bluuebunny/crossref_metadata_2025 huggingface dataset:
An Accurate Determination of the Shear Rate for High-Yield-Stress Drilling Fluids Using Concentric Cylinder Fann 35 Viscometer Data
Authors: Gautam Sidharth , Guria Chandan
Published: June 2020

Rheology is very important for drilling fluid because it directly influences the cutting transportability, hole cleaning ability, lubricity, and filtration loss behavior while drilling. Over the years, the concentric cylinder Fann® 35 viscometer (Houston, Texas, USA) has been used regularly to monitor the properties of drilling fluids because of its simplicity in operations. In the Fann 35 viscometer, the dial readings at different rotor rotations are converted into shear stress; in contrast, the rotor rotation is transformed into the equivalent shear rate using a priori assumed Newtonian behavior of the test drilling fluids. Because the real-life drilling fluids are mostly non-Newtonian with a finite yield stress, the applicability of the simple shear-rate equation, which is frequently used to monitor drilling-fluid rheology, is questionable. A fluid exhibiting sufficiently high yield stress and an unsheared plug flow region near the vicinity of the cup also complicates the estimation of the shear rate. Besides this, the inaccurate values of true yield stress may also result in a poor estimate of the shear rates at different rotor rotations. In the present study, a comprehensive mathematical model is developed to estimate the rheology of drilling fluids with high-yield stress accounting for the fundamentals of rheology using the Fann 35 viscometer data. A generalized difference equation and subsequent Taylor series expansions are used to obtain the accurate wall shear-rate equation for the high-yield-stress non-Newtonian drilling fluids. The true yield stress, an input parameter for the shear-rate prediction, is also accurately determined with the proposed yield-stress model based on the capillary-rise method using two different capillaries.

Six different experimental fluids involving aqueous suspension of polyanionic cellulose (PAC; a salt-resistant filtration loss control agent), xanthan gum (XG; a viscosifying agent exhibiting the low shear rate viscosity), carboxymethyl cellulose (CMC; a fluid loss control additive), bentonite nanoclay (an additive for filtration and rheology control), and high-pressure and high-temperature synthetic drilling fluids based on American Petroleum Institute (API)-grade bentonite (BEN) and α-glycol functionalized fly ash (FNFA) were studied to validate the proposed yield stress and the shear-rate model. Finally, the shear rate, apparent viscosity, plastic viscosity, and Bingham yield point are predicted using the proposed models, and the results are compared with the existing shear-rate models.
24-month clinical, immune-virological outcomes and HIV status disclosure in adolescents living with perinatally-acquired HIV in the COHADO cohort, in Togo and Côte d’Ivoire, 2015-2017
Authors: Revegue Marc Harris Dassi Tchoupa , Takassi Elom , Eboua François Tanoh , Desmonde Sophie , Amoussou-Bouah Ursula Belinda , Bakai Tchaa Abalo , Jesson Julie , Dahourou Désiré Lucien , Malateste Karen , Raynaud Jean-Philippe , Arrivé Elise , Leroy Valériane
Published: June 2020

