bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing Trypanosoma cruzi farnesyl pyrophosphate synthase as a viable target for biosensor driven fragment‐based lead discovery
Authors: Opassi Giulia , Nordström Helena , Lundin Arne , Napolitano Valeria , Magari Francesca , Dzus Tom , Klebe Gerhard , Danielson U. Helena 
Published: January 2020

AbstractProcedures for producing and exploring Trypanosoma cruzi farnesyl pyrophosphate synthase (tcFPPS) for surface plasmon resonance (SPR) biosensor‐driven fragment‐based discovery have been established. The method requires functional sensor surfaces with high sensitivity for extended times and appropriate controls. Initial problems with protein stability and lack of useful reference compounds motivated optimization of experimental procedures and conditions. The improved methods enabled the production of pure, folded and dimeric protein, and identified procedures for storage and handling. A new coupled enzymatic assay, using luciferase for detection of pyrophosphate, was developed and used to confirm that the purified enzyme was active after purification and storage. It also confirmed that sensor surfaces prepared with structurally intact protein was active. An SPR‐biosensor assay for fragment library screening and hit confirmation was developed. A thermal shift assay was used in parallel. A library of 90 fragments was efficiently screened by both assays at a single concentration in the presence and absence of the catalytic cofactor Mg2+. Hits were selected on the basis of response levels or ΔT
m > 1°C and selectivity for tcFPPS in the presence of Mg2+. Characterization of hits by SPR showed that all had low affinities and the relationships between steady‐state responses and concentrations were not sufficiently hyperbolic for determination of KD‐values. Instead, ranking could be performed from the slope of the linear relationship at low concentrations. This pilot screen confirms that the procedures developed herein enables SPR‐biosensor driven fragment‐based discovery of leads targeting tcFPPS, despite the lack of a reference compound.Significance StatementTo enable the discovery of drugs, it is essential to have access to relevant forms of the target protein and valid biochemical methods for studying the protein and effects of compounds that may be evolved into drugs. We have established methods for the discovery of drugs for treatment of American Trypanosomiasis (Chagas disease), using farnesyl pyrophosphate synthase from Trypanosoma cruzi as a target.
Differential roles and activation of mammalian target of rapamycin complexes 1 and 2 during cell migration in prostate cancer cells
Authors: Venugopal Smrruthi Vaidegi , Caggia Silvia , Gambrell‐Sanders DaJhnae , Khan Shafiq A. 
Published: January 2020

AbstractBackgroundMammalian target of rapamycin (mTOR) is a downstream substrate activated by PI3K/AKT pathway and it is essential for cell migration. It exists as two complexes: mTORC1 and mTORC2. mTORC1 is known to be regulated by active AKT, but the activation of mTORC2 is poorly understood. In this study, we investigated the roles and differential activation of the two mTOR complexes during cell migration in prostate cancer cells.MethodsWe used small interfering RNA to silence the expression of Rac1 and the main components of mTOR complexes (regulatory associated protein of mTOR [RAPTOR] and rapamycin‐insensitive companion of mTOR [RICTOR]) in LNCaP, DU145, and PC3 prostate cancer cell lines. We performed transwell migration assay to evaluate the migratory capability of the cells, and Western blot analysis to study the activation levels of mTOR complexes.ResultsSpecific knockdown of RAPTOR and RICTOR caused a decrease of cell migration, suggesting their essential role in prostate cancer cell movement. Furthermore, epidermal growth factor (EGF) treatments induced the activation of both the mTOR complexes. Lack of Rac1 activity in prostate cancer cells blocked EGF‐induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the overexpression of constitutively active Rac1 resulted in significant increase in cell migration and activation of mTORC2 in PC3 cells, but had no effect on mTORC1 activation. Active Rac1 was localized in the plasma membrane and was found to be in a protein complex, with RICTOR, but not RAPTOR.ConclusionWe suggest that EGF‐induced activation of Rac1 causes the activation of mTORC2 via RICTOR. This mechanism plays a critical role in prostate cancer cell migration.
Ilex paraguariensis, white mulberry and chromium picolinate in patients with pre‐diabetes
Authors: Derosa Giuseppe , D’Angelo Angela , Maffioli Pamela 
Published: January 2020

