bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Midazolam RAMPART Study Medical Records Project: A Unique Use of Real-World Data in a Complex Collaborative Partnership to Support a New Drug Application
Authors: Sherman Nancy A. , Silbergleit Robert , Bengelink Erin M. , Durkalski Valerie , Wolter Kevin D. 
Published: August 2022

Abstract
Introduction
This project aimed to retrospectively obtain, review, and extract key safety data from medical records of participants enrolled in RAMPART, the NIH-supported Rapid Anticonvulsant Medication Prior to ARrival Trial of intramuscular midazolam versus intravenous lorazepam for pre-hospital treatment of status epilepticus, to support a US new drug application (NDA) for intramuscular midazolam.

Methods
A collaborative partnership was established between the NDA sponsor, the RAMPART trial lead academic institution, US government agencies, and contract research organizations to retrieve, review, and extract relevant safety data from the medical records of RAMPART participants and summarize those data to include in an NDA submitted to the US Food and Drug Administration (FDA).

Results
Key data in the medical records of 890 RAMPART trial participants (1020 enrollments, including 130 repeat enrollments) were reviewed and extracted into a project database. Safety events occurred in 771 (86.6%) participants, and included additional information not collected in the RAMPART trial. This database also enabled subgroup analyses based on medical history and prior/concurrent medications, building upon previous analyses according to age, sex, and race. No previously unrecognized safety patterns were identified, and no association was observed between efficacy and medical history or medication usage.

Conclusions
The use of unstructured real-world retrospective medical record data can effectively support an NDA submission in place of conducting another interventional clinical trial. This retrospective medical records review and extraction of additional safety data contributed to the FDA approval of intramuscular midazolam for the pre-hospital treatment of status epilepticus in 2018.

ClinicalTrials.gov
NCT00809146.
The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial
Authors: Chen Huirong , Li Zheng , Li Xianchen , Yang Yong , Dai Yutian , Xie Zuogang , Xiao Jiaquan , Liu Xiaoqiang , Yang Luo , Shi Chenkun , Zhi Erlei , Tian Ruhui , Li Peng , Chen Huixing , Zhao Fujun , Hu Jianlin , Yao Chencheng , Lin Guiting , Lue Tom F. , Xia Shujie 
Published: August 2022

ABSTRACTBackgroundA recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval.AimTo study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED.MethodsA randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions.OutcomesThe primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire.ResultsResponse rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of −0.01% [95% confidence interval −0.11 to 0.10%] within the acceptable margin (−14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported.Clinical ImplicationsLow-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients’ needs.Strengths & LimitationsThis is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations.ConclusionLow-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED.
Precursors Identification for Forecasting UHF‐Band Ionospheric Scintillation Events Over Chinese Low‐Latitude Region by Deep Learning
Authors: Zhang Hongbo , Wang Feifei , Sheng Dongsheng , Ban Panpan , Liu Yumei 
Published: August 2022

AbstractThe occurrences of the UHF‐band ionospheric scintillation events caused by Equatorial Plasma Bubbles (EPBs) in the low‐latitude region depend on many factors. Nowadays, it is also a hard work for researchers to analyze and find out the useful precursory signatures of the generation of EPBs from several kinds of observations, which is a necessary work to build a forecasting model base on the priori knowledge. Many studies have revealed that there are distinctive features of daytime background ionosphere characteristics on scintillation and nonscintillation days. Deep learning technique (DLT) could automatically discover the distinctive variations from the daytime background ionospheric observations of scintillation and nonscintillation days. It is found that the forecasting problem of postsunset ionospheric scintillation events could be converted to a classification problem, and easily solved by DLT. The effectiveness of DLT for building a forecasting model of the UHF‐band ionospheric scintillation events over Chinese low‐latitude region is studied and evaluated. By analyzing the performance metrics of different combinations of related factors as the input parameters of DLT, a new important precursor for forecasting the UHF‐band ionospheric scintillation events over Chinese low‐latitude region is identified for the first time. It is suggested that the latitudinal and diurnal variations of the transequatorial Total Electron Content (TEC) profile in the east of the forecasting area is one of the key precursors.
A Nonlinear Numerical Model for Comparative Study of Acoustic‐Gravity Wave Propagation in Planetary Atmospheres: Application to Earth and Mars
Authors: Srivastava Sarthak , Chandran Amal , Thiemann Edward M. B. 
Published: August 2022

