bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards compound identification of synthetic opioids in nontargeted screening using machine learning techniques
Authors: Klingberg Joshua , Cawley Adam , Shimmon Ronald , Fu Shanlin 
Published: November 2020

AbstractThe constant evolution of the illicit drug market makes the identification of unknown compounds problematic. Obtaining certified reference materials for a broad array of new analogues can be difficult and cost prohibitive. Machine learning provides a promising avenue to putatively identify a compound before confirmation against a standard. In this study, machine learning approaches were used to develop class prediction and retention time prediction models. The developed class prediction model used a naïve Bayes architecture to classify opioids as belonging to either the fentanyl analogues, AH series or U series, with an accuracy of 89.5%. The model was most accurate for the fentanyl analogues, most likely due to their greater number in the training data. This classification model can provide guidance to an analyst when determining a suspected structure. A retention time prediction model was also trained for a wide array of synthetic opioids. This model utilised Gaussian process regression to predict the retention time of analytes based on multiple generated molecular features with 79.7% of the samples predicted within ±0.1 min of their experimental retention time. Once the suspected structure of an unknown compound is determined, molecular features can be generated and input for the prediction model to compare with experimental retention time. The incorporation of machine learning prediction models into a compound identification workflow can assist putative identifications with greater confidence and ultimately save time and money in the purchase and/or production of superfluous certified reference materials.
Regeneration and development. An amphibian call to arms
Authors: Khan Paul A. , Crawford Michael J. 
Published: November 2020

AbstractBackgroundUnlike axolotls, the urodele Notophthalmus viridescens completes two metamorphoses and emerges from its aquatic environment to mate as a fully terrestrial adult. Larval and adult limb regeneration are commonly treated as roughly equivalent processes and, at least in part, as a recapitulation of embryonic development.ResultsWe compared larval limb development to regeneration of both larval and adult forelimbs and found that there are substantial differences in developmental pattern among larvae and adults. The larval pattern of preaxial dominance is absent in adult regenerates: adult regenerates instead develop digits synchronously, and they do so before proximal autopodial elements have formed discrete aggregation zones. By contrast, larval regenerates follow a pattern of sequential digit formation from anterior to posterior, like their embryonic limb buds.ConclusionsBased upon these morphological clues, we conclude that larval regenerates are unlikely to exhibit features of epimorphic regeneration seen in adults, but are more likely to represent a form of developmental regulation. Furthermore, we confirm that post‐metamorphic limb regeneration is not a simple recapitulation of ontology at the morphological level. These distinctions may help to explain and interpret some experiments and observations of regeneration in neotenic or paedomorphic urodeles.
Increased microclimatic variation in artificial nests does not create ecological traps for a secondary cavity breeder, the European roller
Authors: Schwartz Timothée , Genouville Arnaud , Besnard Aurélien 
Published: November 2020

AbstractArtificial devices are increasingly used in conservation measures to mitigate the disappearance of natural habitats. However, few studies have demonstrated their benefits for the target species, and they may pose a risk of creating ecological traps. This occurs when lower individual fitness is found in artificial habitats that are more attractive than their natural equivalents. In this study, we tested the ecological trap hypothesis on a dense population of European rollers Coracias garrulus breeding in both natural cavities and nest boxes. Our initial prediction was that the more stressful microclimatic conditions of nest boxes would lead to reduced fitness of European rollers, thus creating an ecological trap. The results showed that nest boxes were preferred over natural cavities. Despite significantly more extreme microclimatic conditions in nest boxes, we found similar breeding parameters between artificial and natural nest types. Our results also suggest that European rollers selected the nest boxes which best buffered the temperature, thus avoiding potential ecological traps. Overall our results led to the conclusion that nest boxes do not create ecological traps for European rollers in this study area. However, other species may be more sensitive to microclimatic variations or less able to avoid the least favorable nest boxes. These findings could help to inform the placement of nest boxes in order to reduce extreme temperatures and variation in humidity rates. Future studies could compare nest types for other fitness parameters, such as juvenile body condition or survival. We also recommend the ecological trap hypothesis as a useful framework to evaluate the outcomes of artificial devices used for conservation.
Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients
Authors: Lachmet‐Thebaud Lucie , Marchandot Benjamin , Matsushita Kensuke , Sato Chisato , Dagrenat Charlotte , Greciano Stephane , De Poli Fabien , Leddet Pierre , Peillex Marilou , Hess Sébastien , Carmona Adrien , Jimenez Charline , Heger Joe , Reydel Antje , Ohlmann Patrick , Jesel Laurence , Morel Olivier 
Published: November 2020

