bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics of Ipatasertib and Its Metabolite in Cancer Patients
Authors: Yoshida Kenta , Wilkins Justin , Winkler Julia , Wade Janet R. , Kotani Naoki , Wang Nina , Sane Rucha , Chanu Pascal 
Published: July 2021

AbstractIpatasertib is a selective AKT kinase inhibitor currently in development for the treatment of several solid tumors, including breast and prostate cancers. This study was undertaken to characterize pharmacokinetic profiles of ipatasertib and its metabolite M1 (G‐037720) and to understand the sources of variability. Population pharmacokinetic models of ipatasertib and M1 were developed separately using data from 342 individuals with cancer from 5 phase 1 and 2 studies. The final population pharmacokinetic models for ipatasertib and M1 were 3‐compartmental, with first‐order elimination and sequential zero‐ and first‐order absorption. Ipatasertib bioavailability and M1 formation increased after multiple dosing, resulting in an increase in exposure beyond that expected from accumulation alone. Covariate effects of ipatasertib include decreased oral clearance with increasing age and with coadministration of abiraterone, as well as decreased bioavailability with increasing weight. For ages 37 and 80 years, steady‐state area under the curve (AUCss) was predicted to be 81% and 109%, respectively, of the typical population value (64 years). For body weight of 49 and 111 kg, AUCss was predicted to be 132% and 78%, respectively, of the typical population value (75 kg). The small magnitude of change in ipatasertib exposure is not likely to be clinically relevant. For M1, the peripheral distribution volume and intercompartmental clearance increased with increasing weight. Coadministration of abiraterone was estimated to increase M1 exposure by 61% at steady state. Mild and moderate renal impairment, mild hepatic impairment, and race were not identified as significant covariates in the final models for ipatasertib and M1.
AAA stewardship: managing high‐risk medications with dedicated antimicrobial, anticoagulation and analgesic stewardship programs
Authors: Bui Thuy , Bortz Hadley , Cairns Kelly A. , Graudins Linda V. , Corallo Carmela E. , Konstantatos Alex , Tran Huyen , Cheng Allen , Dooley Michael J. 
Published: July 2021

AbstractThe first and most widely publicised pharmaceutical stewardship program has been for antimicrobials. Lack of care with antimicrobial management is a recognised risk to both patient and community safety. The core components of antimicrobial stewardship (AMS) can also be applied to other high‐risk medications, such as anticoagulants and analgesics. The authors discuss the implementation of anticoagulation and analgesic stewardship programs, based on the local AMS program principles, together forming the Antimicrobial, Anticoagulation, Analgesic (AAA) program. Amalgamated stewardship programs that focus on improving patient safety and optimising clinical outcomes beyond antimicrobials should be encouraged and adopted.
Origin of the blue‐shifted hydrogen bond in the vibrational Raman spectra of pyridine–water complexes: A density functional theory study
Authors: Sharma Vinay , Schlücker Sebastian , Srivastava Sunil K. 
Published: July 2021

AbstractDespite extensive scientific efforts to understand the exact nature of hydrogen bonding in Pyridine (Py) aqueous solutions, the exact mechanism causing the blue‐shift in Py ring breathing mode has remained unclear so far. The present study is an attempt to investigate the possible causes of the experimentally observed blue‐shifts using density functional theory (DFT) by computing the complexation‐induced electronic charge redistribution due to hydrogen bonding in distinct Py–water complexes. Electron density difference map (EDDM) calculations, natural population analysis (NPA), and natural bond orbital (NBO) analysis were used to explore the blue‐shift in Py ring breathing mode upon complexation with water. The combined NPA and NBO analysis yielded that interaction between the nitrogen lone pair in Py and hydrogen atom of W causes a net charge transfer from Py to W, which—through hyperconjugation—depopulates the σ* (C–C) orbitals. This finally leads to the strengthening of the local C–C force constants. The relative contributions of normal coordinates were obtained by potential energy distribution (PED) calculations. Our computation reveals that increasing contributions of C–C stretching motions to the Py ring breathing mode (ν1) are de facto causing a blue‐shift in the ν1 vibration upon water addition. Overall, this analysis suggests that complementary information from both (a) electronic charge redistribution and (b) potential energy distribution of normal coordinates is required to explain the blue‐shift in ν1 (Py) mode in aqueous solutions.
Accuracy of the Standardized Early Fetal Heart Assessment in Excluding Major Congenital Heart Defects in High‐Risk Population: A Single‐Center Experience
Authors: Turan Sifa , Asoglu Mehmet Resit , Ozdemir Halis , Seger Lindsey , Turan Ozhan Mehmet 
Published: July 2021