Background: Adolescents living with perinatally-acquired HIV (APHIV) face challenges including the disclosure of their HIV-serostatus that we explored in the West-African COHADO cohort. We assessed the 24-month outcomes among APHIV in relation to the disclosure of their own HIV-serostatus.Methods: Nested within the International epidemiologic Database to Evaluate AIDS pediatric West African prospective cohort (IeDEA pWADA), the COHADO cohort included antiretroviral (ART)-treated APHIV aged 10–19 years, enrolled in HIV-care <10 years, in Abidjan (Côte d’Ivoire) and Lomé (Togo) in 2015. An unfavorable outcome was defined when either death, loss to follow-up, progression to WHO-AIDS stage, a decrease of CD4 count >10% compared to baseline, or a detectable viral load (>50copies/mL) were notified at 24 months. None of these events defined a favorable outcome. We investigated correlates of APHIV favorable 24-month outcome using a logistic regression model.Results: Overall, 209 APHIV were included, 51.6% in Abidjan, 54.5% were females. At inclusion, median CD4 cell count was 521/mm3 (IQR[281-757]); 29.6% had a VL measurement of whom 3.2% in virological suppression. APHIV were younger in Lomé (median age: 12 years (interquartile range [IQR]:11-15) compared to Abidjan (14 years (IQR:12-15, p=0.01). Full HIV-disclosure increased from 41.6% at inclusion to 74.1% after 24 months. After 24 months of follow-up, 6 (2.9%) died, 8 (3.8%) were lost to follow-up, 4 (1.9%) were transferred out. Overall, 73.7% did not progress to WHO-AIDS stage, 62.7% had CD4 count above (± 10%) of the baseline value (48.6% in Abidjan versus 69.0% in Lomé, p<0.001). Among the 83.7% with VL measurements, 48.8% were in virological suppression (Abidjan: 45.4%, Lomé: 52.5%, p<0.01). The 24-month combined outcome was favorable for 45% (29.6% in Abidjan and 61.4% in Lomé, p<0.01): adjusted on baseline variables, it was not significantly associated with HIV-disclosure but significantly higher for APHIV living in Lomé compared to those in Abidjan (aOR: 17.24, 95%CI [3.69-80.44]).Conclusions: 24-month favorable outcome rates were low among West-African APHIV and differed across countries. HIV-disclosure frequency improved over time but remained low. Context-specific responses are urgently needed to improve adolescent’s care to reach the UNAIDS 90% target of virological success for those on ART.
Identification of Significant Climatic Risk Factors and Machine Learning Models in Dengue Outbreak Prediction
Authors: Nejad Felestin Yavari , Varathan Kasturi Dewi
Published: June 2020

Background: Dengue fever is a widespread viral disease and one of the world’s major pandemic vector-borne infections, causing serious hazard to humanity. The World Health Organisation (WHO) reported that the incidence of dengue fever has increased dramatically across the world in recent decades. WHO currently estimates an annual incidence of 50–100 million dengue infections worldwide. To date, no tested vaccine or treatment is available to stop or prevent dengue fever. Thus, the importance of predicting dengue outbreaks is significant. The current issue that should be addressed in dengue outbreak prediction is accuracy. A limited number of studies have conducted an in-depth analysis of climate factors in dengue outbreak prediction. Methods: The most important climatic factors that contribute to dengue outbreaks were identified in the current work. Correlation analyses were performed in order to determine these factors and these factors were used as input parameters for machine learning models. Top five machine learning classification models (Bayes network (BN) models, support vector machine (SVM), RBF tree, decision table and naive Bayes) were chosen based on past research. The models were then tested and evaluated on the basis of four-years data (January 2010 to December 2013) collected in Malaysia. Results: This research has two major contributions. A new risk factor, called the TempeRain Factor (TRF), was identified and used as an input parameter for the model of dengue outbreak prediction. Moreover, TRF was applied to demonstrate its strong impact on dengue outbreaks. Experimental results showed that the Bayes Network model with the new meteorological risk factor identified in this study increased accuracy to 92.35% and reduced the root-mean-square error to 0.26 for predicting dengue outbreaks. Conclusions: This research explored the factors used in dengue outbreak prediction systems. The major contribution of this study is identifying new significant factors that contribute to dengue outbreak prediction. From the evaluation result, we obtained a significant improvement in the accuracy of a machine learning model for dengue outbreak prediction.
Management of urinary tract infections what do doctors recommend and patients do? An observational study in German primary care
Authors: Gágyor Ildikó , Strube-Plaschke Stephanie , Rentzsch Katrin , Himmel Wolfgang
Published: June 2020

