bluuebunny/crossref_metadata_2025 huggingface dataset:
UV Irradiation and Near Infrared Characterization of Laboratory Mars Soil Analog Samples: the case of Phthalic Acid, Adenosine 5’-Monophosphate, L-Glutamic Acid and L-Phenylalanine Adsorbed onto the Clay Mineral Montmorillonite in the Presence of Magnesium Perchlorate
Authors: Fornaro Teresa , Brucato John , Poggiali Giovanni , Corazzi Maria Angela , Biczysko Malgorzata , Jaber Maguy , Foustoukos Dionysis , Hazen Robert , Steele Andrew
Published: March 2020

The search for molecular biosignatures at the surface of Mars is complicated by an intense irradiation in the mid- and near- ultraviolet (UV) spectral range for several reasons: (i) many astrobiologically relevant molecules are electronically excited by efficient absorption of UV radiation and rapidly undergo photochemical reactions; (ii) even though the penetration depth of UV radiation is limited, aeolian erosion continually exposes fresh material to radiation; and (iii) UV irradiation generates strong oxidants such as perchlorates that can penetrate deep into soils and cause subsurface oxidative degradation of organics.As a consequence, it is crucial to investigate the effects of UV radiation on organic molecules embedded in mineral matrices mimicking the martian soil, in order to validate hypotheses about the nature of the organic compounds detected so far at the surface of Mars by the Curiosity rover, as well as organics that will be possibly found by the next rover missions Mars 2020 and ExoMars 2020. In addition, studying the alteration of possible molecular biosignatures in the martian environment will help to redefine the molecular targets for life detection missions and devise suitable detection methods.Here we report the results of mid-UV irradiation experiments of Mars soil analog samples obtained adsorbing relevant organic molecules on a clay mineral that is quite common on Mars, i.e. montmorillonite, doped with 1 wt% of magnesium perchlorate. Specifically, we chose to investigate the photostability of a plausible precursor of the chlorohydrocarbons detected on Mars by the Curiosity rover, namely phthalic acid, along with the biomarkers of extant life L-phenylalanine and L-glutamic acid, which are proteomic amino acids, and adenosine 5’-monophosphate, which is a nucleic acid component.We monitored the degradation of these molecules adsorbed on montmorillonite through in situ spectroscopic analysis, investigating the reflectance properties of the samples in the Near InfraRed (NIR) spectral region. Such spectroscopic characterization of molecular alteration products provides support for two upcoming robotic missions to Mars that will employ NIR spectroscopy to look for molecular biosignatures, through the instruments SuperCam on board Mars 2020, ISEM, Ma_Miss and MicrOmega on board ExoMars 2020.
Factorization of Odd Integers with a Divisor of the Form $2^au \pm 1$
Authors: Wang Xingbo
Published: March 2020

The paper proves that an odd composite integer $N$ can be factorized in at most $O( 0.125u(log_2N)^2)$ searching steps if $N$ has a divisor of the form $2^a{u} +1$ or $2^a{u}-1$ with $a > 1$ being a positive integer and $u > 1$ being an odd integer. Theorems and corollaries are proved with detail mathematical reasoning. Algorithms to factorize the kind of odd composite integers are designed and tested by factoring certain Fermat numbers. The results in the paper are helpful to factorize the related kind of odd integers as well as some big Fermat numbers
Escape Education: A Systematic Review on Escape Rooms in Education
Authors: Veldkamp Alice , van de Grint Liesbeth , Knippels Marie-Christine , van Joolingen Wouter
Published: March 2020

The global increase of recreational escape rooms has inspired teachers around the world to implement escape rooms in educational settings. As escape rooms are increasingly popular in education, there is a need to evaluate their use, and a need for guidelines in order to develop and implement escape rooms in the classroom. This systematic review synthesizes current practices and experiences, focussing on important educational and game design aspects. Subsequently, relations between the game design aspects and the educational aspects are studied. Finally, student outcomes are related to the intended goals. In different disciplines, educators appear to have different motives to use aspects such as time constraints or teamwork. These educators make different choices for related game aspects such as the structuring of the puzzles. Other educators base their choices on common practices in recreational escape rooms. However, in educational escape rooms players need to reach the game goal by achieving the educational goals. More alignment in game mechanics and pedagogical approaches are recommended. These and more results lead to recommendations for developing and implementing escape rooms in education, and will help educators creating these new learning environments, and eventually help students’ foster knowledge and skills more effectively.
Pengembangan Buku Panduan Pengurusan SIUP dan TDP untuk PT di PTSP Jakarta
Authors: Fhala Risda Nur , Suprayekti Suprayekti , Widyaningrum Retno
Published: March 2020

