bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program
Authors: Tillman Emma , Nikirk Miley G. , Chen Jeanne , Skaar Todd C. , Shugg Tyler , Maddatu Judith P. , Sharfuddin Asif A. , Eadon Michael T. 
Published: April 2023

AbstractTacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence‐based guidelines for CYP3A5 normal/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive CYP3A genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for CYP3A5 and CYP3A4 was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic‐recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third‐party payers. CYP3A5 normal/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only ≈66% of African Americans in our cohort were normal/intermediate metabolizers who required higher doses. Routine CYP3A5 genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.
The environmental impact of inhaler replacement: A carbon footprint and economic calculation of the National Database of Health Insurance Claims in Japan
Authors: Nagasaki Kazuya , Kaji Yuki , Wada Yoshiki , Sasaki Takafumi 
Published: April 2023

AbstractBackgroundDrugs are a major source of greenhouse gas (GHG) emissions from healthcare systems. Pressurized metered‐dose inhalers (pMDIs) have raised concerns over their environmental impact due to GHG emissions. Evaluations and reduction strategies for GHGs have been primarily studied in Europe, but not in other regions, including Japan. Therefore, our objective was to calculate the carbon footprint of inhalers in Japan and evaluate their reduction scenarios.MethodsUsing the National Database of Health Insurance Claims, our analysis was conducted on inhaler prescriptions in Japan for the fiscal year of 2019. We calculated the number of inhalers used, GHG emissions, and total costs. Next, we simulated the environmental and economic impacts of three reduction scenarios: the first scenario replaced pMDI with dry power inhalers, followed by age‐based replacements. In the last scenario, we replaced pMDI with a propellant with a lower global warming potential.ResultsAll inhaler‐related GHG emissions were 202 ktCO2e, of which 90.9% were attributed to pMDI use. Scenario analysis demonstrated that replacing 10% pMDI with DPI would reduce emissions by 6.7%, with a relatively modest increase in cost; substituting 10% of pMDI used by adults (excluding children and older adults) with alternative inhalers would reduce emissions by 6.1%, with a 0.7% increase in cost; and, replacing 10% of pMDI propellants with lower global warming potential would reduce emissions by 9.3%.ConclusionsSelecting appropriate inhalers can mitigate GHG emissions in Japan, but its impact will be less than in other countries. Nevertheless, collaborative efforts between physicians, patients, and pharmaceutical companies are necessary to reduce GHG emissions.
Multi‐level habitat selection of boreal breeding mallards
Authors: Johnstone Ryan P. H. , Dyson Matthew E. , Slattery Stuart M. , Fedy Bradley C. 
Published: April 2023

AbstractCanada's western boreal forest is a vital breeding habitat for North American duck populations. This region has experienced considerable demand for its valuable natural resources (e.g., oil and gas, forestry) resulting in extensive industrial development (e.g., infrastructure), which is predicted to continue. The potential effects of industrial development on breeding ducks in the western boreal forest, however, remains largely unexplored. We used backpack harness global positioning system (GPS) transmitters to document habitat selection by breeding female mallards (Anas platyrhynchos) across a gradient of industrial development in the western boreal forest of Alberta, Canada. We modeled breeding home range (second order) selection and habitat selection within the home range (third order) using resource selection functions, and spatially predicted our models across the landscape to highlight important breeding habitat. Contrary to our predictions, breeding female mallards did not avoid all industrial development at the second and third orders. Females established home ranges (second order) with greater proportions of marsh, graminoid fen, and well pads, and lower proportions of forest. Within their home range (third order), females selected shrub swamp, graminoid fen, marsh, well pads, and borrow pits, and avoided open water, swamp, treed peatland, forest, forest harvest areas, and industrials (e.g., buildings). Females also selected habitat that was close to pipelines and roads. Our results suggest that the magnitude and direction of breeding season habitat selection by female mallards varies depending on the scale and landscape features, but current levels of industrial development within our study area still allowed for the establishment of breeding season home ranges. Our spatially predicted maps contribute to the increasing body of work surrounding boreal waterfowl ecology by highlighting important breeding habitat for mallards in Canada's western boreal forest.
Climate change, wildfire, and past forest management challenge conservation of Canada lynx in Washington, USA
Authors: Lyons Andrea L. , Gaines William L. , Lewis Jeffrey C. , Maletzke Benjamin T. , Werntz Dave , Thornton Daniel H. , Hessburg Paul F. , Begley James , Vanbianchi Carmen , King Travis W. , Blatz Gretchen , Fitkin Scott 
Published: April 2023

