment. This manuscript presents a novel open-source platform for the derivation of analytical fragility and vulnerability models, covering state-of-the-art methodologies, and addressing critical issues in vulnerability modelling such as uncertainty propagation, validation/verification of results and sufficiency/efficiency of intensity measure types. This framework is divided into six modules designed to guide users through the different stages of analytical vulnerability modelling from the selection of ground motion records to the validation and verification of the models. The platform was implemented in the Python programming language and it is freely accessible through a public GitHub repository. A graphical user interface is included with the toolkit and is intended to be a general-purpose method for modellers to interact with the VMTK. Experienced users are encouraged to use Python’s scripting capabilities to explore all the features of the VMTK source code and to contribute to future releases of the toolkit.