Penelitian pengembangan ini bertujuan untuk menghasilkan, media cetak berupa buku panduan pengurusan SIUP dan TDP PT di PTSP Jakarta. Sasaran pengguna buku ini ialah para pelaku usaha pemula. Penelitian dikembangkan berdasarkan model ADDIE yang memiliki 5 tahapan yaitu; analisis, desain, pengembangan, implementasi, dan evaluasi. Evaluasi yang dilakukan pada penelitian ini dilakukan melalui expert review dan one to one tryouts, evaluasi tersebut melibatkan 1 orang ahli materi, 1 orang ahli media, dan 4 orang pengguna. Nilai rata-rata yang diperoleh dari tahap expert review oleh ahli materi ialah 3.53 dan menunjukan kategori sangat baik. Nilai rata-rata yang diperoleh dari tahap expert review oleh ahli media ialah 3.12 dan menunjukan kategori baik. Pada tahap one to one tryouts, diperoleh nilai rata-rata 3.53 yang menandakan secara keseluruhan buku panduan ini sangat baik dan dapat digunakan untuk memandu pelaku usaha pemula dalam mengurus izin SIUP dan TDP secara online di website PTSP Jakarta dengan baik.
Diagnostic Performance of a Combination of Shear Wave Elastography and B-Mode Ultrasonography in Differentiating Benign From Malignant Thyroid Nodules
Authors: Yeon Eung Koo , Sohn Yu-Mee , Seo Mirinae , Kim Eui-Jong , Eun Young-Gyu , Park Won Seo , Yun Seong Jong
Published: March 2020

Objectives. This study was conducted to compare clinicopathologic and radiologic factors between benign and malignant thyroid nodules and to evaluate the diagnostic performance of shear wave elastography (SWE) combined with B-mode ultrasonography (US) in differentiating malignant from benign thyroid nodules.Methods. This retrospective study included 92 consecutive patients with 95 thyroid nodules examined on B-mode US and SWE before US-guided fine-needle aspiration biopsy or surgical excision. B-mode US findings (composition, echogenicity, margin, shape, and calcification) and SWE elasticity parameters (maximum [Emax], mean, minimum, and nodule-to-normal parenchymal ratio of elasticity) were reviewed and compared between benign and malignant thyroid nodules. The diagnostic performance of B-mode US and SWE for predicting malignant thyroid nodules was analyzed. The optimal cutoff values of elasticity parameters for identifying malignancy were determined. Diagnostic performance was compared between B-mode US only, SWE only, and the combination of B-mode US with SWE.Results. On multivariate logistic regression analysis, age (odds ratio [OR], 0.90; P=0.028), a taller-than-wide shape (OR, 11.3; P=0.040), the presence of calcifications (OR, 15.0; P=0.021), and Emax (OR, 1.22; P=0.021) were independent predictors of malignancy in thyroid nodules. The combined use of B-mode US findings and SWE yielded improvements in sensitivity, the positive predictive value, the negative predictive value, and accuracy compared with the use of B-mode US findings only, but with no statistical significance.Conclusion. When SWE was combined with B-mode US, the diagnostic performance was better than when only B-mode US was used, although the difference was not statistically significant.
Influencia de la realidad socioeconómica de Galicia en la dinámica de producción de incendios forestales
Authors: De Diego Abad Jaime , Fernández García Mercedes , Rúa Vieites Antonio
Published: March 2020

Galicia, con un 5,8 % de la superficie de España, concentró el 50% de los incendios forestales del país en el siglo XXI. Las investigaciones han analizado principalmente las características físicas y meteorológicas, las situaciones post- incendio y sus capacidades destructivas. Los factores socioeconómicos existentes antes del incendio en los territorios afectados han sido menos estudiados. Este artículo analiza la dinámica de los incendios forestales en Galicia entre 2001 y 2015. Concretamente, examina las tendencias espaciotemporales de su ocurrencia, la superficie afectada y la relación entre los incendios forestales y las características socioeconómicas de los distintos municipios gallegos. Para ello se realizó un análisis descriptivo exploratorio y un modelo de regresión lineal múltiple con dos variables dependientes diferentes, las Hectáreas quemadas y la Intensidad de los incendios; las variables independientes incluyeron tanto factores ambientales como aquellos aspectos socioeconómicos más relevantes. Los resultados muestran que existe una relación entre determinadas variables socioeconómicas indicativas de vulnerabilidad social (envejecimiento, tasa de masculinidad, baja densidad poblacional o pérdida de valor catastral) y los incendios forestales. Estos resultados pueden resultar de utilidad para la mejora en el diseño de acciones de prevención de incendios por parte de las autoridades responsables.
تدريس النحو في ضوء النظرية المعرفية لطلاب الصف الرابع بمعهد دار النجا الإسلامي السلفي فونوروغو
Authors: Mujib Ahmad , Rikza Muhammad Noval
Published: March 2020