AbstractThe synergistic effects of climate change, wildfires, fire suppression, and past forest management are challenging efforts to protect and recover Canada lynx (Lynx canadensis) in the North Cascades of Washington, USA. Canada lynx is a threatened species in the United States and a focal species used to gain insights into the structure and function of boreal forest ecosystems. To understand how multiple stressors are influencing lynx populations and the boreal forest in Washington, we developed a spatially explicit carrying capacity model in HexSim using local data on lynx resource selection and life history. We used this model to estimate changes in carrying capacity and population persistence for 3 time steps: year 2000, which represented limited historical wildfire and aggressive fire suppression; year 2013, after nearly 2,000 km2 of wildfires burned about 17% of lynx habitat; and year 2020, after an additional 2,000 km2 of wildfires burned another 15% of lynx habitat in our study area. Fires altered habitat distribution and landscape capacity to support Canada lynx. There was a 66–73% reduction in lynx carrying capacity in our study area because of large, high‐severity fires that have occurred from 2000–2020, despite aggressive fire suppression. This reduction in carrying capacity was concurrent with decreases in the probability of lynx persistence from year 2000 to year 2020 simulations and was most pronounced for simulations that included no immigration and the largest home range size. The negative synergistic influences of long‐term fire suppression, timber harvest, increased drought, longer wildfire seasons, declining mountain snowpack, and increasingly frequent large fires pose considerable challenges to the conservation and recovery of Canada lynx and the boreal forest ecosystem upon which they depend. We discuss an alternative approach to vegetation and fire management to conserve and restore lynx habitat and populations in Washington.
Error in demographic ratios from aerial surveys of white‐tailed deer in semi‐arid rangelands
Authors: Foley Aaron M. , DeYoung Randy W. , Hewitt David G. 
Published: April 2023

AbstractAerial surveys can efficiently monitor populations of large animals in geographically extensive management units but are time‐ and cost‐intensive. Biologists often design population surveys to balance cost, spatial coverage, and precision in estimates of population size. Demographic ratio data from aerial surveys are an important component of population monitoring and management, yet the error of ratio data remains under‐appreciated, especially for low‐density populations. We quantified error in juvenile:female, male:female, and young:mature male ratios from 177 helicopter surveys of white‐tailed deer (Odocoileus virginianus) in 37 wildlife management units encompassing 3,269 km2 of semi‐arid grasslands and brush in South Texas, USA, during 2011–2015. We classified error (the % difference between the mean and the limits of the confidence interval) of surveys as appropriate for research‐based (≤25% error) or monitoring surveys (≤50% error). Overall, error usually met criteria for monitoring surveys but not for research‐based surveys; male:female (x̄ = 32% error) and juvenile:female (x̄ = 37%) ratios had smaller errors than young:mature male ratios (x̄ = 51%). As number of detections increased, errors declined; minimum number of detections for both components of a given ratio needed for monitoring and research‐based surveys was about 30–40 and 150–185 at the 90% confidence interval and 45–60 and 210–230 at the 95% confidence interval, respectively. Acceptable error to reliably detect changes in demographic ratios may require greater survey effort or a different survey design for low‐density populations. Furthermore, obtaining sufficient detections for acceptable error of male age structure estimates may not be feasible. Error of demographic ratios is an important consideration given their role in the design of harvest plans, evaluation of the effects of management, and tracking the effect of diseases, such as chronic wasting disease. The high effort required to obtain acceptable error with ratio data in areas with low deer densities indicates that helicopter surveys may not be an ideal platform to investigate fine‐scale variation in demographic data. Managers will have to consider trade‐offs between expenses and variance of ratio data collected from aerial surveys and whether obtaining acceptable error with ratio data is feasible given deer densities and detection probabilities are site‐specific.
Three‐dimensional simulation on spatiotemporal variation of salinity in reclaimed saline soil and yield reduction risk assessment
Authors: Song Jianghui , Shi Xiaoyan , Wang Haijiang , Zhu Yongqi , Li Weidi , Wang Jingang , Tian Tian , Zhong Mingtao , Lv Xin , Li Baoguo 
Published: April 2023

