bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence: perspectives on challenges, value, and alignment of regulatory and national health technology assessment data collection requirements
Authors: Sievers Hannah , Joos Angelika , Hiligsmann Mickaël 
Published: February 2021

Abstract

Objective
This study aims to assess stakeholder perceptions on the challenges and value of real-world evidence (RWE) post approval, the differences in regulatory and health technology assessment (HTA) real-world data (RWD) collection requirements under the German regulation for more safety in drug supply (GSAV), and future alignment opportunities to create a complementary framework for postapproval RWE requirements.

Methods
Eleven semistructured interviews were conducted purposively with pharmaceutical industry experts, regulatory authorities, health technology assessment bodies (HTAbs), and academia. The interview questions focused on the role of RWE post approval, the added value and challenges of RWE, the most important requirements for RWD collection, experience with registries as a source of RWD, perceptions on the GSAV law, RWE requirements in other countries, and the differences between regulatory and HTA requirements and alignment opportunities. The interviews were recorded, transcribed, and translated for coding in Nvivo to summarize the findings.

Results
All experts agree that RWE could close evidence gaps by showing the actual value of medicines in patients under real-world conditions. However, experts acknowledged certain challenges such as: (i) heterogeneous perspectives and differences in outcome measures for RWE generation and (ii) missing practical experience with RWD collected through mandatory registries within the German benefit assessment due to an unclear implementation of the GSAV.

Conclusions
This study revealed that all stakeholder groups recognize the added value of RWE but experience conflicting demands for RWD collection. Harmonizing requirements can be achieved through common postlicensing evidence generation (PLEG) plans and joint scientific advice to address uncertainties regarding evidence needs and to optimize drug development.
Mobile isolation wards in a fever clinic: a novel operation model during the COVID-19 pandemic
Authors: Cheng Anbang , Chen Yilin , Gao Yong , Sun Peng , Chang Rui , Zhou Bin , Qiu Hui , Cheng Fanjun 
Published: February 2021

Abstract
A fever clinic within a hospital plays a vital role in pandemic control because it serves as an outpost for pandemic discovery, monitoring and handling. As the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan was gradually brought under control, the fever clinic in the West Campus of Wuhan Union Hospital introduced a new model for construction and management of temporary mobile isolation wards. A traditional battlefield hospital model was combined with pandemic control regulations, to build a complex of mobile isolation wards that used adaptive design and construction for medical operational, medical waste management and water drainage systems. The mobile isolation wards allowed for the sharing of medical resources with the fever clinic. This increased the capacity and efficiency of receiving, screening, triaging and isolation and observation of patients with fever. The innovative mobile isolation wards also controlled new sudden outbreaks of COVID-19. We document the adaptive design and construction model of the novel complex of mobile isolation wards and explain its characteristics, functions and use.
Cellular and molecular alterations of buffalo oocytes cultured under two different levels of oxygen tension during in vitro maturation
Authors: Ghanem Nasser , Ahmed Dalia Abd-El Rahman , Dessouki Sherif Mohamed , Faheem Marwa Said , Gad Ahmed Yehia , Peippo Jaana , Barkawi Ashraf Hesham 
Published: February 2021

SummaryThis study was conducted to monitor the cellular and molecular changes of buffalo cumulus–oocytes complexes (COCs) cultured under high or low oxygen levels. Morphologically good quality COCs (n = 1627) were screened using brilliant cresyl blue (BCB) staining and placed into three groups (BCB+, BCB− and control). All groups of COCs were cultured under low (5%) or high (20%) oxygen tensions. Intracellular and molecular changes including oocyte ultrastructure, lipid contents, mitochondrial activity and transcript abundance of genes regulating different pathways were analyzed in the matured oocyte groups. The results revealed that oxygen tension did not affect cumulus expansion rates, however the BCB+ group had a higher (P ≤ 0.05) expansion rate compared with the BCB− group. BCB− oocytes recorded the lowest meiotic progression rate (P ≤ 0.05) under high oxygen levels that was linked with an increased level of reactive oxygen species (ROS) compared with the BCB+ oocytes. Ultrastructure examination indicated that BCB+ oocytes had a higher rate of cortical granules migration compared with BCB− under low oxygen tension. In parallel, our results indicated the upregulation of NFE2L2 in groups of oocytes cultured under high oxygen tension that was coupled with reduced mitochondrial activity. In contrast, the expression levels of MAPK14 and CPT2 genes were increased (P ≤ 0.05) in groups of oocytes cultured under low compared with high oxygen tension that was subsequently associated with increased mitochondrial activity. In conclusion, data from the present investigation indicated that low oxygen tension is a favourable condition for maintaining the mitochondrial activity required for nuclear maturation of buffalo oocytes. However, low-quality oocytes (BCB−) responded negatively to high oxygen tension by reducing the expression of gene-regulating metabolic activity (CPT2). This action was an attempt by BCB− oocytes to reduce the increased levels of endogenously produced ROS that was coupled with decreased expression of the gene controlling meiotic progression (MAPK14) in addition to nuclear maturation rate.
Improved outcomes after implementation of a specialized pediatric cardiac rapid response team
Authors: McKeta Angela S. , Hlavacek Anthony M. , Chowdhury Shahryar M. , Scheurer Mark , Graham Eric M. , Zyblewski Sinai C. , Buckley Jason R. 
Published: February 2021