ObjectiveTo evaluate the ability of standardized early fetal heart assessment (EFHA) that includes the 4‐chamber view, outflow tract relationship (OTR), and transverse arches views (TAV) of the great arteries in excluding major congenital heart defects (CHDs) in high‐risk populations.MethodsThis retrospective study included high‐risk pregnancies for CHDs undergoing EFHA at 11–14 weeks of gestation. Risk factors for CHDs were diabetes mellitus, a family history of CHDs, a history of a CHD use of teratogenic medications, seizure disorder, assisted reproductive treatment‐conceived pregnancy, presence of at least one of the ultrasound markers: enlarged nuchal translucency (>95th percentile), tricuspid regurgitation, and reversed a‐wave in the ductus venosus, presence of an extracardiac or a suspected cardiac anomaly, a high‐risk first trimester combined screen result, and multiple pregnancies. EFHA consisted of visualization of 4ChV, OTR, and TAV, with and without power Doppler ultrasound. The primary outcome was the negative predictive value of EFHA in excluding major CHDs.ResultsEFHA was performed on 1055 fetuses. Of these, 1024 were used for the final analysis. Of these, 94.9% (n = 923) were singleton. The most common indication for EFHA was maternal DM (n = 231, 22.6%). The sensitivity, specificity, false positive, false negative, and accuracy of EFHA were 93.2%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001), respectively, in entire included cases. The performance of EFHA was 88%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001) respectively when the terminated cases were excluded.ConclusionEarly fetal heart assessment is feasible for screening for major CHDs in high‐risk populations. This approach may be expanded to the general obstetric population.
An Ultrasound Screening Exam During Medicare Wellness Visits May Be Beneficial
Authors: Rosborough Terry K. , Becker Joshua S. , Desautels Christine N. , Fennell Naomi N. , Lange Anna K. S. , Porter Jean L. , Post Bryan D. , Shepherd Michele F. , St. Hill Catherine A. , Tierney David M. 
Published: July 2021

ObjectivesThe physical exam component of a periodic health visit in the elderly has not been considered useful. Standard Medicare Wellness visits require no physical exam beyond blood pressure and most physicians perform limited exams during these visits. The objective of this study was to test the feasibility, potential benefit, and costs of performing a screening ultrasound (US) exam during Medicare Wellness visits.MethodsA physician examiner at an academic internal medicine primary care clinic performed a screening US exam targeting important abnormalities of patients 65–85 years old during a Medicare Wellness visit. The primary care physician (PCP) recorded the follow‐up items for each abnormality identified by the US examiner and assessed the benefit of each abnormality for the participant. Abnormality benefit, net exam benefit per participant, follow‐up items and costs, participant survey results, and exam duration were assessed.ResultsParticipants numbered 108. Total abnormalities numbered 283 and new diagnoses were 172. Positive benefit scores were assigned to 38.8%, neutral (zero) scores to 59.4%, and negative benefit scores to 1.8% of abnormalities. Net benefit scores per participant were positive in 63.9%, 0 in 34.3%, and negative in 1.8%. Follow‐up items were infrequent resulting in 76% of participants without follow‐up cost. Participant survey showed excellent acceptance of the exam.ConclusionsThe US screening exam identified frequent abnormalities in Medicare Wellness patients. The assessed benefits were rarely negative and often mild to moderately positive, with important new chronic conditions identified. Follow‐up costs were low when the PCPs were also US experts.
Mothers' Movements: Shifts in Calving Area Selection by Partially Migratory Elk
Authors: Berg Jodi E. , Reimer Jody , Smolko Peter , Bohm Holger , Hebblewhite Mark , Merrill Evelyn H. 
Published: July 2021