The purpose of this study to find out: 1) the appropriateness of learning nahwu with the principles of cognitive theory and 2) the problem of learning nahwu with in the perspective of cognitive theory for 4th grade students at Salaf Boarding School Daarunnajaa Ponorogo. This study uses a descriptive method of analysis with qualitative approach. The results of this study are as follows: 1) Learning nahwu for 4th grade students at Salaf Boarding School Daarunnajaa Ponorogo in accordance with some learning procedures in the cognitive perspective and reflects its realization in the learning process nahwu and also not out or different from some basic procedures include: preparation of the title of the material in textbooks, teachers entering the classroom and greeting the students, the teacher starts the lesson by explaining the rules and then giving examples, the education has a meaningful activity position, the teacher uses an intermediate language, error correction is an integral part of the linguistic activities in the classroom, the learning takes place with one the concept begins with a conscious understanding and ends with training and learning rules. 2) The problem of learning nahwu in the perspective of cognitive theory that includes from the problem of intelligence, attention and memory
Identiﬁcation and application of piwi-interacting RNAs from seminal plasma exosome in Cynoglossus semilaevis
Authors: Zhang Bo , zhao Na , Jia Lei , Che Jinyuan , He Xiaoxu , Liu Kefeng , Bao baolong
Published: March 2020

Abstract
Background : Piwi-interacting RNAs (piRNAs) have been linked to epigenetic and post-transcriptional gene silencing of retrotransposons in germ line cells, particularly in spermatogenesis. Exosomes are important mediators of vesicle transport, and the piRNAs in exosomes might play an important role in cell communication and signal pathway regulation. Moreover, exosomic piRNAs are promising biomarkers for disease diagnosis and physiological status indication. We used C. semilaevis because of its commercial value and its sexual dimorphism, particularly the sex reversed ''pseudo-males'' who have a female karyotype, produce sperm, and copulate with normal females to produce viable offspring.
Results : To determine whether piRNAs from fish germ line cells have similar features, seminal plasma exosomes from half-smooth tongue sole, Cynoglossus semilaevis , were identified, and their small RNAs were sequenced and analysed. We identiﬁed six signature piRNAs as biomarkers in seminal plasma exosomes from males and pseudo-male C. semilaevis . Bioinformatic analysis showed that all six signatures were sex-related, and four were DNA methylation-related and transposition-related piRNAs. Their expression proﬁles were veriﬁed using real-time quantitative PCR. The expression of the signature piRNAs was markedly higher in males than in pseudo-males. The signature piRNAs could be exploited as male-specific biomarkers in this fish.
Conclusions : These signatures provide an effective tool to explore the regulatory mechanism of sex development in C. semilaevis and may provide guidance for future research on the function of piRNAs in the generative mechanism of sex reversed ''pseudo-males'' in C. semilaevis .
Understanding factors influencing care seeking for sick children in Ebonyi and Kogi states, Nigeria
Authors: Dougherty Leanne , Gilroy Kate , Olayemi Abimbola , Ogesanmola Omitayo , Ogaga Felix , Nweze Chinwe , Banerjee Joya , Oduenyi Chioma , Pacqué Michel
Published: March 2020

Background : Nigeria has one of the highest child mortality rates in the world, with an estimated 750,000 deaths annually among children under age five. The majority of these deaths are due to pneumonia, malaria, or diarrhea. Many parents do not seek sick-child care from trained, biomedical providers, contributing to this high rate of mortality.
Methods : This qualitative study explores factors enabling or preventing parents from seeking care for sick under-five children in Nigeria’s Kogi and Ebonyi states, including gender-related roles and social norms. Interviews were conducted with parents of sick under-five children and service providers, and focus group discussions were held with community leaders to assess how care-seeking behavior was influenced by four modes from the Colvin et al conceptual framework for household decision-making and pathways to care. These include (1) caregivers’ recognition and response to illness, (2) seeking advice and negotiating access within the family, (3) making use of community-based treatment options, and (4) accessing biomedical services.
Results: Parents were found to have a general understanding of illness symptoms but did not always attribute illness to biomedical causes. Intra-household decision-making processes were shaped by gender dynamics between men and women, and were found to have great effects on decisions to seek care. Use of traditional medicine and self-treatment were found to be common first steps in treatment before turning to the biomedical care system. Once the decision to seek biomedical care was taken, the route of seeking care varied between seeking care at chemists and then continuing to health facilities or starting with a health facility and then accessing prescriptions from a chemist.
Conclusion: We conclude that care-seeking decisions do not follow a linear process; that intra-household decision-making processes particularly among parents should not be underestimated in addressing sick-child care seeking; and that, given the role of mothers as primary caregivers, their knowledge in illness recognition and agency in care-seeking decision-making, and seeking biomedical care, is deserving of future study.
The Correlation Analysis between the Oxford Classification of Chinese IgA Nephropathy Children and Renal Outcome -A retrospective cohort study
Authors: Wu Heyan , Xia Zhengkun , Gao Chunlin , Zhang Pei , Yang Xiao , Wang Ren , Wang Meiqiu , Peng Yingchao
Published: March 2020