Aimto evaluate if a nutraceutical compound containing Ilex paraguariensis, White Mulberry and Chromium Picolinate can ameliorate glycemic status in patients with pre‐diabetes.Methodswe enrolled patients with IFG or IGT, not taking other hypoglycemic compounds. Patients were randomized to take placebo or the nutraceutical compound for 3 months, in a randomized, double‐blind, placebo‐controlled design. Both treatments were self‐administered once a day, 1 tablet during the breakfast.Resultsa reduction of FPG was observed with the nutraceutical combination (−7.8%). Furthermore, there was a decrease of HOMA‐IR with the nutraceutical combination (−7.9%). M value was higher (p < 0.05 vs baseline and p < 0.05 vs placebo) at the end of the treatment. We obtained a reduction of Tg with the nutraceutical combination (−8.3%). About 16.6% of patients treated with nutraceutical returned to have a normal glycemia (< 100 mg/dL), and all patients had an improvement of insulin‐resistance, in particular 67% of patients returned to have a M value inside range of normal insulin sensitivity.Conclusionsa nutraceutical containing Ilex paraguariensis, White Mulberry and Chromium Picolinate at 500 mg can be helpful in improving glycemia and Tg value, in patients with pre‐diabetes.
An extension of water retention and conductivity functions to dryness
Authors: Inforsato Leonardo , de Jong van Lier Quirijn , Pinheiro Everton Alves Rodrigues 
Published: January 2020

AbstractWater retention (WR) and hydraulic conductivity (HC) are essential properties to predict water flow in soils. Commonly, these soil physical properties are represented by equations relating pressure head, soil water content, and hydraulic conductivity. The commonly used empirical equations used for this purpose have a limited range of reliability, not functioning properly in the very dry range. An approach to extend the reliability and applicability of these models has been p hed piecewise equations added to the base model and implying in changes in the base model paramete. We propose a modification of the model commonly known as Peters‐Durner‐Iden (PDI), extending the reliability of most common base models without the need to change the original parameters. The transformation is analytically equivalent, interchangeable and allows to anchor the retention function at any point instead of the residual water content. The Van Genuchten, Kosugi, Brooks‐Corey and Groenevelt equations can easily be combined to the proposed model, which may be used to predict water flow in the dry range where the commonly used equations are not reliable.
Analysis of microbial utilization of rice straw in paddy soil using a DNA‐SIP approach
Authors: Guo Tengfei , Zhang Qian , Ai Chao , Liang Guoqing , He Ping , Lei Qiuliang , Zhou Wei 
Published: January 2020

AbstractConsidering the close connection between soil microorganisms with carbon (C) cycling, the aim of this study was to identify the specific bacterial and fungal microbes that assimilate 13C from incorporated rice straw and explore their dynamics and characteristics during straw decomposition in paddy soil. Soil microcosms based on 12/13C‐labeled rice straw were incubated with the determination of CO2 production at 1, 3, 7, 14, 28, 56 and 90 days after straw incorporation. Meanwhile, the targeted soil bacterial and fungal communities were characterized using a DNA‐based stable isotope probing (DNA‐SIP) approach combined with Illumina MiSeq sequencing. Rice straw decomposed rapidly in the first 2 weeks, coupled with a large turnover of soil native organic matter. During this process, Actinobacteria including the orders Streptomycetales, Caternulisporales and Corynebacteriales dominated the community utilizing rice straw‐derived C with a succession from Streptomyces, to Kitasatospora, to Catenulispora. At Days 56 to 90, the dominant orders assimilating rice straw‐derived 13C were Micrococcales, Sphingobacteriia, Gammaproteobacteria from phyla Actinobacteria, Bacteroidetes and Proteobacteria, respectively. The fungal orders Onygenales, Capnodiales, Sordariales and Pleosporales showed stronger ability of 13C utilization at late decomposition stage. Taken together, along with stimulation of soil organic matter mineralization after rice straw addition, dynamics of 13C‐assimilating bacterial and fungal groups with various characteristics were identified.
Multifunction covalent coatings for separation of amino acids, biogenic amines, steroid hormones, and ketoprofen enantiomers by capillary electrophoresis and capillary electrochromatography
Authors: Kravchenko Anastasia , Kolobova Ekaterina , Kartsova Liudmila 
Published: January 2020