ABSTRACTLoss of migratory behavior or shifts in migratory ranges are growing concerns to wildlife managers. How ungulates prioritize safety from predators at the expense of high‐quality foraging opportunities during calving may be key to understanding these shifts and long‐term reproductive success. We compared trade‐offs in selection for forage and predation risk by elk (Cervus canadensis) following 3 migratory tactics (western and eastern migration and resident) during 2 time periods in a declining (by almost 70% from 2002–2016), partially migratory elk population adjacent to Banff National Park in Alberta, Canada. We hypothesized that regardless of migratory tactic, maternal elk would show stronger trade‐offs between high‐quality foraging associated with higher predation risk and forage resources of lower‐quality yet lower risk on calving ranges than on ranges used during summer because of vulnerability of their offspring. Additionally, we hypothesized these trade‐offs would occur at high (2002–2006) and low (2013–2016) elk population sizes. We used a machine‐learning algorithm to predict dates of parturition based on global positioning system (GPS) movements of elk equipped with vaginal implants (n = 60) and predictions were within 1.43 ± 0.85 (SE) days of the known date. We applied the model to an additional 58 GPS‐collared elk without vaginal implants. Based on changes in localized movements, we defined calving areas as the 26 days post‐parturition and compared habitat characteristics of calving areas to 10 similar‐sized areas centered on random locations during summer for the same individual in a latent selection framework. Across the 2 time periods, parturition occurred from 8 May–11 July with median parturition dates differing among migratory tactics and residents shifting towards an earlier parturition date in the later period. All elk, regardless of migratory tactic and time period, selected calving areas with greater forage resources than were available on areas used during summer, with no evidence for greater selection of areas that reduced predation risk at the expense of higher‐quality foraging. Calving season selection for areas with abundant forage exposed western migrants to high risk of bear (Ursusspp.) predation, residents to high risk of wolf (Canis lupus) predation, and eastern migrants to low risk of bear and wolf predation. Patterns in exposure to predation risk during calving between migratory tactics were consistent with the recent decline in western migrants and increase in eastern migrants, implying that conditions on calving areas contributed to observed changes in the number of elk following these tactics. © 2021 The Wildlife Society.
Silicon accumulation by Phragmites australis positively responds to rise in groundwater depth in the desert oasis areas of the HeXi Corridor, China
Authors: Kang Jianjun , Zhao Wen Zhi , Zhang Cai Xia , Wang Zhiwei , Li Hong 
Published: July 2021

AbstractOur study investigated the characteristics of Phragmites australis (Gramineae) silicon (Si) accumulation, and the response relationship between P. australis Si accumulation and groundwater depth changes. Plants were dug out and taken back to the laboratory for Si accumulation analysis, and a supplementary survey of P. australis Si accumulation was conducted among different groundwater depths. Result showed that Si absorbed and accumulated by P. australis mainly came from the soil and the Si accumulation differed significantly in tissues and growth stages, and the total Si accumulations (withering stage) of P. australis in sand dune (SD), desert steppe (DT), interdune lowland (IL), saline meadow (SM), and wetland (W) habitats were 7.09%, 6.77%, 5.72%, 7.73%, and 8.12%, respectively. More importantly, P. australis Si accumulation was almost equal to the total accumulation of nitrogen, phosphorus, and potassium, and even higher than of the total accumulation of calcium, magnesium, and sulfur. P. australis Si accumulation (withering stage) reduced first from SD to DT habitat, and then increased remarkably from DT to W habitat with a significant increase of −23.95% and 41.96%, respectively. P. australis Si accumulation positively responds to the groundwater depths, and the relationship was an increasing linear function of one variable. Our findings suggested that accumulating Si might be one of the effective strategies for P. australis to adapt to adverse habitats, and the Si‐rich characteristic of P. australis was likely to lay a solid theoretical foundation for exploring effective measures to restore and reconstruct the degraded ecosystems in desert oasis areas.
Effects of percutaneous injection laryngoplasty on voice and swallowing problems in cancer‐related unilateral vocal cord paralysis
Authors: Kang Min‐Gu , Seo Han Gil , Chung Eun‐Jae , Lee Hyun Haeng , Yun Seo Jung , Keam Bhumsuk , Kim Tae Min , Kwon Seong Keun , Oh Byung‐Mo 
Published: July 2021