Background Uncomplicated urinary tract infections (UTIs) in women are usually managed in primary care with antibiotics. However, many women seem to prefer to handle UTI symptoms with nonsteroidal anti-inflammatory drugs (NSAIDs) and other remedies. The aim of this study was to compare UTI management as recommended by physicians with the patients’ management at home.Methods This prospective cohort study in German primary care is based on clinical data from local practices and patient questionnaires. Participating women completed a baseline data sheet in the practice; their urine sample was tested by a dipstick in the practice and cultured by a laboratory. The women reported treatment and symptom-related impairment on an eight-item symptom questionnaire daily for 7 days. Using growth curve models, we analysed the influence of time on the total severity score to examine how symptoms changed across days. We then examined whether symptom severity and symptom course differed between patients who took antibiotics or NSAIDs.Results A total of 120 women (mean age of 43.3 ± 16.6 years) were enrolled. The urine dipstick was positive for leucocytes in 92%, erythrocytes in 87%, and nitrites in 23%. Physicians prescribed antibiotics for 102 (87%) women and recommended NSAIDs in 14 cases. According to the women’s reports, only 60% (72/120) took antibiotics, while the remainder took NSAIDs and other remedies. Symptoms declined from day 0 to day 6, irrespective of whether women decided to take an antibiotic, NSAIDs, none or both, as confirmed by a significant curvilinear time effect (B = 0.06, SE = 0.005, p < .001). The symptom course, however, was moderated by taking antibiotics so that the change in symptom severity was somewhat more pronounced in women taking antibiotics (B = 0.06) than in the remainder (B = 0.04).Conclusion A substantial proportion of women did not follow their physicians’ treatment recommendations, and many used NSAIDs. All women had a good chance of recovery irrespective of whether they decided to take antibiotics. A sensitive listening to patient preferences in the consultation may encourage physicians to recommend and prescribe symptomatic treatment with NSAID more often than antibiotic medicines.
Predictors of total hip replacement in community based older adults: a cohort study
Authors: Mezhov Veronica , Laslett Laura L , Ahedi Harbeer , Blizzard C Leigh , Aspden Richard M , Gregory Jennifer S , Saunders Fiona R , Munugoda Ishanka P , Cai Guoqi , Cicuttini Flavia , Jones Graeme
Published: June 2020

Background: Hip osteoarthritis (OA) commonly affects older adults and leads to high morbidity. There is no preventative treatment available and total hip replacement (THR) is offered for end stage disease. Known predictors of THR include pain and radiographic OA. Hip structure has also been shown to worsen hip OA and predict THR. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. The purpose of this study is to describe predictors of THR in community dwelling older adults. Methods: At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiographs), shape mode scores (from dual energy X-ray absorptiometry (DXA)) and hip bone mineral density (BMD) (from DXA). After 2.6 and 5 years, participants reported hip pain using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), and had hip structural changes assessed using magnetic resonance imaging (MRI). Risk of THR was analysed using mixed-effect Poisson regression.Results: Incidence of THR for OA over 14 years was 5.0% (40 / 802). As expected, WOMAC hip pain and hip radiographic OA both predicted risk of THR. Additionally, shape mode 2 score (decreasing acetabular coverage) (RR 1.57 per SD; 95% CI 1.01-2.46), shape mode 4 score (non-spherical femoral head) (RR 0.65/SD; 95% CI 0.44-0.97), cam morphology (α >60°) (RR 2.66/SD; 95% CI 1.38-5.13), neck of femur BMD (RR 1.85/SD, 95% CI 1.4-2.44) and bone marrow lesions (BMLs) increased risk of THR (RR 5.62/unit; 95% CI 1.1 – 28.81). Conclusion: In addition to hip pain and radiographic hip OA, measures of hip shape, cam morphology, BMD and BMLs independently predict risk of THR. This supports the role of hip bone geometry and structure in the pathogenesis of end stage hip OA and has identified factors that can be used to improve prediction models for THR.
Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level
Authors: Wong Chee-Yin , Chang Yao-Ming , Tsai Yu-Shuen , Ng Wailap Victor , Cheong Soon-Keng , Chang Ting-Yu , Chung I-Fang , Lim Yang-Mooi
Published: June 2020

Background: Mesangial cells play an important role in the glomerulus, providing mechanical support to it, and maintaining efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells as well as to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.Results : Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. Additionally, not only can TO-GCN analysis classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation, but it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.Conclusions: A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes existing in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts as MSC differentiate into mesangial cells.
Developing a roadmap to improve trial delivery for underserved groups: results from a UK multi-stakeholder process
Authors: Witham Miles D , Anderson Eleanor , Carroll Camille , Dark Paul M , Down Kim , Hall Alistair S , Knee Joanna , Maier Rebecca H , Mountain Gail A , Nestor Gary , Oliva Laurie , Prowse Sarah R , Tortice Amanda , Wason James , Rochester Lynn
Published: June 2020

