bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of drug–drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling
Authors: Chang Ming , Bathena Sai , Christopher Lisa J. , Shen Hong , Roy Amit 
Published: February 2022

Abstract
Purpose
Recent in vitro studies demonstrated that dasatinib inhibits organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), and organic anion transporting polypeptide 1B1/1B3 (OATP1B1/1B3). We developed a physiologically based pharmacokinetic (PBPK) model to assess drug–drug interaction (DDI) potential between dasatinib and known substrates for these transporters in a virtual population.

Methods
The dasatinib PBPK model was constructed using Simcyp® Simulator by combining its physicochemical properties, in vitro data, in silico predictions, and pharmacokinetic (PK) results from clinical studies. Model validation against three independent clinical trials not used for model development included dasatinib DDI studies with ketoconazole, rifampin, and simvastatin. The validated model was used to simulate DDIs of dasatinib and known substrates for OCT2 and MATEs (metformin) and OATP1B1/1B3 (pravastatin and rosuvastatin).

Results
Simulations of metformin PK in the presence and absence of dasatinib, using inhibitor constant (Ki) values measured in vitro, produced estimated geometric mean ratios (GMRs) of the maximum observed concentration (Cmax) and area under the concentration–time curve (AUC) of 1.05 and 1.06, respectively. Sensitivity analysis showed metformin exposure increased < 30% in both AUC and Cmax when dasatinib Ki was reduced by tenfold for OCT2 and MATEs simultaneously, and < 40% with a 20-fold Ki reduction. The estimated GMRs of Cmax and AUC for pravastatin and rosuvastatin with co-administration of dasatinib were unity (1.00).

Conclusions
This PBPK model accurately described the observed PK profiles of dasatinib. The validated PBPK model predicts low risk of clinically significant DDIs between dasatinib and metformin, pravastatin, or rosuvastatin.
Target and non-target vessel related events at 10 years post percutaneous coronary intervention
Authors: Coughlan J. J. , Aytekin Alp , Xhepa Erion , Cassese Salvatore , Joner Michael , Koch Tobias , Wiebe Jens , Lenz Tobias , Rheude Tobias , Pellegrini Constanza , Gewalt Senta , Ibrahim Tareq , Laugwitz Karl-Ludwig , Schunkert Heribert , Kastrati Adnan , Kufner Sebastian 
Published: February 2022

Abstract
Aims
To define the incidence of events related to the stented vessel (target vessel related events: TVRE) and events related to non-stented vessels (non-target vessel related events: NTVRE) through to 10-year follow-up in patients post-PCI with newer generation drug eluting stents (DES).

Methods and results
The current study is a post-hoc analysis of patient level data from two randomised controlled trials in Germany. Patients older than 18 years with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% de novo stenosis located in the native coronary vessels were considered eligible. The endpoints of interest were TVRE (a composite of first target vessel myocardial infarction or target vessel revascularization) and NTVRE (a composite of first non-target vessel MI or non-target vessel revascularization) through to 10 years post PCI.
We included 4953 patients in this analysis. Through to 10-years post-PCI, TVRE occurred in 1238 of 4953 patients (cumulative incidence: 25.8%) and NTVRE occurred in 1442 of 4953 patients (cumulative incidence: 30.3%). The majority of TVRE and NTVRE were revascularization events. From 0 to 1 years, the cumulative incidence of TVRE was 15.9% and of NTVRE was 12.3%. From 1 to 10 years, the cumulative incidences of TVRE and NTVRE were 11.2% and 22.4%, respectively.

Conclusion
At 10-year post-PCI with new generation drug eluting stents, events related to remote vessel disease progression account for a higher proportion of events than events related to the stented vessel.

Trial registration
ISAR TEST 4 ClinicalTrials.gov Identifier: NCT00598676. ISAR TEST 5 ClinicalTrials.gov Identifier: NCT00598533.

