bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOuble SEquential External Defibrillation for Refractory Ventricular Fibrillation (DOSE VF): study protocol for a randomized controlled trial
Authors: Drennan Ian R. , Dorian Paul , McLeod Shelley , Pinto Ruxandra , Scales Damon C. , Turner Linda , Feldman Michael , Verbeek P. Richard , Morrison Laurie J. , Cheskes Sheldon 
Published: November 2020

Abstract
Background
Despite high-quality cardiopulmonary resuscitation (CPR), early defibrillation, and antiarrhythmic medications, some patients remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. These patients have worse outcomes compared to patients who respond to initial treatment. Double sequential external defibrillation (DSED) and vector change (VC) defibrillation have been proposed as viable options for patients in refractory VF. However, the evidence supporting the use of novel defibrillation strategies is inconclusive. The objective of this study is to compare two novel therapeutic defibrillation strategies (DSED and VC) against standard defibrillation for patients with treatment refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest.

Research question
Among adult (≥ 18 years) patients presenting in refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest, does DSED or VC defibrillation result in greater rates of survival to hospital discharge compared to standard defibrillation?

Methods
This will be a three-arm, cluster randomized trial with repeated crossover conducted in six regions of Ontario, Canada (Peel, Halton, Toronto, Simcoe, London, and Ottawa), over 3 years. All adult (≥ 18 years) patients presenting in refractory VF (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts during out-of-hospital cardiac arrest of presumed cardiac etiology will be treated by one of three strategies: (1) continued resuscitation using standard defibrillation, (2) resuscitation involving DSED, or (3) resuscitation involving VC (change of defibrillation pads from anterior-lateral to anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. Secondary outcomes will include return of spontaneous circulation (ROSC), VF termination after the first interventional shock, VF termination inclusive of all interventional shocks, and number of defibrillation attempts to obtain ROSC. We will also perform an a priori subgroup analysis comparing rates of survival for those who receive “early DSED,” or first DSED shock is shock 4–6, to those who receive “late DSED,” or first DSED shock is shock 7 or later.

Discussion
A well-designed randomized controlled trial employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is urgently required to determine if the treatments of DSED or VC defibrillation impact clinical outcomes.

Trial registration
ClinicalTrials.gov NCT04080986. Registered on 6 September 2019.
Epigenetic modification mechanisms involved in keloid: current status and prospect
Authors: Lv Wenchang , Ren Yuping , Hou Kai , Hu Weijie , Yi Yi , Xiong Mingchen , Wu Min , Wu Yiping , Zhang Qi 
Published: November 2020

AbstractKeloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.
Ursodeoxycholic acid and bezafibrate were useful for steroid-refractory, immune-related hepatitis: a case report
Authors: Onishi Sachiyo , Tajika Masahiro , Bando Hideaki , Matsubara Yuki , Hosoda Waki , Muro Kei , Niwa Yasumasa 
Published: November 2020

Abstract
Background
Immune checkpoint inhibitors have shown clinically significant antitumor efficacy and have been approved for the treatment of various kinds of advanced malignancies. On the other hand, these immunotherapies show unique adverse events, termed “immune-related adverse events,” which are distinctly associated with conventional cytotoxic chemotherapy. Hepatotoxicity is recognized as an immune-related adverse event; prompt treatment with corticosteroids is recommended. However, some cases are refractory to steroids. Here, we report the first case (to our knowledge) of steroid-refractory immune-related hepatitis that was successfully treated with ursodeoxycholic acid and bezafibrate.

Case presentation
A 68-year-old Asian man, came to our hospital for the treatment of malignant melanoma involving the gingiva and presenting with multiple lymph node and bone metastases was administered nivolumab as a first-line treatment. Two months into treatment, the patient developed diarrhea as a result of immune-related colitis; the colitis was treated successfully with prednisolone 60 mg/ day, resulting in improvement in the patient’s symptoms. However, when steroids were being tapered, acute elevation of liver enzymes was observed. Autoimmune hepatitis was suspected as an immune-related adverse event, and treatment with intravenous prednisolone 60 mg/ day was reinitiated. However, restoration of the steroid treatment failed to improve the patient’s liver enzymes. On the basis of histological findings from liver biopsy and exclusion of other etiologies such as viral infection and other drug-induced hepatitis, steroid-refractory hepatic immune-related adverse event was deemed the most likely cause of the patient’s acute hepatitis. In general, mycophenolate mofetil or tacrolimus is known to provide benefits in cases of steroid-refractory hepatitis. We therefore decided to add oral ursodeoxycholic acid and bezafibrate in consideration of the patient’s background of repeated aspiration pneumonia. Administration of this regimen resulted in an improvement in liver function, which remained normal even after tapering of prednisolone.