AbstractIn this study, the preparation process of multifunctional coating based on imidazole and β‐cyclodextrin has been developed. The synthesis includes several steps: activation of fused silica capillary walls via alkali, then process of silylation and finally functionalization with imidazole and β‐cyclodextrin derivative. The latter step was carried over 22 h at 100°C at 750 mg/mL concentration of p‐toluenesulfonyl‐β‐cyclodextrin. It was established that the coatings thus obtained are stable within pH 2–7 range but decompose in alkaline medium. The stationary phase developed in this study allows simultaneous separation of hydrophobic and hydrophilic analytes. Chiral separation of ketoprofen enantiomers was also achieved with the newly developed covalent coating. It was found that covalent coating based on imidazole and β‐cyclodextrin exceeded the dynamic coatings of similar structure in terms of repeatability, analysis time and the limits of detection.
Developmental dynamics of cloned Mexican bighorn sheep embryos using morphological quality standards
Authors: Hernández Martínez Sarahí , Hernández Pichardo José E. , Vazquez Avendaño José R. , Ambríz García Demetrio Alonso , Navarro Maldonado María del Carmen 
Published: January 2020

AbstractThe developmental dynamics of cloned Mexican bighorn sheep (Ovis canadensis mexicana) embryos were evaluated based on morphological quality standards. Categories determined by standards were correlated with the embryonic development stage, number of nuclei and viability. The results showed no differences in the blastocyst rate between the experimental (cloned Mexican bighorn sheep embryos) and control (parthenogenetic domestic sheep embryos) groups (p > .05), while type IV fragmentation was higher in clones (p < .05). The standards allowed for the identification of embryos that divided at least once or fragmented after 24 hr of culture. The highest percentage of morulae appeared at 96 hr, the final stages of development: nonsegmented, blocked, fragmented and blastocysts appeared at 192 hr. Embryonic quality decreased over time, making 96 hr the ideal time point to predict the final morphological quality of embryos. Nuclear staining of the morulae and blastocysts showed that higher embryo quality was associated with a higher percentage of normal and viable blastomeres. The evaluated criteria allowed for descriptions of the dynamics, stage and quality of cloned Mexican bighorn sheep embryos with a high degree of reliability. In addition, developmental anomalies, including fragmentation, multinucleation and blocking, were identified.
Simulation and engineering demonstration of the advanced treatment of rainy overflow wastewater using a combined system of storage tank‐wastewater treatment plant‐wetland
Authors: Jin Zhujing , Wu Weizhong , Li Jinhua , Yang Fengle , Zhou Baoxue 
Published: January 2020

AbstractWe propose a new technology to advanced treat overflow wastewater from a combined sewer system using a storage tank‐wastewater treatment plant (STP)‐constructed wetland (CW) system. The engineering demonstration (a 7,500 m3 storage tank and a 3,436 m2 CW) has been built to treat the combined sewer overflows (CSOs) at the largest combined rainwater/wastewater overflow outlet in the middle reaches of the Xinbaoxiang River, which is the second largest river in the Dianchi Lake Basin. During the rainfall period, CSOs enter the storage tank. After sedimentation purification, the higher concentration CSOs at the bottom enter the STP, and the upper low‐concentration CSOs enter CWs, thereby linking the multiple means of treating CSOs and minimizing the impact of CSOs on the STP. During the dry season, CWs can also assist in purification of polluted river water. The supernatant (COD <80 mg/L) and the bottom part water (COD >200 mg/L) of the storage tank were sent to CWs and STP, respectively, for treatment. The project was stably operated over 6 months. The final effluent qualities were 12, 1.79, and 0.18 mg/L for COD, TN, and TP, respectively, which achieved the surface water class V standard.Practitioner points

A combined system of storage tank‐wastewater treatment plant‐wetland was proposed to advanced treat overflow wastewater of rainy season.