AbstractBackgroundUnilateral vocal cord paralysis may result from nerve compression by tumors or direct nerve injuries during tumor resections, which can cause dysphonia or dysphagia, and reduced quality of life.ObjectivesThis prospective, single‐group study aimed to investigate the effect of percutaneous injection laryngoplasty on voice and swallowing function in patients with cancer‐related unilateral vocal cord paralysis.MethodsPatients underwent percutaneous injection laryngoplasty with hyaluronic acid under local anesthesia. Stroboscopy and videofluoroscopic swallowing study were conducted to evaluate the voice‐ and swallowing‐related outcome measures, respectively. The participants were evaluated before injection laryngoplasty, as well as after two weeks and three months.ResultsInjection laryngoplasty significantly improved the glottal gap, vocal fold position, Maximum Phonation Time, and Voice Handicap Index‐10. Post‐hoc analysis using Bonferroni correction showed that the improvements occurred within two post‐treatment weeks and remained at three post‐treatment months. In the subgroup analysis, the patients who underwent injection laryngoplasty within 8 weeks from onset showed significantly higher improvements in the videofluoroscopic dysphagia scale and swallowing function than the patients who received the procedure after 8 weeks or more.ConclusionPercutaneous injection laryngoplasty improves glottal closure and voice in patients with cancer‐related unilateral vocal cord paralysis. Early injection laryngoplasty may lead to greater benefits on swallowing function.Level of Evidence4.
Light Confinement by Local Index Tailoring in Inhomogeneous Dielectrics
Authors: Krešić I. , Makris K. G. , Rotter S. 
Published: July 2021

AbstractThe engineering of light confinement is a topic with a long history in optics and with significant implications for the control of light‐matter interaction. In inhomogeneous and disordered media, however, multiple scattering prevents the application of conventional approaches for the design of light fields with desired properties. This is because any local change to such a medium typically affects these fields in a non‐local and complicated fashion. Here, we present a theoretical methodology for tailoring an inhomogeneous 1D Hermitian dielectric index distribution that allows us to control the intensity profile of an incoming light field purely locally, that is, with little or no influence on the field profile outside of a designated region of interest. Strongly increasing or decreasing the light's intensity at arbitrary positions inside the medium thereby becomes possible without, in fact, changing the external reflectance or transmittance. These local modifications of the medium can thus be made undetectable to far field measurements. We apply this approach to locally control the confinement of light inside 1D materials with inhomogeneous continuous refractive index profiles and extend it to multilayer films as well as to chains of coupled micro‐resonators.
PVA‐Based Hydrogels: Promising Candidates for Articular Cartilage Repair
Authors: Chen Yuru , Song Jian , Wang Song , Liu Weiqiang 
Published: July 2021

AbstractThe complex, gradient physiological structure of articular cartilage is a severe hindrance of its self‐repair, leaving the clinical treatment of cartilage defects a demanding issue to be addressed. Currently applied tissue engineering treatments and traditional non‐tissue engineering treatments have different limitations, for example, cell dedifferentiation, immune rejection, and prosthesis‐related complications. Thus, studies have been focusing on seeking promising candidates for novel cartilage repair methods. Polyvinyl alcohol (PVA) hydrogels with excellent biocompatibility and tunable material properties have become the alternatives. For pure PVA hydrogels, the mechanical strength and lubricity are not capable of replacing articular cartilage until proper modifications are done. This paper summarizes the research progress in PVA hydrogels, including the preparation, modification, and cartilage‐repair‐aimed biomimetic improvements. Design guidance of PVA hydrogels is put forward as assistance to functional hydrogel preparation. Finally, the prospects and main obstacles of PVA hydrogels are discussed.
Effects of Hesperidin Consumption on the Cardiovascular System in Pre‐ and Stage 1 Hypertensive Subjects: Targeted and Non‐Targeted Metabolomic Approaches (CITRUS Study)
Authors: Pla‐Pagà L. , Pedret A. , Valls R. M. , Calderón‐Pérez L. , Llauradó E. , Companys J. , Martín‐Luján F. , Moragas A. , Canela N. , Puiggròs F. , Caimari A. , del Bas J. M. , Arola L. , Solà R. , Mayneris‐Perxachs J. 
Published: July 2021