AbstractA two‐dimensional nonlinear numerical model has been developed to study atmospheric coupling due to vertically propagating acoustic gravity waves (AGWs) on different planets. The model is able to simulate both acoustic and gravity waves due to inclusion of compressibility. The model also considers dissipative effects due to viscosity, conduction, and radiative damping. The hyperbolic inviscid advection equations are solved using the Lax‐Wendroff method. The parabolic diffusion terms are solved implicitly using a linear algebra‐based Direct method. The model is validated by comparing numerical solutions against analytical results for linear propagation, critical level absorption, and mountain wave generation over an isolated hill. Acoustic wave generation in Martian atmosphere due to a pressure pulse is also demonstrated. A case study of tsunami‐generated AGWs is presented for the 2004 Sumatra earthquake whereby the model is forced through tsunamigenic sea‐surface displacement. The properties of simulated AGWs closely match those derived from ionospheric sounding observations reported in literature. Another application for Martian ice cloud formation is discussed where gravity waves from topographic sources are shown to create cold pockets with temperatures below the CO2 condensation threshold. The simulated cold pockets coincide with the cloud echo observations from the Mars Orbiting Laser Altimeter aboard Mars Global Survey spacecraft.
Insight Into Io Enabled by Characterization of Its Neutral Oxygen Torus
Authors: Smith H. T. , Koga R. , Tsuchiya F. , Dols V. J. 
Published: August 2022

AbstractThe Jovian system is very intriguing with extremely different particle sources. As the dominant source of particles to Jupiter's magnetosphere, Io is of particular importance. The JAXA Hisaki (SPRINT‐A) mission is providing insightful observations with regard to Io. In particular, its UV neutral oxygen line of sight observations provide the best glimpse so far of Jovian neutral particle populations. This is exciting in that for the first time, the neutral tori can be directly observed on time scales that constrain satellite sources. This data also sheds unprecedented insight into neutral torus distributions, which could subsequently provide essential information about the sources and mechanisms from Io. However, 3‐D modeling is also required to interpret the complex and dynamic observational geometries. Here, we present the first 3‐D distribution of the Io‐generated neutral oxygen torus using JAXA Hisaki neutral oxygen observations as modeling constraints to provide characterization of the Io magnetospheric source and the resulting neutral tori. Major findings of our research include: (a) the effective total original SO2 source rate from Io during a low activity period is ∼800 kg/s; (b) Io has two separate exospheric sources: O at ∼200 kg/s and SO2 at ∼400 kg/s; (c) particles escape from Io preferentially on the Jupiter upstream facing hemisphere; (d) the oxygen neutral torus populates the entire orbit and significantly dominates over the SO2, SO, and S neutral toroidal clouds; and (e) large ionization and dissociation rates limit the significant expansion of Io‐genic neutral particles in Jupiter's magnetosphere beyond ∼2 Rj from Io's orbit.
Effect of IMF By on the Entry of Solar Wind Ions Into the Near‐Earth Tail Lobe: Global Hybrid Simulation and MMS Observation
Authors: Wang Chih‐Ping , Xing Xiaoyan , Wang Xueyi , Avanov Levon A. , Lin Yu , Strangeway Robert J. , Wei H. Y. 
Published: August 2022

AbstractGlobal simulations predict that the low‐latitude mantle may be an important pathway for the solar wind entry into the tail magnetosphere close to the current sheet when interplanetary magnetic field (IMF) By dominates over IMF Bz. To evaluate this entry mechanism in the near‐Earth tail (X ∼ −10–−20 RE), we investigate the predictions from 3D global hybrid simulations as well as in situ observations by magnetospheric multiscale (MMS) spacecraft. The simulations predict that the low‐latitude mantle plasma can appear in the near‐Earth tail lobe extending inward approximately 5 RE from the flank magnetopause. The low‐latitude mantle plasma appears in the dawnside northern lobe and duskside southern lobe during positive IMF By, while the opposite asymmetry is seen during negative IMF By. After a change in the IMF By direction arriving at the bow shock nose, it takes another ∼15–30 min for the asymmetry to completely reverse to the opposite sense in the near‐Earth tail. We present six MMS events in the tail lobe showing that the existence and absence of the low‐latitude mantle plasma is consistent with the predicted asymmetries. Statistical analysis of 5 years of MMS observations shows that the dependencies of the magnitudes of the lobe densities and tailward field‐aligned flow speeds on the IMF By directions are consistent with the predicted contributions from the low‐latitude mantle plasma in the expected lobe regions.
Viscosity of Crystal‐Mushes and Implications for Compaction‐Driven Fluid Flow
Authors: Connolly James A. D. , Schmidt Max W. 
Published: August 2022