AbstractAmelioration of saline soil to grow crops could increase food production and improve food security. However, the long‐term effects of different methods for ameliorating saline soil still need to be evaluated. In this study (2014–2021), the salinity variations of saline soils under different amelioration methods (T1: salt isolation by a stone layer + cropping; T2: subsurface drainage + cropping; T3: 5‐year cropping; T4: 3‐year cropping; CK: bare land) were monitored using electromagnetic induction. Besides, the long‐term effects of different amelioration methods and yield reduction risk were assessed using the three‐dimensional sequential Gaussian simulation (3D‐SGS). The 3D‐SGS results showed that soil salinity increased during abandonment (2014–2015) and then decreased during reclamation (2016–2021). Salt accumulated in the 0–40 cm soil layer in T3, T4, and CK treatments, while it accumulated in the 40–80 cm soil layer in T1 and T2 treatments. The proportion of high‐risk areas in T1, T2, T3, and T4 treatments reduced after reclamation, but soil salinity only slightly reduced in T3 and T4 treatments, showing a high risk of yield reduction. Besides, the time‐specific regression model had the highest prediction accuracy for soil salinity. Therefore, probabilistic evaluation based on 3D‐SGS is an effective method to evaluate the effectiveness of saline soil amelioration methods, and could help decision‐makers formulate scientific saline soil amelioration plans.
Statistical Copolymers Comprising Bio‐Based Aromatic Methacrylate Segments and Their Influence on the Glass Transition Temperature
Authors: Heinz Markus , Kepkow Maximilian , Strehmel Veronika 
Published: April 2023

AbstractSynthesis of statistical copolymers is described from bio‐based 4‐(4‐methacryloyloxyphenyl)butan‐2‐one (1) with an aliphatic methacrylate, such asn‐butyl methacrylate (2),N,N‐(dimethylamino)ethyl methacrylate (3), and lauryl methacrylate (4), using mostly dimethyl sulfoxide as solvent in the free radical polymerization. Though4 is insoluble in dimethyl sulfoxide, diethyl carbonate is the preferred solvent for the copolymerization using this monomer although both yield and molecular weight are lower even for poly(4‐(4‐methacryloyloxyphenyl)butan‐2‐one) than using dimethyl sulfoxide as solvent.1H NMR spectroscopic analysis gives information about the content on the monomer segments in all copolymers. Furthermore, elementary analysis additionally supports the results obtained for the copolymers made from1 and3. As shown by the copolymerization diagrams and the copolymerization parameters, the copolymerization of1with2is a nearly ideal copolymerization using short polymerization time (20 min). Extending the polymerization time results in slight deviation from an ideal copolymerization. Furthermore, the glass transition temperature of the copolymers determined by DSC and calculated using both the Fox equation and the Gibbs‐DiMarzio equation show the strong influence of the copolymer composition. As expected, the glass transition temperature increases with increasing content on aromatic segments in the copolymer that may be interesting for application in coatings and adhesives, respectively.
A variant in CYP26B1 associated with esophageal squamous cell carcinoma risk by affecting retinoic acid metabolism
Authors: Niu Siyuan , Shi Ke , Yue Xinying , Pan Miaoxin , Song Lina , Gu Linglong , Tan Yuqian , Miao Xiaoping , Tian Jianbo , Chang Jiang 
Published: April 2023

