bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors
Authors: Yap Timothy A. , O’Carrigan Brent , Penney Marina S. , Lim Joline S. , Brown Jessica S. , de Miguel Luken Maria J. , Tunariu Nina , Perez-Lopez Raquel , Rodrigues Daniel Nava , Riisnaes Ruth , Figueiredo Ines , Carreira Suzanne , Hare Brian , McDermott Katherine , Khalique Saira , Williamson Chris T. , Natrajan Rachael , Pettitt Stephen J. , Lord Christopher J. , Banerji Udai , Pollard John , Lopez Juanita , de Bono Johann S. 
Published: June 2020

PURPOSE Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging drugs such as carboplatin. PATIENTS AND METHODS This phase I trial assessed the ATR inhibitor M6620 (VX-970) as monotherapy (once or twice weekly) and combined with carboplatin (carboplatin on day 1 and M6620 on days 2 and 9 in 21-day cycles). Primary objectives were safety, tolerability, and maximum tolerated dose; secondary objectives included pharmacokinetics and antitumor activity; exploratory objectives included pharmacodynamics in timed paired tumor biopsies. RESULTS Forty patients were enrolled; 17 received M6620 monotherapy, which was safe and well tolerated. The recommended phase II dose (RP2D) for once- or twice-weekly administration was 240 mg/m2. A patient with metastatic colorectal cancer harboring molecular aberrations, including ATM loss and an ARID1A mutation, achieved RECISTv1.1 complete response and maintained this response, with a progression-free survival of 29 months at last assessment. Twenty-three patients received M6620 with carboplatin, with mechanism-based hematologic toxicities at higher doses, requiring dose delays and reductions. The RP2D for combination therapy was M6620 90 mg/m2 with carboplatin AUC5. A patient with advanced germline BRCA1 ovarian cancer achieved RECISTv1.1 partial response and Gynecologic Cancer Intergroup CA125 response despite being platinum refractory and PARP inhibitor resistant. An additional 15 patients had RECISTv1.1 stable disease as best response. Pharmacokinetics were dose proportional and exceeded preclinical efficacious levels. Pharmacodynamic studies demonstrated substantial inhibition of phosphorylation of CHK1, the downstream ATR substrate. CONCLUSION To our knowledge, this report is the first of an ATR inhibitor as monotherapy and combined with carboplatin. M6620 was well tolerated, with target engagement and preliminary antitumor responses observed.
Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch
Authors: Matić Josip , Paudel Amrit , Bauer Hannes , Garcia Raymar Andreina Lara , Biedrzycka Kinga , Khinast Johannes G. 
Published: June 2020

AbstractThis paper presents a rational workflow for developing enabling formulations, such as amorphous solid dispersions, via hot-melt extrusion in less than a year. First, our approach to an integrated product and process development framework is described, including state-of-the-art theoretical concepts, modeling, and experimental characterization described in the literature and developed by us. Next, lab-scale extruder setups are designed (processing conditions and screw design) based on a rational, model-based framework that takes into account the thermal load required, the mixing capabilities, and the thermo-mechanical degradation. The predicted optimal process setup can be validated quickly in the pilot plant. Lastly, a transfer of the process to any GMP-certified manufacturing site can be performed in silico for any extruder based on our validated computational framework. In summary, the proposed workflow massively reduces the risk in product and process development and shortens the drug-to-market time for enabling formulations.
Scientific Rationale for RPE Use in Fitness Assessment and Exercise Participation
Authors: Kilpatrick Marcus , Newsome A’Naja , Foster Carl , Robertson Robert , Green Matt 
Published: June 2020

Apply It!
• Fitness professionals will learn the different ways that RPE scales can be used.
• Fitness professionals will have newfound confidence in the importance of regulating exercise by using RPE scales.
• Fitness professionals will be able to properly use RPE scales during exercise testing and prescription.
Mutation profiling of anaplastic ependymoma grade III by Ion Proton next generation DNA sequencing
Authors: Butt Ejaz , Alyami Sabra , Nageeti Tahani , Saeed Muhammad , AlQuthami Khalid , Bouazzaoui Abdellatif , Athar Mohammad , Abduljaleel Zainularifeen , Al-Allaf Faisal , Taher Mohiuddin 
Published: June 2020

