bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer’s mouse model
Authors: Sankar Sitara B. , Infante-Garcia Carmen , Weinstock Laura D. , Ramos-Rodriguez Juan Jose , Hierro-Bujalance Carmen , Fernandez-Ponce Cecilia , Wood Levi B. , Garcia-Alloza Monica 
Published: February 2020

AbstractBackgroundDiabetes is a risk factor for developing Alzheimer’s disease (AD); however, the mechanism by which diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain, including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes have been associated with increased Aβ pathology and increased expression of glial activation markers in APPswe/PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes associated with diabetic conditions.MethodsTo more fully elucidate neuroinflammatory changes associated with diabetes that may drive AD pathology, we combined the APP/PS1 mouse model with either high-fat diet (HFD, a model of pre-diabetes), the genetic db/db model of type 2 diabetes, or the streptozotocin (STZ) model of type 1 diabetes. We then used a multiplexed immunoassay to quantify cortical changes in cytokine proteins.ResultsOur analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded upregulation of a broadprofileof cytokines, including chemokines (e.g., MIP-1α, MIP-1β, and MCP-1) and pro-inflammatory cytokines, including IL-1α, IFN-γ, and IL-3. Moreover, multivariate partial least squares regression analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that circulating levels of Aβ1-40, Aβ1-42, glucose, and insulin all correlated with cytokine expression in the brain, suggesting a strong relationship between peripheral changes and brain pathology.ConclusionsAltogether, our multiplexed analysis of cytokines shows that Alzheimer’s and diabetic pathologies cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the identified cytokines promote neuronal injury, Aβ and tau pathology, and breakdown of the blood-brain barrier, our data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for intervening in the development of diabetes-associated AD.
Nutrition therapy in critical illness: a review of the literature for clinicians
Authors: Lambell Kate J. , Tatucu-Babet Oana A. , Chapple Lee-anne , Gantner Dashiell , Ridley Emma J. 
Published: February 2020

AbstractNutrition therapy during critical illness has been a focus of recent research, with a rapid increase in publications accompanied by two updated international clinical guidelines. However, the translation of evidence into practice is challenging due to the continually evolving, often conflicting trial findings and guideline recommendations. This narrative review aims to provide a comprehensive synthesis and interpretation of the adult critical care nutrition literature, with a particular focus on continuing practice gaps and areas with new data, to assist clinicians in making practical, yet evidence-based decisions regarding nutrition management during the different stages of critical illness.
Fluorescence-based method is more accurate than counting-based methods for plotting growth curves of adherent cells
Authors: Pereira Túlio Felipe , Levin Gabriel , DeOcesano-Pereira Carlos , Caodaglio Amanda Schiersner , Fujita André , Tonso Aldo , Sogayar Mari Cleide 
Published: February 2020

Abstract
Objective
Cell growth curves constitute one of the primary assays employed to analyze cell proliferation dynamics of in vitro cultured cells under specific culture conditions. From the cell growth curve, it is possible to assess the behavior of proliferating cells under different conditions, such as drug treatment and genomic editions. Traditionally, growth curves for adherent cells are obtained by seeding the cells in multiple-well plates and counting the total number of cells at different time points. Here, we compare this traditional method to the fluorescence-based method, which is based on the CFSE fluorescence decay over time.

Results
The fluorescence-based method is not dependent on the determination of the total number of cells, but rather is approached by assessing the fluorescence of a sample of single cells from a cell population at different time points after plating. Therefore, this method is not biased due to either cell loss during harvesting or to the presence of cellular debris and cell clumps. Moreover, the fluorescence-based method displays lower variation among different measurements of the same time point, which increases the reliability on the determination of lag, log and stationary phase transitions.
Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial
Authors: Levy Donald S. , Farkas Henriette , Riedl Marc A. , Hsu Florence Ida , Brooks Joel P. , Cicardi Marco , Feuersenger Henrike , Pragst Ingo , Reshef Avner 
Published: February 2020

Abstract
Background
Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this post hoc subgroup analysis, we evaluated the efficacy and safety of C1-INH (SC) in female subjects with HAE-C1INH enrolled in an open-label extension of the pivotal phase III COMPACT trial.

