bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of FOXD2‐AS1 enhances proliferation and impairs differentiation of glioma stem cells by activating the NOTCH pathway via TAF‐1
Authors: Wang Yang , Cheng Yanli , Yang Qi , Kuang Lei , Liu Guolei 
Published: April 2022

AbstractEmerging data have highlighted the importance of long noncoding RNAs (lncRNAs) in exerting critical biological functions and roles in different forms of brain cancer, including gliomas. In this study, we sought to investigate the role of lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2‐AS1) in glioma cells. First, we used sphere formation assay and flow cytometry to select U251 glioma stem cells (GSCs). Then, we quantified the expression of lncRNA FOXD2‐AS1, TATA‐box binding protein associated factor 1 (TAF‐1) and NOTCH1 in glioma tissues and GSCs, as well as the expression of GSC stem markers, OCT4, SOX2, Nanog, Nestin and CD133 in GSCs. Colony formation assay, sphere formation assay, and flow cytometry were used to evaluate GSC stemness. Next, the correlations among lncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were investigated. LncRNA FOXD2‐AS1, TAF‐1 and NOTCH1 were found to be elevated in glioma tissues and GSCs, and silencing lncRNA FOXD2‐AS1 inhibited stemness and proliferation, while promoting apoptosis and differentiation of GSCs. LncRNA FOXD2‐AS1 overexpression also led to increased NOTCH1 by recruiting TAF‐1 to the NOTCH1 promoter region, thereby promoting stemness and proliferation, while impairing cell apoptosis and differentiation. Mechanistically, lncRNA FOXD2‐AS1 elevation promoted glioma in vivo by activating the NOTCH signalling pathway via TAF‐1 upregulation. Taken together, the key findings of our investigation support the proposition that downregulation of lncRNA FOXD2‐AS1 presents a viable and novel molecular candidate for improving glioma treatment.
Informed trading of out‐of‐the‐money options and market efficiency
Authors: Kang Chang‐Mo , Kim Donghyun , Kim Junyong , Lee Geul 
Published: April 2022

AbstractWe examine the stock return predictability of out‐of‐the‐money (OTM) put‐to‐call trading volume ratio (OTMPC). Our numerical analysis predicts that in the US equity option market, informed investors rarely write OTM options because the leverage effect is not sufficient to compensate for transaction costs. OTMPC thus captures the informed investors’ OTM put purchase volume relative to their OTM call purchase volume. After controlling for existing empirical proxies for informed option trading, we find that OTMPC predicts future stock returns and corporate news. The return predictability offers implementable stock portfolio strategies. Our findings suggest that market inefficiency can emerge from uninformed investors’ limited knowledge about how transaction costs influence the trading strategies of informed investors.
Short selling and options trading: A tale of two markets
Authors: Cashman George D. , Harrison David M. , Sheng Hainan 
Published: April 2022

AbstractRecent research documents both short selling and option volume are predictive of future real estate investment trust (REIT) returns, suggesting informed investors exploit their informational advantage in both the traditional equity and derivative security markets. However, little work has explicitly examined the factors influencing which of these markets informed investors choose to engage when transacting. We address this gap in the literature and find clear evidence that the risk associated with short selling is a significant driver of this decision. Specifically, using a sample of 124 unique equity REITS with both active short selling and option markets over the past 10 years, we find that when short selling is riskier, option volume is more predictive of future returns. These results suggest that investors view options as an alternative to shorting, and their decision to transact in the derivatives market is materially influenced by short‐selling risk.
Permanent private equity: Market performance and transactions
Authors: McCourt Maurice 
Published: April 2022

AbstractUsing market data for a comprehensive sample of publicly listed permanent capital private equity funds, I confirm existing results in the private equity literature and establish new empirical facts for private equity investments. Over 2000–2019, only mezzanine funds outperformed public markets, whereas buyout, growth, and funds of funds underperformed somewhat, and venture capital funds underperformed significantly. Buyout funds exhibit performance persistence. Larger funds with higher asset turnover have higher performance, and funds with higher expenses have lower performance. Finally, contemporaneous and out‐of‐sample performance of buyout and mezzanine funds is associated with deal and exit transaction characteristics.
Bond covenants and investment policy
Authors: Docgne Sandrine 
Published: April 2022

