bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in dispensing of individual prescription opioid formulations, Canada 2005–2020
Authors: Jones Wayne , Kaoser Ridhwana , Rudoler David , Fischer Benedikt 
Published: March 2022

Abstract
Background
Canada has experienced a distinctly bifurcated pattern of (strong) opioid utilization post-2000, with multifold increases rendering it one of the world’s highest opioid consumption rates, followed by subsequent substantive declines since 2011/2012. Several interventions to control especially high-risk opioid use have been implemented post-2010 at different levels, yet with their effects assessed mostly for overall opioid utilization. Little knowledge exists for over-time patterns of individual opioid formulations.

Methods
Raw information on community-based prescription opioid dispensing for years 2005–2020 were obtained from a large national database based on a stratified sample of 6500 retail pharmacies across Canada (IQVIA/Compuscript), These data were converted into Defined-Daily-Doses/1000 population/day (DDD/1000/day) for individual (strong and weak) opioid formulations—specifically: fentanyl, hydromorphone, hydrocodone, morphine, oxycodone, codeine—per standard methods. Descriptive data on individual opioid dispensing were computed, and segmented regression (or ‘broken-stick’) analysis was applied to the overtime dispensing towards assessing potentially significant ‘breakpoints’ interrupting linear utilization trends. Akaike information criterion (AIC) values were computed to assess the resulting models’ quality-of-fit.

Results
Five of the six opioid formulations featured a lower dispensing level in 2020 compared with 2005, but mostly with peak values in years between, contributing to the overall inversion pattern. For five of the six opioid formulations, a three-segmented model emerged as the best fit for the dispensing observed; only hydrocodone presented a linear (downward) dispensing trend. Among the five interrupted trend models for individual formulations, four (fentanyl, morphine, oxycodone, codeine but not hydromorphone) indicated their initial breakpoint during 2011–2014 introducing a downward dispensing trend. Inconsistently, morphine also featured a recent breakpoint (2018) towards a dispensing increase.

Conclusions
While all opioids showed marked declines, we found heterogeneous patterns of dispensing for individual opioid formulations. While we cannot estimate direct causal effects, opioid control interventions appear to have had differential impacts on dispensing of individual formulations. The earliest breakpoint occurred towards substantive decreases for oxycodone dispensing in 2011; subsequently, there were increases in dispensing of hydromorphone and fentanyl likely due to substitution effects, followed by across-the-board declines post-2015/2016. Recent ‘safer opioid’ distribution programs to reduce illicit/toxic opioid exposure linked with high levels of poisoning fatalities seem to fuel resurgences in select opioid (e.g., morphine) dispensing.
The effects of personalized gamification on students’ flow experience, motivation, and enjoyment
Authors: Oliveira Wilk , Hamari Juho , Joaquim Sivaldo , Toda Armando M. , Palomino Paula T. , Vassileva Julita , Isotani Seiji 
Published: March 2022

AbstractGamification refers to the attempt to transform different kinds of systems to be able to better invoke positive experiences such as the flow state. However, the ability of such intervention to invoke flow state is commonly believed to depend on several moderating factors including the user’s traits. Currently, there is a dearth of research on the effect of user traits on the results of gamification. Gamer types (personality traits related to gaming styles and preferences) are considered some of the most relevant factors affecting the individual’s susceptibility to gamification. Therefore, in this study we investigate how gamer types from the BrainHex taxonomy (achiever, conqueror, daredevil, mastermind, seeker, socializer and survivor) moderate the effects of personalized/non-personalized gamification on users’ flow experience (challenge-skill balance, merging of action and awareness, clear goals, feedback, concentration, control, loss of self-consciousness andautotelicexperience), enjoyment, perception of gamification and motivation. We conducted a mixed factorial within-subject experiment involving 121 elementary school students comparing a personalized version against a non-personalized version of a gamified education system. There were no main effects between personalization and students’ flow experience, perception of gamification and motivation, and enjoyment. Our results also indicate patterns of characteristics that can lead students to the high flow experience (e.g., those who prefer to play multiplayer have a high flow experience in both personalized and non-personalized versions). Based on our results, we provided recommendations to advance the design of gamifed educational systems.
Emerging trends of online assessment systems in the emergency remote teaching period
Authors: Topuz Arif Cem , Saka Eda , Fatsa Ömer Faruk , Kurşun Engin 
Published: March 2022