AbstractCentrifuge experiments on olivine, chromite, and plagioclase aggregates saturated in basaltic liquid show evidence of viscous compaction by grain‐boundary diffusion‐controlled creep. The experiments confirm that the exponential dependence of shear viscosity on melt fraction, observed at low porosities in earlier shear deformation experiments, extends to sedimentary porosities. The compaction profiles are inconsistent with the porosity‐dependence commonly ascribed to viscosity in macroscopic compaction models, which underestimate the effect of matrix disaggregation and consequently overestimate the viscosities of crystal mushes by 1–2 orders of magnitude. The time to halve the porosity of natural olivine igneous sediments by compaction is estimated from the centrifuge experiments to be O(103)y. Half‐times for plagioclase and chromite layers are O(104–105)y, suggesting that such layers compact on magmatic time scales only if they are loaded by additional sedimentation. At conditions relevant to melt flow in asthenospheric settings and trans‐crustal magmatic systems, the bulk and shear viscosities inferred for olivine and plagioclase are O(1017)Pa s, 4 orders of magnitude less than inferred from earlier experimental studies of the diffusion creep rheology. The reduced viscosities imply time‐ and length‐scales for compaction processes that are substantially shorter than previously anticipated. Our analysis serendipitously reveals that the oft‐neglected solidity term of the Carman‐Kozeny porosity‐permeability relation is essential to prevent non‐physical behavior in models of cumulate compaction.
A Method to Account for the Impact of Water Vapor on Observation‐Based Estimates of the Clear‐Sky Shortwave Direct Radiative Effect of Mineral Dust
Authors: Kuwano A. , Evan A. 
Published: August 2022

AbstractThe shortwave direct radiative effect of dust, the difference between net shortwave radiative flux in a cloud free and cloud and aerosol free atmosphere, is typically estimated using forward calculations made with a radiative transfer model. However, estimates of the direct radiative effect made via this initial method can be highly uncertain due to difficultly in accurately describing the relevant optical and physical properties of dust used in these calculations. An alternative approach to estimate this effect is to determine the forcing efficiency, or the direct radiative effect normalized by aerosol optical depth. While this approach avoids the uncertainties associated with the initial method for calculating the direct effect, random errors and biases associated with this approach have not been thoroughly examined in literature. Here we explore biases in this observation‐based approach that are related to atmospheric water vapor. We use observations to show that over the Sahara Desert dust optical depth and column‐integrated atmospheric water vapor are positively correlated. We use three idealized radiative models of varying complexity to demonstrate that a positive correlation between dust and water vapor produces a positive bias in the dust forcing efficiency estimated via the observation‐based method. We describe a simple modification to the observation‐based method that correctly accounts for the correlation between dust and water vapor when estimating the forcing efficiency and use this method to estimate the instantaneous forcing efficiency of dust over the Sahara Desert using satellite data, obtaining −12.3 ± 6.68 to 20.9 ± 11.9 W m−2 per unit optical depth.
Substantial Uncertainties in Arctic Aerosol Simulations by Microphysical Processes Within the Global Climate‐Aerosol Model CAM‐ATRAS
Authors: Matsui Hitoshi , Liu Mingxu 
Published: August 2022

AbstractAerosols can modulate the Arctic climate through their interactions with radiation, clouds, and snow and ice surfaces. Atmospheric simulations of Arctic aerosols remain highly uncertain, for which the importance of aerosol microphysical properties and processes has not been properly evaluated. To identify the cause of this large uncertainty, we evaluate the variability ranges of aerosols in the Arctic resulting from uncertainties in various aerosol microphysical properties/processes, including particle size distributions at emission, particle mixing states, activation efficiency, and wet removal processes, by using a global climate‐aerosol model Community Atmosphere Model with the Aerosol Two‐dimensional bin module for foRmation and Aging Simulation. We find that the combined uncertainties associated with these multiple microphysical properties/processes yield a factor of 10–50 differences (maximum‐to‐minimum ratio) in the concentrations and radiative effects of aerosols in the Arctic. Black carbon shows the highest variability among aerosol species because its lower hygroscopicity and higher critical supersaturation cause the fraction of activation and wet removal during transport to be highly sensitive to the model treatment of aerosol and cloud microphysics. Aerosol‐radiation‐cloud interactions at the top of atmosphere vary from −0.40 to +0.30 W m−2 in the Arctic (from the preindustrial to present day) and can be positive or negative depending on the treatment of microphysical properties/processes. These results indicate that microphysical properties/processes are more important than previously thought in aerosol simulations in the Arctic and demonstrate that a better understanding and more sophisticated model representation of aerosol microphysical properties/processes are required to improve the accuracy of Arctic aerosol simulations and their impacts on climate.
Effect of Impact Velocity and Angle on Deformational Heating and Postimpact Temperature
Authors: Wakita S. , Genda H. , Kurosawa K. , Davison T. M. , Johnson B. C. 
Published: August 2022