AbstractI provide evidence that covenants in bond indentures affect firms’ investment policies outside of covenant violations. After controlling for the self‐selectivity of covenant inclusion, I find that firms decrease (increase) capital expenditure after issuing bonds with investment (financing) restrictions. Firms that are more financially constrained or overinvesting are the most affected by investment restrictions, whereas only underinvesting firms see a positive effect from financing restrictions. My results provide empirical evidence that bond covenants help mitigate agency problems related to investment distortions, and especially that covenants restricting financing activities can alleviate the underinvestment problem.
Long‐term impact of a geriatric prescribing context
Authors: De Lima Bryanna , DeVane Kenneth , Drago Kathleen 
Published: April 2022

AbstractBackgroundThe medication‐related death of a hospitalized older adult elucidated the inappropriateness of medication default doses in our electronic health record (EHR) for older adults. In response, we created and implemented the Geriatric Prescribing Context (GPC), an EHR‐based set of age‐specific dose and frequency defaults for patients 75 years and older, in July 2017. Inpatient medication orders aligned with GPC defaults and showed significant dose decreases at one year for nine of ten most commonly used medications. This follow‐up investigation examined GPC alignment of dose and frequency over the 42‐month time period after its implementation.MethodsOrder data for the ten most commonly used medications at OHSU Hospital were collected retrospectively from July 2016 through December 2020. We used Statistical Process Control charts to assess the proportion of medication orders aligning with the GPC's recommendations. Signals of special cause were evaluated to identify time periods when shifts in process averages likely occurred and suspected shifts were assessed using binomial proportion tests. We used RStudio (RStudio, Inc., version 1.2.5001) and Microsoft Excel (2016) to perform statistical analyses and control charts, respectively.ResultsThe preimplementation phase of all medications displayed no special causes. After significant initial improvement in 2017, control charts revealed three different patterns of performance. Eight medications maintained the initial improvement with one medication displaying a second significant improvement at a later date. Two medications showed a subsequent decline in performance not statistically different from baseline. Overall, eight of the ten medications were prescribed at more age‐friendly doses and frequencies compared to baseline after 42 months.ConclusionsThe GPC is an effective method to support safer prescribing for hospitalized older patients, but long‐term impacts may be medication‐specific. Further investigation is needed to ensure appropriate prescribing across drug classes and understand the GPC's impact on patient outcomes like adverse drug events.
Evaluating augmented reality for ‘real life’ teaching of food portion concepts
Authors: Mellos Ioannis , Probst Yasmine 
Published: April 2022

AbstractBackgroundEstimation of food portions is a vital skill for dietitians, which is developed during formal nutrition training. Skill development is often accomplished by training with food portion estimation tools. These tools can vary in design but evaluations often reveal them to be limited in their effectiveness and generally impractical for everyday use. The aim of this study was to develop and evaluate an augmented reality (AR) tool for the estimation food portions.MethodsAn online, quasi‐experimental, randomised pre‐test post‐test study was conducted to evaluate the effectiveness of three food portion tools with nutrition students. These tools consisted of an online, AR, and an infographic tool (control). Students tested 10 different food images and were asked to estimate food portion sizes with and without assistance of a portion tool to determine absolute error, relative error, and overall improvement in estimation.ResultsA total of 33 participants enrolled in the study with 26 (72.0%) completing the study. The mean absolute error was lowest in the online group (53.0%), followed by AR (59.5%) and control (64.0%). Relative error scores revealed higher accuracy for the AR group (45.5%) followed by online (43.5%), and control group (29.0%). Overall improvement in estimation was highest in the AR group (+12.2%) followed by the online (+11.6%) tool with a decrease seen for the infographic (−1.7%) tool.ConclusionsThe use of technology, notably AR technology, may provide some advantage when training nutrition students in food portion estimation, although further investigation is advised.
Tagetes lucida Cav. essential oil and the mixture of its main compounds are antibacterial and modulate antibiotic resistance in multi-resistant pathogenic bacteria
Authors: Torres-Martínez R. , Moreno-León A. , García-Rodríguez Y.M. , Hernández-Delgado T. , Delgado-Lamas G. , Espinosa-García F.J. 
Published: April 2022