Graphical abstract
Bayesian statistics in anesthesia practice: a tutorial for anesthesiologists
Authors: Introna Michele , van den Berg Johannes P. , Eleveld Douglas J. , Struys Michel M. R. F. 
Published: February 2022

AbstractThis narrative review intends to provide the anesthesiologist with the basic knowledge of the Bayesian concepts and should be considered as a tutorial for anesthesiologists in the concept of Bayesian statistics. The Bayesian approach represents the mathematical formulation of the idea that we can update our initial belief about data with the evidence obtained from any kind of acquired data. It provides a theoretical framework and a statistical method to use pre-existing information within the context of new evidence. Several authors have described the Bayesian approach as capable of dealing with uncertainty in medical decision-making. This review describes the Bayes theorem and how it is used in clinical studies in anesthesia and critical care. It starts with a general introduction to the theorem and its related concepts of prior and posterior probabilities. Second, there is an explanation of the basic concepts of the Bayesian statistical inference. Last, a summary of the applicability of some of the Bayesian statistics in current literature is provided, such as Bayesian analysis of clinical trials and PKPD modeling.
The concept of the mobilized domain: how it can explain and predict the forces exerted by a cohesive granular avalanche on an obstacle
Authors: Kyburz M. L. , Sovilla B. , Gaume J. , Ancey C. 
Published: February 2022

Abstract
The calculation of the impact pressure on obstacles in granular flows is a fundamental issue of practical relevance, e.g. for snow avalanches impacting obstacles. Previous research shows that the load on the obstacle builds up, due to the formation of force chains originating from the obstacle and extending into the granular material. This leads to the formation of a mobilized domain, wherein the flow is influenced by the presence of the obstacle. To identify the link between the physical mobilized domain properties and the pressure exerted on obstacles, we simulate subcritical cohesionless and cohesive avalanches of soft particles past obstacles with circular, rectangular or triangular cross-section using the Discrete Element Method. Our results show that the impact pressure decreases non-linearly with increasing obstacle width, regardless of the obstacle’s cross-section. While the mobilized domain size is proportional to the obstacle width, the pressure decrease with increasing width originates from the jammed material inside the mobilized domain. We provide evidence that the compression inside the mobilized domain governs the pressure build-up for cohesionless subcritical granular flows. In the cohesive case, the stress transmission in the compressed mobilized domain is further enhanced, causing a pressure increase compared with the cohesionless case. Considering a kinetic and a gravitational contribution, we are able to calculate the impact pressure based on the properties of the mobilized domain. The equations used for the pressure calculation in this article may be useful in future predictive pressure calculations based on mobilized domain properties.

Graphic Abstract
Symptoms related to gastrointestinal tract involvement and low muscularity in systemic sclerosis
Authors: Rosato Edoardo , Gigante Antonietta , Pellicano Chiara , Villa Annalisa , Iannazzo Francesco , Alunni Fegatelli Danilo , Muscaritoli Maurizio 
Published: February 2022

Abstract
Introduction/objectives
Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients.

Methods
Sixty-nine consecutive patients (60 females, median age 53 (IQR 43–63), body mass index (BMI) 23.2 (IQR 20.9–24.6) kg/m2) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales.

Results
Mean FFMI was 16.2 kg/m2 (IQR 15.2–17.6). The median UCLA total score was 0.53 (IQR 0.19–0.89). FFMI showed a significant negative correlation with UCLA total score (r = −0.29, p = 0.016) and UCLA distention/bloating (r = −0.35, p < 0.01). In 16 patients (23.1%), FFMI was reduced and UCLA distention/bloating was significantly higher (p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75–2.12) vs 0.75 (IQR 0.25–1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient − 0.315 (95% CI of beta coefficient: −0.591; −0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient − 0.033 (95% CI of beta coefficient: −0.059; −0.007), p = 0.015].

Conclusions
In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating.