AbstractThe record of impact‐induced shock heating in meteorites is an important key for understanding the collisional history of the solar system. Material strength is important for impact heating, but the effect of impact angle and impact velocity on shear heating remains poorly understood. Here, we report three‐dimensional oblique impact simulations, which confirm the enhanced heating due to material strength and explore the effects of impact angle and impact velocity. We find that oblique impacts with an impact angle that is steeper than 45‐degrees produce a similar amount of heated mass as vertical impacts. On the other hand, grazing impacts produce less heated mass and smaller heated regions compared to impacts at steeper angles. We derive an empirical formula of the heated mass, as a function of the impact angle and velocity. This formula can be used to estimate the impact conditions (velocity and angle) that occurred and caused Ar loss in the meteoritic parent bodies. Furthermore, our results indicate that grazing impacts at higher impact velocities could generate a similar amount of heated material as vertical impacts at lower velocities. As the heated material produced by grazing impacts has experienced lower pressure than the material heated by vertical impacts, our results imply that grazing impacts may produce weakly shock‐heated meteorites.
Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study
Authors: Lago-Sampedro Ana , Lhamyani Said , Valdés Sergio , Colomo Natalia , Maldonado-Araque Cristina , González-Molero Inmaculada , Doulatram-Gamgaram Viyey , Delgado Elias , Chaves Felipe J. , Castaño Luis , Calle-Pascual Alfonso , Franch-Nadal Josep , Rojo-Martínez Gemma , García-Serrano Sara , García-Escobar Eva 
Published: August 2022

Abstract
Background/Objectives
Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up.

Subjects/Methods
A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria.

Results
A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category.

Conclusion
Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.
Schizophrenia-associated differential DNA methylation in brain is distributed across the genome and annotated to MAD1L1, a locus at which DNA methylation and transcription phenotypes share genetic variation with schizophrenia risk
Authors: McKinney Brandon C. , McClain Lora L. , Hensler Christopher M. , Wei Yue , Klei Lambertus , Lewis David A. , Devlin Bernie , Wang Jiebiao , Ding Ying , Sweet Robert A. 
Published: August 2022

AbstractDNA methylation (DNAm), the addition of a methyl group to a cytosine in DNA, plays an important role in the regulation of gene expression. Single-nucleotide polymorphisms (SNPs) associated with schizophrenia (SZ) by genome-wide association studies (GWAS) often influence local DNAm levels. Thus, DNAm alterations, acting through effects on gene expression, represent one potential mechanism by which SZ-associated SNPs confer risk. In this study, we investigated genome-wide DNAm in postmortem superior temporal gyrus from 44 subjects with SZ and 44 non-psychiatric comparison subjects using Illumina Infinium MethylationEPIC BeadChip microarrays, and extracted cell-type-specific methylation signals by applying tensor composition analysis. We identified SZ-associated differential methylation at 242 sites, and 44 regions containing two or more sites (FDR cutoff of q = 0.1) and determined a subset of these were cell-type specific. We found mitotic arrest deficient 1-like 1 (MAD1L1), a gene within an established GWAS risk locus, harbored robust SZ-associated differential methylation. We investigated the potential role of MAD1L1 DNAm in conferring SZ risk by assessing for colocalization among quantitative trait loci for methylation and gene transcripts (mQTLs and tQTLs) in brain tissue and GWAS signal at the locus using multiple-trait-colocalization analysis. We found that mQTLs and tQTLs colocalized with the GWAS signal (posterior probability >0.8). Our findings suggest that alterations in MAD1L1 methylation and transcription may mediate risk for SZ at the MAD1L1-containing locus. Future studies to identify how SZ-associated differential methylation affects MAD1L1 biological function are indicated.