Background: Ependymomas are glial tumors derived from differentiated ependymal cells. In contrast to other types of brain tumors, histological grading is not a good prognostic marker for these tumors. In order to determine genomic changes in an anaplastic ependymoma, we analyzed its mutation patterns by next generation sequencing (NGS). Methods: Tumor DNA was sequenced using an Ion PI v3 chip on Ion Proton instrument and the data were analyzed by Ion Reporter 5.6. Results: NGS analysis identified 19 variants, of which four were previously reported missense variants; c.395G>A in IDH1, c.1173A>G in PIK3CA, c.1416A>T in KDR and c.215C>G in TP53. The frequencies of the three missense mutations (PIK3CA c.1173A>G, KDR c.1416A>T, TP53, c.215C>G) were high, suggesting that these are germline variants, whereas the IDH1 variant frequency was low (4.81%). However, based on its FATHMM score of 0.94, only the IDH1 variant is pathogenic; other variants TP53, PIK3CA and KDR had FATHMM scores of 0.22, 0.56 and 0.07, respectively. Eight synonymous mutations were found in FGFR3, PDGFRA, EGFR, RET, HRAS, FLT3, APC and SMAD4 genes. The mutation in FLT3 p.(Val592Val) was the only novel variant found. Additionally, two known intronic variants in KDR were found and intronic variants were also found in ERBB4 and PIK3CA. A known splice site mutation at an acceptor site in FLT3, a 3’-UTR variant in the CSF1R gene and a 5’_UTR variant in the SMARCB1 gene were also identified. The p-values were below 0.00001 for all variants and the average coverage for all variants was around 2000x. Conclusions: In this grade III ependymoma, one novel synonymous mutation and one deleterious missense mutation is reported. Many of the variants reported here have not been detected in ependymal tumors by NGS analysis previously and we therefore report these variants in brain tissue for the first time.
Effect of supraneural transforaminal epidural steroid injection combined with caudal epidural steroid injection with catheter in chronic radicular pain management: Double blinded randomized controlled trial.
Authors: Munjupong Sithapan , Kumnerddee Wipoo 
Published: June 2020

Background: Epidural steroid injection (ESI) has been used in managing chronic radicular pain. Regarding various techniques of ESI, the synergistic effect of caudal ESI (CESI) on transforaminal ESI (TFESI) in chronic lumbosacral radicular pain in prospective randomized controlled trial has not been determined. Methods: A total of 54 eligible patients with lumbosacral radicular pain were randomly allocated to undergo TFESI plus CESI (TC group) or TFESI alone (T group). The effective response to treatment was predefined by at least a 50% reduced verbal numerical rating scale (VNRS) from baseline between group comparison and the functional outcomes as measured by improved Oswestry Disability Index by least 15 points from baseline. All participants were evaluated using a single blinded outcome assessor before the procedure and at 1, 3 and 6 months after the procedure. P <0.05 was considered as statistically significant. Results: Average VNRS reduced significantly from baseline after receiving procedure at 1, 3 and 6 months in both groups (P-value <0.05). However, the TC group showed significant pain relief compared with the T group in spondylolisthesis and failed back surgery syndrome at 1 month. No statistical difference was observed between group comparisons of functional outcomes. Conclusions: A treatment combining TFESI and CESI showed significant pain relief over TFESI alone in spondylolithesis and failed back surgery syndrome at 1 month. No effect was found concerning functional evaluation. Registration: Thai Clinical Trials Registry ID TCTR20171101002 01/11/2017
The University And Its Role in the Process of European Integrations
Authors: Jaric Isidora 
Published: June 2020