ScopeThe aim of the present work is to determine new biomarkers of the biological effects of hesperidin in orange juice (OJ) applying a non‐targeted metabolomics approach validated by targeted metabolomics analyses of compliance biomarkers.Methods and ResultsPlasma/serum and urine targeted (HPLC‐MS/MS) and untargeted (1H‐NMR) metabolomics signatures are explored in a subsample with pre‐ and stage‐1 hypertension subjects of the CITRUS study (N = 159). Volunteers received 500 mL day−1 of control drink, OJ, or hesperidin‐enriched OJ (EOJ) for 12‐weeks. A 6‐h postprandrial study is performed at baseline. Targeted analyses reveals plasma and urine hesperetin 7‐O‐β‐d‐glucuronide as the only metabolite differing between OJ and EOJ groups after 12‐weeks consumption, and in urine is correlated with a decreased systolic blood pressure level. The non‐targeted approach shows that after single dose and 12‐weeks consumption of OJ and EOJ change several metabolites related with an anti‐inflammatory and antioxidant actions, lower blood pressure levels and uremic toxins.ConclusionsHesperetin 7‐O‐β‐d‐glucuronide can be a candidate marker for distinguishing between the consumption of different hesperidin doses at 12‐weeks consumption as well as a potential agent mediating blood pressure reduction. Moreover, changes in different endogenous metabolites can explain the mechanisms of action and the biological effects of hesperidin consumption.
Rectangular‐cavity‐like feed for radiation of phase gradient metasurface
Authors: Yu Xinhua , Sun Guiyu , Wan Jianfeng , Wu Xianxi , Mo Jinjun , Jiang Yannan , Wang Yiying 
Published: July 2021

AbstractIn this letter, a rectangular‐cavity‐like structure is proposed to feed the phase gradient metasurface (PGM), where two symmetrical long slots are cut on side walls along wave propagation direction of the rectangular waveguide cavity resonator. It consists of rectangular waveguide, transition section, slotted‐waveguide feed section, and shorted end of the cavity. The PGMs are placed in the slotted‐waveguide section and the slot is wide enough to accommodate PGMs. The antenna prototype is fabricated and measured whose measurements agree well with simulations in 7.8–11.0GHz.
Quantification of airway dimensions using a high‐resolution CT scanner: A phantom study
Authors: Zhao Yixiao , Hernandez Andrew M. , Boone John M. , Molloi Sabee 
Published: July 2021

AbstractPurposeSmall airways with inner diameters less than 2 mm are sites of major airflow limitations in patients with chronic obstructive pulmonary disease (COPD) and asthma. The purpose of this study is to investigate the limitations for accurate assessment of small airway dimensions using both high‐resolution CT (HRCT) and conventional normal‐resolution CT at low dose levels.MethodsTo model the normal human airways from the 3rd to 20th generations, a cylindrical polyurethane phantom with 14 airway tubes of inner diameters (ID) ranging from 0.3 to 3.4 mm and wall thicknesses (WT) ranging from 0.15 to 1.6 mm was placed within an Anthropomorphic QRM‐Thorax phantom. The Aquilion Precision (Canon Medical Systems Corporation) HRCT scanner was used to acquire images at 80, 100, and 120 kV using high resolution mode (HR, 0.25 mm × 160 detector configuration) and normal‐resolution (NR) mode (0.5 mm × 80 detector configuration). The HR data were reconstructed using a 1024 × 1024 matrix (0.22 × 0.22 × 0.25 mm voxel size) and the NR data were reconstructed using a 512 × 512 matrix (0.43 × 0.43 × 0.50 mm). Two reconstruction algorithms (filtered back projection; FBP and an adaptive iterative dose reduction 3D algorithm; AIDR 3D) and three reconstruction kernels (FC30, FC52, and FC56) were investigated. Thedose values ranged from 0.2 to 6.2 mGy. A refined automated full‐width half‐maximum (FWHM) method was used for the measurement of airway dimensions, where the density profiles were computed by radial oversampling using a polar coordinate system. Both ID and WT were compared to the known dimensions using a regression model, and the root‐mean‐square error (RMSE) and average error were computed across all 14 airway tubes.ResultsThe results indicate that the ID can be measured within a 15% error down to approximately 0.8 and 2.0 mm using the HR and NR modes, respectively. The overall RMSE (and average error) of ID measurements for HR and NR were 0.10 mm (−0.70%) and 0.31 mm (−2.63%), respectively. The RMSE (and average error) of WT measurements using HR and NR were 0.10 mm (23.27%) and 0.27 mm (53.56%), respectively. The WT measurement using HR yielded a factor of two improvement in accuracy as compared to NR.ConclusionsHigh‐resolution CT can provide more accurate measurements of airway dimensions as compared with NR CT, potentially improving quantitative assessment of pathologies such as COPD and asthma. The HR mode acquired and reconstructed with AIDR3D and the FC52 kernel provides most accurate measurement of airway dimensions. Low‐dose HR measurements at dose level above 0.9 mGy can provide improved accuracy on both inner diameters and wall thicknesses compared to full dose NR airway phantom measurements.