Background: The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy, but it lacks large cohort validation in children with IgAN in China. We sought to verify that the MEST-C score can be used to predict the renal outcome of children with IgAN. Methods : A retrospective cohort analysis of data from 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital from January 2000 to December 2017.We studied the relationship between the Oxford Classification and renal outcome [a combined renal endpoint:50% estimated glomerular filtration rate (eGFR) loss or end-stage renal disease (ESRD)]. Results :There were 29% of patients with mesangial proliferation (M1), 35% with endocapillary proliferation (E1),37% with segmental sclerosis/adhesion lesion (S1), 23% with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred),4.3% with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred),44% with crescent in< 25% of glomeruli(C1), and 4.6% with crescent in>25% of glomeruli(C2).During a median follow-up duration of 86.8 months,171children (14%) developed ESRD or 50% decline in renal function. An early diagnosis seems to be the major reason for a low frequency of chronic and severe lesions such as S,T and C lesions.In the multivariate Cox regression model, Only S( HR 2.7,95% CI ,1.8～4.2, P ＜0.001) and T lesions ( HR 6.6,95% CI ,3.9～11.3, P ＜0.001) were associated with the rate of eGFR loss in the whole cohort, whereas C lesion showed this association only in patients not treated with immunosuppression. Conclusions We found that S and T lesions were valid in predicting a renal outcome in Chinese IgAN Children.
Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies
Authors: Nie Daijing , Zhang Jing , Wang Fang , Zhang Wei , Liu Lili , Chen Xue , Zhang Yang , Cao Panxiang , Xiong Min , Wang Tong , Wu Ping , Ma Xiaoli , Tian Wenjun , Wang Mangju , Chen Kylan N. , Liu Hongxing
Published: March 2020

Background: Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet. Methods: We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA.Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied. Results: A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2 -G/A genotype have a significantly younger age of BMF onset ( p =0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection. Conclusion: The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.
Clinical characteristics and risk factors of 47 cases with ruptured neuroblastoma in children
Authors: Qin Hong , Yang Shen , Cai Siyu , Ren Qinghua , Han Wei , Yang Wei , Cheng Haiyan , Ma Xiaoli , Wang Huanmin
Published: March 2020

Backgroud: Neuroblastoma (NB) tumor rupture is a rare oncology emergency with a poor prognosis. We aimed to evaluate patient clinical characteristics and risk factors for ruptured NB. Methods: A retrospective study of 47 patients with confirmed NB rupture between January 2009 and January 2019 at Beijing Children's Hospital was conducted. To identify tumor rupture risk factors in high-risk NB patients, we included 93 consecutive non-ruptured high-risk NB patients from January 2017 to January 2019. Results: The median age at presentation was 29 months (adrenal and retroperitoneum origin) for 47 ruptured NB patients. Spontaneous tumor rupture occurred in 22 cases; 18 cases occurred during or after the first chemotherapy cycle, and 7 occurred after core needle biopsy. Five patients died of tumor rupture, and 17 patients’ parents refused further antitumor therapy. Among the 25 remaining patients, 6 survived without disease, 5 received ongoing treatment and achieved stable disease, and 14 died. According to multivariate logistic regression analysis, a maximum primary tumor diameter > 13.20 cm and MYCN gene amplification were independent risk factors for tumor rupture within high-risk NB. Conclusions: Tumor rupture is an uncommon, life-threatening event for NB patients; these patients are most likely to have poor outcomes due to tumor recurrence or rapid progression. Several treatment modalities, including symptomatic support therapy and chemotherapy, are important for saving lives and for developing NB risk-based treatment in the future.
Encephalopathy Following ingestion of Lead-Contaminated Opium; Magnetic Resonance Imaging Findings
Authors: Haghighi-Morad Maryam , Zamani Nasim , Hassanian-Moghaddam Hossein , Shojaei Maziar
Published: March 2020

Background Encephalopathy is an uncommon but serious presentation of lead toxicity. Objective We aimed to determine and follow-up the brain magnetic resonance imaging (MRI) abnormalities in the patients with lead encephalopathy due to ingestion of lead contaminated opium. Methods In a cross-sectional study during lead-contaminated opium outbreak, all lead-poisoned patients with any signs/symptoms of encephalopathy were included. Results Of 19 patients with lead encephalopathy, five died early and other five could not be sent to MRI during their hospitalization period. Mean age was 51±11 years and males were dominant (89%). Median [IQR] blood lead level (BLL) was 101 [81, 108] µg/dL (range; 50 to 200 µg/dL). There was no correlation between MRI findings and signs/symptoms. MRI was normal in six and abnormal in three. Bilateral symmetric involvement of parieto-occipital lobes was observed. Gray matter, gray-white matter junction, and subcortical white matter were also affected. Follow-up MRI was performed in two with abnormal MRI which showed complete and near complete resolution of the abnormalities after cessation of opium use and treatment. Conclusion: There was no correlation between MRI findings and BLL. Complete recovery of brain MRI lesions was detected after cessation of opium use.
Value of T1 Mapping on Gadoxetic acid-enhanced MRI for Microvascular Invasion of Hepatocellular Carcinoma: A Retrospective Study
Authors: Rao chenyi , Wang Xinquan , Li Minda , Zhou Guofeng , Gu Hongmei
Published: March 2020

