bluuebunny/crossref_metadata_2025_split huggingface dataset:
In from the cold: M‐protein light chain glycosylation is positively associated with cold agglutinin titer levels
Authors: Juskewitch Justin E. , Murray Josiah D. , Norgan Andrew P. , Moldenhauer Sheila K. , Tauscher Craig D. , Jacob Eapen K. , Murray David L. 
Published: January 2021

AbstractBackgroundPrimary cold agglutinin disease (CAD) is a monoclonal antibody (M‐protein) and complement‐mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half‐life and complement fixation. Recently, M‐protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M‐protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA‐mediated hemolysis.Study Design and MethodsA cross‐sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M‐proteins and M‐protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M‐protein and M‐protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates.ResultsBoth M‐protein and M‐protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M‐protein LC glycosylation occurred almost exclusively on IgM kappa M‐proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M‐protein LC glycosylation status.ConclusionM‐protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half‐life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.
Palpation Sensitivity of an Embedded Nodule Using the Finite Element Method
Authors: Mukherjee Abhishek , Gupta Abhishek , Sen Shamik , Yan Wenyi , Saigal Anil , Singh Ramesh K. 
Published: January 2021

Abstract
A physician palpates a tissue to detect an embedded tumor nodule by sensing an increase in local tissue stiffness and nodule size. The Hertz contact model, however, is unable to predict the material or physical properties of a tumor nodule embedded in a healthy tissue of finite thickness. In this study, utilizing a hyperelastic material model, we propose a general methodology to analyze the extent to which the stiffness, size, and depth of a nodule embedded in a tissue affect its detectability. Using dimensional analysis, we generate simple power-law relations to predict physical and material properties of tumor nodules embedded in healthy tissue during indentation. Our results indicate that indenter radius and indentation depth are critical parameters in nodule detection and a thin indenter and large indentation depth increase detection sensitivity of an embedded tumor nodule. Our results also show that anisotropic material properties of either a tissue or an embedded nodule render the embedded tumor nodule undetectable using indentation. We define palpation sensitivity maps that can be used to predict material and physical properties of tumor nodules in healthy tissues. The analysis and results presented in this study might increase accuracy and precision in instrumented probe-based laparoscopic or robotic surgeries.
Dimensional Characterizations Using Scanning Electron Microscope and Surface Improvement With Electrochemical Polishing of Additively Manufactured Microchannels
Authors: Min Zheng , Wu Yingjie , Yang Kailai , Xu Jin , Parbat Sarwesh Narayan , Chyu Minking K. 
Published: January 2021

Abstract
Microchannel manufacturing is one of the fastest growing areas in advanced manufacturing with numerous applications, including turbine blade cooling structures, compact microchannel heat exchangers, and electronic cooling devices. Recent development of metallic additive manufacturing (AM) based on direct metal laser sintering technology is capable of fabricating microscale structures with high complexity and design flexibility. However, powder bed laser sintering process produces rough surface characteristics caused by hatch overlaps and particle attachments, leading to channel size reductions and rough surfaces. In this paper, dimensional metrology of cross-sectional views of multirow microchannels made by AM was conducted by a scanning electron microscope (SEM) at different locations along the printing direction. Channel size reduction, surface roughness, and circularity tolerance of the as-printed channels were analyzed based on micrographs captured by SEM. Results showed that both channel sizes and hole pitches affected the printing qualities of microchannels. The as-printed channel sizes reduced by more than 15% compared to the designed values. Two approaches were made in this paper to improve printing qualities. The first one was to redesign channel size in computer-aided design (CAD) model to make the as-printed channel sizes closer to the objective values. Electrochemical polishing (ECP) was then applied as a second way using sulfuric acid solutions. Surface roughness value was reduced by more than 40% after the ECP process.
Optimization of CO Turndown for an Axially Staged Gas Turbine Combustor
Authors: Rivera Jacob E. , Gordon Robert L. , Talei Mohsen , Bourque Gilles 
Published: January 2021