AbstractAimsRecent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS.Methods and resultsPatients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty‐five patients with TTS were split into three subgroups, according to tertiles of C‐reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure.Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025).ConclusionsResidual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high‐risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.
Aortic valve replacement: validation of the Toronto Aortic Stenosis Quality of Life Questionnaire
Authors: Frank Derk , Kennon Simon , Bonaros Nikolaos , Stastny Lukas , Romano Mauro , Lefèvre Thierry , Di Mario Carlo , Stefàno Pierluigi , Ribichini Flavio , Himbert Dominique , Urena‐Alcazar Marina , Salgado‐Fernandez Jorge , Castillo Jose Joaquin Cuenca , Garcia del Blanco Bruno , Deutsch Cornelia , Sykorova Lenka , Kurucova Jana , Thoenes Martin , Lüske Claudia M. , Bramlage Peter , Styra Rima 
Published: November 2020

AbstractAimsThere is no quality of life tool specifically developed for patients with severe aortic stenosis (AS) to assess how this chronic condition and its treatment affect patients. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) has been developed to overcome this gap. The results of the validation of the TASQ in patients undergoing treatment for severe AS are presented.Methods and resultsProspective study at 10 centres in Europe and Canada, which enrolled 274 patients with severe symptomatic AS undergoing surgical or transcatheter aortic valve replacement. Mean TASQ score at baseline was 71.2 points and increased to 88.9 three months after aortic valve implantation (P < 0.001). Increases were seen for the emotional impact (32.0 to 39.0; P < 0.001), physical limitations (14.8 to 22.0; P < 0.001), and physical symptoms (8.5 vs. 11.0; P < 0.001) domains. Internal consistency was good/excellent for overall TASQ score (α = 0.891) and for the physical limitation, emotional impact, and social limitation domains (α = 0.815–0.950). Test–retest reliability was excellent or strong for the overall TASQ (intraclass correlation coefficient of 0.883) and for the physical symptoms, physical limitation, emotional impact, and social limitation domains (intraclass correlation coefficient of 0.791–0.895). Responsiveness was medium overall (Cohen's d = 0.637) and medium/large for physical symptoms, emotional impact, and physical limitations (0.661–0.812). Sensitivity to change was significant for physical symptoms, physical limitations (both P < 0.001), emotional impact (P = 0.003), and social limitations (P = 0.038).ConclusionsThe TASQ is a new, brief, self‐administered, and clinically relevant health‐specific tool to measure changes in quality of life in patients with AS undergoing an intervention.
Implication of inhaled nitric oxide for the treatment of critically ill COVID‐19 patients with pulmonary hypertension
Authors: Feng Wen‐Xia , Yang Yang , Wen Junmin , Liu Ying‐Xia , Liu Lei , Feng Cheng 
Published: November 2020