The University And Its Role in the Process of European Integrations. The Dystopian Fairy Tale of Serbian University
The paper discusses the contemporary social role of the university in the three referent contexts: (a) the wider global context, (b) the regional context of European integrations, and (c) the local context of Serbian Society. The analysis discusses challenges of global context and university transformation, initial ideas of the Bologna process and the main directions of its implementation, and contemporary political and social challenges with the relationship between the university and its referent social environment and the value concepts shaping that relation. The latest tendencies of the abandonment of the university from its civil mission (Ćulum and Ledić, 2011) as one of the fundamental value concepts of modern universities has led to new escapist strategy that breaks the links between the university and the social environment in an almost artificial way. The paper discuss this tendency on the example of Serbian society and its university system, showing that the Serbian project of European integration has reached the point where it is necessary to articulate future directions of development so that they do not spontaneously take on malignant forms. On the one hand, breaking the link between the university and community jeopardizes the survivalof the university as we know it, and on the other hand, it eliminates serioussocial dialogue on the directions of future development.
Drainmod-Linked Interface for Evaluating Drainage System Response to Climate Scenarios
Authors: Adhikari Nidhi , Davidson Paul C. , Cooke Richard A. , Book Ruth S. 
Published: June 2020

Abstract.This article presents the development of a drainage-climate interface that incorporates climatological data, crop drainage requirements, and drainage theory into a procedure for characterizing drainage system response under different climate scenarios. The drainage-climate interface is suitable for assessing potential county-level impacts of climate change on crop production, soil hydrology and subsequently on subsurface drainage design. Climate model projections from two general circulation models (GCMs), namely CCSM4 (Community Climate System Model) and MIROC5 (Model for Interdisciplinary Research on Climate), were used to create the climatological database for the drainage-climate interface. DRAINMOD was integrated into the Visual Basic for Applications (VBA) portion of the interface to simulate the performance of subsurface drainage systems in Illinois for the near future (2040 to 2069) and the far future (2070 to 2099) periods. Case studies were developed with the interface for Adams and Champaign Counties in Illinois for their predominant soil types. Hydrologic simulations from the interface were used to determine the optimal depth and spacing of tile drains that maximize crop yield for corn and soybean during the mid and late 21st century. Drainage water management (DWM) was incorporated into the drainage-climate interface to investigate the potential of DWM in the future climate scenarios to maintain water quality, reduce nutrient losses and minimize pollutant loading from drained fields by controlling the timing and amount of water discharged from agricultural drainage systems. Results from DRAINMOD simulations with MIROC5 show a significant decline in crop yield due to extreme heat stress. Corn yield in the future showed a severe reduction while the yield for soybean demonstrated a gradual decline over the years. DWM had only a minimal effect on future crop yield trends. The drainage-climate interface simulated subsurface drainage conditions and made evident the consequences of environmental conditions on crop physiological processes under scenarios of climate change predicted by MIROC5. Keywords: Agricultural system models, Climate change impacts, Drainage-climate interface, Drainage water management, Subsurface drainage, Tile drain depth, Tile drain spacing.
Experimental Evaluation of Chain-Driven Mesh Belt Sorting System for Machine-Plucked Fresh Tea Leaves
Authors: Rongyang Wang , Liang Sun , Zhiwei Chen , Wenguang Zheng , Yudong Zhang , Junhua Tong , Yang Ye , Chuanyu Wu 
Published: June 2020

HighlightsA chain-driven mesh belt sorting system for machine-plucked fresh leaves was developed.The sorting system are evaluated with respect to provide the quality and consistency necessary to produce famous green tea.The Grade-A-, Grade-B, and Grade-C leaves can be sorted out from raw Grade-D machine-plucked fresh leaves.Abstract. Due to the varying contents of machine-plucked fresh tea leaves when harvesting in summer/autumn green tea at different times, they can only be used to produce bulk green tea, it is difficult to produce famous high-quality green tea, limiting the economic benefits of using mechanical plucking technology. In this study, a chain-driven mesh belt sorting system was developed to address the uneven quality grade of machine-plucked fresh leaves in order to grade high-quality leaves for famous green tea according to their shape and consistency. The operating parameters and the sorting effectiveness of the proposed method were evaluated using separation experiments. The results show that raw collected Grade-D machine-plucked fresh leaves can be sorted into Grade-A-, Grade-B, and Grade-C material by a series of four collectors. The mass of debris (old stems, leaves, fragments, or buds) in the final collector accounted for 94.38% of the remaining material, while 47.65% of leaves from the initial collector were separated out as one-bud-multi-leaves. The application of additional separation cycles using the same stage collector was found to further increase the classification of the separated high-quality tea leaves from Grade-A- to Grade-A to Grade-A+. The results of these experiments reveal that the proposed system can classify fresh leaves according to their shape and tenderness, providing high-quality leaves for subsequent mechanized tea production and improving the economics of tea production. These findings are of considerable theoretical significance for the design of high-efficiency and low-damage automatic grading devices for machine-plucked fresh tea leaves. Keywords: Agricultural machinery, Chain-driven mesh belt, Grading, Machine-plucked fresh leaves, Tea sorting.
Experimental Research on Sugarcane Under-the-Ground Basecutting
Authors: Bai Jing , Ma Shaochun , Ke Wenli , Wang Fenglei , Xing Haonan , Ma Jinzhi , Gao Shili 
Published: June 2020