Abstract
This paper reports on an optimization study of the CO turndown behavior of an axially staged combustor, in the context of industrial gas turbines (GTs). The aim of this work is to assess the optimally achievable CO turndown behavior limit given system and operating characteristics, without considering flow-induced behaviors such as mixing quality and flame spatial characteristics. To that end, chemical reactor network (CRN) modeling is used to investigate the impact of various system and operating conditions on the exhaust CO emissions of each combustion stage, as well as at the combustor exit. Different combustor residence time combinations are explored to determine their contribution to the exhaust CO emissions. The two-stage combustor modeled in this study consists of a primary (Py) and a secondary (Sy) combustion stage, followed by a discharge nozzle (DN), which distributes the exhaust to the turbines. The Py is modeled using a freely propagating flame (FPF), with the exhaust gas extracted downstream of the flame front at a specific location corresponding to a specified residence time (tr). These exhaust gases are then mixed and combusted with fresh gases in the Sy, modeled by a perfectly stirred reactor (PSR) operating within a set tr. These combined gases then flow into the DN, which is modeled by a plug flow reactor (PFR) that cools the gas to varying combustor exit temperatures within a constrained tr. Together, these form a simplified CRN model of a two-stage, dry-low emissions (DLEs) combustion system. Using this CRN model, the impact of the tr distribution between the Py, Sy, and DN is explored. A parametric study is conducted to determine how inlet pressure (Pin), inlet temperature (Tin), equivalence ratio (ϕ), and Py–Sy fuel split (FS), individually impact indicative CO turndown behavior. Their coupling throughout engine load is then investigated using a model combustor, and its effect on CO turndown is explored. Thus, this aims to deduce the fundamental, chemically driven parameters considered to be most important for identifying the optimal CO turndown of GT combustors. In this work, a parametric study and a model combustor study are presented. The parametric study consists of changing a single parameter at a time, to observe the independent effect of this change and determine its contribution to CO turndown behavior. The model combustor study uses the same CRN, and varies the parameters simultaneously to mimic their change as an engine moves through its steady-state power curve. The latter study thus elucidates the difference in CO turndown behavior when all operating conditions are coupled, as they are in practical engines. The results of this study aim to demonstrate the parameters that are key for optimizing and improving CO turndown.
The Spinebot—A Robotic Device to Intraoperatively Quantify Spinal Stiffness
Authors: Büchler Philippe , Räber Jonas , Voumard Benjamin , Berger Steve , Bell Brett , Sutter Nino , Funariu Stefan , Hasler Carol , Studer Daniel 
Published: January 2021

Abstract
Degenerative spine problems and spinal deformities have high socio-economic impacts. Current surgical treatment is based on bony fusion that can reduce mobility and function. Precise descriptions of the biomechanics of normal, deformed, and degenerated spinal segments under in vivo conditions are needed to develop new approaches that preserve spine function. This study developed a system that intraoperatively measures the three-dimensional segmental stiffness of patient's spine. SpineBot, a parallel kinematic robot, was developed to transmit loads to adjacent vertebrae. A force/torque load cell mounted on the SpineBot measured the moment applied to the spinal segment and calculated segmental stiffnesses. The accuracy of SpineBot was characterized ex vivo by comparing its stiffness measurement of five ovine specimens to measurements obtained with a reference spinal testing system. The SpineBot can apply torques up to 10 N·m along all anatomical axes with a total range of motion of about 11.5 deg ± 0.5 deg in lateral bending, 4.5 deg ± 0.3 deg in flexion/extension, and 2.6 deg ± 0.5 deg in axial rotation. SpineBot's measurements are noisier than the reference system, but the correlation between SpineBot and reference measurements was high (R2 &gt; 0.8). In conclusion, SpineBot's accuracy is comparable to that of current reference systems but can take intraoperative measurements. SpineBot can improve our understanding of spinal biomechanics in patients who have the pathology of interest, and take these measurements in the natural physiological environment, giving us information essential to developing new “nonfusion” products.
Research of Exhaust Gas Recirculation on Commercial Turbocharged Gasoline Direct Injection Engine With Intense Tumble Flow
Authors: Yin Congbo , Chen Quanwei , Zhang Zhendong , Zhu Haibing , Shen Kai 
Published: January 2021

