bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of sirolimus in a patient with a novel heterozygous FAS mutation leading to severe autoimmune lymphoproliferative syndrome
Authors: Gu Hao , Chen Zhenping , Ma Jie , Ma Jingyao , Fu Lingling , Zhang Rui , Wang Tianyou , Wu Runhui
Published: February 2021

Here we report a patient with a novel mutation in the FAS gene associated with a severe phenotype of the autoimmune lymphoproliferative syndrome. FAS gene identified as a novel spontaneous somatic heterozygous missense mutation (c.857G > A, p.G286E) in exon 9, causing an amino acid exchange was identified using sequencing. Consequently, the treatment with sirolimus (1mg/d, blood concentration 5-15ng/L) was initiated. Subsequently, the patient’s platelet count and clinical condition improved rapidly. Moreover, our in vitro data showed that G286E could inhibit cell proliferation and induce apoptosis compared with the wild type. To sum up, these data indicated that defective apoptosis might contribute to the clinical phenotype of lymphoproliferation in FAS deficient patients. The polarization of DNT/Treg axis may be an operative target of the sirolimus application.
Stability and Dynamical Analysis of Generalized Tumor-Immune Interaction Model with Conformable Fractional Derivative
Authors: Pal Rimpi , Afroz  , Khan Ayub , PADDER MOHMAD AUSIF
Published: February 2021

Fractional order tumor-immune interaction models are being frequently used for understanding the complex behaviour of immune system and tumor growth. In this paper, a generalized fractional order tumor-immune interaction model has been developed by introducing immunotherapy (IL2) as third variable in the model. The study of generalized model is done by using conformable fractional order derivative. The stability analysis is done for both fractional order tumor model and its conformable fractional order version. By considering some biological fixed points for both versions of the model, the stability analysis around these fixed points shows that both the systems are stable at some fixed point under some stability conditions, which are defined in the model analysis. The numerical and graphical analysis is also done for both the systems by varying two parameters and keeping other parameters fixed for better understanding the dynamics of proposed model.
Preparation of low-toxic cadmium selenide nanoparticles using the plant extract: A comparative study on the extraction techniques, characterization, biological potentials
Authors: Rajabi Hamidreza , Alvand Zinab Moradi , Mirzaei Ali , Sajadiasl Farideh
Published: February 2021

The present study reported a green approach for sonochemical-assisted synthesis (SAS) of cadmium selenide nanoparticles (CdSe NPs) by using the aqueous extract of Leontice Leontopetalum plant. The aqueous extract was obtained by ultrasonic- assisted extraction (UAE; 15 min, 50°C) and microwave- assisted extraction (MAE; 15 min, 180, and 270 W) as two instrumental techniques. Next, the as-prepared aqueous extracts were used in a plant-mediated synthetic approach for the synthesis of CdSe NPs by applying the SAS technique. The synthesized samples were characterized via different techniques; including transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), ultraviolet-visible absorption; photoluminescence, and Fourier transform infrared spectroscopy. The average particle size of the prepared CdSe NPs was estimated below 50 nm. UV-Vis absorption and fluorescence techniques indicate a wide absorption band around 360–420 nm and an intense emission peak around 460 nm, respectively. After green synthesis and characterization, antimicrobial, antioxidant, and antifungal properties of the aqueous plant extracts as well as their corresponded CdSe NPs were evaluated by different assays, comparatively. Moreover, the genotoxicity and toxicity potential of the samples were investigated. The results indicate the significant antimicrobial activity of the extracts as well as the CdSe NPs, with the negligible toxicity and genotoxicity impacts.
C-ALB - Collaborative Assembly Line Balancing: A New Approach in Cobot Solutions
Authors: Boschetti Giovanni , Faccio Maurizio , Milanese Mattia , Minto Riccardo
Published: February 2021

Collaborative robots can be a proper solution to improve the throughput of manual systems without reducing their flexibility. To effectively use cobots in productive systems it is fundamental to develop a suitable task allocation model that considers collaboration. Hence, we present a model for collaborative assembly line balancing (C-ALB) which considers paralleling tasks and collaboration in the balancing resolution. Indexes that take into account both the product and process characteristics are defined to evaluate the quality of the proposed task allocation model and comparing it to others. The results confirm the influence of the product characteristics on the system performance, leading to the definition of a new paradigm for product design.
Awareness Of Skin Cancer And Practice Of Photoprotective Behaviours Among Medical Students
Authors: Revelles-Peñas Leonor , Dompablo José María García , Puebla-Tornero Laura , Revilla-Nebreda David , Rodríguez-Baeza Daniel , Conde-Ferreirós Alberto , Román-Curto Concepción , Cañueto Javier
Published: February 2021