Abstract
We evaluated an essential oil (EO) of Tagetes lucida Cav. and the mixture of its main compounds against multi-drug resistant bacteria. We found that EO and the partially reconstituted blend of its main components have antibacterial activity and inhibit antibiotic resistance (ampicillin, chloramphenicol, nalidixic acid, vancomycin and imipenem) in strains of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa HIM-MR01. The T. lucida EO alone or added to the antibiotics showed antimicrobial activity against S. aureus and P. aeruginosa. The EO main bioactive compounds were methyl eugenol (relative abundance in EO: 46·15%), estragole (32·93%), linalool (2·48%) and geraniol (0·33%). The mixture (PREO) of those compounds at those proportions inhibited the growth of P. aeruginosa in 45% at 683·62 µg ml−1 and that of S. aureus in 51·7% at 39·04 µg ml−1. The PREO had higher antibacterial and modulatory activities than the original EO. In conclusion, we overcame the unpredictability of EO activity (due to their natural variability) by determining which EO components inhibited bacteria and then producing a PREO to generate a reproducible mixture with predictable antibacterial and modulation of resistance activities. Thus, the PREO, and its components, show potential as alternatives to manage multidrug-resistant pathogens.
Variation in White spruce needle respiration at the species range limits: A potential impediment to Northern expansion
Authors: Griffin Kevin L. , Griffin Zoe M. , Schmiege Stephanie C. , Bruner Sarah G. , Boelman Natalie T. , Vierling Lee A. , Eitel Jan U. H. 
Published: April 2022

AbstractWhite spruce (Picea glauca) spans a massive range, yet the variability in respiratory physiology and related implications for tree carbon balance at the extremes of this distribution remain as enigmas. Working at both the most northern and southern extents of the distribution range more than 5000 km apart, we measured the short‐term temperature response of dark respiration (R/T) at upper and lower canopy positions. R/T curves were fit to both polynomial and thermodynamic models so that model parameters could be compared among locations, canopy positions, and with previously published data. Respiration measured at 25°C (R25) was 68% lower at the southern location than at the northern location, resulting in a significantly lower intercept in R/T response in temperate trees. Only at the southern location did upper canopy leaves have a steeper temperature response than lower canopy leaves, likely reflecting canopy gradients in light. At the northern range limit respiration is nearly twice that of the average R25 reported in a global leaf respiration database. We predict that without significant thermal acclimation, respiration will increase with projected end‐of‐the‐century warming and will likely constrain the future range limits of this important boreal species.
Drought and warming alter gross primary production allocation and reduce productivity in a widespread pasture grass
Authors: Chandregowda Manjunatha H. , Tjoelker Mark G. , Power Sally A. , Pendall Elise 
Published: April 2022

AbstractCarbon allocation determines plant growth, fitness and reproductive success. However, climate warming and drought impacts on carbon allocation patterns in grasses are not well known, particularly following grazing or clipping. A widespread C3 pasture grass, Festuca arundinacea, was grown at 26 and 30°C in controlled environment chambers and subjected to drought (65% reduction relative to well‐watered controls). Leaf, root and whole‐plant carbon fluxes were measured and linked to growth before and after clipping. Both drought and warming reduced gross primary production and plant biomass. Drought reduced net leaf photosynthesis but increased the leaf respiratory fraction of assimilated carbon. Warming increased root respiration but did not affect either net leaf photosynthesis or leaf respiration. There was no evidence of thermal acclimation. Moreover, root respiratory carbon loss was amplified in the combined drought and warming treatment and, in addition to a negative carbon balance aboveground, explained an enhanced reduction in plant biomass. Plant regrowth following clipping was strongly suppressed by drought, reflecting increased tiller mortality and exacerbated respiratory carbon loss. These findings emphasize the importance of considering carbon allocation patterns in response to grazing or clipping and interactions with climatic factors for sustainable pasture production in a future climate.
Comparison of Balloon-Expandable Valve and Self-Expandable Valve in Transcatheter Aortic Valve Replacement: A Patient-Specific Numerical Study
Authors: Li Jianming , Yan Wentao , Wang Wenshuo , Wang Shengzhang , Wei Lai 
Published: April 2022