Abstract
The application of exhaust gas recirculation (EGR) technology on gasoline direct injection (GDI) engines can suppress knocking, reduce fuel consumption, and reduce NOx emissions. The effects of EGR with enhanced intake tumble flow, on the combustion phase, combustion duration, knock index and combustion cycle variation of the engine, were studied at two speeds of 1500 r/min and 2000 r/min from low to medium and to full load. The research shows that although the commercial engine has been well calibrated and optimized, the optimization of EGR and enhanced tumble flow together with the optimization of the ignition angle can improve the engine's economy and emission characteristics, while maintaining relatively fast burning speed and low combustion cycle variation. From medium to heavy load, the economy can be improved by 2.6–10%, and the minimum fuel consumption can be reduced to 213 g/kW. h. Under heavy load conditions (brake mean effective pressure (BMEP) more than 14 bars), power performance deteriorates due to insufficient boost performance. The 5–20% EGR rate brings 10% power loss. EGR combined with tumble intake has a significant effect on reducing the engine's NOx and CO, with average reductions of 60% and 22%, but HC increased by 32%.
Evaluation of Length Scales and Meshing Requirements for Resolving Two-Phase Flow Regime Transitions Using the Level Set Method
Authors: Zimmer Matthew D. , Bolotnov Igor A. 
Published: January 2021

Abstract
New criteria for fully resolving two-phase flow regime transitions using direct numerical simulation with the level set method for interface capturing are proposed. A series of flows chosen to capture small scale interface phenomena are simulated at different grid refinements. These cases include droplet deformation and breakup in a simple shear field, the thin film around a Taylor bubble, and the rise of a bubble toward a free surface. These cases cover the major small scale phenomena observed in two-phase flows: internal recirculation, interface curvature, interface snapping, flow of liquid in thin films, and drainage/snapping of thin films. The results from these simulations and their associated grid studies were used to develop new meshing requirements for simulation of two-phase flow using interface capturing methods, in particular the level set method. When applicable, the code used in this work, PHASTA, was compared to experiments in order to contribute to the ongoing validation process of the code. Results show that when the solver meets these criteria, with the exception of resolving the nanometer scale liquid film between coalescing bubbles, the code is capable of accurately simulating interface topology changes.
Gaze Accuracy Differences During Single-Leg Balance Following Anterior Cruciate Ligament Reconstruction
Authors: Bodkin Stephan G. , Hertel Jay , Hart Joseph M. 
Published: January 2021

Context: Individuals following anterior cruciate ligament reconstruction (ACLR) demonstrate altered postural stability and functional movement patterns. It is hypothesized that individuals following ACLR may compensate with sensory adaptations with greater reliance on visual mechanisms during activities. It is unknown if visual compensatory strategies are implemented to maintain postural stability during functional tasks. Objective: To examine visual gaze accuracy during a single-leg balance task in individuals following ACLR compared with healthy, active controls. Design: Case control. Setting: Controlled laboratory. Participants: A total of 20 individuals (10 ACLR and 10 healthy controls) participated in the study. Data Collection and Analysis: Visual gaze patterns were obtained during 20-second single-leg balance trials while participants were instructed to look at presented targets. During the Stationary Target Task, the visual target was presented in a central location for the duration of the trial. The Moving Target Task included a visual target that randomly moved to 1 of 9 target locations for a period of 2 seconds. Targets were stratified into superior, middle, and inferior levels for the Moving Target Task. Results: The Stationary Target Task demonstrated no differences in visual error between groups (P = .89). The Moving Target Task demonstrated a significant interaction between group and target level (F2,36 = 3.76, P = .033). Individuals following ACLR demonstrated greater visual error for the superior targets (ACLR = .70 [.44] m, healthy = .41 [.21] m, Cohen d = 0.83 [0.06 to 1.60]) and inferior targets (ACLR = .68 [.25] m, healthy = .33 [.16] m, Cohen d = 1.67 [0.81 to 2.52]). Conclusion: Individuals following ACLR demonstrate greater visual error during settings of high or low visual stimuli compared with healthy individuals to maintain single-limb postural stability. This population may rely on visual input to compensate for the somatosensory changes following injury.
Effects of modified lipoproteins on human trophoblast cells: a role in pre-eclampsia in pregnancies complicated by diabetes
Authors: McLeese Rebecca Helen , Zhao Jiawu , Fu Dongxu , Yu Jeremy Y , Brazil Derek P , Lyons Timothy J 
Published: January 2021