AbstractThe COVID-19 pandemic caused many educational institutions in the world to switch to the distance education process, and this process was called "Emergency Remote Teaching". This urgent transition process has caused many problems in educational environments. One of the problems is the subject of measurement and evaluation. Along with the pandemic, many institutions have used various online assessment systems to make measurements and evaluations online, and researchers have conducted research on these online assessment systems. This research focus on the features of the online assessment systems and aims to examine the trends towards the prominent features of the online assessment systems in the Emergency Remote Teaching period. For this purpose, the prominent online assessment systems have been determined by systematically analyzing academic studies published in 2020, and answers have been sought to the following research questions: (1) which platforms they support, (2) which security features they have, and (3) what common features they have. Identifying trends in the characteristics of online assessment systems is expected to guide practitioners, decision-makers, researchers, and system developers in the process of selecting and/or developing an online assessment system for use in online measurement and evaluation.
Peridotites with back-arc basin affinity exposed at the southwestern tip of the Mariana forearc
Authors: Oya Shoma , Michibayashi Katsuyoshi , Ohara Yasuhiko , Martinez Fernando , Kourim Fatma , Lee Hao-Yang , Nimura Kohei 
Published: March 2022

AbstractPeridotites at water depths of 3430 to 5999 m have been discovered using the submersible Shinkai6500 (dives 6K-1397 and 6K-1398) on the southwestern slope of the 139°E Ridge (11°12′N, 139°15′E), a small ridge at the southwesternmost tip of the Mariana forearc near the junction with the Yap Trench and Parece Vela Basin. The peridotites studied consist of 17 residual harzburgites and one dunite and show various textures with respect to their depths. Peridotites with coarse-grained (> 1 mm) textures were sampled from the shallowest part (3705–4042 m) of the dive area, and peridotites with fine-grained (< 0.5 mm) textures were sampled deeper (5996 m). Olivine crystal-fabrics vary with grain size, with (010)[100] A-type patterns for the coarse-grained peridotites, {0kl}[100] D-type patterns for the fine-grained peridotites, and various indistinct patterns in samples of variable grain sizes. Fine-grained peridotites with D-type olivine crystal-fabrics could result from deformation under relatively higher flow stresses, suggesting that a ductile shear zone in the lithospheric mantle could occur in the deepest part of 139°E Ridge. Spinel Cr# range from relatively low (0.36) to moderately high (up to 0.57), and correlate with Ti contents (0.07–0.45 wt.%). The trace element patterns of clinopyroxene similarly exhibit steepening slopes from the middle to the light REEs regardless of textural variations. These mineralogical and geochemical features would result from melt-rock interactions under conditions of relatively shallow lithospheric mantle, which are much more comparable with the Parece Vela Basin peridotites than the Mariana forearc peridotites. Consequently, the Parece Vela Basin mantle is more likely exposed on the inner slope of the westernmost Mariana Trench, presumably due to the collision of the Caroline Ridge.
Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE
Authors: Malcolm Javian C. , Falzone Nadia , Gains Jennifer E. , Aldridge Matthew D. , Mirando David , Lee Boon Q. , Gaze Mark N. , Vallis Katherine A. 
Published: March 2022

Abstract
Purpose
Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [177Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [177Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL). We investigated whether predictions based on an assumption of unchanging AD per unit AA (Gy/GBq) prove robust to cyclical changes in biokinetics.