AbstractIntroduction:The efficacy of a specialized pediatric cardiac rapid response team is unknown. We hypothesized that a specialized cardiac rapid response team would facilitate team-wide communication between the cardiac stepdown unit and cardiac intensive care unit (ICU) teams and improve patient care.Materials and methods:A specialized pediatric cardiac rapid response team was implemented in June 2015. All pediatric cardiac rapid response team activations and outcomes from implementation through December 2018 were reviewed. Cardiac arrests and unplanned transfers to the cardiac ICU were indexed to 1000 patient-days to account for inpatient volume trends and evaluated over time.Results:There were 202 cardiac rapid response team activations in 108 unique patients during the study period. After implementation of the pediatric cardiac rapid response team, unplanned transfers from the cardiac stepdown unit to the cardiac ICU decreased from 16.8 to 7.1 transfers per 1000 patient days (p = 0.012). The stepdown unit cardiac arrest rate decreased from 1.2 to 0.0 arrests per 1000 patient-days (p = 0.015). There was one death on the cardiac stepdown unit in the 5 years since the implementation of the cardiac rapid response team, compared to four deaths in the previous 5 years.Conclusions:A reduction in unplanned cardiac ICU transfers, cardiac arrests, and mortality on the cardiac stepdown unit has been observed since the implementation of a specialized pediatric cardiac rapid response team. A specialized cardiac rapid response team may improve communication and empower the interdisciplinary care team to escalate care for patients experiencing clinical decline.
Job strain is prospectively associated with a lower frequency of fruit consumption in schoolteachers
Authors: Rodrigues Renne , Birolim Marcela Maria , de Andrade Selma Maffei , González Alberto Durán , Mesas Cézar Eumann , Fernández-Rodríguez Rubén , Mesas Arthur Eumann 
Published: February 2021

AbstractObjective:The current study aimed to analyse the prospective association between perceived work demand and changes in eating behaviours in schoolteachers.Design:This was a prospective cohort study with self-reported information obtained on the Demand Control Support Questionnaire and eating behaviours at baseline and after a 2-year follow-up. The analyses were performed using mixed-effects models adjusted for the main confounders.Setting:The setting consisted of elementary and secondary schools located in a large city in southern Brazil.Participants:The participants were 502 schoolteachers (65·9 % females, median age of 42·7 years [interquartile range 34·2, 49·4]).Results:A total of 39·2 % of the schoolteachers were classified at baseline with job strain, 28·9 % with passive job, 12·2 % with active job and 19·7 % with low-strain job. In the fully adjusted models, compared with teachers who reported low-strain job, those with higher levels of job strain were more likely to reduce (coefficient = 0·064; 95 % CI 0·018, 0·109) and less likely to increase (coefficient = −0·066; 95 % CI −0·115, −0·016) their frequency of fruit consumption regardless of sociodemographic, lifestyle, health conditions and social support at work.Conclusion:Job strain plays a relevant role in the frequency of fruit consumption over time in schoolteachers. The balance between demand and control at work must be considered in strategies for promoting healthy eating despite perceived social support.
Airborne Dust Plumes Lofted by Dislodged Ice Blocks at Russell Crater, Mars
Authors: Dinwiddie Cynthia L. , Titus Timothy N. 
Published: February 2021