Background: Skin cancer is a serious health problem in our society, and UV radiation is the most significant agent in its development. Photoprotection and awareness of the risks of developing skin cancer are the basic pillars in its prevention. As future healthcare professionals, medical students’ knowledge of these questions is likely to influence the effectiveness with which they can promote appropriate behavior regarding sun exposure among their patients. Our objective was to assess the knowledge and awareness of photoprotection among medical students and their behavior regarding sun exposure.Methods: A Google questionnaire comprising 54 questions about the risks of skin cancer and photoprotective habits was developed. 228 participants were recruited to the study, of whom sixth-year and fourth-year students were the most and least strongly represented groups, respectively. Statistical analysis was performed using IBM SPSS Statistics 26.Results: Significantly more fifth- and sixth-year students had knowledge of the meaning of the sun protection factor (SPF) than those in pre-clinical years (P=0.006), and more of them were aware of the risks of developing skin cancer (P=0.039). A higher percentage of female than male students took FPS into account when buying sunscreen (P=0.023), and male students are more likely to be reluctant to apply sunscreen than female students (P=0.022). A higher proportion of women than men in the study used sunscreen for outdoor activities (P=0.015).Conclusions: Prevention of sun overexposure is a public health priority, and medical students will be in charge of informing the general population in the future. Most students who are currently studying medicine have some knowledge of skin cancer prevention, although there are significant differences between sexes and year of study. However, their behavior indicates that their knowledge does not consistently translate from theory into practice.
Mesoscale and Wind-Driven Variability in The East Auckland Current
Authors: Santana Rafael , Suanda Sutara H. , Macdonald Helen , O’Callaghan Joanne
Published: February 2021

East Auckland Current (EAuC) variability was studied using a year-long timeseries of in situ and remotely-sensed velocity, temperature and salinity observations. Satellite-derived velocities correlated well (r > 0.75) with in situ observations and well-represent the long-term (> 30 day) variability of the upper ocean circulation. Four mesoscale eddies were observed during the year (for 260 days) which generated distinct flows between the continental slope and rise. The EAuC dominated the circulation in the continental shelf break, slope and rise for 110 days and generated the most energetic events associated with wind forcing. Current variability on the continental slope was coherent with along-slope wind stress (wind stress curl) at periods between 4 and 12 days (16 and 32 days). We suggest that along-slope winds generated offshore Ekman transport, uplift on the shelf-break, and a downwind geostrophic jet on the slope. In contrast, positive wind stress curl caused convergence of water, downwelling, and increased the current speed in the region. Bottom Ekman transport, generated by the EAuC, was suggested to have caused the largest temperature anomaly (-1.5°C) at the continental shelf-break.
Metagenomic analysis of microbial community structure and function in a improved biofilter with odorous gases
Authors: Ni Jianguo , Chen Liqing , Xu Jiadong , Zheng Liangwei , Xie Guojian , Shen Chenjia , Liu Qi
Published: February 2021

BackgroundBiofilters have been broadly applied to degrade the odorous gases from industrial emissions. To explore biofilter potentials, the microbial community structure and function must be well defined. Using of improved biofilter, changes in microbial community structures and functions were investigated by metagenomic analysis. ResultsOdorous gases have the potential to alter the microbial community structure in the sludge of biofilter. A total of 90,016 unigenes assigned into various functional metabolic pathways were identified. In the improved biofilter, the dominant phyla were Proteobacteria, Planctomycetes, and Chloroflexi, and the dominant were Thioalkalivibrio, Thauera, and Pseudomonas. Several xenobiotic biodegradation-related pathways showed significant changes during the treatment process. Compared with the original biofilter, Thermotogae and Crenarchaeota phyla were significantly up-regulated in the improved biofilter, suggesting its important role in nitrogen-fixing. Furthermore, nitrogen metabolic pathway-related genes, such as nirA and nifA, and sulfur metabolic pathway-related genes, such as fccB and phsA, were considered to be efficient genes involved in removing odorous gases. ConclusionsOur findings can be used for improving the efficiency of biofilter and helping the industrial enterprises to reduce the emission of waste gas.
Assessing The Cost of Medical Care For Patients Hospitalized After A Stroke Event in Gabon
Authors: LIPENGUET Gaetan MOUKOUMBI , AMANI Prudence GNAMIEN , IBINGA Euloge , Engohang-Ndong Jean , NGOUNGOU Edgard Brice NGOUNGO , WITTWER Jérôme
Published: February 2021