Methods
A simulation study, based on dosimetry data from six children with NBL who received four-cycles of [177Lu]Lu-DOTATATE in the LuDO trial (ISRCTN98918118), was performed to explore the effect of variable biokinetics on AD. In the LuDO trial, AA was adapted to the patient’s weight and SPECT/CT-based dosimetry was performed for the kidneys and tumour after each cycle. The largest tumour mass was selected for dosimetric analysis in each case.

Results
The median tumour AD per cycle was found to decrease from 15.6 Gy (range 8.12–26.4) in cycle 1 to 11.4 Gy (range 9.67–28.8), 11.3 Gy (range 2.73–32.9) and 4.3 Gy (range 0.72–20.1) in cycles 2, 3 and 4, respectively. By the fourth cycle, the median of the ratios of the delivered AD (ADD) and the predicted (or “expected”) AD (ADE) (which was based on an assumption of stable biokinetics from the first cycle onwards) were 0.16 (range 0.02–0.92, p = 0.013) for the tumour and 1.08 (range 0.84–1.76, p > 0.05) for kidney. None of the patients had an objective response at 1 month follow up.

Conclusion
This study demonstrates variability in Gy/GBq and tumour AD per cycle in children receiving four administrations of [177Lu]Lu-DOTATATE treatment for NBL. NBL is deemed a radiation sensitive tumour; therefore, dose-adaptive treatment planning schemes may be appropriate for some patients to compensate for decreasing tumour uptake as treatment progresses.
Trial registration ISRCTN ISRCTN98918118. Registered 20 December 2013 (retrospectively registered).
Small lesion depiction and quantification accuracy of oncological 18F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction
Authors: Xu Lei , Li Ru-Shuai , Wu Run-Ze , Yang Rui , You Qin-Qin , Yao Xiao-Chen , Xie Hui-Fang , Lv Yang , Dong Yun , Wang Feng , Meng Qing-Le 
Published: March 2022

Abstract
Background
To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification.

Methods
The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter < 2 cm) were enrolled. Six groups of PET images were reconstructed: routine voxel OSEM (RVOSEM), small voxel OSEM (SVOSEM), and SVB reconstructions with four penalty factors: 0.6, 0.8, 0.9, and 1.0 (SVB0.6, SVB0.8, SVB0.9, and SVB1.0). The routine and small voxel sizes are 4 × 4 × 4 and 2 × 2 × 2 mm3. The recovery coefficient (RC) was calculated by dividing the measured activity by the injected activity of the hot spheres in the phantom study. The SUVmax, target-to-liver ratio (TLR), contrast-to-noise ratio (CNR), the volume of the lesions, and the image noise of the liver were measured and calculated in the patient study. Visual image quality of the patient image was scored by two radiologists using a 5-point scale.

Results
In the phantom study, SVB0.6, SVB0.8, and SVB0.9 achieved higher RCs than SVOSEM. The RC was higher in SVOSEM than RVOSEM and SVB1.0. In the patient study, the SUVmax, TLR, and visual image quality scores of SVB0.6 to SVB0.9 were higher than those of RVOSEM, while the image noise of SVB0.8 to SVB1.0 was equivalent to or lower than that of RVOSEM. All SVB groups had higher CNRs than RVOSEM, but there was no difference between RVOSEM and SVOSEM. The lesion volumes derived from SVB0.6 to SVB0.9 were accurate, but over-estimated by RVOSEM, SVOSEM, and SVB1.0, using the CT measurement as the standard reference.

Conclusions
The SVB reconstruction improved lesion contrast, TLR, CNR, and volumetric quantification accuracy for small lesions compared to RVOSEM reconstruction without image noise degradation or the need of longer emission time. A penalty factor of 0.8–0.9 was optimal for SVB reconstruction for the small tumor detection with 18F-FDG PET/CT.
Single pile in cohesionless soil in sloping ground under lateral loading
Authors: Perumalsamy Kavitha , Ranganathan Sundaravadivelu 
Published: March 2022