The SWMM could calculate the water quality and volume of overflow under different rainfall conditions in the runoff area.

The effluent of the engineering demonstration reached the standard of surface water class V.
Unilaterale Netzhautblutungen bei Säuglingen – 2 Fälle von Schütteltrauma?
Authors: Barth T. , Altmann M. , Batzlsperger C. , Jägle H. , Helbig H. 
Published: January 2020

ZusammenfassungEin 2,5 Monate alter Junge und ein 2 Monate altes Mädchen wurden wegen schwerer Bewusstseinstrübung pädiatrisch behandelt. Bei beiden Kindern fanden sich Subduralhämatome. Bei Verdacht auf nichtakzidentelles Schädel-Hirn-Trauma (NAHI) erfolgte eine Untersuchung des Augenhintergrundes, bei der sich bei beiden Säuglingen unilaterale Netzhautblutungen zeigten. Nach intensiver Differenzialdiagnostik wurde in beiden Fällen der Verdacht auf ein NAHI gestellt und eine rechtsmedizinische Begutachtung initiiert. Wichtig an dieser Fallserie ist, dass die Einseitigkeit von Netzhautblutungen ein NAHI nicht ausschließt.
Challenges for better care based on the course of maternal body mass index, weight gain and multiple outcome in twin pregnancies: a population-based retrospective cohort study in Hessen/Germany within 15 years
Authors: Schubert Julia , Timmesfeld Nina , Noever Kathrin , Arabin Birgit 
Published: January 2020

Abstract
Introduction
Studies on maternal weight, gestational weight gain and associated outcomes in twin pregnancies are scarce. Therefore, we analyzed these items in a large cohort.

Methods
Data from 10,603/13,725 total twin pregnancies from the perinatal database in Hessen, Germany between 2000 and 2015 were used after exclusion of incomplete or non-plausible data sets. The course of maternal and perinatal outcomes was evaluated by linear and logistic regression models.

Results
The rate of twin pregnancies increased from 1.5 to 1.9% (p < 0.00001). Mean maternal age and pre-pregnancy weight rose from 31.4 to 32.9 years and from 68.2 to 71.2 kg, respectively (p < 0.001). The rates of women with a body mass index ≥ 30 kg/m2 increased from 11.9 to 16.9% with a mean of 24.4–25.4 kg/m2 (p < 0.001). The overall increase of maternal weight/week was 568 g, the 25th quartile was 419, the 75th quartile 692 g/week. The total and secondary caesareans increased from 68.6 to 73.3% and from 20.6 to 39.8%, respectively (p < 0.001). Rates of birthweight < 1500 g and of preterm birth < 28 and from 28 to 33 + 6 weeks all increased (p < 0.01). No significant changes were observed in the rates of stillbirth, perinatal mortality and NICU admissions.

Conclusion
The global trend of the obesity epidemic is equally observed in German twin pregnancies. The increase of mean maternal weight and the calculated quartiles specific for twin pregnancies help to identify inadequate weight gain in twin gestations. Policy makers should be aware of future health risks specified for singleton and twin gestations.
Gender-specific differences in valvular heart disease
Authors: Nitsche Christian , Koschutnik Matthias , Kammerlander Andreas , Hengstenberg Christian , Mascherbauer Julia 
Published: January 2020