Methods
In this multicenter, randomized, parallel-arm trial, eligible subjects (age ≥ 6 years with ≥ 4 attacks over 2 consecutive months) received C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 to 140 weeks. Analyses of efficacy endpoints were performed for all female subjects and those of childbearing age (age ≥ 15 to ≤ 45 years), including subjects who became pregnant during the evaluation period.

Results
Overall, 91% (69/76) of female subjects were classified as responders (≥ 50% reduction in HAE attacks relative to the pre-study period); 82% experienced < 1 attack/4 weeks. The median number of attacks/month was 0.10, with 96% median reduction in attacks relative to the pre-study period. Results were similar in the subgroup of subjects of childbearing age. Four women who became pregnant during the trial and were exposed to C1-INH (SC) during the first trimester delivered healthy babies with no congenital abnormalities.

Conclusions
C1-INH (SC) prophylaxis was safe and effective in women with HAE-C1INH, including those of childbearing age. Four women exposed to C1-INH (SC) during the first trimester had uneventful pregnancies and delivered healthy babies.
Trial registration Clinicaltrials.gov identifier NCT02316353 (Registered December 10, 2014); https://clinicaltrials.gov/ct2/show/NCT02316353.
Stancu type q-Bernstein operators with shifted knots
Authors: Mursaleen M. , Qasim Mohd , Khan Asif , Abbas Zaheer 
Published: February 2020

AbstractIn the present paper, Stancu type generalizations of theq-analog of Lupaş Bernstein operators with shifted knots are introduced. Some approximation results and rate of convergence for these operators are investigated. A Voronovskaja type theorem and local approximation results for the mentioned operators are studied. The extra parametersγ,δ,q,aandbprovide more flexibility for approximation.
Recent advances in control technologies for non-point source pollution with nitrogen and phosphorous from agricultural runoff: current practices and future prospects
Authors: Xia Yinfeng , Zhang Ming , Tsang Daniel C. W. , Geng Nan , Lu Debao , Zhu Lifang , Igalavithana Avanthi Deshani , Dissanayake Pavani Dulanja , Rinklebe Jörg , Yang Xiao , Ok Yong Sik 
Published: February 2020

AbstractEutrophication of natural water is a universal problem. Nitrogen (N) and phosphorus (P) from agricultural runoff are the main sources of nutrient input, provided that emissions from industrial point sources (IPS) are under control. Therefore, it is of great environmental importance to reduce pollution associated with agricultural runoff as a means of regulating eutrophication levels in natural water. Numerous methods proposed for treating agricultural runoff can be classified into three categories: source control, process control, and end treatment. In this review, major technologies for N and P control from agricultural runoff are summarized along with discussion of newly proposed technologies such as biochar biomimetics and microbial catalyst. Because agricultural runoff (from farmlands to receiving waters) is a complicated pollution process, it is difficult to regulate the nutrients discharged via such process. This review will thus offer a comprehensive understanding on the overall process of agricultural runoff and eutrophication to help establish control strategies against highly complicated agricultural non-point sources.
Identification of pAKT as a pharmacodynamic marker for MER kinase in human melanoma G361 cells
Authors: Chen Yaoyu , Favata Margaret , Pusey Michelle , Li Jun , Lo Yvonne , Ye Min , Wynn Richard , Wang Xiaozhao , Yao Wenqing , Chen Yingnan 
Published: February 2020

Abstract
Background
The MER signaling pathway represents an attractive therapeutic target for human cancers. Growth arrest–specific protein 6 (GAS6)–induced MER phosphorylation is often unstable and difficult to detect without pervanadate pretreatment in human cancer cells, posing a challenge for the development of selective MER kinase inhibitors. Here, we identified phosphorylated AKT (pAKT) as a specific pharmacodynamic marker for MER kinase inhibitors in human melanoma G361 cells.