AbstractPile foundations are adopted if a soil of low bearing capacity extends to a considerable depth or if the structure is heavy or the settlement due to the structure is large. It transfers the load to a strong, stable stratum of soil. The behaviour of soil in slope and piles embedded in it is an elaborated soil-structure interaction problem. This paper presents the results of experimental investigations on a single pile subjected to lateral load by varying relative density of soil in the horizontal and sloping ground with three different slopes of 1V: 2H, 1V: 2.5H and 1V: 3H. The lateral load carrying capacity of the pile is considerably decreased when the lateral load is applied in the direction of the slope. It is found that the lateral load carrying capacity of the pile is increased for higher relative density of sand and the lateral capacity of the pile is greater in flatter slope than in steeper slope. The effect of different slopes on normalized lateral load versus displacement for the lateral load applied in the direction along and against slope is quantified. A set of empirical equations are formulated to determine the deflection, fixity depth and moment for the pile in sloping ground.
Soil microbial communities following 20 years of fertilization and crop rotation practices in the Czech Republic
Authors: Kracmarova Martina , Uhlik Ondrej , Strejcek Michal , Szakova Jirina , Cerny Jindrich , Balik Jiri , Tlustos Pavel , Kohout Petr , Demnerova Katerina , Stiborova Hana 
Published: March 2022

Abstract
Background
Although fertilization and crop rotation practices are commonly used worldwide in agriculture to maximize crop yields, their long-term effect on the structures of soil microorganisms is still poorly understood. This study investigated the long-term impact of fertilization and crop rotation on soil microbial diversity and the microbial community structure in four different locations with three soil types. Since 1996, manure (MF; 330 kg N/ha), sewage sludge (SF; 330 and SF3x; 990 kg N/ha), and NPK (NPK; 330 kg N/ha) fertilizers were periodically applied to the soils classified as chernozem, luvisol and cambisol, which are among the most abundant or fertile soils used for agricultural purposes in the world. In these soils, potato (Solanum tuberosum L.), winter wheat (Triticum aestivum L.), and spring barley (Hordeum vulgare L.) were rotated every three years.

Results
Soil chemistry, which was significantly associated with location, fertilization, crop rotation, and the interaction of fertilization and location, was the dominant driver of soil microbial communities, both prokaryotic and fungal. A direct effect of long-term crop rotation and fertilization on the structure of their communities was confirmed, although there was no evidence of their influence on microbial diversity. Fungal and bacterial communities responded differently to fertilization treatments; prokaryotic communities were only significantly different from the control soil (CF) in soils treated with MF and SF3x, while fungal communities differed across all treatments. Indicator genera were identified for different treatments. These taxa were either specific for their decomposition activities or fungal plant pathogens. Sequential rotation of the three crops restricted the growth of several of the indicator plant pathogens.

Conclusions
Long-term fertilization and crop rotation significantly altered microbial community structure in the soil. While fertilization affected soil microorganisms mainly through changes in nutrient profile, crop rotations lead to the attraction and repulsion of specific plant pathogens. Such changes in soil microbial communities need to be considered when planning soil management.
Influence and Mechanisms of Action of Environmental Stimuli on Work Near and Above the Severe Domain Boundary (Critical Power)
Authors: Richard Normand A. , Koehle Michael S. 
Published: March 2022

Abstract
The critical power (CP) concept represents the uppermost rate of steady state aerobic metabolism during work. Work above CP is limited by a fixed capacity (W′) with exercise intensity being an accelerant of its depletion rate. Exercise at CP is a considerable insult to homeostasis and any work done above it will rapidly become intolerable. Humans live and exercise in situations of hypoxia, heat, cold and air pollution all of which impose a new environmental stress in addition to that of exercise. Hypoxia disrupts the oxygen cascade and consequently aerobic energy production, whereas heat impacts the circulatory system’s ability to solely support exercise performance. Cold lowers efficiency and increases the metabolic cost of exercise, whereas air pollution negatively impacts the respiratory system. This review will examine the effects imposed by environmental conditions on CP and W′ and describe the key physiological mechanisms which are affected by the environment.