Background: The increasing incidence of recorded stroke cases is straining the economies of many developing countries. Very few studies have assessed the financial burden of stroke management in Gabon. The aim of this study was to assess the direct costs of stroke management in the neurology and cardiology departments at the University Hospital of Libreville.Methods: This retrospective study was based on a detailed review of financial records directly associated with the management of stroke cases admitted and treated in the CHUL between January 2018 and December 2019. The records reviewed were those of all stroke patients admitted and treated in the aforementioned timeframe, regardless of treatment outcome. The analysis of data focused on direct hospital cost.Results: Three hundred and thirteen stroke patients were admitted over the aforementioned period, 72.52% in neurology and 27.48% in cardiology. The average age of the patients was 58.44 (± 13.73) years. 56.23% of patients had health insurance. Ischemic stroke was more common than hemorrhagic stroke, 79.55% and 20.45% respectively. The expenditure per patient was estimated at 570,023 CFA francs.Of this global direct cost, government assistance in the form of health insurance was estimated at 422,883 CFA francs while the balance of approximately 147,140 CFA francs was paid by the patient.Conclusion: The hospital cost of stroke is very high for both patients and administrations. This observation pleads for the implementation of prevention programs for this pathology. The results of this study may be useful for work on the efficiency of these programs.
High-level Exposure of Uric Acid in Asymptomatic Hyperuricemia Could Be An Isolated Risk Factors of Cardio-Cerebrovascular Diseases: A Prospective Cohort Study
Authors: Cheng Zhiyuan , Zheng Tongzhang , Zhang Desheng , Yang Jingli , Hu Xiaobin , Yin Chun , Ren Xiaowei , Li Juansheng , shi dian , Li Na , Zheng Shan , Wang Minzhen , Bai Yana
Published: February 2021

Background: Whether the asymptomatic hyperuricemia (AH) raises the risk of cardiovascular disease with or without hyperuricemia-related comorbidities still remains contentious. Our study was aimed to quantitatively access the incidence risk of coronary heart disease (CHD) and stroke associated with AH.Methods: Multivariate-adjusted Cox regression models were applied to evaluate the risk of cardiovascular disease (CVD). Serum uric acid beyond normouricemia was quarterly stratified based on the distribution of healthy population without CVD onset.Results: 1,062 CVD first attack cases were collected among the 48,001 cohort participants (age range: 18-92, mean age: 47.2±13.9 years-old) with a mean follow-up duration of 5.78±0.83 years. 14,464 baseline population with comorbidities were excluded to further study the association between AH and CVD incidence. The AH showed overall non-association with CVD incident. However, significantly increased adjusted hazard ratio (HR) of CVD with 95% confidence interval (CI) were observed when the fourth quartile compared with normouricemia stratum in the total cohort population (CHD: 1.70, 1.34-2.16; stroke: 1.55, 1.13-2.13), male (CHD: 1.94, 1.47-2.56), female (CHD: 1.71, 1.03-2.35; stroke: 2.02, 1.14-3.58) and aged over 50 years-old population. Meanwhile, the age-standardized incidence rate of CVD in the fourth quartile was 2 to 3 time higher than the normouricemia population. Consistent results were also observed in the AH population in absence of comorbidities (CHD: 2.40, 1.39-4.14; stroke: 1.85, 1.12-3.59).Conclusion: Asymptomatic hyperuricemia patients exposed to higher level of uric acid (male>487 mmol/L, female>422 mmol/L) could significantly increase the incidence risk of CHD and stroke, with or without hyperuricemia-related comorbidities.
Ecological Land Conservation Strategies Explained By Urban Growth and Climate Change
Authors: Zhao Shi , Shao Quan
Published: February 2021

Rising urban population throughout the world have boosted land use demand, intensifying pressure of ecological land resources linked with climate change. By incorporating risk into assessment, people can discourage excessive growth in megacity areas. Here, we propose a generalized analysis framework of ecological land conservation by devising a public goods game, which simultaneously considers population gravity and climate change along with interactions. Our method describes strategic conservation under the growth risk of urban boundary, where recurs across multiple rounds. We find that a compact and reasonable city with spatial structure will reduces erosion risk of ecological land and the lower costs of conservation, and higher its benefits. The conservation costs at the equilibrium do not increase with the degree of emphasis on the future, which show threshold effect. Ecological lands at the city boundaries have highest eroding risk, but rather pay a disproportionate amount of cost in this asymmetric game environment, which makes controlling erosion of ecological land less sustainable. Overall, our results suggest that implementing conservation strategies will efficiently reduce aggregate damages of urban growth and mitigate climate change, otherwise it may increase increases ecological land damages substantially.
A society ill-equipped to deal with the effects of climate change on cultural heritage and landscape: A qualitative assessment of planning practices in transport infrastructure
Authors: ANTONSON Hans , Buckland Philip , Nyqvist Roger
Published: February 2021