Abstract
Transcatheter aortic valve replacement (TAVR) is a minimally invasive strategy for the treatment of aortic stenosis. The complex postoperative complications of TAVR were related to the type of implanted prosthetic valve, and the deep mechanism of this relationship may guide the clinical pre-operative planning. This technical brief developed a numerical method of TAVR to compare the outcome difference between balloon-expandable valve and self-expandable valve and predict the postoperative results. A complete patient-specific aortic model was reconstructed. Two prosthetic valves (balloon-expandable valve and self-expandable valve) were introduced to simulate the implantation procedure, and postprocedural function was studied with fluid–structure interaction method, respectively. Results showed similar stress distribution for two valves, but higher peak stress for balloon-expandable valve model. The balloon-expandable valve was associated with a better circular cross section and smaller paravalvular gaps area. Hemodynamic parameters like cardiac output, mean transvalvular pressure difference, and effective orifice area (EOA) of the balloon-expandable valve model were better than those of the self-expandable valve model. Significant outcome difference was found for two prosthetic valves. Balloon-expandable valve may effectively decrease the risk and degree of postoperative paravalvular leak, while self-expandable valve was conducive to lower stroke risk due to lower aortic stress. The numerical TAVR simulation process may become an assistant tool for prosthesis selection in pre-operative planning and postoperative prediction.
Design Synthesis of a Robotic Uniaxial Torque Device for Orthopedic Haptic Simulation
Authors: Cotter Trevor , Mongrain Rosaire , Driscoll Mark 
Published: April 2022

Abstract
Robotic devices are commonly used in surgical simulators to provide tactile, or haptic, feedback. They can provide customized feedback that can be rapidly modified with minimal hardware changes in comparison to nonrobotic systems. This work describes the design, development, and evaluation of one such tool: a novel uniaxial torque haptic device for a surgical training simulator. The objective of the work was to design a single connection haptic device that could augment an existing six degree-of-freedom haptic device to mimic a Concorde Clear vacuum curette. Design and evaluations focused on the tool's ability to deliver adequate torque, imitate a surgical tool, and be integrated into the haptic device. Twenty-nine surgeons tested the tool in the simulator and evaluated it via a questionnaire. The device was found to deliver the 800 N⋅mm of torque necessary to mimic an orthopedic procedure. Surgeons found it accurately imitated surgical tools physical appearance and maneuverability, scoring them 3.9 ± 1.0 and 3.3 ± 1.2, respectively, on a 1–5 Likert scale. By virtue of the functionality necessary for testing and evaluation, the device could be connected to the haptic device for mechanical and electrical engagement. This device is a step forward in the field of augmentable haptic devices for surgical simulation. By changing the number of robotically controlled degrees-of-freedom of a haptic device, existing devices can be tuned to meet the demands of a particular simulator, which has the potential to improve surgeon training standards.
Horizontal Chimney Effect
Authors: Floryan J. M. , Haq N. N. , Panday S. 
Published: April 2022

Abstract
An analysis of natural convection in horizontal slots has been carried out. It is demonstrated that a proper combination of heating and groove patterns can create a net horizontal fluid movement, which we refer to as the horizontal chimney effect. Groove shapes that can be easily manufactured as well as heating patterns that can be easily created using heating wires were considered. It has been shown that both patterns must be properly tuned. The direction of the net horizontal flow can be changed by changing the relative positions of the patterns. Changes of groove geometry can change the flow rate by up to 100%. Simultaneous use of grooves and heating at both plates can nearly double the system effectiveness. The strength of the flow increases with reduction of the Prandtl number.
Laser-ablation Lu-Hf dating reveals Laurentian garnet in subducted rocks from southern Australia
Authors: Brown Dillon A. , Simpson Alexander , Hand Martin , Morrissey Laura J. , Gilbert Sarah , Tamblyn Renée , Glorie Stijn 
Published: April 2022