Background Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of underserved groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of underserved groups in clinical trials. Methods The project comprised three main strands: 1) a targeted scoping review of literature to identify previous work characterising underserved groups and barriers to inclusion; 2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice; 3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans, and a strategic roadmap for future development work in this area. Results ‘Underserved groups’ was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of underserved groups did not currently exist; definition was challenging and context-specific but exemplar groups (e.g. those with language barriers or mental illness) were identified as underserved. Barriers to successful inclusion of underserved groups could be clustered into: communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with underserved groups; developing training resources to improve design and delivery of trials for underserved groups; developing infrastructure and systems to support this work, and working with funders, regulators and other stakeholders to remove barriers to inclusion. Conclusions The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different underserved groups to improve the representativeness of trial populations.
Molecular characterization of Leishmania tropica and Leishmania major from stray dogs and patients in Saudi Arabia
Authors: Alanazi Abdullah D , Alouffi Abdulazi S Alouffi S , Alyousif Mohamed S Alyousif S , Rahi Abdulsadah A , Ali Magda A , Brayner Fabio A , Mendoza-Roldan Jairo Alfonso , Otranto Domenico
Published: June 2020

Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when occurring in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. Methods: To determine the prevalence and to identify the species of Leishmania that infects humans and stray dogs in Riyadh and Al-Qassim (Saudi Arabia), 311 stray dogs and 27 human patients, suspected for Leishmania, were examined for CL by a nested PCR (nPCR). Results: Nested PCR (nPCR) detected seven patients (25.9%) positive for cutaneous leishmaniasis. Five patients from Riyadh were infected by L. major and two from Al-Qassim by L. tropica. In addition, five dogs (1.6%) were infected by L. tropica . Conclusions: This is one of the first molecular studies of leishmaniasis from Saudi Arabia. The relationship between the sand fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and further epidemiological investigations of domestic and wild canids infected with L. major and L. tropica are needed towards a control and prevention of the infection in canine and human populations.
Molecular analysis of methicillin-resistant Staphylococcus aureus isolates from four teaching hospitals in Iran: The emergence of novel MRSA clones
Authors: Firoozeh Farzaneh , Omidi Mitra , Saffari Mahmood , Sedaghat Hossein , Zibaei Mohammad
Published: June 2020

Background: The global spread of methicillin-resistant Staphylococcus aureus (MRSA) infections necessitates the use of validated methods for the identification and typing of this bacterium. This study aimed to determine the distribution of main molecular types of MRSA strain circulating among hospitalized patients in teaching hospitals in Isfahan and Kashan. Methods: A total of 146 Staphylococcus aureus strains were isolated from patients in four teaching hospitals in Isfahan and Kashan during June 2017 to September 2018. The antimicrobial resistance patterns of Staphylococcus aureus strains were performed by disc diffusion method. The MRSA strains were identified phenotypically and confirmed by PCR assay. The prevalence of microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) genes among MRSA strains was evaluated by multiplex PCR. The genotypes of MRSA strains were determined by multilocus sequence typing and SCCmec typing. Results: Of 146 Staphylococcus aureus isolates, 24 (16.4%) isolates were identified as MRSA strains. According to antimicrobial susceptibility testing the highest resistance rates were seen for tetracycline, erythromycin, ciprofloxacin and gentamicin. All of Staphylococcus aureus isolates were susceptible to vancomycin whereas 3 (2.1%) isolates were resistant to linezolid. Three different SCCmec types were obtained among MRSA strains including 16 (66.7%) SCCmec type V, 3 (12.5%) SCCmec type III and 5 (20.8%) SCCmec type II. Of 24 MRSA isolates 20 (83.3%) carried MSCRAMMs genes including eno (70.8%), fib (54.1%), cna (25.0%), fnbB (16.6%), ebps 5 (20.8%), and the fnbA, bbp and clfA genes were not detected in any MRSA isolate. MLST analysis revealed 11 sequence types among MRSA isolates as follows: ST239, ST291, ST22, ST861, ST889, ST8, ST59, ST343, ST772, ST6 and ST1465. Also seven MLST-based clonal complexes (CCs) were identified among MRSA strains including: CC8, CC7, CC398, CC59, CC22, CC1 and CC5. Conclusions: A relatively high diversity was found in MRSA genotypes in Kashan and Isfahan hospitals, and seven clonal complexes were identified. Pandemic MRSA clones including CC8 and CC22 were the most prevalent clones and the novel ST types including ST1465, ST861, ST 889 and ST772 are reported for the first time in Iran in the present study. In addition the high prevalence of MSCRAMMs genes in MRSA isolates demonstrates the high potential of these strains for pathogenicity.
Effects of physical exercise on cognitively impaired older adults: a systematic review and meta-analysis of randomized control trials
Authors: Sontakova Lenka , Bartova Alzbeta , Dadova Klara , Holmerova Iva , Steffl Michal
Published: June 2020