Key Points• FFMI is associated with symptoms related to GIT involvement.• Low FFMI is associated with symptoms related to UCLA distention/bloating.• Malnutrition is not associated with symptoms related to GIT involvement.
Cell signalling compound improves pasture and livestock productivity and the environment
Authors: Amaranathan Usha , Balasingham Nathan 
Published: February 2022

AbstractA biogenic agricultural compound enables pasture to synthesise more soluble sugars and delivers benefits attributable to bioactive molecules: phenylpropanoids. Phenylpropanoids are plant secondary compounds that help plants overcome biotic and abiotic stress to increase pasture quality and yield. When consumed by ruminants, phenylpropanoids improve the conversion efficiency of pasture protein to milk and meat. The effect of this compound, trademarked Biozest™, on pasture and ruminant efficiency was evaluated via split block trials followed by full scale, full life cycle, on-farm trials. Aspects measured include pasture resilience, quality and productivity, livestock productivity and urea excretion. Biozest™ improved pasture resilience, quality, and yield by over 75%. Soluble sugar content of the pasture increased (18%). When livestock grazed Biozest™ treated pasture, urea excretion was reduced (20–48%), and milk and meat production increased (30%). The pasture, livestock productivity and urea benefits of Biozest™ have been established. Trial results support the following inferences. First, the fermentation of the increased soluble carbohydrates in Biozest treated pasture would result in increased propionates and less acetoclastic methanogenesis. Second, the reduction in urea excretion and increase in livestock productivity would result from a reduction in the proportion of dietary protein digested to ammonia and reduced deamination of some of the ammonia to urea. Further, due to the reduced deamination, fewer carbonyls and hydride moieties would be available for methylotrophic and hydrogenotrophic methanogenesis. Future work may include quantification or modelling of increased carbon dioxide sequestration and quantification of the reduction in nitrous oxide and methane emissions.
Non-linear Finite-Time Tracking Control of Uncertain Robotic Manipulators Using Time-Varying Disturbance Observer-Based Sliding Mode Method
Authors: Razmjooei Hamid , Shafiei Mohammad Hossein , Palli Gianluca , Arefi Mohammad Mehdi 
Published: February 2022

AbstractIn this paper, a time-varying chattering-free disturbance observer-based position tracking control law of serial robotic manipulators is presented to track a reference signal in a finite time. The key idea is to employ a positive-increasing function associated with the control/observer objectives to improve the control performance. First, the model of an uncertain robotic manipulator is presented as the case study of the proposed strategy. Then, the time-varying form of the robotic manipulator model is obtained to provide finite-time boundedness using the first-order sliding mode method. Moreover, without any knowledge about the upper bounds of the uncertainties, a reduced-order observer is presented to estimate the uncertainties in a finite time. Subsequently, a disturbance observer-based finite-time position tracking control law is designed. The time-varying gains are provided to converge the position tracking error to a neighborhood of zero in a finite time. Finally, comparative simulations are presented to show the effectiveness of the proposed scheme compared to other existing strategies.
Variation in foraging patterns as reflected by floral resources used by male vs female bees of selected species at Badlands National Park, SD, USA
Authors: Larson Diane L. , Portman Zachary M. , Larson Jennifer L. , Buhl Deborah A. 
Published: February 2022

AbstractFemale and male bees forage for different reasons: females provision nests with pollen appropriate for larval development and consume nectar for energy while males need only fuel their own energetic requirements. The expectation, therefore, is that females should visit fewer floral resource species than males, due to females’ focus on host plant species and their tie to the nest location. We used pollen collected from bees’ bodies and the flowers they were collected on to infer floral resource use in 2010–2012 at Badlands National Park, SD, USA. We collected bees on 24 1-ha plots centered on particular plant species. We compared number of floral species and families (1) associated with individual female and male bees (via generalized linear mixed models) and (2) accumulated by each sex (using rarefaction); and (3) effect of variation between sexes in plant-bee interactions via modularity analyses. Analyses were restricted to bee species with ≥ 5 individuals per sex. Contrary to expectation, female and male bees differed infrequently in the number of floral resources they had visited, both on single foraging bouts and collectively when accumulated across all males and females of a species. When males and females did differ, males visited fewer floral species than females. Generalist and specialist bee species did not differ markedly in floral resource use by females and males. When separated by sex, seven of eleven species occupied different modules than they did when analyzed as a species; most of the bee species were connectors, thus important for stability of the network during perturbations.
Effect of Ultrasound on the Activity of Mushroom (Agaricus bisporous) Polyphenol Oxidase and Observation of Structural Changes Using Time-resolved Fluorescence
Authors: Tsikrika Konstantina , Lemos M. Adília , Chu Boon-Seang , Bremner David H. , Hungerford Graham 
Published: February 2022