AbstractLinear dune gullies on poleward‐facing Martian slopes are enigmatic. Formation by CO2‐ice block or snow cornice falls has been proposed based on optical imagery of bright, high‐albedo features inside gully channels. Because these features often resemble patchy frost residue rather than three‐dimensional blocks, more evidence is needed to support the ice‐block formation mechanism. Satellite imagery captured two simultaneous airborne plumes with in‐channel sources at the Russell crater megadune, thrust up, and dispersed outward along the path of linear dune gullies. We use spectral data analyses, climatic analyses of bolometric temperatures, and thermal modeling to further develop the mechanistic framework for linear dune gully development. Basal sublimation and CO2 gas venting likely cause CO2‐ice‐block detachment and falls from gully alcoves in southern early spring, accompanied by ice‐block off‐gassing and saltation of sands and coarse silts that are redeposited around gully channels, and lofting of sublimation lag (coarse dust/silt) into airborne plumes.
Crustal Radial Anisotropy of the Iran Plateau Inferred From Ambient Noise Tomography
Authors: Movaghari R. , JavanDoloei G. , Yang Y. , Tatar M. , Sadidkhouy A. 
Published: February 2021

AbstractThis study presents a three‐dimensional (3D) model of the crustal and uppermost mantle shear wave velocity and radial anisotropy beneath the Iran Plateau constructed by Rayleigh and Love waves from ambient noise. We correlate three years of continuous seismic ambient noise data recorded in 98 stations to obtain cross correlation functions. Then, we measure Rayleigh (8–60 s) and Love (8–50 s) wave dispersion curves from these cross‐correlation functions to generate two‐dimensional dispersion maps using a fast marching surface tomography method. Finally, we build a quasi‐3D shear wave velocity and radial anisotropy model by jointly inverting Rayleigh and Love local phase velocity dispersion curves using a Bayesian Markov chain Monte Carlo inversion method. Observed radial anisotropy beneath Central Iran is weaker than adjacent areas. Negative radial anisotropy is observed in the shallow structures across our study region, which is most likely attributed to vertically aligned cracks in the upper crust. Strong positive radial anisotropy in the middle to the lower crust beneath the Zagros is imaged, which is associated with ductile shear zones in the crust. Radial anisotropy changes from positive values in the crust to negative values in the upper mantle beneath the Zagros, which may be evidence for the decoupling of the crust from the upper mantle beneath the Zagros.
Electrical Resistivity Structure Around the Atotsugawa Fault, Central Japan, Revealed by a New 2‐D Inversion Method Combining Wideband‐MT and Network‐MT Data Sets
Authors: Usui Yoshiya , Uyeshima Makoto , Ogawa Tsutomu , Yoshimura Ryokei , Oshiman Naoto , Yamaguchi Satoru , Toh Hiroaki , Murakami Hideki , Aizawa Koki , Tanbo Toshiya , Ogawa Yasuo , Nishitani Tadashi , Sakanaka Shin 'ya , Mishina Masaaki , Satoh Hideyuki , Goto Tada‐nori , Kasaya Takafumi , Mogi Toru , Yamaya Yusuke , Shiozaki Ichiro , Honkura Yoshimori 
Published: February 2021

AbstractThe Atotsugawa fault is one of the most active faults in Japan, and the strain accumulation at the fault is considered to be caused by an aseismic shear zone in the fluid‐rich lower crust. To identify the shear zone and investigate the origin of the aqueous fluid in the lower crust, we deployed a Network‐MT survey in addition to a conventional wideband‐MT survey around the fault and performed an inversion combining both the MT data sets. In the inversion, by modifying a conventional inversion algorism, we accurately represented kilometer‐scale dipoles of the Network‐MT measurement to provide constraints on the electrical resistivity structure. In the lower crust under the study area, there are localized conductive anomalies below the Atotsugawa fault, the Ushikubi fault, and the Takayama‐Oppara fault zone. Comparing our electrical resistivity structure with the seismic velocity structure, we interpreted that the lower‐crustal conductors are localized ductile shear zones with highly connected fluid. We considered that the localized ductile shear zones are responsible for the strain accumulation along the respective active faults. In addition, in the mantle wedge above the subducting Philippine Sea slab and its downward extension, a highly conductive portion is detected, which may be attributed to the fluid dehydrated from the Philippine Sea slab and/or the Pacific slab. The existence of the large conductive area supports the suggestion of previous seismic and geochemical studies that the fluid of the lower crust around the Atotsugawa fault originated from subducting slabs.
Microphysical Modeling of Carbonate Fault Friction at Slip Rates Spanning the Full Seismic Cycle
Authors: Chen Jianye , Niemeijer A. R. , Spiers Christopher J. 
Published: February 2021