SummaryThe development of new devices and treatment options has greatly increased the interest in heart valve diseases. In this context, the consideration of gender differences in diagnosis, treatment success, and prognosis is of great importance. Available data show that women and men with heart valve disease have different risk profiles, which have a significant impact on treatment outcomes and prognosis.It is the purpose of this review article to give an overview of gender-related differences in patients with valvular heart disease, regarding clinical presentation, treatment, and outcomes. In light of the emerging treatment possibilities, future research should emphasize the role of gender since both sexes benefit from tailored management.
Segmental coupling effects during correction of three-dimensional lumbar deformity using lateral lumbar interbody fusion
Authors: Yamaguchi Hiroto , Nojiri Hidetoshi , Miyagawa Kei , Inoue Nozomu , Kaneko Kazuo 
Published: January 2020

Abstract
Purpose
Lateral lumbar interbody fusion (LLIF) has been performed to correct spinal deformity associated with lumbar degenerative disease. Although its usefulness has been studied, there are no reports of quantitative evaluation in three dimensions. Our purpose is to quantitate 3D deformity of the patients with lumbar degenerative disease and correction of the deformity by LLIF using patient-specific 3D CT models.

Methods
We measured the disc height and 3D alignment of the lumbar spine in 28 patients with degenerative disease undergoing LLIF using patient-specific 3D CT models created preoperatively and 3 months after surgery. The 3D alignment was calculated as wedge, lordosis and axial rotation angles at each motion segment. The disc height and the rotational angles were compared between before and after LLIF.

Results
A strong positive correlation was found between the wedge angle and the axial rotation angles (r = 0.718, P < 0.001) in the patients with lumbar degenerative disease preoperatively. The wedge and axial rotation angles decreased after surgery (P < 0.001 and P < 0.001, respectively). A positive correlation was found between the corrected wedge angle and the corrected axial rotation angle (r = 0.46, P < 0.001).

Conclusion
The present study demonstrated positive correlations between the wedge deformity and the axial rotational deformity in the patients with lumbar degenerative disease. The axial rotational deformity was simultaneously corrected with LLIF only by leveling the intervertebral wedge deformity via cage insertion without additional correction procedure.

Graphic abstract
These slides can be retrieved under Electronic Supplementary Material.
Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study
Authors: Kalamo Mari H. , Mäenpää J. U. , Seppälä T. T. , Mecklin J. P. , Huhtala H. , Sorvettula K. , Pylvänäinen K. , Staff S. 
Published: January 2020

AbstractTo prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers’ attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p < 0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p < 0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery.
Influence of Horizontal and Vertical Barriers on Fire Development for Ventilated Façades
Authors: Čolić Antonela , Pečur Ivana Banjad 
Published: January 2020

AbstractAlthough using various innovative materials for ventilated facade systems positively contribute to the energy efficiency of buildings, the application of such materials can also pose a certain risk of fire propagation through the façade. In the last decade, medium and large-scale tests, as well as numerical analysis have been performed to assess the impact of fire barriers on fire propagation through ventilated façades. However, the number of fire barriers and their specific positions can also have an effect on the fire safety of facades, which has not been studied. Consequently, the question arises whether real fire exposure on a façade can be adequately simulated and analysed in sufficient detail, by using large-scale testing methods. This paper aims to conduct a parametric analysis on a broader range of large-scale samples by using the procedure given in the standard BS 8414-1:2015 + A1:2017. To understand better the impact of the number and position of cavity barriers for different types of insulation materials (stone wool/PIR/phenolic foam) used in modern façade systems with non-combustible cladding (ACM-A2). Seven tests were carried out in Croatia between October 2017 and April 2018. In the case of combustible insulation, two horizontal barriers were insufficient in preventing fire propagation. Temperatures accumulated above 600°C, reaching 840°C in PIR insulation and 979°C in phenolic foam insulation. For the same sample designed with non-combustible insulation, the maximum temperature measured was 133°C. Facades with combustible insulation passed the test only when four horizontal barriers were used. The existence of vertical barriers had a positive impact on preventing the fire propagation because the insulation on the left side of the chamber, behind the vertical barrier, remained undamaged. Vertical barriers on the right side of the chamber delayed the horizontal fire propagation from the main wall to the wing wall depending on the type of insulation. The results from these tests can serve as a basis for future research on the effects of fire barriers on fire propagation.