Abstract.Basecutting, an important process in mechanical sugarcane harvesting, has important influence on the development of sugarcane mechanical harvesting. Previous studies mainly focus on kinematic and dynamic models in theory and indoor basecutting tests. However, few studies have explored the cutting mode of basecutter and power consumption with under-the-ground basecutting mode. The objective of this study was to compare two different basecutting modes (above-the-ground basecutting and under-the-ground basecutting), investigate the cutting power consumption and the cutting quality when sugarcane was cut in the optimal cutting mode. Through the means of simulation analysis and contrast experiment comparison, it concluded that the under-the-ground basecutting mode was better than above-the-ground basecutting mode to improve the cutting quality but it has increased the cutting power consumption of basecutters. In the under-the-ground basecutting mode, the orthogonal experiment was carried out using the existing sugarcane harvester, in order to minimize the power consumption while keeping the stubble broken rate to an acceptable level. With the power consumption and stubble broken rate being set as the indexes, the effects of basecutting depth, disc rotational speed, and the harvester forward speed on basecutting performance were investigated. Through the analysis of variance and range analysis, the influence of each factor on the evaluation index was obtained, and the best parameter combination with minimum stubble broken rate and power consumption were determined: the basecutting depth was 40 mm, the disc rotation speed was 600 rpm, and the harvester forward speed was 0.6 m/s. This study provided necessary information to guide engineers to design high-performance basecutter with under-the-ground basecutting mode. Keywords: Basecutter, Cutting mode, Power consumption, Stubble broken rate, Under-the-ground basecutting.
Influence of Drying Parameters on Drying Efficiency of a Rapeseed Hot Air Cyclone Dryer
Authors: MANGEH III FONDZENYUY CEDRIC , WU Ming Liang , LOOH George ASHWEHMBOM 
Published: June 2020

HIGHLIGHTSThis research was conducted with aims of investigating the influence of drying parameters on drying efficiency of a hot air cyclone dryer.Varying both diameter and height of the dryer, affected drying capacity, drying rate, temperature distribution and drying efficiency.Variations in the dryer’s inlet vent (Ram) caused most significant influences on drying efficiency.It was realized that speed of incoming hot air had the least significant influence on drying efficiency.Abstract. The purpose of this research was to investigate the influence of drying parameters such as height, diameter, ram width of the drying chamber and air speed, on drying efficiency of a hot air cyclone dryer. Experiments were run in two phases. One phase was in the field where the rapeseed hot air cyclone dryer was used to conduct physical experiments. The second and greater phase of the experiment involved mostly mathematical simulations using ANSYS Workbench software version 18.1. Two groups of simulations were conducted: single-factor simulations and multi-factor simulations. The number of simulations to be run were obtained using Taguchi Orthogonal Array (TOA) design of experiments in Minitab 18 software. Regression analysis were done to determine effects of factor variations on efficiency values and to obtain a regression equation from which optimal efficiency can be predicted. We concluded that moisture content of rapeseed is directly proportional to mass of seeds and radius of gyration subsequently. Furthermore, varying drying parameters of the dryer, affected drying capacity, drying rate, temperature distribution, and drying efficiency. Ram width had the most significant influence on the numerically calculated efficiency values, followed by the height, and then diameter of the chamber. The least influence was provided by speed of incoming air. Optimal value for each variable were also suggested from analysis with 2950 mm for height, 250 mm for diameter, 90 mm for ram width, and 20 m s-1 for air speed. Lastly, a regression equation was provided for estimation of efficiency for each parameter change. Using the optimization regression equation, drying efficiency for optimal values obtained from analysis, an efficiency of 83.9135% was obtained which is greater than the efficiency of 80.87%. Keywords: Drying efficiency, Numerical simulations, Optimization, Parameters, Regression equation, Rapeseed drying, Taguchi orthogonal arrays (TOA).
Indiana Farm Occasional Wood Cutter Fatalities Involving Individuals 55 Years and Older
Authors: Tormoehlen Sean A. , Field William E. , Ehlers Shawn G. , Ferraro Kenneth F. 
Published: June 2020