Objectives: The main aim of this study was to compare the effects of different physical activities on cognitive functions in older adults divided according to cognitive impairment levels.Methods: We searched Web of Science, Scopus, and PubMed for randomized control trials (RCT). A standardized mean difference (SMD) of the pre-post intervention score of global cognitive function tests was calculated by the random model in the Cochrane meta-analyses for people with cognitive impairment generally and across three levels - borderline intact, mild, and moderate cognitive impairment separately. Additionally, an unstandardized coefficient beta (B) was calculated in generalized linear models to estimate the effects of exercise, cognitive impairment severity, age, female ratio, duration and frequency of exercise program on the global cognitive function.Results: Data from 40 studies involving 1,780 participants from intervention groups and 1,508 participants from control groups were analyzed. After sensitivity analysis, physical exercise had a positive effect on cognitive functions in people across all levels of cognitive impairments, SMD (95 % confidence interval [CI]) = 0.41 (0.29 - 1.54). All the activities were significantly associated with better results in global cognitive functions when compared to active control (B = 0.538 in aerobic, 0.999 in resistance, 0.640 in combined exercise and 0.746 in Tai Chi). Age was significantly associated with global cognitive functions decreasing and a higher number of female participants in intervention groups had a statistically significant effect on the global cognitive function (B = 0.021).Conclusions: Physical exercise was associated with cognitive function improvement in older people with cognitive impairments. Cognitive impairment severity was not associated with cognitive functions changes after exercise interventions.
Delay in treatment initiation and its association with clinical severity and infectiousness among new adult pulmonary tuberculosis patients in Tigray, Northern Ethiopia
Authors: Tedla kiros , Medhin Girmay , Berhe Gebretsadik , Mulugeta Afework , Berhe Nega
Published: June 2020

Background: Delayed treatment initiation of tuberculosis (TB) increases disease progression and development of complications which may lead to a higher level of infectiousness, clinical severity and increased mortality. But published evidences that investigated the effect of delayed initiation of treatment on clinical severity and level of infectiousness of pulmonary tuberculosis patients is scarce in Tigray, Northern Ethiopia. Objective: To investigate the association of delayed treatment initiation of new adult Pulmonary Tuberculosis patients with clinical severity and level of infectiousness. Methods: In this cross-sectional study design, a total of 875 newly diagnosed adult pulmonary tuberculosis patients were recruited from 21 health facilities from October 2018 to October 2019. Health facilities and study participants were selected by a simple random sampling method. Data were collected using questionnaires through face-to-face interviews of patients within the first 2 weeks of treatment initiation. Clinical severity was assessed by Bandim tuberculosis score and level of infectiousness was assessed by smear positivity or lung cavitations. Data were analyzed using SPSS version 21 software program. Logistic regression analysis was used to ascertain the association of delay with clinical severity and level of infectiousness. P-value of less than 0.05 was reported as being statistically significant.Results: Those who had initiated treatment without delay and those who have initiated treatment after a medium delay of 31 to 60 days were significantly associated with decreased clinical score compared to those who initiated treatment after a delay of more than two months. Compared with patients who have initiated treatment within one month, the level of infectiousness was greater for delay of 30-60 days and above 60 days. Patients having more than 3 family members have higher level of infectiousness as compared to those who have a maximum of 3 family members. Whereas, patients having at least two rooms and being HIV negative had lower levels of infectiousness compared to their counter patients. Conclusion: Narrowing the gap between their initial occurrence of TB symptoms and treatment initiation is the way forward to improve clinical courses of TB patients and to reduce the level of infectiousness of TB to other people from these patients.
Slip surface layer estimation of shallow landslides on Aso volcanic mountains in Japan based on tephra layer-soil properties
Authors: Istiyanti Mega Lia , Goto Satoshi
Published: June 2020