AbstractLaboratory studies suggest that seismogenic rupture on faults in carbonate terrains can be explained by a transition from high friction, at low sliding velocities (V), to low friction due to rapid dynamic weakening as seismic slip velocities are approached. However, consensus on the controlling physical processes is lacking. We previously proposed a microphysically based model (the “Chen–Niemeijer–Spiers” [CNS] model) that accounts for the (rate‐and‐state) frictional behavior of carbonate fault gouges seen at low velocities characteristic of rupture nucleation. In the present study, we extend the CNS model to high velocities (1 mm/s ≤ V ≤ 10 m/s) by introducing multiple grain‐scale deformation mechanisms activated by frictional heating. As velocity and hence temperature increase, the model predicts a continuous transition in dominant deformation mechanisms, from frictional granular flow with partial accommodation by plasticity at low velocities and temperatures, to grain boundary sliding with increasing accommodation by solid‐state diffusion at high velocities and temperatures. Assuming that slip occurs in a localized shear band, within which grain size decreases with increasing velocity, the model results capture the main mechanical trends seen in high‐velocity friction experiments on room‐dry calcite‐rich rocks, including steady‐state and transient aspects, with reasonable quantitative agreement and without the need to invoke thermal decomposition or fluid pressurization effects. The extended CNS model covers the full spectrum of slip velocities from earthquake nucleation to seismic slip rates. Since it is based on realistic fault structure, measurable microstructural state variables, and established deformation mechanisms, it may offer an improved basis for extrapolating lab‐derived friction data to natural fault conditions.
Mixed‐Phase Clouds and Precipitation in Southern Ocean Cyclones and Cloud Systems Observed Poleward of 64°S by Ship‐Based Cloud Radar and Lidar
Authors: Alexander S. P. , McFarquhar G. M. , Marchand R. , Protat A. , Vignon É. , Mace G. G. , Klekociuk A. R. 
Published: February 2021

AbstractMixed‐phase clouds (MPCs), composed of both liquid and ice, are prevalent in Southern Ocean cyclones. A characterization of these clouds on fine vertical scales is required in order to understand the microphysical processes within these clouds, and for model and satellite evaluations over this region. We investigated three examples of cloud systems collected by ship‐mounted remote‐sensing instruments adjacent to East Antarctica at latitudes between 64°S and 69°S. These cases allow us to examine the properties of midlevel MPCs, with cloud tops between 2 and 6 km. Midlevel MPCs contain multiple layers of supercooled liquid water (SLW) embedded within ice during the passage of cyclones. SLW layers are capped by strong temperature inversions and are observed at temperatures as low as −31°C. Convective generating cells (GCs) are present inside supercooled liquid‐topped midlevel MPCs. The horizontal extent, vertical extent, and maximum upward Doppler velocity of these GCs were 0.6–3.6 km, 0.7–1.0 km, and 0.5–1.0 m s−1, respectively, and are consistent with observations from previous lower‐latitude studies. Ice precipitation is nearly ubiquitous, except in the thinnest clouds at the trailing end of the observed systems. Seeding of lower SLW layers from above leads to periods with either larger ice particles or greater ice precipitation rates. Periods of supercooled drizzle lasting up to 2 h were observed toward the end of two of the three cyclone systems. This supercooled drizzle turns into predominantly ice precipitation as the result of seeding by ice clouds located above the precipitating SLW layer.
Leak Detection in a Real Transmission Main Through Transient Tests: Deeds and Misdeeds
Authors: Meniconi S. , Capponi C. , Frisinghelli M. , Brunone B. 
Published: February 2021