AbstractPolyphenol oxidase (PPO) is an enzyme associated with the browning process that can occur from mechanical injury and postharvest storage. Thus, its inactivation to inhibit this process is of great interest to the food industry. Recently a nonthermal technology, high frequency ultrasound (100–1 MHz), has found usage in this aspect. In this work, the application of high-frequency (378 kHz, 583 kHz, 1144 kHz, and 1175 kHz) and low frequency (20 kHz) treatment on a PPO extract (from mushrooms) by monitoring the residual enzymatic activity is described. A control thermal treatment at 40 °C was also performed for comparison purposes. High-frequency inactivation data fitted well using the Weibull model, whereas those obtained upon low frequency followed first-order kinetics. The inactivation rate constant obtained ranged from 0.0054 (20 kHz) to 0.028 min−1 (at 583 kHz). To elucidate changes in the enzyme structure time-resolved spectroscopy of a commercial PPO enzyme model was employed. Results indicated that ultrasound-induced structural changes in PPO, in keeping with the activity behaviour upon sonication.
Research progress on drugs targeting the TGF-β signaling pathway in fibrotic diseases
Authors: Shi Ning , Wang Zhihong , Zhu Hecheng , Liu Weidong , Zhao Ming , Jiang Xingjun , Zhao Jin , Ren Caiping , Zhang Yan , Luo Longlong 
Published: February 2022

AbstractTissue fibrosis is a key factor leading to disability and death worldwide; however, thus far, there are no approved treatments for fibrosis. Transforming growth factor (TGF)-β is a major pro-fibrotic cytokine, which is expected to become a target in the treatment of fibrosis; however, since TGF-β has a wide range of biological functions involving a variety of biological processes in the body, a slight change in TGF-β may have a systematic effect. Indiscriminate inhibition of TGF-β can lead to adverse reactions, which can affect the efficacy of treatment. Therefore, it has become very important to explore how both the TGF-β signaling pathway is inhibited and the safe and efficient TGF-β small molecule inhibitors or neutralizing antibodies are designed in the treatment of fibrotic diseases. In this review, we mainly discuss the key role of the TGF-β signaling pathway in fibrotic diseases, as well as the development of fibrotic drugs in recent years, and explore potential targets in the treatment of fibrotic diseases in order to guide subsequent drug development.
Using Intervention Mapping to Develop ISAC, a Comprehensive Intervention for Early Detection and Prevention of Oral Cancer in Saudi Arabia
Authors: Jafer Mohammed , Moafa Ibtisam , Crutzen Rik , van den Borne Bart 
Published: February 2022

Abstract
Oral cancer forms a major public health issue. In Saudi Arabia, Jazan region has the highest rate of oral cancer; > 35% of total cases. Furthermore, dentists’ engagement in oral cancer screening and patient education in Jazan region is limited. This paper aimed to describe the process used to develop a comprehensive oral cancer (OC) practice intervention to be implemented in dental clinics. The intervention was informed by the six steps of intervention mapping (IM). Steps 1–3 included mixed methods approach of reviewing relevant existing literature, focus group discussions, observations, one-on-one interviews, and questionnaires utilizing the community participatory approach. Step 4 used information form steps 1–3 to develop the intervention components and its associated tools to facilitate its delivery. Steps 5 and 6 specified the prospective plans for implementation and evaluation. ISAC is the developed intervention that comprises the following: Informing dental patients about performing routine OC screenings, Screenings for OC, Advising patients, and Connecting patients to the required services. ISAC practical applications were clustered into two components: (a) didactical session covering aspects related to OC practices and introducing ISAC and (b) practical session that included a step-by-step modeling of the intervention. Using IM facilitated the systematic planning of the ISAC intervention that covers the main issues revealed by the need’s assessments. Working towards developing the ISAC required extensive work in assessing dental public health issues in a specific context with limited data — and this constituted a great challenge. The development of the ISAC was a lesson that casts light on the advantages of engaging multidisciplinary expertise to tackle serious public health issue like OC.
GIS-based comparative assessment of groundwater potential zone using MIF and AHP techniques in Cooch Behar district, West Bengal
Authors: Senapati Ujjal , Das Tapan Kumar 
Published: February 2022