Methods
The expression of MER, TYRO3, and AXL were profiled among multiple human cancer cells. To determine whether they play a role in the activation of pAKT, MER and TYRO3 were selectively depleted by small, interfering RNA knockdown. In addition, using AKT phosphorylation as a readout, a high-throughput cell-based assay was established in G361 cells for evaluation of the potency of potential inhibitors of MER pathway activation.

Results
We demonstrated that high levels of MER and TYRO3, but not AXL, were expressed in G361 cells. In these cells, pAKT was induced by GAS6 treatment, which could be reversed by AXL/MER inhibitors. We showed that GAS6-induced pAKT is only dependent on MER kinase, but not TYRO3, in G361 cells. Furthermore, we observed a correlation in potency between inhibition of pAKT in G361 cells and pMER in MER-overexpressing Ba/F3 cells by these inhibitors.

Conclusions
In summary, we have demonstrated that GAS6-induced pAKT is a possible pharmacodynamic marker for the inhibition of MER kinase, and we have successfully developed a cell-based functional assay for screening small-molecule inhibitors of MER kinase for potential therapeutic utility in treating GAS6/MER-deregulated human cancers.
Characterization of structural failures founded on soils in Panyam and some parts of Mangu, Central Nigeria
Authors: Igwe Ogbonnaya , Umbugadu Allu Augustine 
Published: February 2020

AbstractStructural failure of buildings, roads, and other infrastructures has led to the loss of lives and monumental damage to the economy. In developing countries such as Nigeria, the failures are always attributed to the nature/type of soils in the area without considering other factors. With the increase in civil engineering constructions and the scramble for a limited portion of competent soils for such constructions, land, therefore, is becoming man’s most priced commodity for agriculture, residential and industrial purposes. No works of such have been done in the area, it is, therefore, imperative to study the cause(s) to prevent further loss of lives and the negative effects of such on the economy. The study was carried out at Panyam and some surrounding localities on latitudes N9021′ and N9026′ and longitudes 9011′E and 9016′E an area of 72 km2. A total of forty samples were collected out of which twenty were selected for swelling potentials determination due to their cohesive nature within the 1.5 m depth. To characterize the swelling of the soils, inferential testing methods; direct method comprising Liquid Limit and Plasticity Index with values ranging from 30% – 70% and 10% – 27% respectively, and the indirect method (Free Swell Index, FSI) whose values range from 9.1% – 90% were used. Most of the soils analyzed based on the geotechnical standards were categorized relatively safe for civil infrastructure. Structural studies employed the direct measurements of surface structures to get the orientations of structures measured. Landsat image and Total Magnetic Intensity (TMI) map of the area was acquired from the Nigerian Geological Survey Agency (NGSA) for subsurface structural analysis. The RTP-TMI (reduce to pole) grid data of the area were processed to improve magnetic anomalies associated with edges of surface/near-surface geological structures using the MAGMAP two-dimensional fast fourier transform (2D-FFT) filters package in Oasis Montaj v7.2 software. Geophysical studies using aeromagnetic data at a near-surface depth of 40 m and fractures measured on the surface both revealed a major trend in the NNE – SSW. It was observed that structures constructed across the major trend suffered little to moderate damage while those constructed along the major fractures trend suffered severe damage. It was concluded that both soils and fractures played individual roles in the collapse of infrastructure in the area.
Study of the anti-inflammatory effect of the combined extract BNO 1016 in a leukotriene-dependent in vivo inflammation model
Authors: Zupanets Igor A. , Shebeko Sergii K. , Popovych Vasyl I. , Zimin Stanislav M. 
Published: February 2020

Abstract
A significant role in the pathogenesis of rhinosinusitis is played by an inflammatory reaction in the maxillary sinuses of the nasal cavity. Leukotrienes are the most powerful mediators of inflammation, especially at the early stages. The effect of combined dry extract BNO 1016 could be useful for the inhibition of the inflammation in rhinosinusitis. Thus, it appears reasonable to study the anti-inflammatory activity of the combined dry extract BNO 1016.