Graphical Abstract
Effect of pneumatic vitreolysis in management of patients with symptomatic focal vitreomacular traction
Authors: Fouad Ahmed N. , Eissa Iman M. , Nassar Ghada A. , Leila Mahmoud , Fathy Adel M. 
Published: March 2022

Abstract
Purpose
To evaluate the efficacy of single intravitreal injection of an expansile concentration of sulphur hexafluoride gas (SF6) in treating patients with symptomatic focal vitreomacular traction (VMT) documented by spectral domain optical coherence tomography (SD-OCT) preoperatively.

Methods
This is a prospective interventional case series including 30 eyes of 29 patients with symptomatic focal VMT evident on SD-OCT. Pre-operatively, mean best corrected visual acuity (BCVA) was 20/125 (range 20/400–20/40). Mean central foveal thickness (CFT) was 382 μm (range 149–576 μm; SD ± 91.88). All eyes received single intravitreal injection of 0.3 mL of 100% SF6 gas. Postoperatively, we performed SD-OCT at one week, one month, and three months for all eyes. Primary outcome measure was release of VMT. Secondary outcome measures were changes in postoperative BCVA andCFT.

Results
Overall, VMT release occurred in 24 of 30 eyes by the final follow-up visit (80% final release rate); furthermore, 76.9% of eyes with diabetic maculopathy and 25% of eyes with concurrent epiretinal membrane (ERM) had successful VMT release. VMT release was documented on SD-OCT at an average of 3 weeks (range, 1–12 weeks). The rate of release in phakic eyes was 90% (18 of 20 eyes) versus 60% in pseudophakic eyes (6 of 10 eyes). One patient developed a retinal break at upper nasal retina after two weeks of injection.

Conclusion
Pneumatic vitreolysis (PVL) with limited face-down position is a viable option for treating focal VMT with few adverse events. Further studies are needed to evaluate its indications, benefits, and risks.
Promises of eukaryotic ribonucleases for cancer treatment: a systematic review
Authors: Siraj Yesuf Adem 
Published: March 2022

Abstract
Background
Following an increasing interest in exploration of anticancer chemotherapeutic agents, ribonucleases are currently under investigations for alternative anticancer chemotherapy.

Objective
The current review scrutinizes information on the potential capability of eukaryotic ribonucleases for cancer treatment.

Methods
Predefined searching terms were applied to PubMed, Scopus, eLibrary databases and other search engines such as Google Scholar and bioRvix preprints. Twenty four research articles on eukaryotic ribonuclease were included in the review. Qualitative and quantitative information of these studies were extracted, analyzed and explained in text, tables and figures.

Results
Majority of eukaryotic ribonucleases (46%, 11/24) included in the review were extracted from various species of frogs, 21% (5/24) were from bovine sources and others were from human bodies, edible mushrooms, fungal and plant species. Molecular characteristics of eukaryotic ribonucleases were illustrated in tables and figures. According to the reports, ranpirnase with a trademark of Onconase® is the sole ribonuclease granted with an orphan and fast-track drug status by FDA, USA. Most other eukaryotic ribonucleases are undergoing various preclinical stages of research for their potential anticancer effect. Hence, the mean of half – maximal inhibitory concentrations (IC50) of eukaryotic ribonucleases of several research outcomes showed their selective cytotoxicity towards cancerous cells. In some reports, pre-tumor-xenografted animals treated with ribonucleases also demonstrated diminished tumor volume, lower tumor metastasis and increased survival rates. In addition, overall safety and toxicity parameters were also indicated as tolerable by the experimental hosts. However, a single study indicated degeneration of spermatogenic epithelia in wheat leave RNase treated animals.

Conclusions
Though several clinical trials on eukaryotic ribonucleases are expected, existing results from in vitro and in vivo preclinical studies showed promising alternative chemotherapy to treat cancer diseases. Hence, further human safety and efficacy studies are still necessary to explore well established applications of eukaryotic ribonucleases in clinical medicine.