AbstractThis paper concerns the use of Transient Test‐Based Techniques (TTBTs) for fault detection in a long transmission main. It reports the results of two series of transient tests executed in a real and operating pipe system. Because of the complexity of the investigated pipeline that includes several stubs, different pressure wave generators were used at both the end sections. Precisely, transients were caused by a pump shut‐down and the Portable Pressure Wave Maker device. The analysis of the results shows that, according to the characteristics of the transient tests and the investigated system, only a part of the system can be explored properly from a given generation point. The proposed test procedure allows overcoming the negative effect of a change in the initial and boundary conditions. In fact, contrary to laboratory, in a real system, it is quite impossible to repeat tests in the same flow conditions. The success of the survey—with two leaks detected with a good precision—confirms the potential of the TTBTs for fault detection in real systems.
The impact of particulate electron paramagnetic resonance oxygen sensors on fluorodeoxyglucose imaging characteristics detected via positron emission tomography
Authors: Schaner Philip E. , Tran Ly-Binh-An , Zaki Bassem I. , Swartz Harold M. , Demidenko Eugene , Williams Benjamin B. , Siegel Alan , Kuppusamy Periannan , Flood Ann Barry , Gallez Bernard 
Published: February 2021

AbstractDuring a first-in-humans clinical trial investigating electron paramagnetic resonance tumor oximetry, a patient injected with the particulate oxygen sensor Printex ink was found to have unexpected fluorodeoxyglucose (FDG) uptake in a dermal nodule via positron emission tomography (PET). This nodule co-localized with the Printex ink injection; biopsy of the area, due to concern for malignancy, revealed findings consistent with ink and an associated inflammatory reaction. Investigations were subsequently performed to assess the impact of oxygen sensors on FDG-PET/CT imaging. A retrospective analysis of three clinical tumor oximetry trials involving two oxygen sensors (charcoal particulates and LiNc-BuO microcrystals) in 22 patients was performed to evaluate FDG imaging characteristics. The impact of clinically used oxygen sensors (carbon black, charcoal particulates, LiNc-BuO microcrystals) on FDG-PET/CT imaging after implantation in rat muscle (n = 12) was investigated. The retrospective review revealed no other patients with FDG avidity associated with particulate sensors. The preclinical investigation found no injected oxygen sensor whose mean standard uptake values differed significantly from sham injections. The risk of a false-positive FDG-PET/CT scan due to oxygen sensors appears low. However, in the right clinical context the potential exists that an associated inflammatory reaction may confound interpretation.
Aortic root movement correlation with the function of the left ventricle
Authors: Karwat Piotr , Klimonda Ziemowit , Styczyński Grzegorz , Szmigielski Cezary , Litniewski Jerzy 
Published: February 2021

AbstractEchocardiographic assessment of systolic and diastolic function of the heart is often limited by image quality. However, the aortic root is well visualized in most patients. We hypothesize that the aortic root motion may correlate with the systolic and diastolic function of the left ventricle of the heart. Data obtained from 101 healthy volunteers (mean age 46.6 ± 12.4) was used in the study. The data contained sequences of standard two-dimensional (2D) echocardiographic B-mode (brightness mode, classical ultrasound grayscale presentation) images corresponding to single cardiac cycles. They also included sets of standard echocardiographic Doppler parameters of the left ventricular systolic and diastolic function. For each B-mode image sequence, the aortic root was tracked with use of a correlation tracking algorithm and systolic and diastolic values of traveled distances and velocities were determined. The aortic root motion parameters were correlated with the standard Doppler parameters used for the assessment of LV function. The aortic root diastolic distance (ARDD) mean value was 1.66 ± 0.26 cm and showed significant, moderate correlation (r up to 0.59, p < 0.0001) with selected left ventricular diastolic Doppler parameters. The aortic root maximal diastolic velocity (ARDV) was 10.8 ± 2.4 cm/s and also correlated (r up to 0.51, p < 0.0001) with some left ventricular diastolic Doppler parameters. The aortic root systolic distance (ARSD) was 1.63 ± 0.19 cm and showed no significant moderate correlation (all r values < 0.40). The aortic root maximal systolic velocity (ARSV) was 9.2 ± 1.6 cm/s and correlated in moderate range only with peak systolic velocity of medial mitral annulus (r = 0.44, p < 0.0001). Based on these results, we conclude, that in healthy subjects, aortic root motion parameters correlate significantly with established measurements of left ventricular function. Aortic root motion parameters can be especially useful in patients with low ultrasound image quality precluding usage of typical LV function parameters.