Materials and methods
The tested drug is the combined dry extract BNO 1016 produced by “Bionorica SE”. The reference drug is Ibuprofen. Leukotriene inflammation was induced by subplantar injection of zymozan into the right hind paw of male and female Wistar rats. Volumes of the resulting edema were measured and levels of anti-inflammatory activity together with mean effective dose (ED50) were calculated.

Results
The highest anti-inflammatory activity was observed at a dose level of 500 mg/kg of BNO 1016 during all time-points of the experiment and reached 65.2% 2 h after induction of inflammation. The anti-inflammatory activity of BNO 1016 at 500 mg/kg was credibly higher than that of Ibuprofen at all time-points of the experiment. Based on the data obtained from this leukotriene-dependent inflammation experiment the mean effective dose (ED50) for anti-inflammatory activity of dry combined extract BNO 1016 was calculated with help of Probit analysis.

Conclusion
The combined dry extract BNO 1016 shows a high level of anti-inflammatory activity in leukotriene-dependent inflammation which is very promising for the improvement of the treatment of patients. However, additional preclinical and clinical research on this drug should be carried out.
Biomaterials in orthopaedics: the past and future with immune modulation
Authors: Im Gun-Il 
Published: February 2020

Abstracts
Orthopaedics owes its current status of advanced care to the development of biomaterial science more than any other clinical medical specialty. The purpose of this brief review is to introduce the history and present status of biomaterials in orthopaedic field and cast a perspective on the future use of biomaterials to treat musculoskeletal disorders with particular emphasis on immune modulation. While the biomaterials in orthopaedics started from inert materials to replace the function and structure of hard tissue such as bone and cartilage, regenerative medicine will play a greater role in preventing the traumatic loss of tissues, as well as in the earlier stages of diseases. The understanding and modulation of immune response to biomaterials will further lead to the better incorporation of implants into host tissue or the near-perfect regeneration of host tissue.
Comparison between Erigo tilt-table exercise and conventional physiotherapy exercises in acute stroke patients: a randomized trial
Authors: Kumar Suraj , Yadav Ramakant , Aafreen  
Published: February 2020

Abstract
Background
Stroke is a common, serious, and disabling health-care problem throughout the world. Although great advances have been made in acute stroke management, the most of post-stroke care to reduce a patient’s dependency relies on rehabilitation.

Purpose
To compare the effectiveness of exercises using an Erigo tilt-table and conventional physiotherapy in the rehabilitation of acute stroke patients.

Methods
A total of 110 acute stroke patients (age 51.08 ± 7.48 years, 8.69 ± 4.62 days after stroke) were assigned randomly into two groups, 55 in each for 30 days of conventional physiotherapy (Group A) or Erigo tilt-table (Group B) rehabilitation. The National Institutes of Health Stroke Scale (NIHSS), Mini-Mental Scale Examination (MMSE), Modified Ashworth Scale were used to measure muscle tone, quality of life (QOL) and muscle strength (MMT), Affected upper (UE) and lower limb (LE) outcomes were assessed at baseline (day 0), after day 30 of the intervention and on 90th day of follow up. Repeated measures ANOVA followed by a Bonferroni post-hoc test and independent Student’s t-test were used for statistical analysis to evaluate the improvement in outcome variables within and between the groups.

Results
Both the treatments were effective. Notably, Group B patients showed a significant improvement in both QOL (p < 0.001) and lower limb strength (p = 0.030) at day 90 and muscle tone (p = 0.011) at day 30 compared to Group A.