AbstractAimsThis study aims to analyse whether inhaled nitric oxide (iNO) was beneficial in the treatment of coronavirus disease 2019 (COVID‐19) patients with pulmonary hypertension.Methods and resultsFive critically ill COVID‐19 patients with pulmonary hypertension designated Cases 1–5 were retrospectively included. Clinical data before and after iNO treatment were serially collected and compared between patients with or without iNO treatment. The five cases experienced pulmonary artery systolic pressure (PASP) elevation (≥50 mmHg) at 30, 24, 33, 23, and 24 days after illness onset (d.a.o), respectively. Cases 1–3 received iNO treatment on the 24th, 13th, and 1st day after the first elevation of PASP, with concentrations varied from 10 to 20 ppm based on the changes of PASP and blood pressure for 10, 9, and 5 days, respectively. Upon iNO treatment, PASP of Cases 1 and 2 returned to normal on the 10th day and 1st day, and maintained between 50 and 58 mmHg in Case 3. Pa02/Fi02 increased from 88 to 124, 51 to 118, and 146 to 244, respectively. SPO2 increased from 91% to 97% for Case 1 and maintained a high level above 97% for Case 2. Cardiac function remained normal in the three patients after treatment. Moreover, Cases 1 and 3 survived from severe acute respiratory syndrome coronavirus 2 infection, while Case 2 finally died on the 36th day after the first elevation of PASP due to severe complications. Both cases who did not receive iNO treatment experienced a sudden decrease of PASP and Pa02/Fi02 due to right heart failure and then died.ConclusionsInhaled nitric oxide treatment was beneficial in reducing and stabilizing the PASP and might also reduce the risk of right heart failure in COVID‐19 with pulmonary hypertension.
Binary Metal Oxide Adsorbed Graphene Modified Glassy Carbon Electrode for Detection of Riboflavin
Authors: Grace Arockiajawahar Anancia , Thillaiarasi Sukumar , Dharuman Venkataraman 
Published: November 2020

AbstractTungsten oxide (W) decorated titanium oxide (T) adsorbed onto a graphene (Gr) and modified the glassy carbon electrode for the electrochemical quantification of riboflavin (RF) in edible food and pharmaceuticals. For comparison, nanocomposites are formed using graphene oxide (GO), reduced graphene oxide (rGO) and pure graphite (G) sheets to study the electrochemical activities towards riboflavin. The ternary WTGr modified GCE shows the highest electrocatalytic activity due to synergetic interactions between the metal oxide and graphene. The electrochemical observations are supported by the SEM, HRTEM, XRD, UV‐Vis, Zeta potential (ζ) and size data. The sensor shows a wide linear range 20 nM–2.5 μM with a detection limit 25.24 nM and sensitivity (4.249×10−8 A/nM). The fabricated sensor is validated in real samples.
Advanced modification of scandia‐stabilized zirconia electrolytes for solid oxide fuel cells application—A review
Authors: Zakaria Zulfirdaus , Kamarudin Siti Kartom 
Published: November 2020

SummarySolid oxide fuel cells (SOFCs) are recognized as an energy generation device with high power density and energy conversion efficiency, low noise, low greenhouse gas emissions, positive environmental effect, and high fuel consumption versatility. Nevertheless, the high operating temperature of SOFCs has restricted the development in various applications due to challenges in material compatibility and working process. To address these issues, scandia‐stabilized zirconia (ScSZ) electrolytes are commonly utilized to explore its potentials as a solid electrolyte toward lowering the operating temperature due to high conductivity properties at low‐to‐intermediate temperature conditions. Thus, this paper provides an advanced modification of ScSZ electrolytes in SOFCs toward lowering the operating temperature. This review presents the potential properties and the progress modification of ScSZ electrolyte including challenges, and advances, summary, and future perspectives in the low‐to‐intermediate operating temperature of SOFCs. This review can serve as a first reference for identifying specific parameters and prospective studies to enhance the properties of ScSZ electrolytes for the application of SOFCs. Based on the literature review, there are no previous review works that have been published on the modification of ScSZ electrolytes.
Process optimization of spray‐dried Moldavian balm (Dracocephalum moldavica L.) extract powder
Authors: Rahmati Edris , Sharifian Faroogh , Fattahi Mohammad 
Published: November 2020