Shallow landslides are known to appear frequently on the Aso volcanic mountains. The soil material on the Aso volcanic mountains consists of tephra layers obtained from volcanic activities. This study is aimed at determining the soil property factors that correlate with the slip surface of a shallow landslide on the volcanic mountain area. Tephra layers consist of kuroboku and scoria layers and the differences between these layers have been determined using soil property tests. This study determined that the plasticity index and the fine fraction content can be used as factors showing the slip surface indication in the Aso volcanic area.
Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled trial
Authors: Ni Jun , Chen Huisheng , Chen Guofang , Ji Yong , Yi Fei , Zhang Zhuobo , Yang Yi , Wu Jin , Cai Xueli , Shao Bei , Wang Jianfeng , Liu Yafang , Geng Deqin , Qu Xinhui , Li Xiaohong , Wei Yan , Ding Jianping , Lu Hua , Huang Yining , Huang Yonghua , Xiao Bo , Gong Tao , Cui Liying
Published: June 2020

Background: Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 hours of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke.Methods: Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram.Results: In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p=0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p=0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups.Conclusions: The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported.Trial registration: Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827. Retrospectively registered June 13, 2019.
Slope Mass Rating-based Analysis to Assess Rockfall Hazard on Yogyakarta Southern Mountain, Indonesia
Authors: Triana Karlina , Hermawan Koko
Published: June 2020

In the Parangtritis Beach tourism area located in the Southern Mountain of Yogyakarta, karst hills were excavated to build the main accessing road and produce some of long and very steep slopes along the sides of the road. But still, there was none of the slope reinforcement installed along the road. Meanwhile, at several nearby locations within Southern Mountain, rockfall incidents have occurred many times even caused casualties. The potential of rockfall hazard could also occur in the main road of Parangtritis Beach as the study area. The purpose of this study is to determine the rockfall hazard assessment along the main road using Slope Mass Rating (SMR) analysis with the additional parameter of the slope height and the rock block size. The necessary data obtained by direct measurement and laboratory test. Geomechanics analysis, stereographic projection analysis, and hazard parameters weighting were carried out to produce the Rockfall Hazard Zonation Map of the study area. Based on 17 measurement stations, there are 4 (four) rockfall hazard classes in the study area, i.e. very low, low, intermediate, and high. The very low class, which also included road segments without slope, has the largest percentage of 83.83%, followed by the classes of intermediate, low, and high with the percentage of 7.16%, 4.28%, and 4,19%, respectively. SMR was assumed as the most significant parameter that influences the rockfall hazard zonation. To validate the predicted hazard zones, historical rockfall points were overlaid over the Rockfall Hazard Zonation Map. Since 91.23% of the rockfall occurred in the intermediate and high hazard classes, the zonation can be considered reliable to predict future rockfall. This study also identified several landslide potential zones and provides the recommendation of slope reinforcement to be installed in the study area.
Anopheles funestus mosquitoes from rural south-eastern Tanzania may have stronger resistance to pyrethroids than the other malaria vector, Anopheles arabiensis
Authors: Pinda Polius Gerazi , Eichenberger Claudia , Ngowo Halfan S , Msaky Dickson S , Abbasi Said , Kihonda Japhet , Bwanaly Hamis , Okumu Fredros O
Published: June 2020