Background: To evaluate the utility of non-invasive parameters derived from T1 mapping and diffusion-weighted imaging (DWI) on gadoxetic acid-enhanced MRI for predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods: A total of 94 patients with single HCC undergoing partial hepatectomy was analyzed in this retrospective study. Preoperative T1 mapping and DWI on gadoxetic acid-enhanced MRI was performed. The parameters including precontrast, postcontrast and reduction rate of T1 relaxation time and apparent diffusion coefficient (ADC) values were measured for differentiating MVI-positive HCCs (n=38) from MVI-negative HCCs (n=56). The receiver operating characteristic curve (ROC) was analyzed to compare the diagnostic performance of the calculated parameters.Results: MVI-positive HCCs demonstrated a significantly lower reduction rate of T1 relaxation time than that of MVI-negative HCCs (39.4% vs 49.9, P<0.001). The areas under receiver operating characteristic curve (AUC) were 0.587, 0.728, 0.824, 0,690 and 0.862 for the precontrast, postcontrast, reduction rate of T1 relaxation time, ADC and the combination of reduction rate and ADC, respectively. The cut-off value of the reduction rate and ADC calculated through maximal Youden index in ROC analyses was 44.9% and 1553.5 s/mm2. To achieve a better diagnostic performance, the criteria of combining the reduction rate lower than 44.9% and the ADC value lower than 1553.5 s/mm2 was proposed with a high specificity of 91.8% and accuracy of 80.9%.Conclusions: The proposed criteria of combining the reduction rate of T1 relaxation time lower than 44.9% and the ADC value lower than 1553.5 s/mm2 on gadoxetic acid-enhanced MRI holds promise for evaluating MVI status of HCC.
Relationships of Accelerometer-based Measured Objective Physical Activity and Sedentary Behaviour with Cognitive Function: A Comparative Cross-sectional Study of China’s Elderly Population
Authors: Wu Zhi jian , Wang Zhu ying , Hu Bing qian , Zhang Xu hui , Zhang Fan , Wang Hou lei , Li Fang hui
Published: March 2020

This study explored the effects of physical activity and sedentary behaviour on the decline of cognitive ability among the elderly. To compensate for the limitations of self-reported physical activity, objective measures were used. A cross-sectional survey of 308 aged people mean 68.66±5.377 years, in Nanjing, China, was conducted. Physical activity was measured using the ActiGraph GT3X+, and cognitive function was measured using the Montreal Cognitive Assessment. The overall participant model, adjusted for age, BMI, education, and monthly average income, found that light physical activity (β=0.006, p<0.01), moderate-vigorous physical activity (β=0.068, p<0.001), and total physical activity (β=0.006, p<0.01) had a significant linear relationship with cognitive ability, while sedentary time did not (β=-0.020, p＞0.05). Further, light physical activity only affects the cognitive ability of elderly females (β=0.006, p<0.05). There was an inverted ‘U’ association between moderate-vigorous physical activity and cognitive ability. The association models found that moderate-vigorous physical activity in the 22.13 min·day –1 ～38.79 min·day –1 range affected cognitive ability most beneficially, with the highest beta coefficient among all groups (β=0.091, p<0.05). In conclusion, while physical activity can significantly improve cognitive ability among the elderly, sedentary behaviour is associated with decreased cognitive function across genders.
Porous gold nanoparticles for attenuating infectivity of influenza A virus
Authors: Kim Jinyoung , Yeom Minjoo , Lee Taeksu , Kim Hyun-Ouk , Na Woonsung , Kang Aram , Lim Jong-Woo , Park Geunseon , Park Chaewon , Song Daesub , Haam Seungjoo
Published: March 2020

Background

Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations.

Main body

In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA.

Conclusion

We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.
Cattle gastrointestinal nematode egg-spiked faecal samples: high recovery rates using the Mini-FLOTAC technique
Authors: Amadesi Alessandra , Bosco Antonio , Rinaldi Laura , Cringoli Giuseppe , Claerebout Edwin , Maurelli Maria Paola
Published: March 2020

Background: Faecal egg count (FEC) techniques are commonly used to detect gastrointestinal nematode (GIN) in cattle and to determine anthelmintic efficacy/resistance through the faecal egg count reduction test (FECRT). Mini-FLOTAC is one of the techniques recommended for a standardised FEC/FECRT of helminth eggs in cattle. However, only one paper evaluated the recovery rate of GIN eggs by Mini-FLOTAC (compared to McMaster and modified-Wisconsin) in cattle, using only the level of contamination of 200 eggs per gram (EPG) of faeces and using GIN eggs collected from goat faeces to spike faecal samples from cattle. To further study the recovery rate of added GIN eggs from cattle, this study was conducted in two laboratories, one in Belgium and one in Italy to evaluate sensitivity, accuracy, precision and reproducibility of Mini-FLOTAC and McMaster (at two reading levels: grids and chambers) for the detection of GIN eggs in spiked bovine faecal samples. Methods: In both countries, spiked cattle faecal samples with five different levels of egg contamination (10, 50, 100, 200 and 500 EPG) of GINs were used. The study was performed in both laboratories by the same expert operator and using the same standard operating procedures (SOPs) for Mini-FLOTAC and McMaster. Sensitivity, accuracy and precision were calculated for each technique and for each level of contamination. Moreover, statistical analyses were performed to evaluate differences between performances of techniques used. Results: Mini-FLOTAC had a higher sensitivity (100% at all EPG levels for Mini-FLOTAC vs 0-66.6% for McMaster chambers and grids at levels <100 EPG), a higher accuracy (98.1% mean value for Mini-FLOTAC vs 83.2% for McMaster grids and 63.8% for McMaster chambers) and a lower coefficient of variation (10.0% for Mini-FLOTAC vs 47.5% for McMaster grids and 69.4% for McMaster chambers) than McMaster. There was no significant difference between the recovery of GIN eggs from the two studies performed in Belgium and in Italy. Conclusions: The high GIN eggs recovery rate detected by Mini-FLOTAC and the similar results obtained in Belgium and in Italy indicated that the diagnostic performance of a FEC technique was not regard to the laboratory environment.
Gait speed and handgrip strength as predictors of all-cause mortality and cardiovascular events in hemodialysis patient
Authors: Lee Yu Ho , Kim Jin Sug , Jung Su Woong , Hwang Hyeon Seok , Moon Ju-Young , Jeong Kyung-Hwan , Lee Sang-Ho , Lee So-Young , Ko Gang Jee , Lee Dong-Young , Lee Hong joo , Kim Yang Gyun
Published: March 2020