This paper provides insights into the handling of climate change issues related to cultural heritage at different government decision levels dealing with physical planning, and in particular roads. Data are derived from a qualitative analysis of official reports and interviews with local and regional planners in three Swedish regions with contrasting climates. The theoretical lens of Institutional Interplay is applied to an analysis grouped into six themes: Climate threats to cultural heritage; Adaptation measures; Preparedness; Institutional preconditions; Institutional interplay, and Challenges. The results suggest that despite a strong environmental reputation internationally, Sweden is not particularly well prepared for dealing with future climate change impacts on cultural heritage and landscape. The lack of national standards and standardized methods risks regional and sectoral variation in the treatment of similar tasks; a problem which deficiencies in knowledge and continuing education are perpetuating. The degree to which discussions and cooperation occurs between divisions within the same authority, between authorities, and in national networks, varies considerably. Routines and criteria for prioritization of cultural heritage mitigation, essential under conditions of limited resources, have yet to have been implemented. We conclude with five recommendations for improving the planning process with respect to climate change risks to cultural heritage.
Differential expression of circRNA in amyotrophic lateral sclerosis and validation of identified circRNA biomarker
Authors: Glavač Damjan , Mezzavilla Massimo , Dolinar Ana , Koritnik Blaž , Glavač Metka Ravnik
Published: February 2021

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are in desperate need for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have been already proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based under the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With an FDR threshold of 0.1, only six circRNAs passed the filtering and merely one of them remained statistically significant after Bonferroni correction: hsa_circ_0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa_circ_0060762 and CSE1L . In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa_circ_0060762 . Hsa_circ_0060762 thus represent a novel potential peripheral blood circRNA biomarker for ALS.
The co-development of models with expert judgement suppresses model diversity and underestimates risk
Authors: Thompson Erica
Published: February 2021

It is well-understood that mathematical models are developed with the aid of expert judgement about the relevant real-world processes. Here, I first consider the influence of the mathematical model itself upon our expert judgement. Having established a two-way relationship between model and expert judgement, I then consider some epistemic concerns arising from the difficulty of separating model information from expert judgement, concluding that statistical methods for assessing uncertainty in climate sensitivity are inadequate. I offer two potential solutions to these epistemic concerns. One: pre-registration of model experiments prior to the development of a model, and another: active exploration of other possible model structures based on different starting points and (ideally) different expert input. Next, I offer some practical recommendations for communication of climate information: we must distinguish statements about a model from statements about the real world, and it could be useful to consider ending climate simulations at a threshold of temperature change rather than on an arbitrary time scale. Having identified the climate modelling community (of researchers/modellers and the mathematical and computational entities which are the models themselves) as a cognitive assemblage, I suggest that policy-relevant science and decision-making would benefit from closer examination of the kinds of models and expertise that are privileged within this system and from actively encouraging greater model diversity. The current suppression of diversity results in underestimation of risk. Although I use climate as an example, these recommendations are generalisable to other policy-relevant modelling communities.
Development and Psychometric Evaluation of a Reproductive Health need Assessment Scale for violated Women
Authors: Dolatian Mahrokh , Ebadi Abbas , Hasanpoor-Azghady Seyedeh Batool , Nayebinia AnvarSadat
Published: February 2021

Violence as a serious health problem and one of the main manifestations of gender inequality brings about adverse health effects for women. Therefore, it is of utmost importance to recognize the reproductive health status of women subjected to violence in order to provide the health services they need. Considering that one of the ways to determine reproductive health status is the use of valid questionnaires in this field, the present study was conducted based on a mixed-method design. The first part of the study (qualitative section) was conducted based on conventional content analysis. In this part, unstructured in-depth interviews were conducted with 18 violated women and 9 experts. In the next stage, the item pool was formed and the Reproductive Health Needs of Violated Women Scale (RHNVWS) was designed based on the review of the literature and the results of the qualitative section with 39 items using the Waltz approach. For psychometric assessment of the above instrument, face and content validity, item analysis, and construct validity were examined using exploratory factor analysis. Based on the results of factor analysis, the four following factors were extracted with a total variance of 47.62: "men's participation", "self-care", "support and health services", as well as "sexual and marital relationships. The internal consistency of the instrument was calculated at α = 0.70–0.89 and α = 0.94 for different constructs and the whole instrument, respectively. Moreover, intra-cluster correlation coefficients were obtained at ICC = 0.96–0.99 and ICC = 0.98 for constructs and the whole instruments, respectively. Based on the results of the current study, the RHNVWS is a tool that specifically assesses the reproductive health needs of violated women and has appropriate validity and reliability. The results of the assessment using the aforementioned instruments can be of great help in promoting the reproductive health of women subjected to violence.
Extracellular Volume-Guided Late Gadolinium Enhancement Analysis for Non-Ischemic Cardiomyopathy: the Women’s Interagency HIV Study.
Authors: Kato Yoko , Kizer Jorge R. , Ostovaneh Mohammad R. , Lazar Jason , Peng Qi , Geest Rob van der , Lima Joao A.C. , Venkatesh Bharath Ambale
Published: February 2021

Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. This study develops a robust quantification method by utilizing T1 mapping based extracellular volume (ECV) to guide late gadolinium enhancement (LGE) MRI analysis. Three cohorts of 80 non-ischemic-training (all-female, 73.8% human-immunodeficiency virus [HIV] positive), 20 non-ischemic-validation (all-female, 80% HIV+), and 10 ischemic-validation (all-male with reduced left-ventricular function) were prospectively enrolled and underwent MRI. The reference for obtaining an optimal ECV cut-off for scar/non-scar differentiation was determined visually by an expert user at the region of highest signal intensity (SI). An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity:86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). An LGE threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was then identified ensuring correspondence between LGE and ECV images. The identified threshold varied widely (range 3SD to 18SD), and was independent of scar amount (β= -0.01, p=0.92). In the non-ischemic cohorts, results suggested that manual analysis overestimated scar (%) in comparison to ECV-guided analysis (training: 4.5 [3.2–6.4] vs. 0.92 [0.1–2.1]; validation: 2.5 [1.2–3.7] vs. 0.2 [0–1.6]; P<0.01 for both). Intra- and inter-observer variability assessed in a subset of 40 non-ischemic cases showed ECV-guided analysis was more reproducible than manual analysis (CCC=0.94 and 0.78 vs. CCC=0.86 and 0.73, respectively; p<0.01 for all). In ischemic-validation, ECV-guided analysis was comparable to the standard full-width half-maximum method. In conclusion, ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort.Trial Registration: Clinical trial registration was documented on ClinicalTrials.gov with an identifier of NCT00000797. Registered on August 31st, 2001. (https://clinicaltrials.gov/ct2/show/NCT00000797)
Clinical prognosis of isolated anterior cerebral artery territory infarction: A retrospective study
Authors: Park Hyungjong , Jeong Young Seok , Lee Seo Hyun , Jang Seong Hwa , Kwon Doo Hyuk , Hong Jeong-Ho , Sohn Sung-Il , Yoo Joonsang
Published: February 2021

Background
Isolated anterior cerebral artery territory (ACA) infarction is a rare phenomenon and had known to have distinctive clinical features. Little is known about the clinical prognosis of isolated ACA territory infarction with associated factors and its impact on dwelling and job status. We investigated the short- and long-term outcomes and associated factors involved in the development of the distinctive symptoms of anterior cerebral artery (ACA) territory infarction.
Methods
This retrospective study in a prospective cohort of acute ischaemic stroke patients included consecutively enrolled patients with isolated ACA territory infarction. We investigated the functional status using the modified Rankin scale (mRS) score at discharge, three months post-discharge, and one-year post-discharge. We also investigated the occlusion site of the ACA (proximal vs. distal); presence of distinctive symptoms of ACA territory infarction including behaviour changes, indifference, aphasia, and urinary incontinence; and the effect of these symptoms on dwelling and job status one year after discharge.
Results
From April 2014 to March 2019, 47 patients with isolated ACA territory infarction were included. Twenty-nine patients (61.7%) had good outcomes (mRS ≤ 2) at discharge; however, the mRS score increased at three months (40; 85.1%, p < 0.001) and one year (41; 87.2%) post-discharge. Occlusion of the ACA proximal segment was independently associated with the development of distinctive symptoms (adjusted odds ratio, 17.68; 95% confidence interval: 2.55–122.56, p < 0.05). Twenty-one (48.8%) patients with good outcomes at one year experienced a change in dwelling status and job loss; 20 (95.2%) of them had distinctive ACA territory symptoms with proximal ACA occlusion.
Conclusions
Short- and long-term outcomes of isolated ACA territory infarction were favourable. However, proximal segment occlusion was associated with the development of distinctive symptoms, possibly related to future dwelling and job status.
Failure behavior of the surrounding rock of jointed rock masses in a gold mine under impact disturbance
Authors: Li Peng , Wu Yunquan , Cai Meifeng
Published: February 2021