Conclusions
Ursodeoxycholic acid and bezafibrate may be useful for treatment of steroid-refractory immune-related adverse event hepatitis.
Epidemiology of the association between serum 25-hydroxyvitamin D levels and musculoskeletal conditions among elderly individuals: a literature review
Authors: Arima Kazuhiko , Mizukami Satoshi , Nishimura Takayuki , Tomita Yoshihito , Nakashima Hiroki , Abe Yasuyo , Aoyagi Kiyoshi 
Published: November 2020

Abstract
Background
Vitamin D deficiency is associated with osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. Elderly individuals are more likely to present with poor musculoskeletal conditions. Recently, several epidemiological studies have assessed the correlation between serum 25-hydroxyvitamin D (25(OH)D) levels and musculoskeletal conditions in elderly individuals.

Main text
Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Numerous studies have shown a positive association between serum 25(OH)D levels and bone mineral density. Only a few studies have reported an association between serum 25(OH)D levels and quantitative ultrasound (QUS) parameters. Low serum 25(OH)D level may be a risk factor for hip fracture. However, data on the association between vitamin D deficiency and the incidence of non-hip fracture are contrasting. Falls are a major cause of mortality and morbidity in older adults. Several prospective population-based cohort studies have shown that low 25(OH)D levels are associated with an increased risk of falls. Reduced muscle strength and physical performance are risk factors for adverse events, including disability, institutionalization, and mortality. The role of vitamin D in musculoskeletal functionality (muscle weakness and physical performance) among elderly individuals is still controversial. Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability among older adults. Data on the association between serum 25(OH)D levels and OA are contrasting.

Conclusion
Some studies have shown that vitamin D deficiency may be a risk factor for poor musculoskeletal conditions, such as osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. However, other studies did not find an association between serum 25(OH)D levels and musculoskeletal conditions.
Two-point normalization for reducing inter-laboratory discrepancies in δ17O, δ18O, and Δ′17O of reference silicates
Authors: Kim Nak Kyu , Park Changkun , Kusakabe Minoru 
Published: November 2020

AbstractThe δ17O and δ18O values of a number of terrestrial minerals and rocks have been determined using laser fluorination method worldwide. For the comprehensive and congruous interpretation of oxygen isotope data, the δ-values should be normalized by the two-point method (i.e., the VSMOW-SLAP scale) to eliminate inter-laboratory bias. In this study, the δ17O and δ18O values of VSMOW and SLAP were measured to calibrate our laboratory working standard O2 gas. The O2 gas liberated from the water samples was purified using the preparation line normally employed for solid samples, and analyzed by the same mass spectrometer. From the analyses of VSMOW and SLAP, the oxygen isotope compositions of the international silicate standards (UWG2 garnet, NBS28 quartz, and San Carlos olivine) were normalized to the VSMOW-SLAP scale (two-point calibration), and then the Δ′17O values were determined. Using the δ-values obtained in this way, the inter-laboratory discrepancy of the δ17O and δ18O results of the silicate standards could be reduced. The VSMOW-SLAP scaling for δ17O and δ18O analysis of silicates provides the most effective way to obtain accurate and precise data. In reporting the Δ′17O values, it is important to make the choice of the reference fractionation line into account because the Δ′17O value is quite variable owing to the slope and y-intercept of the linear relation of the δ-values. The reference fractionation line obtained from the measurement of the low- and high-δ18O reference silicates would help to compare ∆′17O values. We confirmed that the ∆′17O results of the international silicate standards based on the two-point silicate reference line were consistent with the results from other laboratories.
Effect of core electrical conductivity on core surface flow models
Authors: Matsushima Masaki 
Published: November 2020