AbstractGlobal warming, change in climate and rapid growth of population have put a huge strain on the world's groundwater resources. The use of excess groundwater has created a drop in the water table. Increased use of groundwater for agriculture in agro-based areas increases the demand for groundwater. The current study has been conducted in Cooch Behar, an agro-based remote district of North Bengal in the Indian state of West Bengal, where the use of high groundwater in agriculture has reduced groundwater levels. Comparative assessment of Multi-Influencing Factor (MIF) and Analytical Hierarchy Process (AHP) techniques has been used to create a perspective mapping of groundwater potential zone for the research region. Land use and land cover (LULC), rainfall, soil texture, geomorphology, lithology, drainage density, Normalized Differential Vegetation Index (NDVI), and Topographic Wetness Index (TWI) have been used to create the map. The MIF and AHP techniques have been used for Groundwater Potential Zones (GPZ) mapping. Output GPZ has been classified into 5 classes, i.e., very poor, poor, moderate, good, and excellent. MIF technique shows that the groundwater potential classes are covering 9% (285 km2), 21% (67 km2), 30% (944 km2), 27% (837 km2) and 13% (410 km2) of the study area, respectively, whereas the output GPZ from AHP technique shows that the groundwater potential classes are covering 8% (271 km2), 15% (508 km2), 24% (813 km2), 33% (1118 km2) and 20% (677 km2), respectively. Finally, the maps have been verified using groundwater fluctuation data through Receivers Operating Characteristic curve (ROC). The MIF technique's Area Under Curve (AUC) score is 76.5%, while the AHP technique reveals 88.9% accuracy. Both techniques for assessing and monitoring GPZ have been accurate and reasonable. Thus, this type of research is reliable for a more appropriate framework for swiftly analyzing groundwater recharge and directing the location of artificial recharge structures and other groundwater management operations of agricultural-based areas.
Geochemical characterization, deciphering groundwater quality using pollution index of groundwater (PIG), water quality index (WQI) and geographical information system (GIS) in hard rock aquifer, South India
Authors: Sunitha V. , Reddy B. Muralidhara 
Published: February 2022

AbstractFifty groundwater samples were obtained pre and post-monsoon seasons in parts of hard rock terrain in Andhra Pradesh, South India, in order to assess the drinking water quality. PIG values of groundwater samples ranged from 0.95–1.53 and 0.83–1.28 during pre and post-monsoon seasons. PIG values are slightly higher in the pre-monsoon season when compared to the post-monsoon season. In the pre monsoon season, 96% of the groundwater samples showed insignificant pollution class (< 1), 4% of the groundwater samples are low pollution (1–1.5). 82% of the groundwater samples showed insignificant pollution status (< 1), 18% of the groundwater samples fall under the low pollution (1–1.5), is noticed in post-monsoon season, respectively. WQI values of groundwater samples ranged from 108.5–204 mg/L and 112.6–170 mg/L during pre and post-monsoon seasons; its shows that 100% are very poor for drinking purpose. Piper diagram reveals that groundwater is majorly mixed Ca2+-Mg2+-Cl−, Ca2+-Mg2+-Cl−-SO42−, Na+-K+-Cl−- SO42− type in this region. The Gibbs plot indicates that groundwater samples fall within the field of rock dominance. Through applying GIS techniques, the spatial distribution of groundwater quality analysis reveals that most of the groundwater samples do not comply drinking water quality standards and water needs to be prior treatment before consumption.