The impact disturbance has an important influence on the safety of underground engineering openings. In this paper, based on the in-situ stress measurement and structural plane investigation, the model of jointed rock roadway was established using the discrete element method (3DEC) to study the instability and failure characteristic of roadway surrounding rock with dominant joint planes under impact disturbance and to further analyze the influence of different buried depths, impact stress wave peaks, and stress wave delays on the stability of the surrounding rock. The results show that the stability of the surrounding rock is poor, and the whole convergence deformation of the surrounding rock occurs under the impact stress wave. There are three failure modes in the surrounding rock: tensile-shear failure, tensile failure, and shear failure. Tensile-shear failure mainly occurs in a small range close to the roof and floor of the roadway and the free surfaces of the two sides, and tensile failure occurs locally, while shear failure mainly occurs along the joint plane outside this range. Moreover, the greater the buried depth and stress wave peak value, the more serious the deformation of the surrounding rock. With the increase of stress wave delay, the deformation of the surrounding rock shows complex characteristics. In addition, the impact failure mechanism of the surrounding rock in jointed rock masses was discussed. The research results have important guiding significance for the prevention and control of underground engineering cavern disasters.
High fidelity simulation to assess task load index and performance: a prospective observational study
Authors: Favre-Félix Jérémy , Dziadzko Mikhail , Bauer Christian , Duclos Antoine , Lehot Jean-Jacques , Rimmelé Thomas , Lilot Marc
Published: February 2021

Background

The NASA Task Load IndeX (NASA-TLX) is a questionnaire widely used in aviation. This index might help for attesting the quality of a scenario in high-fidelity simulation (HFS) in healthcare.
The main purpose of this study was to
observe whether the score of NASA-TLX for critical care simulated
scenarios, designed for residents, was consistent with the values
reported in the literature.

The second purpose was to describe relationships between NASA-TLX, performance and generated stress during HFS.
Methods

All residents in anaesthesia and intensive care undergoing HFS were included. The primary endpoint was the task load generated by each scenario assessed by NASA-TLX. Based on literature, the NASA-TLX scores between 39 and 61 were considered as acceptable level. Stress level (Visual Analogue Scale for stress), specific technical and non-technical skills performances (Team Emergency Assessment Measure) were also assessed.
Results

Fifty-three residents actively participated in one of ten different scenarios, between June to December 2017. Median NASA-TLX score of scenarios was 61 [48–65]. Five scenarios (50%) generated acceptable task load level. There was no association between NASA-TLX score and technical or Team Emergency Assessment Measure performance scores, but an association between NASA-TLX and the stress level (rho = 4.7, p = 0.001) was observed.
Conclusions

Simulation scenarios generate different task loads for residents; the task load was deemed acceptable for half of the scenarios. The NASA-TLX could be considered as a tool to assess the pedagogic adequacy of scenarios. Scenario and generated stress level, but not task load, can modify residents’ performance during simulation. This should be considered when planning normative simulation.
Dimeric Tacrine (10)-Hupyridone Effectively Combats Alzheimer’s Disease as A Multi-Target-Directed Ligand
Authors: Xuan Zhenquan , Gu Xingmei , Yan Sicheng , Xie Yanfei , Zhou Yiying , Zhang Hui , Jin Haibo , Hu Shengquan , Mak Marvin Shinghung , Zhou Dongsheng , Tsim Karl Wahkeung , Carlier Paul R. , Han Yifan , Cui Wei
Published: February 2021

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder with multiple pathological features. Therefore, multi-target-directed ligands (MTDLs) strategy has been developed to combat this disease. We have previously designed and synthesized dimeric tacrine (10)-hupyridone (A10E), a novel tacrine derivative with acetylcholinesterase (AChE) inhibition and brain-derived neurotrophic factor (BDNF) activation activity, by linking tacrine and a fragment of huperzine A. However, it was largely unknown whether A10E could act on other AD targets and produce cognition-enhancing ability in AD animal models.
Methods

Behavioral and biochemical methods were applied to evaluate multi-target cognitive-enhancing effects and mechanisms of A10E in APP/PS1 transgenic mice and β-amyloid (Aβ) oligomers-treated mice. The neuroprotective mechanisms of A10E were explored in SH-SY5Y cells. And the anti-aggregation effects of A10E on Aβ were directly investigated in vitro.
Results

A10E could prevent cognitive impairments in both APP/PS1 mice and Aβ oligomers-treated mice, with higher potency than tacrine and huperzine A. Moreover, A10E could effectively inhibit Aβ production and deposition, reduce neuroinflammation, enhance brain derived brain-derived neurotrophic factor (BDNF) expression, and elevate cholinergic neurotransmission in vivo. A10E, at nanomolar concentrations, could also inhibit Aβ oligomers-induced neurotoxicity via the activation of the TrkB/Akt pathway. Furthermore, Aβ oligomerization and fibrillization could be directly disrupted by A10E.
Conclusion