IntroductionPre-eclampsia (PE) is increased ~4-fold by maternal diabetes. Elevated plasma antiangiogenic factors, soluble fms-like tyrosine kinase (sFLT-1) and soluble endoglin (sENG), precede PE onset. We investigated whether diabetes-related stresses, modified lipoproteins and elevated glucose enhance trophoblast sFLT-1 and sENG release and/or alter placental barrier function and whether oxidized low-density lipoprotein (Ox-LDL) is in placental tissue.Research design and methodsHTR8/SVneo cells were exposed to ‘heavily-oxidized, glycated’ LDL (HOG-LDL) versus native LDL (N-LDL) (10–200 mg protein/L) for 24 hours ±pretreatment with glucose (30 mmol/L, 72 hours). Concentrations of sFLT-1 and sENG in supernatants (by ELISA) and expressions ofsFLT-1-I13andsFLT-1-E15Aisoforms,endoglin (ENG) andmatrix metalloproteinase-14(MMP-14; by RT-PCR) were quantified. For barrier studies, JAR cells were cultured in Transwell plates (12–14 days), then exposed to LDL. Transepithelial electrical resistance (TEER) was measured after 6, 12 and 24 hours. In placental sections from women with and without type 1 diabetes, immunostaining of apolipoprotein B100 (ApoB, a marker of LDL), Ox-LDL and lipoxidation product 4-hydroxynonenal was performed.ResultsHOG-LDL (50 mg/L) increased sFLT-1 (2.7-fold, p<0.01) and sENG (6.4-fold, p<0.001) in supernatants versus N-LDL. HOG-LDL increased expression ofsFLT-1-I13(twofold, p<0.05),sFLT-1-E15A(1.9-fold, p<0.05),ENG(1.6-fold, p<0.01) andMMP-14(1.8-fold, p<0.05) versus N-LDL. High glucose did not by itself alter sFLT-1 or sENG concentrations, but potentiated effects of HOG-LDL on sFLT-1 by 1.5-fold (p<0.05) and on sENG by 1.8-fold (p<0.01). HOG-LDL (200 mg/L) induced trophoblast barrier impairment, decreasing TEER at 6 hours (p<0.01), 12 hours (p<0.01) and 24 hours (p<0.05) versus N-LDL. Immunostaining of term placental samples from women both with and without diabetes revealed presence of intravillous modified lipoproteins.ConclusionThese findings may explain, in part, the high risk for PE in women with diabetes. The trophoblast culture model has potential for evaluating novel therapies targeting barrier dysfunction.
Development of an electrocardiogram-based risk calculator for a cardiac cause of syncope
Authors: Zimmermann Tobias , du Fay de Lavallaz Jeanne , Walter Joan Elias , Strebel Ivo , Nestelberger Thomas , Joray Lydia , Badertscher Patrick , Flores Dayana , Widmer Velina , Geigy Nicolas , Miro Oscar , Salgado Emilio , Christ Michael , Cullen Louise , Than Martin , Martín-Sánchez Francisco Javier , Di Somma Salvatore , Peacock W Frank , Keller Dagmar , Costabel Juan Pablo , Wussler Desiree Nadine , Kawecki Damian , Lohrmann Jens , Gualandro Danielle Menosi , Kuehne Michael , Reichlin Tobias , Sun Benjamin , Mueller Christian 
Published: January 2021

ObjectiveTo develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.MethodsIn a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.ResultsIn the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.ConclusionIn patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.Trial registration numberNCT01548352 (BASEL IX), NCT01802398 (SRS study).
A systemically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer
Authors: Marelli Giulia , Chard Dunmall Louisa S , Yuan Ming , Di Gioia Carmela , Miao Jinxin , Cheng Zhenguo , Zhang Zhongxian , Liu Peng , Ahmed Jahangir , Gangeswaran Rathi , Lemoine Nicholas , Wang Yaohe 
Published: January 2021

BackgroundPancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved.MethodsVVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer.ResultsVVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1.ConclusionsIntravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.
DMS research and MODREC – a guide for potential researchers
Authors: Roberts SAG 
Published: January 2021

AbstractFollowing and during recent conflict, the UK Defence Medical Services (DMS) research programme has resulted in significant advancements in care. There are opportunities to work in medical research with the backing of either MOD funding and/or 3rd sector support. Research may require Ministry of Defence Research Ethics Committee (MODREC) approval, a process that can be daunting and confusing for those new to research. Often researchers have a finite period in which to complete their research; any delay in the process can be frustrating and may decrease the effectiveness of the research period. Here, we use recent experience to describe the development of a research idea and its submission through the MODREC process. We identify considerations and potential pitfalls in order to streamline and inform the process for those considering DMS research in the future.