AbstractThe present study was aimed to develop the powder from Moldavian balm extract using a spray dryer to preserve the valuable phytochemicals such as hydroxycinnamic acid and flavonoids. In order to produce optimum Moldavian balm spray‐dried powder, response surface methodology was applied. The inlet air temperature (120–180°C), compressed airflow rate (5–10 L/min), and carriers’ concentration (10%–30%) were kept as independent variables, while moisture content, drying performance, porosity, total phenol content, total flavonoid content, and antioxidant activity were selected as responses. The process was optimized with inlet air temperature of 140.36°C, compressed airflow rate of 9.13 L/min and carriers’ concentration of 18%, resulting in powder with moisture content of 7.68%, drying performance of 62.52%, porosity of 76.4%, total phenol content of 6.295 mg GAE/g, total flavonoid content of 0.378 mg QUE/g, and antioxidant activity of 51.78%. The optimized process led to attain the powder having significantly better phytochemical properties compared with others.
Patch‐wise brain age longitudinal reliability
Authors: Beheshti Iman , Potvin Olivier , Duchesne Simon 
Published: November 2020

AbstractWe recently introduced a patch‐wise technique to estimate brain age from anatomical T1‐weighted magnetic resonance imaging (T1w MRI) data. Here, we sought to assess its longitudinal reliability by leveraging a unique dataset of 99 longitudinal MRI scans from a single, cognitively healthy volunteer acquired over a period of 17 years (aged 29–46 years) at multiple sites. We built a robust patch‐wise brain age estimation framework on the basis of 100 cognitively healthy individuals from the MindBoggle dataset (aged 19–61 years) using the Desikan‐Killiany‐Tourville atlas, then applied the model to the volunteer dataset. The results show a high prediction accuracy on the independent test set (R2 = .94, mean absolute error of 0.63 years) and no statistically significant difference between manufacturers, suggesting that the patch‐wise technique has high reliability and can be used for longitudinal multi‐centric studies.
Unravelling the hydrological effects on spatiotemporal variability of water chemistry in mountainous rivers from Southwest China
Authors: Zhong Jun , Chen Shuai , Wang Wanfa , Yan Zelong , Ellam Rob M. , Li Si‐Liang 
Published: November 2020

AbstractUnderstanding the effects of hydrological processes on solute dynamics is critical to interpret biogeochemical processes. Water chemistry and isotopic compositions of surface water (δ18Ow and δDw) were investigated in rivers from Southwest China to study the effects of hydrological variability on biogeochemical processes. The inverse relationship between deuterium excess (d‐excess) and δ18Ow could be ascribed to non‐equilibrium fractionation processes, and the slope of the Local River Water Line was much lower than the Local Meteoric Water Line, suggesting the post‐precipitation evaporation pattern. The evaporation fraction (1–f) was estimated by the d‐excess method, varying from 0.01 to 0.18. (1–f), was a function of water temperature and drainage mean elevation, indicating that evaporation easily occurs at high temperatures in low‐elevation regions. The hydrological processes co‐varied with solute dynamics in the river network, and fluid transit time and temperature were likely responsible for the co‐variations. Also, we found that hydrological processes played an important role in solute dynamics through shifting the geochemical processes (e.g., enrichment, water‐rock reaction, photosynthesis, and secondary mineral precipitation). This study highlights that biogeochemical processes co‐vary with hydrological processes, and we suggest that investigating hydrological processes can help to understand biogeochemical processes.
Optoacoustic monitoring of water content in tissue phantoms and human skin
Authors: Perkov Sergei A. , Gorin Dmitry A. , Esenaliev Rinat O. 
Published: November 2020