Background Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods of assessing physical performance. Methods We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationships with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia. Results The prevalence of low gait speed and handgrip strength was 28.2% and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index score, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with different determining factors (older age, the presence of diabetes, and lower serum albumin level for low gait speed, and lower body mass index and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risks for all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Elderly patients with low gait speed and handgrip strength were at the highest risk for poor clinical outcomes. Conclusion Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and the use of both factors improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator of poor patient outcomes than is handgrip strength.
Intravenous Calcium Gluconate Alleviates Lead-Induced Abdominal Pain, A Randomized Clinical Trial
Authors: Mayel Masoud , Hamzeh Saleh , Rabori Salile Shahabi Shahabi , Ghasemirad Sareh , Zamani Nasim , Hassanian-Moghaddam Hossein
Published: March 2020

Background : In 2016, in a lead poisoning outbreak in Iran, physicians reported thousands of opium users who presented to emergency departments (EDs) with intractable severe abdominal pain which did not respond to any narcotic medication. During the same period of time, we investigated the efficacy of intravenous calcium gluconate in alleviating lead-induced abdominal pain. Methods: In a single-center, single blinded, randomized controlled trial, a convenient sample of adult opium-addicted patients who presented to an academic ED with abdominal pain and had an initial diagnosis of lead poisoning were included and randomly subjected to two treatment groups receiving conventional treatment (morphine 0.1 mg/kg + normal saline; group 1) and conventional treatment plus 1 gram of intravenous calcium gluconate (group 2) to alleviate their abdominal pain. The visual analogue scale (VAS) was determined by each patient (0 to 100 mm) before treatment, and 15, 30, and 60 minutes after intervention. Results: A total of 50 patients (25 in each group) were enrolled. Blood lead levels, VAS scores before treatment, and mean administered dose of morphine were similar between the two groups. After treatment, mean VAS score dropped to 64.7±10.4 vs. 67.1±10.9 at 15 minutes (P=0.437), 64.6±10.9 vs. 58.0±11.2 at 30 minutes (P= 0.041), and 63.8±10.7 vs. 53.6±10.9 at 60 minutes (P= 0.002) in groups 1 and 2, respectively. Conclusion: Intravenous calcium gluconate administration along with morphine can improve abdominal pain in lead poisoning due to the ingestion of lead-contaminated opium. Further interventional studies are recommended to see if response to calcium salts in suspected lead-induced abdominal pain can rule in lead toxicity. Trial registration: IRCT20171009036661N2. Registered 27 May 2018 - Retrospectively registered, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20171009036661N2
Coccydynia – the efficacy of available treatment options: a systematic review protocol
Authors: Jensen Mads Moss , Andersen Gustav Østerheden , Milosevic Stefan , Andersen Mikkel Østerheden , Carreon Leah , Simony Ane , Rasmussen Mikkel Mylius
Published: March 2020

Background context:
Coccydynia is a painful condition which may severely impair quality of life in affected patients. Treatment of coccydynia is a field of interest with limited knowledge. The objective of this study is to evaluate the efficacy of current available treatments for coccydynia in adults, by systematically reviewing existing original peer-reviewed publications according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Methods/design:
A systematic literature search will be conducted in EMBASE.com, PubMed.com, Scopus and Web of Science bibliographic databases from their inception to January 17th, 2020, alongside a search for published studies and Epubs ahead of print in journals with relevance to spine surgery. Studies eligible for inclusion are original peer-reviewed papers addressing treatment of chronic coccydynia in adults. The articles will be screened by two authors independently, involving a third author in case of disagreement. Quality assessment and data extraction will be conducted using Covidence software. A meta-analysis will be conducted given that data is suitable.

Discussion:
This systematic review and meta-analysis may contribute to the existing knowledge on the efficacy of treatment options for coccydynia.