AbstractAll‐trans retinoic acid (ATRA) is the natural and synthetic analogue of vitamin A, playing an essential tumor suppressive role in multiple cancers including the esophageal squamous cell carcinoma (ESCC). Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) exerts a critical regulator of ATRA levels through specific inactivation of ATRA to hydroxylated forms. Our previous exome‐wide analyses revealed a rare missense variant in CYP26B1 significantly associated with ESCC risk in the Chinese population. However, it is still unclear whether there are common variants in CYP26B1 affect the susceptibility of ESCC and the tumor promotion role of CYP26B1 in vivo. In this research, we conducted a two‐stage case‐control study comprised of 5057 ESCC cases and 5397 controls, followed by a series of biochemical experiments to explore the function of CYP26B1 and its common variants in the tumorigenesis of ESCC. Intriguingly, we identified a missense variant rs2241057[A>G] in the fourth exon of CYP26B1 significantly associated with the ESCC risk (combined odds ratio = 1.28; 95% confidence interval = 1.15–1.42; p = 2.96 × 10−6). Through further functional analysis, we demonstrated that ESCC cells with the overexpression of rs2241057[G] had a significant lower level of retinoic acid, compared with the overexpression of rs2241057[A] or the control vector. In addition, the CYP26B1 overexpression and knock‐out ESCC cells affected cell proliferation rate both in vitro and in vivo. These results highlighted the carcinogenicity of CYP26B1 related to the ATRA metabolism in ESCC risk.
Some fundamental issues associated with theoretical analyses of reactive infiltration instability in fluid‐saturated porous media
Authors: Zhao Chongbin , Hobbs Bruce E. , Ord Alison 
Published: April 2023

AbstractThis paper deals with three fundamental issues associated with theoretical analyses of reactive infiltration instability (RII) problems in fluid‐saturated porous media. The first fundamental issue is to determine the spatial shapes of chemical dissolution‐fronts in the limit case of the mineral dissolution ratio approaching zero in both conventional time (daily life time) and unconventional time (abstract time) domains. The chemical dissolution‐front is commonly represented by the spatial shape of the porosity profile. The second fundamental issue is to conduct theoretical analyses of the RII problems associated with the mineral dissolution ratio approaching zero through directly solving dimensional mathematical governing equations in the conventional time domain. The third fundamental issue is to carry out theoretical analyses of the RII problems associated with the mineral dissolution ratio approaching zero through solving dimensionless mathematical governing equations in the unconventional time domain. Through purely mathematical deductions, it has been proven that: (1) the spatially sharp shape of a chemical dissolution‐front, which is theoretically predicted either at a much smaller timescale than the dissolution timescale associated with the daily life time or at a much larger timescale than the dissolution timescale associated with the daily life time, can be observed in the daily life time domain; (2) the theoretical instability criterion of an RII problem can be established directly at three different length‐scales in the daily life time domain; and (3) although the spatial shape of a chemical dissolution‐front at the dissolution timescale associated with the daily life time cannot be observed in the daily life time domain, the theoretical instability criterion of an RII problem at the dissolution timescale associated with the daily life time can be established when a physically consistent mathematical transform is used in the theoretical analysis.
Discrete‐time mean field social control with a major agent
Authors: Ma Xiao , Wang Bing‐Chang , Zhang Huanshui 
Published: April 2023

AbstractThis paper considers a linear‐quadratic mean field control problem involving a major agent and minor agents. We aim to optimize a social cost as a weighted sum of the individual costs under decentralized information. Firstly, the forward‐backward stochastic difference equations (FBSDEs) are obtained for this problem by variational analysis. Then, by decoupling the FBSDEs, we design the decentralized control laws, which are further shown to be asymptotically optimal.
MALDImID: Spatialomics R package and Shiny app for more specific identification of MALDI imaging proteolytic peaks using LC‐MS/MS‐based proteomic biomarker discovery data
Authors: Oliveira Cristiano , Longuespée Rémi 
Published: April 2023