A10E could produce anti-AD neuroprotective effects via multi-target mechanisms, including the inhibition of Aβ aggregation, the activation of the BDNF/TrkB pathway, the reduction of neuroinflammation and the decrease of AChE activity. As MTDLs could produce additional benefits, such as overcoming the deficits of drug combination and enhancing the compliance of AD patients, our results suggested that A10E might be developed as a promising MTDL lead for the treatment of AD.
Nerve reconstruction with muscle-in-vein conduits VS autologous nerve grafts - a systematic review and meta-analysis of preclinical and clinical studies
Authors: Heinzel Johannes C. , Nguyen Mai Q. , Kefalianakis Laura , Prahm Cosima , Daigeler Adrien , Hercher David , Kolbenschlag Jonas
Published: February 2021

The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work’s main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.
Genome-wide identification of MITE-derived microRNAs and their targets in bread wheat
Authors: Crescente Juan Manuel , Zavallo Diego , Vas Mariana del , Asurmendi Sebastian , Helguera Marcelo , Fernandez Elmer , Vanzetti Leonardo
Published: February 2021

Plant microRNAs (miRNAs) are a class of small non-coding RNAs that are 20–24 nucleotides length and can repress gene expression at post-transcriptional levels by target degradation or translational repression. There is increasing evidence that some microRNAs can be derived from a group of non-autonomous class II transposable elements called Miniature Inverted-repeat Transposable Elements (MITEs) in plants. We used public small RNA, degradome libraries and the common wheat (Triticum aestivum) genome to screen miRNAs production and target sites. We also created a comprehensive wheat MITE database using known and identifying novel elements. We found high homology between MITEs and 14% of all the miRNAs production sites in wheat. Furthermore, we show that MITE-derived miRNAs have preference for target degradation sites with MITE insertions in 3' UTR regions in wheat.
Geometrical Optimization of Centerless Grinding Process by Profiled Workrest
Authors: Leonesio Marco , Wojcicki jeremi , Bianchi Giacomo Davide
Published: February 2021

This work presents a method to optimize centerless grinding geometrical configuration. It is based on the regulation of the horizontal axes of operating and rubbing wheels of the machine machine coupled with an opportune blade profile, allowing a continuous selection of workrest angle and workpiece height, without requiring blade substitution and/or manual interventions. The regulation of workrest angle and height cannot be done independently: their relationship is defined during blade profile design. In machines with two independent axes for regulating wheel and blade horizontal displacement, this regulation can be performed in process or in the setup phase and does not require manual blade adjustment/replacement. This results in optimal processing parameter choice leading to improved quality and shorter time of processing as well as reduced setup time.
Differential Effects of HIF2α Antagonist and HIF2α Silencing in Renal Cancer and Sensitivity to Repurposed Drugs
Authors: Arnaiz Esther , Miar Ana , Bridges Esther , Prasad Naveen , Hatch Stephanie B. , Ebner Daniel , Lawrie Charles H. , Harris Adrian L.
Published: February 2021

Background: in clear cell renal cell carcinoma, 80% of cases have biallelic inactivation of the VHL gene, leading to constitutive activation of both HIF1α and HIF2α. As HIF2α is the driver of the disease promoting tumour growth and metastasis, drugs targeting HIF2α have been developed. However, resistance is common, therefore new therapies are needed. Methods: we assessed the effect of the HIF2α antagonist PT2385 in several steps of tumour development and performed RNAseq to identify genes differentially expressed upon treatment. A drug screening was used to identify drugs with antiproliferative effects on VHL-mutated HIF2α-expressing cells and could increase effectiveness of PT2385. Results: PT2385 did not reduce cell proliferation or clonogenicity but, in contrast to the genetic silencing of HIF2α, it reduced in vitro cell invasion. Many HIF-inducible genes were down-regulated upon PT2385 treatment, whereas some genes involved in cell migration or extracellular matrix were up-regulated. HIF2α was associated with resistance to statins, addition to PT2385 did not increase the sensitivity. Conclusions: this study shows key differences between inhibiting a target versus knockdown, which are potentially targetable.
Long-Read-Sequenced Reference Genomes of the Seven Major Lineages of Enterotoxigenic Escherichia Coli (ETEC) Circulating in Modern Time 
Authors: von Mentzer Astrid , Blackwell Grace A , Pickard Derek , Boinett Christine J , Joffré Enrique , Page Andrew J , Svennerholm Ann-Mari , Dougan Gordon , Sjöling Åsa
Published: February 2021