Systematic review registration: PROSPERO submission-ID: 166379

Keywords: Coccydynia, Pain, Treatment, Efficacy
Combined Effects of Lifestyle Risk Factors on Fatty Liver Index
Authors: Nivukoski Ulla , Niemelä Markus , Bloigu Aini , Bloigu Risto , Aalto Mauri , Laatikainen Tiina , Niemelä Onni
Published: March 2020

Background Factors of lifestyle may have a major impact on liver-related morbidity and mortality. We examined independent and joint effects of lifestyle risk factors on fatty liver index (FLI), a biomarker of hepatic steatosis, in a population-based cross-sectional national health survey. Methods The study included 12,368 participants (5,784 men, 6,584 women) aged 25–74 years. Quantitative estimates of alcohol use, smoking, adiposity and physical activity were used to establish a total score of risk factors, with higher scores indicating an unhealthier lifestyle. FLI was calculated based on an algorithm including body mass index, waist circumference, serum gamma-glutamyltransferase and triglycerides. Results The occurrence of FLI ≥ 60% indicating fatty liver increased from 2.4% in men with zero risk factors to 81.9% in those with a total risk score of 7–8 (p < 0.0005 for linear trend) and in women from 0% to 73.5% (p < 0.0005). The most striking individual impacts on the likelihood for FLI above 60% were observed for physical inactivity (p < 0.0005 for both genders) and alcohol consumption (p < 0.0005 for men). Interestingly, coffee consumption was also found to increase with increasing risk factor scores (p < 0.0005 for linear trend in both genders). Conclusions The data indicates that unfavorable combinations of lifestyle risk factors lead to a high likelihood of hepatic steatosis. Use of FLI as a diagnostic tool may benefit the assessment of interventions aimed at maintaining a healthy lifestyle and prevention of liver-related morbidity.
Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation – A randomized controlled clinical trial
Authors: Reiterer Christian , Hu Karin , Sljivic Samir , von Sonnenburg Markus Falkner , Fleischmann Edith , Kainz Alexander , Kabon Barbara
Published: March 2020

Background

Ischaemia/reperfusion (I/R) injury is associated with renal tissue damage during deceased donor renal transplantation. Evidence is weak regarding the effect of mannitol attenuating I/R injury during graft reperfusion in renal transplant recipients. We tested the effect of mannitol to reduce renal graft injury represented by 16 serum biomarkers, which are involved in different relevant pathophysiological pathways. Our primary outcome were differences in biomarker concentrations between the mannitol and the placebo group 24 hours after graft reperfusion. Additionally, to account for biomarker concentrations before transplantation, a linear mixed model was applied.

Methods

34 patients undergoing deceased donor renal transplantation were randomly assigned at the Medical University of Vienna to receive either 20% mannitol or 0.9% NaCl placebo solution before and after graft reperfusion. 16 serum biomarkers (MMP1, CHI3L1, CCL2, MMP8, HGF, GH, FGF23, Tie2, VCAM1, TNFR1, IGFBP7, IL18, NGAL, Endostatin, CystC, KIM1) were measured preoperatively and 24 hours after graft reperfusion using Luminex assays and ELISA.

Results

16 patients in each group were analysed. Tie2 differed 24 hours after graft reperfusion between both groups ( p = 0.011). Change of log2 transformed concentration levels over time differed significantly in four biomarkers (VCAM1,Endostatin, KIM1, GH; p=0.007; p = 0.013; p = 0.004; p = 0.033; respectively) out of 16 between both groups.

Conclusion

Our study showed insufficient effects of mannitol on I/R injury in patients undergoing deceased renal transplantation. Thus, we do not support the routinely use of mannitol to attenuate I/R injury.
Large- Scale Analysis of MicroRNA Expression in Motor Neuron- like Cells derived from Human Umbilical Cord Blood Mesenchymal Stem Cells
Authors: Sanooghi Davood , Lotfi Abolfazl , Faghihi Faezeh , Karimi Afzal , Bagher Zohreh , Yousefi Behnam , Lotfi Erfan , Joghataei Mohammad Taghi
Published: March 2020