Abstract. Forestry activities, such as tree cutting and harvesting of forest resources, have been documented as dangerous tasks with increased risk of injuries and fatalities. These hazards are well known in the professional logging community, but less attention is given to farmers who perform occasional tree trimming and cutting activities, especially for the older farmer population. This study examined Indiana farm work-related fatalities from 1988 to 2017 involving farmers 55 years and older who performed occasional wood cutting activities. Fatality cases were mined from the Purdue University Agricultural Safety and Health Program’s fatality database. A total of 40 fatality cases were reported, representing 10.3% of all reported farm fatalities of farmers 55 years and older over the time period. The average age of the victims was 67.4, with 65% of cases involving victims 65 years or older. All victims were males. Wood cutting fatalities increased over the observation period. The most frequently reported fatal injury type was being crushed by tree or tree limbs, with 16 cases (40%), and the most common cause of fatality was due to cutting and trimming of trees, with 27 cases (67.5%). It was determined that the incidents were largely preventable and that future injury prevention strategies should address the risks associated with aging, the added risk of being struck by limbs or trees due to unsafe felling practices, the need for appropriate personal protective equipment, and the hazards involved in operating agricultural tractors in wooded areas. Keywords: Agriculture, Farm fatalities, Older farmers, Preventable fatalities, Tree felling.
Microsphere-assisted super-resolved Mueller matrix microscopy
Authors: Abbasian Vahid , Moradi Ali-Reza 
Published: June 2020

Mueller matrix microscopy (MMM) is a powerful approach to probe microstructural and optical information of many important specimens (e.g., tissue and bacteria), which otherwise cannot be obtained directly from intensity or spectral images. Achieving high lateral resolution in MMM, similar to other microscopy approaches, remains a challenge. Here, we extend the idea of microsphere (MS) -assisted microscopy into MMM toward resolution-enhanced polarimetric imaging. The goal is achieved by insertion of a transparent MS in the working distance of the imaging microscope objective in the optical train of an MMM system. We experimentally show that an MS close to the sample in MMM may increase the resolution beyond the intrinsic diffraction limit of the system by redirecting the higher spatial frequencies of the sample into the acceptance cone. In order to be a case in point, the experiment is conducted on a standard holographic diffraction grating with 1 µm line-width, which is beyond the diffraction limit of a

10
×

objective. Two-dimensional images of the Mueller matrix and some of the widely used quantitative polarimetric parameters of the sample are calculated and compared in the two cases before and after insertion of MS. The proposed arrangement is easy to implement and has the potential to serve as a high-resolution polarimetric microscope for visualizing the polarization characteristics of the microscopic objects.
Building Science and the Physics of Building Enclosure Performance
Authors: Lemieux Daniel J. , Keegan Jennifer 
Published: June 2020

Description
Get 20 peer-reviewed papers from international building experts from both the public and private sectors.
This book includes the latest research on building science and the physics of building enclosure _x000D_ and whole-building performance, including testing and assessment of building envelope heat, air, and moisture transfer, energy use, and our environment. Learn more about
The papers featured were presented at the first joint symposium of ASTM International Committees D08 on Roofing and Waterproofing and E06 on Performance of Buildings held in 2018.