Background: Long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) have greatly reduced malaria transmission in sub-Saharan Africa, but are threatened by insecticide resistance. In south-eastern Tanzania, pyrethroid-resistant Anopheles funestus are now implicated in > 80% of malaria infections, even in villages where the species occurs at lower densities than the other vector species, Anopheles arabiensis. This study compared the intensities of resistance between the two malaria vectors, so as to improve options for control. Methods: The study used WHO assays with 1×, 5× and 10× insecticide doses to assess levels of resistance, followed by synergist bioassays to understand possible mechanisms of the observed resistance phenotypes. The tests involved adult mosquitoes collected from villages across two districts in south-eastern Tanzania and identified using morphological and molecular approaches.Findings: At baseline doses (1×), both species were resistant to the two pyrethroids (permethrin and deltamethrin) but susceptible to the organophosphate (pirimiphos-methyl). An. funestus, but not An. arabiensis was also resistant to the carbamate (bendiocarb) at baseline doses. Both species were generally resistant to DDT, except An.arabiensis from one village. An. funestus showed strong resistance to pyrethroids, surviving the 5× and 10× doses except in one village. Pre-exposure to the synergist, piperonyl butoxide (PBO), enhanced the potency of pyrethroid in both An. arabiensis and An. funestus achieving mortalities >98%, except for An. funestus from two villages for which permethrin-associated mortalities exceeded 90% but not 98%. Conclusions: In these communities where An. funestus dominates malaria transmission, this study may suggest that the species also have much stronger resistance to pyrethroids than its counterpart, An. arabiensis and can survive more classes of insecticides, including carbamates. The pyrethroid resistance in both species appears to be mostly metabolic and may be temporarily addressed using synergists, e.g. PBO. These findings may explain the continued persistence and dominance of An. funestus despite widespread use of pyrethroid-treated LLINs, and inform new choices of interventions to tackle malaria transmission in such settings. These may include PBO-based LLINs or improved IRS with compounds to which the vectors are susceptible. Additional field validation of these indications will be necessary using age-synchronized mosquitoes.
Influence of automated visual field testing on intraocular pressure
Authors: Bertaud S , Borowski E Skarbek , Abbas R , Baudouin C , Labbé A
Published: June 2020

Background: To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma.Methods: We conducted a prospective observational study in the glaucoma department at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 minutes before and after VF testing. Sub analyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations.Results: There was no significant change in IOP after VF testing, with IOP’s 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R²=0.12), whether based on duration of the VF test (P=0.18) or the MD (P=0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (P=0.36), chronic angle closure glaucoma (P=0.85) and OHT (P=0.42). The subgroup of patients with an IOP elevation ≥ 2mmHg had a significantly higher VF test duration (P=0.002).
The changes of corneal biomechanical properties with long-term treatment of prostaglandin analogue measured by Corvis ST
Authors: Wu Na , Chen Yuhong , Yang Yaping , Sun Xinghuai
Published: June 2020

Background: To investigate the corneal biomechanical changes in primary open angle glaucoma (POAG) patients treated with long-term prostaglandin analogue (PGA). Methods: 111 newly diagnosed POAG patients, including 43 high tension glaucoma (HTG) and 68 normal tension glaucoma (NTG), were measured by Corvis ST to obtain intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters at baseline and at each follow-up visit after initiation of PGA treatment. The follow-up measurements were analyzed by the generalized estimate equation model with an exchangeable correlation structure. Restricted cubic spline was employed to estimate the dose-response relation between follow-up time and corneal biomechanics． Results: The mean follow-up time was 10.3 ± 7.02 months. Deformation amplitude (DA, β=-0.0015, P =0.016), the first applanation velocity (AV1, β=-0.0004, P =0.00058) decreased and the first applanation time (AT1, β=0.0089, P <0.000001) increased statistically significantly with PGA therapy over time after adjusting for age, gender, axial length, corneal curvature, IOP and CCT. In addition, AT1 was lower (7.2950 ± 0.2707 in NTG and 7.5889 ± 0.2873 in HTG, P =0.00011) and AV1 was greater (0.1478 ± 0.0187 in NTG and 0.1314 ± 0.0191 in HTG, P =0.00002) in NTG than in HTG after adjusting for confounding factors. Conclusions: Chronic use of PGA probably could influence the corneal biomechanical properties directly, which is to make cornea less deformable. Besides, corneas in NTG tended to be more deformable compared to those in HTG with long-term treatment of PGA.
Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model
Authors: Kim Jae Yeon , Choi Jong Ho , Jun Ji Hye , Park Sohae , Jung Jieun , Bae Si Hyun , Kim Gi Jin
Published: June 2020

Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model. Methods: PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 were intravenously administered into cirrhotic rats using a nonviral system (2x106 cells/animal). The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed. Results: PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p<0.05). Furthermore, transplantation of PD-MSCsPRL-1 using a nonviral AMAXA system promoted engraftment into injured target liver tissues of a rat BDL cirrhotic model and enhanced the metabolism of mitochondria via increased mtDNA and ATP production, thereby improving therapeutic efficacy. Conclusions: Our findings will further our understanding of the therapeutic mechanism of enhanced MSCs and provide useful data for the development of next-generation MSC-based cell therapy and therapeutic strategies for regenerative medicine in liver disease.
Investigating selected host and parasite factors potentially impacting upon seasonal malaria chemoprevention in Bama, Burkina Faso
Authors: Somé Anyirékun , Bazié Thomas , Y. Ehrlich Hanna , Goodwin Justin , Lehane Aine , Neya Cathérine , Kabre Zakary , Wade Martina , OUATTARA Jean-Marie , Foy Brian , Dabiré K. Roch , Parikh Sunil , Ouédraogo Jean-Bosco
Published: June 2020

Background: Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under five years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC. Methods: Two sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 and 93 children under five, respectively, at the start of SMC and again three weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility. Results: 2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p=0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95%CI=10.0-24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3. Conclusion: This study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.
Perception of Inappropriate Use of Proton Pump Inhibitors Among Community-Dwelling Older Adults
Authors: Rababa Mohammad , Rababa'h Abeer
Published: June 2020

Background
Long-term use of proton pump inhibitors (PPIs) in older adults is a prevalent issue and associated with adverse health outcomes. There is limited evidence about older adults’ perception of PPI use and its associated side effects. This study aimed to examine the knowledge and awareness of older adults about PPI use and its side effects and willingness to stop PPI and its associated factors.
Methods
This cross-sectional study was conducted on a convenience sample of 120 older adults from three local healthcare centers located in Irbid, Jordan. Older adults’ perception of PPI use was measured by Patients’ Perceptions of Proton Pump Inhibitor Risks and Attempts at Discontinuation Survey.
Results
The majority of older adults were not familiar with any report linking PPI use with side effects, reported no concern related to the chronic side effects of PPI, and had not discussed the benefits and risks of PPI with their primary care providers (PCPs). Although a majority did not try to stop PPI, most older adults were willing to stop PPI due to its side effects, particularly if recommended by PCPs. Factors associated with long-term use of PPI included age, indication for gastrointestinal reflux disease (GERD), improvement of GERD symptoms, and being comfortable to reduce or stop PPI. Recommendations by PCPs to stop PPI (p = 0.049) and a greater level of concern about long-term side effects of PPI (p < 0.0001) were the only two statistically significant predictors of previous attempts to stop PPIs.
Conclusions
Concern about PPIs is associated with attempts to stop PPI, particularly with PCPs’ recommendation. The risks and benefits of PPIs should be discussed with PCPs to avoid making inappropriate decisions regarding PPI therapy. The Long-term use of PPIs should be carefully evaluated.
Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates
Authors: Chitranshi Nitin , Gupta Vivek Kumar , Rajput Rashi , Godinez Angela , Pushpitha Kanishka , Sheng Ting , Mirzaei Mehdi , You Yuyi , Basavarajappa Devaraj , Gupta Veer , Graham Stuart
Published: June 2020

Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. Methods: For this study, we analysed 2,301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. Results: Our results demonstrate that bat-CoV shares >96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. Conclusions: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.