Conclusion
Both the groups improved with time but the Erigo tilt-table group experienced greater improvement in QOL, NIHSS and muscle strength of the lower limb. Thus, Erigo tilt-table can be used for early rehabilitation of acute hemiplegic patients and improving their quality of life and motor system, resulting in better functional performances.
Coagulation assessment with thromboelastography during abdominal endovascular aneurysm repair in a patient with hemophilia A
Authors: Sato Kazuki , Katori Nobuyuki , Suga Yoshifumi , Kiyama Shuya , Uezono Shoichi 
Published: February 2020

AbstractBackgroundAs both APTT and APTT-based coagulation method cannot distinguish heparin effect from intrinsic coagulation factor deficiency, we implemented thromboelastography (TEG) for the coagulation assessment in a patient with hemophilia A undergoing an endovascular surgery with heparinization.Case presentationA 68-year-old male with hemophilia A underwent endovascular aortic repair for abdominal aortic aneurism. TEG results showed recovery of coagulation time (R) in both kaolin assay (CK) and kaolin-heparinase assay (CKH) after factor VIII replacement before heparinization. Against our expectations, R-CKH was slightly prolonged (9.0 min) during heparinization. After the administration of protamine sulfate, R in both assays showed similar values within the normal ranges.ConclusionsThe combination of CK and CKH assays could be useful to estimate factor VIII (FVIII) level when heparin concentration is low or without heparin; however, caution should be necessary for estimation of FVIII level by TEG under the effect of medium- or high-dose heparin.
Ultrasound-guided interventions with augmented reality in situ visualisation: a proof-of-mechanism phantom study
Authors: Farshad-Amacker Nadja A. , Bay Till , Rosskopf Andrea B. , Spirig José M. , Wanivenhaus Florian , Pfirrmann Christian W. A. , Farshad Mazda 
Published: February 2020

Abstract
Background
Ultrasound (US) images are currently displayed on monitors, and their understanding needs good orientation skills. Direct overlay of US images onto the according anatomy is possible with augmented reality (AR) technologies. Our purpose was to explore the performance of US-guided needle placement with and without AR in situ US viewing.

Methods
Three untrained operators and two experienced radiologists performed 200 US-guided punctures: 100 with and 100 without AR in situ US. The punctures were performed in two different phantoms, a leg phantom with soft tissue lesions and a vessel phantom. Time to puncture and number of needle passes were recorded for each puncture. Data are reported as median [range] according to their non-normal distribution.

Results
AR in situ US resulted in reduced time (median [range], 13 s [3–101] versus 14 s [3–220]) and number of needle passes (median [range], 1 [1–4] versus 1 [1–8]) compared to the conventional technique. The initial gap in performance of untrained versus experienced operators with the conventional US (time, 21.5 s [3–220] versus 10.5 s [3–94] and needle passes 1 [1–8] versus 1 [1, 2]) was reduced to 12.5 s [3–101] versus 13 s [3–100] and 1 [1–4] versus 1 [1–4] when using AR in situ US, respectively.

Conclusion
AR in situ US could be a potential breakthrough in US applications by simplifying operator’s spatial orientation and reducing experience-based differences in performance of US-guided interventions. Further studies are needed to confirm these preliminary phantom results.
Are apprenticeships business cycle proof?
Authors: Lüthi Samuel , Wolter Stefan C. 
Published: February 2020

AbstractAlthough there is evidence that apprenticeship training can ease the transition of youth into the labour market and thereby alleviate youth unemployment, many policymakers fear that firms will reduce the number of apprenticeship positions during economic crises, thus exacerbating the problem of youth unemployment. Using recent panel data of Swiss cantons and dynamic regression models, we examine the relationship between newly created apprenticeships and the business cycle. The empirical results suggest that economic shocks induce a pro-cyclical, moderate response in the apprenticeship market, both immediately and in subsequent years.