Abstract Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 fatalities per year, with the highest rates of burden, ca 75 million cases per year, amongst children under five years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide. We used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. We confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades and that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.
Barriers and Facilitators of Alcohol Abstinence During Pregnancy - a Qualitative Study in Rural South Africa
Authors: Rawoot Ismail Allie , Scott Chantelle Jennifer , Urban Michael Francis
Published: February 2021

Background:Fetal Alcohol Spectrum Disorders (FASD) is a common, important and under-recognised health burden in South Africa. There is a limited understanding of why pregnant women drink in the South African context. Existing qualitative research leaves significant knowledge gaps regarding pregnant women in rural settings, where prevalence of FASD is highest.Objective:To provide a qualitative assessment of factors that influence drinking in pregnant women in a rural community in the Northern Cape province of South AfricaMethods:A descriptive phenomenological approach was undertaken to explore the perceptions and experiences of pregnant women who drink, in a purposive sample of 8 women from a rural ante-natal clinic. A semi-structured interview was conducted with each participant and thematic analysis was conducted. Results:Participants appeared more aware of FASD than described in other study populations. Most reduced drinking after pregnancy recognition, although both recognition and cessation were often delayed. Participants described barriers and facilitators of alcohol abstinence. Barriers included social pressure, life stressors, and cravings and habits. Facilitators included desire to avoid FASD, relationships that were supportive without being stigmatising, availability of other “occupations” especially friendships and relationships not centred on drinking, specific body cues such as nausea, and a sense of personal agency. Conclusion:Various personal and contextual factors can act as barriers or facilitators of alcohol abstinence during pregnancy. Addressing barriers at structural, community and individual levels may aid women in reducing harmful drinking during pregnancy. Facilitators of abstinence should be leveraged to effect change in drinking behaviours, and thereby limit the burden of FASD.
Different Behavioral Patterns of SARS-COV-2 in Patients with Various Types of Cancers: A Role for Chronic Inflammation Induced by Macrophages
Authors: Moghanloo Ehsan , Rahimi-Esboei Bahman , Mahmoodzadeh Habibollah , Hadjilooei Farimah , Shahi Farhad , Heidari Sahel , Almassian Bijan
Published: February 2021

SARS-CoV-2 is a single strand RNA virus that causes ongoing pneumonia-like and severe respiratory disease. This disease is very important in immunosuppressed patients. Since not many studies have been done in people with cancer as high risk group, in this study we examined the different behaviors of this virus in different types of cancer. In this study, patients with a variety of solid and hematologic cancers were screened for SARS-CoV-2. The rates of infection, the rate of mortality, in patients with various cancers, as well as in the families of these patients have been studied. In this study, it was found that the prevalence of SARS-CoV-2 in patients with solid cancers was significantly lower than hematological cancers. Also, the mortality rate in hematological cancers was higher than in solid cancers (P<0.05). Assessments the families of these patients, it was found that patients with solid cancers were also less infected than their family members (P<0.05). Researchers of this study attributed these results to the chronic inflammation and M1 macrophages in these patients. It is essential that additional studies are conducted, especially in terms of biological function.
Acetic Acid Acting as a Signal Molecule in Quorum Sensing System Enhances Production of 2,3-Butanediol in Saccharomyces Cerevisiae
Authors: Zhang Chi , Tong Tianqi , Ge Jingping
Published: February 2021

Objectives2,3-butanediol (2,3-BD) has been extensively used in chemical synthese. The traditional 2,3-BD production method has low yield and high cost. This study aimed to explore the use of acetic acid as a signal molecule to initiate a quorum sensing (QS) system in order to promote the production of 2,3-BD in Saccharomyces cerevisiae W141. ResultsWe found that the yield of 2,3-BD from S. cerevisiae W141 is proportional to the cell density. S. cerevisiae W141 does not produce 2,3-BD when cell density was lower than the threshold concentration (OD600 nm = 10 or cell density 4.4 × 108 CFU/mL). When 1.5 g/L acetic acid was added in the fermentation process, the yield of 2,3-BD was the highest reaching 3.01 ± 0.04 g/L (84 h). Subsequently, we found that S. cerevisiae W141 was co-cultured with Acetobacter pasteurianus Huniang 1.01 under the optimal conditions and the acetic acid production was increased by 76.7% and 30.6% compared with the original strain and the strain with 1.5 g/L acetic acid, respectively. In addition, the yield of 2,3-BD was respectively increased by 81.9% and 3.3%. The above results are attributable to the increased activity of acetolactate synthase (ILV2) and 2,3-BD dehydrogenase (BDH1) and the increase of the relative expression of ilv2 and bdh1 genes. ConclusionOur data showed that biosynthesis of 2,3-BD was regulated by acetic acid as a signaling molecule. Moreover the study provides a deeper understanding of the mechanisms underlying between acetic acid and 2,3-BD production.