Background Motor neuron- related disorders such as Spinal Cord Injuries and Amyotrophic Lateral Sclerosis are extremely common around the world. Many efforts have been made to use stem cells to modulate regeneration of spinal cord damages. Human umbilical cord blood mesenchymal stem cells (CB-MSCs) cover a class of cells with self-renewal feature and multilineage differentiation capacity. Retinoic acid(RA) and sonic hedgehog(Shh) are two morphogens responsible in motorneuron commitment during development. This study aims to explore the effect of Shh and RA on differentiation of CB-MSCs into motor neuron- like cells and to determine the related microRNA profile. To do that, human MSCs were isolated and then characterized using flowcytometry. The cells were induced using RA and Shh and the outcomes were assessed by immunocytochemistry, real-time- PCR, and flowcytometry. MicroRNA analysis was performed using Solexa system at three libraries, including Test 1 (with RA and Shh), Test 2 (After removing RA and Shh) and the Control. Results The isolated cells were spindle shape and could express MSC markers confirmed by flowcytometry. The cells could express motorneuron- related markers including Islet-1, Hb-9, SMI-32 and ChAT at the level of mRNA and protein, when treated with RA and Shh. Two weeks after induction, the expression of Neun and Islet-1 declined. The analysis of miRNA sequencing revealed a significant expression of mir-let-7b, mir-137 and mir-324-5p, which were responsible for neuron/motor neuron differentiation and suppression of neural progenitor cell proliferation. Moreover, some novel microRNAs involved in cholinergic, Jak- Stat, Hedgehog and Map kinase signaling pathways were revealed. Conclusion CB-MSC represents a type of cells with convenient accessibility, which can be differentiated into motor neuron- like cells in the presence of RA and Shh. We could also detect the expression of candid microRNAs responsible in motor neuron differentiation and some novel microRNAs involved in cholinergic, Jak- Stat, Hedgehog and Map kinase signaling pathways that must be functionally evaluated in further studies.
Effectiveness of beclometasone dipropionate and formoterol in an extrafine particle formulation for asthma therapy depending on patient smoking status: the CASPER noninterventional, observational trial
Authors: Kuprys-Lipinska Izabela , Debowski Tomasz , Palczynski Cezary , Lacwik Piotr , Kuna Piotr
Published: March 2020

Background: The goal of asthma treatment, outlined by GINA experts, is to achieve and maintain full control of the disease. One critical risk factor for poor asthma control is exposure to tobacco smoke. The purpose of this analysis isto assess the effectiveness and safety of long-term therapy with an extrafine combined aerosol formulation of beclometasone dipropionate and formoterol (BDP/F) in asthmatics for current and ex-smokers vs non-smokers. Methods: The CASPER study was an observational, noninterventional, prospective, multicentre trial. Asthmatics currently being managed long-term with BDP/F pressurized metred-dose inhaler (pMDI) were divided based on smoking status into three groups: current smokers, ex-smokers, and non-smokers. The subjects were evaluated at 0, 3, and 6 months for symptom intensity, asthma control, frequency of exacerbations and dose of inhaled corticosteroids. Adverse drug reactions were also monitored. Results: Out of 16,844 patients, 2833 (16.8%) were ex-smokers and 3312 (19.7%) were current smokers. At the beginning of the observation, the current smokers were the most symptomatic subgroup of patients with the greatest limitation on life activity. During long-term treatment with extrafine BDP/F-pMDI , diurnal and nocturnal asthma symptoms, rescue medication use, and limitations of activity secondary to asthma were markedly decreased in all subgroups, with a statistically significant effect in smokers and ex-smokers, albeit at the end of the observation, a higher percentage of symptomatic patients remained in the groups of current smokers and ex-smokers while a lower percentage of symptomatic patients was observed among the non smokers. At the 6-month follow-up, an improvement in asthma control compared to baseline, according to GINA criteria, was reported in 77.1% of current smokers, 75.2% of exsmokers, and 75% of non-smokers, but full asthma control was more frequently achieved in non smokers (64.0% fulfilled GINA criteria of asthma control) compared to current smokers and ex-smokers (54.9% and 51.5%, respectively). A total of 525 nonserious ADRs were reported in 422 patients (3.2%), all of which were within expectations. Conclusions: Combination therapy with extrafine BDP/F-pMDI is an effective therapy across a broad spectrum of asthmatics, irrespective of smoking status,albeit the overall asthma control is worse in those with a smoking history.
Future Development through the Past: Pathology of the Financing Dimension of Iran’s Health Transformation Plan
Authors: Doshmangir Leila , Najafi Behzad , Modtafavi Hakimeh , Moshiri Esmaeil
Published: March 2020

Introduction: In Iran, during the years, the budgeting model used for healthcare funding is affected by factors such as global oil prices and fluctuation in the exchange rates, so developing or continuing to implement a plan in the health system depends on the current and future global and local economic trends. This study aimed to analyze the future of the recent significant reform called Health Transformation Plan (HTP), started on 15 Jun 2014 in light of potential financial barriers and challenges.Methods: Face to face interviews were conducted with health policymakers at different levels of the health system, health researchers, health insurance officers, and faculty members. Also, published and unpublished documents about HTP in the country and worldwide were reviewed. Data analysis was done using a qualitative inductive content analysis approach and assisted by qualitative data management software.Findings: Instability of financial resources and allocation of Gross Domestic Product (GDP) to the HTP in the traditional way is a challenge in continuing this policy reform. Also, the bureaucratic procedures in allocation and distribution of funds, discrepancy between health insurance funds and affiliated units of Ministry of Health and Medical Education (MoHME) especially Medical Sciences Universities (MSU), the lack of purchaser–provider split, inappropriate payments and compensation mechanisms, and dependence of MSU on especial revenues are the main challenges that threaten the future of HTP in Iran.Conclusion: Given the current situation, where the country's funding resources are often unpredictable, it seems that such funding challenges will lead to poor HTP results. Therefore, the continuance of such high cost-based plan requires the strategies and policies to ensure raising additional funds through various types of innovative financing to overcome challenges.