AbstractThe electrical conductivity of the Earth’s core is an important physical parameter that controls the core dynamics and the thermal evolution of the Earth. In this study, the effect of core electrical conductivity on core surface flow models is investigated. Core surface flow is derived from a geomagnetic field model on the presumption that a viscous boundary layer forms at the core–mantle boundary. Inside the boundary layer, where the viscous force plays an important role in force balance, temporal variations of the magnetic field are caused by magnetic diffusion as well as motional induction. Below the boundary layer, where core flow is assumed to be in tangentially geostrophic balance or tangentially magnetostrophic balance, contributions of magnetic diffusion to temporal variation of the magnetic field are neglected. Under the constraint that the core flow is tangentially geostrophic beneath the boundary layer, the core electrical conductivity in the range from$${10}^{5} ~\mathrm{S}~{\mathrm{m}}^{-1}$$105Sm-1to$${10}^{7}~ \mathrm{S}~{\mathrm{m}}^{-1}$$107Sm-1has less significant effect on the core flow. Under the constraint that the core flow is tangentially magnetostrophic beneath the boundary layer, the influence of electrical conductivity on the core flow models can be clearly recognized; the magnitude of the mean toroidal flow does not increase or decrease, but that of the mean poloidal flow increases with an increase in core electrical conductivity. This difference arises from the Lorentz force, which can be stronger than the Coriolis force, for higher electrical conductivity, since the Lorentz force is proportional to the electrical conductivity. In other words, the Elsasser number, which represents the ratio of the Lorentz force to the Coriolis force, has an influence on the difference. The result implies that the ratio of toroidal to poloidal flow magnitudes has been changing in accordance with secular changes of rotation rate of the Earth and of core electrical conductivity due to a decrease in core temperature throughout the thermal evolution of the Earth.
Solar cycle-related variation in solar differential rotation and meridional flow in solar cycle 24
Authors: Imada Shinsuke , Matoba Kengo , Fujiyama Masashi , Iijima Haruhisa 
Published: November 2020

AbstractWe studied temporal variation of the differential rotation and poleward meridional circulation during solar cycle 24 using the magnetic element feature tracking technique. We used line-of-sight magnetograms obtained using the helioseismic and magnetic imager aboard the Solar Dynamics Observatory from May 01, 2010 to March 26, 2020 (for almost the entire period of solar cycle 24, Carrington rotation from 2096 to 2229) and tracked the magnetic element features every 1 h. We also estimated the differential rotation and poleward meridional flow velocity profiles. The observed profiles are consistent with those of previous studies on different cycles. Typical properties resulting from torsional oscillations can also be observed from solar cycle 24. The amplitude of the variation was approximately ±10 m s$$^{-1}$$

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1

. Interestingly, we found that the average meridional flow observed in solar cycle 24 is faster than that observed in solar cycle 23. In particular, during the declining phase of the cycle, the meridional flow of the middle latitude is accelerated from 10 to 17 m s$$^{-1}$$

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1

, which is almost half of the meridional flow itself. The faster meridional flow in solar cycle 24 might be the result of the weakest cycle during the last 100 years.
Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review
Authors: Bendahan Zita C. , Escobar Lina M. , Castellanos Jaime E. , González-Carrera María C. 
Published: November 2020

Abstract
Background
Folate is a naturally occurring, water-soluble B vitamin. The synthetic form of this compound is folic acid (FA), the deficiency of which is linked to neural tube disorders (NTD), which can be prevented by consuming it before, or during the early months of, pregnancy. However, the effect of FA on oral cleft formation remains controversial. The aim of the present study was to review the evidence concerning the effect of FA on the formation of cleft lip and palate (CLP) in both animals and humans, as well as its impact on different cell types. A search was conducted on various databases, including MEDLINE, EMBASE, and Central, for articles published until January 2020.

Main body
Current systematic reviews indicate that FA, alone or in combination with other vitamins, prevents NTD; however, there is no consensus on whether its consumption can prevent CLP formation. Conversely, the protective effect of FA on palatal cleft (CP) induction has been inferred from animal models; additionally, in vitro studies enumerate a cell-type and dose-dependent effect of FA on cell viability, proliferation, and differentiation, hence bolstering evidence from epidemiological studies.