AbstractMatrix‐assisted laser desorption/ionization (MALDI) imaging of proteolytic peptides from formalin‐fixed paraffin embedded (FFPE) tissue sections could be integrated in the portfolio of molecular pathologists for protein localization and tissue classification. However, protein identification can be very tedious using MALDI‐time‐of‐flight (TOF) and post‐source decay (PSD)‐based fragmentation. Hereby, we implemented an R package and Shiny app to exploit liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based proteomic biomarker discovery data for more specific identification of peaks observed in bottom‐up MALDI imaging data. The package is made available under the GPL 3 license. The Shiny app can directly be used at the following address: https://biosciences.shinyapps.io/Maldimid.
Charge site manipulation to enhance top‐down fragmentation efficiency
Authors: Habeck Tanja , Maciel Edvaldo Vasconcelos Soares , Kretschmer Kevin , Lermyte Frederik 
Published: April 2023

AbstractIn recent years, top‐down mass spectrometry has become a widely used approach to study proteoforms; however, improving sequence coverage remains an important goal. Here, two different proteins, α‐synuclein and bovine carbonic anhydrase, were subjected to top‐down collision‐induced dissociation (CID) after electrospray ionisation. Two high‐boiling solvents, DMSO and propylene carbonate, were added to the protein solution in low concentration (2%) and the effects on the top‐down fragmentation patterns of the proteins were systematically investigated. Each sample was measured in triplicate, which revealed highly reproducible differences in the top‐down CID fragmentation patterns in the presence of a solution additive, even if the same precursor charge state was isolated in the quadrupole of the instrument. Further investigation supports the solution condition‐dependent selective formation of different protonation site isomers as the underlying cause of these differences. Higher sequence coverage was often observed in the presence of additives, and the benefits of this approach became even more evident when datasets from different solution conditions were combined, as increases up to 35% in cleavage coverage were obtained. Overall, this approach therefore represents a promising opportunity to increase top‐down fragmentation efficiency.
Preference matters: New aspects on how foreign bodies should and could be removed from a child's airway
Authors: Freitag Nadine , Möllenberg Leon , Wiemers Anna , Bosse Hans Martin , Kristin Julia , Vicencio Alfin , Schramm Dirk 
Published: April 2023

AbstractBackgroundForeign body aspiration in children is a potentially life‐threatening event that can be diagnosed and treated by airway endoscopy. We aimed to analyze the influence of the examiner's experience and preference on the choice of the technique and the resulting complication rate.MethodsIn this international study, experts in the field documented their preferred and applied technique as well as the outcome of each case of foreign body removal. Personal data of the bronchoscopists and their medical center were collected via an online questionnaire separately from the case specifics.ResultsA total of 399 foreign body removals were performed by 64 examiners. A total of 279 removals were performed using rigid endoscopy, and 120 procedures were performed by flexible. When a difficulty was expected, flexible endoscopy was used significantly more often (χ2(1) = 11.06, p < 0.001). Complications occurred significantly less often when the bronchoscopist used their preferred technique (χ2(1) = 6.41, p = 0.011), had more than 5 years of experience (χ2(1) = 5.13, p = 0.023) or performed more than 100 removals (χ2(2) = 11.51, p = 0.003). In medical centers, complication rates significantly decreased if more than 200 bronchoscopies were performed in children, compared to the centers that perform 50–200 bronchoscopies per year (χ2(1) = 24.56, p < 0.001).ConclusionPreference and experience of a bronchoscopist and his/her medical center with flexible or rigid foreign body removal distinctively affect the outcome of the procedure and cannot be neglected in the discourse on the appropriate technique. This link also emphasizes the importance of a structured training program.