Abstract
Garnet is a fundamental expression of metamorphism and one of the most important minerals used to constrain the thermal conditions of the crust. We used innovative in situ laser-ablation ICP-MS/MS Lu-Hf geochronology to demonstrate that garnet in metapelitic rocks enclosing Cambrian eclogite in southern Australia formed during Laurentian Mesoproterozoic metamorphism. Garnet porphyroblasts in amphibolite-facies metapelitic rocks yielded Lu-Hf ages between 1286 ± 58 Ma and 1241 ± 16 Ma, revealing a record of older metamorphism that was partially obscured by metamorphic overprinting during ca. 510 Ma Cambrian subduction along the East Gondwana margin. Existing detrital zircon age data indicate the protoliths to the southern Australian metapelitic rocks were sourced from western Laurentia. We propose that the metapelitic rocks of southern Australia represent a fragment of western Laurentian crust, which was separated from Laurentia in the Neoproterozoic and incorporated into the East Gondwana subduction system during the Cambrian. The ability to obtain Lu-Hf isotopic data from garnet at acquisition rates comparable to those for U-Pb analysis of detrital zircon means, for the first time, the metamorphic parentage of rocks as expressed by garnet can be efficiently accessed to assist paleogeographic reconstructions.
Evaluation of UAS LiDAR data for tree segmentation and diameter estimation in boreal forests using trunk- and crown-based methods
Authors: Kukkonen Mikko , Maltamo Matti , Korhonen Lauri , Packalen Petteri 
Published: April 2022

Very high point density laser scanning data from unmanned aerial systems (UAS) can be used to segment the trunks of individual trees. Such segmentation (e.g., individual trunk segmentation (ITS)) is useful, for example, in the estimation of diameter at breast height (DBH), which in turn is needed for the estimation of other tree and stand attributes, such as stem volume and diameter of the basal area median tree (DGM). In this paper, we assess the estimation of DBH directly from UAS LiDAR data in open and closed canopy conditions that represent the range of operational conditions encountered in boreal forests in Finland. We also compare trunk-based DBH estimates to corresponding estimates from individual tree crown segmentation (ITC) and fuse the results from the trunk- and crown-based estimates. The results showed that trunk segmentation performed slightly better than ITC in open canopy areas, whereas ITC performed better in closed canopy areas. The DBH prediction error was smaller for ITS (3.0 cm) than ITC (3.9 cm) when considering the trees that were recognized by both methods. We also conclude that a hybrid method, where both segmented tree trunks and tree crowns are fused, considerably increases the number of correctly segmented trees but does not decrease the prediction error associated with DGM compared to using either ITC or ITS individually.
A Phase Ib/II Study of the CDK4/6 Inhibitor Ribociclib in Combination with Docetaxel plus Prednisone in Metastatic Castration-Resistant Prostate Cancer
Authors: de Kouchkovsky Ivan , Rao Arpit , Carneiro Benedito A. , Zhang Li , Lewis Catriona , Phone Audrey , Small Eric J. , Friedlander Terence , Fong Lawrence , Paris Pamela L. , Ryan Charles J. , Szmulewitz Russell Z. , Aggarwal Rahul 
Published: April 2022

AbstractPurpose:Ribociclib, a CDK4/6 inhibitor, demonstrates preclinical antitumor activity in combination with taxanes. We evaluated the safety and efficacy of ribociclib plus docetaxel in a phase Ib/II study in metastatic castration-resistant prostate cancer (mCRPC).Patients and Methods:Patients had chemotherapy-naïve mCRPC with progression on ≥ 1 androgen receptor signaling inhibitor (ARSI). The phase II primary endpoint was 6-month radiographic progression-free survival (rPFS) rate, with an alternative hypothesis of 55% versus 35% historical control. Circulating tumor cells (CTC) were collected at baseline and genomically profiled.Result:Forty-three patients were enrolled (N = 30 in phase II). Two dose-limiting toxicities were observed (grade 4 neutropenia and febrile neutropenia). The recommended phase II dose (RP2D) and schedule was docetaxel 60 mg/m2 every 21 days plus ribociclib 400 mg/day on days 1–4 and 8–15 with filgrastim on days 5–7. At the RP2D, neutropenia was the most common grade ≥ 3 adverse event (37%); however, no cases of febrile neutropenia were observed. The primary endpoint was met; the 6-month rPFS rate was 65.8% [95% confidence interval (CI): 50.6%–85.5%; P = 0.005] and median rPFS was 8.1 months (95% CI, 6.0–10.0 months). Thirty-two percent of evaluable patients achieved a PSA50 response. Nonamplified MYC in baseline CTCs was associated with longer rPFS (P = 0.052).Conclusions:The combination of intermittent ribociclib plus every-3-weeks docetaxel demonstrated acceptable toxicity and encouraging efficacy in ARSI-pretreated mCRPC. Genomic profiling of CTCs may enrich for those most likely to derive benefit. Further evaluation in a randomized clinical trial is warranted.