AbstractSkin water content monitoring is important for diagnostics and management of edema, dehydration, and other skin conditions as well as for cosmetic applications. Because optoacoustic (OA) technique has high (optical) contrast and (ultrasound) resolution and significant probing depth, it may be suitable for accurate, noninvasive water content monitoring in the skin. In this work we studied OA response from skin tissue phantoms and human wrist skin in the wavelength range from 1370 nm to 1650 nm using a novel, tunable OPO OA system. We identified optimal wavelengths for OA water content monitoring in different skin layers. The results of our study suggest that the OA technique may become a valuable, quantitative tool for accurate, high‐resolution water content monitoring in the skin and other tissues and may find wide applications in dermatology, cosmetology, and tissue trauma management.
A Physiological Approach to Pharmacokinetics in Chronic Kidney Disease
Authors: Malik Paul R.V. , Yeung Cindy H.T. , Ismaeil Shams , Advani Urooj , Djie Sebastian , Edginton Andrea N. 
Published: November 2020

AbstractThe conventional approach to approximating the pharmacokinetics of drugs in patients with chronic kidney disease (CKD) only accounts for changes in the estimated glomerular filtration rate. However, CKD is a systemic and multifaceted disease that alters many body systems. Therefore, the objective of this exercise was to develop and evaluate a whole‐body mechanistic approach to predicting pharmacokinetics in patients with CKD. Physiologically based pharmacokinetic models were developed in PK‐Sim v8.0 (www.open-systems-pharmacology.org) to mechanistically represent the disposition of 7 compounds in healthy human adults. The 7 compounds selected were eliminated by glomerular filtration and active tubular secretion by the organic cation transport system to varying degrees. After a literature search, the healthy adult models were adapted to patients with CKD by numerically accounting for changes in glomerular filtration rate, kidney volume, renal perfusion, hematocrit, plasma protein concentrations, and gastrointestinal transit. Literature‐informed interindividual variability was applied to the physiological parameters to facilitate a population approach. Model performance in CKD was evaluated against pharmacokinetic data from 8 clinical trials in the literature. Overall, integration of the CKD parameterization enabled exposure predictions that were within 1.5‐fold error across all compounds and patients with varying stages of renal impairment. Notable improvement was observed over the conventional approach to scaling exposure, which failed in all but 1 scenario in patients with advanced CKD. Further research is required to qualify its use for first‐in‐CKD dose selection and clinical trial planning for a wider selection of renally eliminated compounds, including those subject to anion transport.
Physiologically Based Pharmacokinetic Model‐Informed Drug Development for Polatuzumab Vedotin: Label for Drug‐Drug Interactions Without Dedicated Clinical Trials
Authors: Samineni Divya , Ding Hao , Ma Fang , Shi Rong , Lu Dan , Miles Dale , Mao Jialin , Li Chunze , Jin Jin , Wright Matthew , Girish Sandhya , Chen Yuan 
Published: November 2020

AbstractModel‐informed drug development (MIDD) has become an important approach to improving clinical trial efficiency, optimizing drug dosing, and proposing drug labeling in the absence of dedicated clinical trials. For the first time, we developed a physiologically based pharmacokinetic (PBPK) model‐based approach to assess CYP3A‐mediated drug‐drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti‐CD79b‐vc‐monomethyl auristatin E (MMAE) antibody‐drug conjugate (ADC). The model was developed and verified using data from the existing clinical DDI study for brentuximab vedotin, a similar vc‐MMAE ADC. Analogous to the brentuximab vedotin clinical study, polatuzumab vedotin at the proposed labeled dose was predicted to have a limited drug interaction potential with strong CYP3A inhibitor and inducer. Polatuzumab vedotin was also predicted to neither inhibit nor induce CYP3A. The present work demonstrated a high‐impact application using a PBPK MIDD approach to predict the CYP3A‐mediated DDI to enable drug labeling in the absence of any dedicated clinical DDI study. The key considerations for the PBPK report included in the Biologics License Application/Marketing Authorization Application submission, as well as the strategy and responses to address some of the critical and challenging questions from the health authorities following the submission are also discussed. Our experience and associated perspective using a PBPK approach to ultimately enable a drug interaction label claim for polatuzumab vedotin in lieu of a dedicated clinical DDI study, as well as the interactions with the regulatory agencies, further provides confidence in applying MIDD to accelerate the registration and approval of new drug therapies.