Conclusions
Meta-analysis, animal models, and in vitro studies demonstrated the protective effect of FA against isolated CP; however, the heterogeneity of treatment protocols, doses, and FA administration method, as well as the different cell types used in in vitro studies, does not conclusively establish whether FA prevents CLP formation.
Validating a Numerical Simulation of the ConsiGma(R) Coater
Authors: Boehling Peter , Jacevic Dalibor , Detobel Frederik , Holman James , Wareham Laura , Metzger Matthew , Khinast Johannes G. 
Published: November 2020

AbstractContinuous manufacturing is increasingly used in the pharmaceutical industry, as it promises to deliver better product quality while simultaneously increasing production flexibility. GEA developed a semi-continuous tablet coater which can be integrated into a continuous tableting line, accelerating the switch from traditional batch production to the continuous mode of operation. The latter offers certain advantages over batch production, e.g., operational flexibility, increased process/product quality, and decreased cost. However, process understanding is the key element for process control. In this regard, computational tools can improve the fundamental understanding and process performance, especially those related to new processes, such as continuous tablet coating where process mechanics remain unclear. The discrete element method (DEM) and computational fluid dynamics (CFD) are two methods that allow transition from empirical process design to a mechanistic understanding of the individual process units. The developed coupling model allows to track the heat, mass, and momentum exchange between the tablet and fluid phase. The goal of this work was to develop and validate a high-fidelity CFD-DEM simulation model of the tablet coating process in the GEA ConsiGma® coater. After the model development, simulation results for the tablet movement, coating quality, and heat and mass transfer during the coating process were validated and compared to the experimental outcomes. The experimental and simulation results agreed well on all accounts measured, indicating that the model can be used in further studies to investigate the operating space of the continuous tablet coating process.
The Isopropylation of Naphthalene over USY Zeolite with FAU Topology. The Selectivities of the Products
Authors: Sugi Yoshihiro , Joseph Stalin , Ramadass Kavitha , Indirathankam Sathish Clastinrusselraj , Premkumar Selvarajan , Dasireddy Venkata D B C , Yang Jae-Hun , Al-Muhtaseb Ala'a H , Liu Qing , Kubota Yoshihiro , Komura Kenichi , Vinu Ajayan 
Published: November 2020

Abstract
The isopropylation of naphthalene (NP) over USY zeolite (FAU06, SiO2/Al2O3 = 6) gave all eight possible diisopropylnaphthalene (DIPN) isomers: β,β- (2,6- and 2,7-), α,β- (1,3-, 1,6-, and 1,7-), and α,α- (1,4- and 1,5-). The catalyses are operated under kinetic and/or thermodynamic controls depending on the reaction temperatures because the cavities of FAU topology are wide enough to form all DIPN isomers. Enhanced selectivities for β,β-DIPN were observed at the early stages at 200, 250, and 300 °C although the selectivities decreased with the increasing periods, accompanying the increase in α,α- and α,β-DIPN. The enhancement occurs under new types of thermodynamic controls through thermodynamically preferred transition states to β,β-DIPN. Triisopropylnaphthalene (TriIPN) isomers are also formed in the isopropylation. Unstable α,α,β-TriIPN (1,4,6- and 1,3,5-) is predominantly formed at lower temperatures; however, decreased with the increase of stable α,β,β-TriIPN (1,3,6- and 1,3,7-) at higher temperatures. The predominant formation of 1,4,6-TriIPN was also observed in the initial stages in the range of 200, 250 and 300 °C, as reaction period was increased, while the selectivity for the isomer was decreased with concomitant increase in the selectivities for the other isomers. These changes of the selectivities operated under kinetic and/or thermodynamic controls. Large cavities of the zeolite allow the formation of all TriIPN isomers without steric restriction.
A study of using a deep learning image reconstruction to improve the image quality of extremely low-dose contrast-enhanced abdominal CT for patients with hepatic lesions
Authors: Cao Le , Liu Xiang , Li Jianying , Qu Tingting , Chen Lihong , Cheng Yannan , Hu Jieliang , Sun Jingtao , Guo Jianxin 
Published: November 2020

Objective:
To investigate the feasibility of using deep learning image reconstruction (DLIR) to significantly reduce radiation dose and improve image quality in contrast-enhanced abdominal CT.

Methods:
This was a prospective study. 40 patients with hepatic lesions underwent abdominal CT using routine dose (120kV, noise index (NI) setting of 11 with automatic tube current modulation) in the arterial-phase (AP) and portal-phase (PP), and low dose (NI = 24) in the delayed-phase (DP). All images were reconstructed at 1.25 mm thickness using ASIR-V at 50% strength. In addition, images in DP were reconstructed using DLIR in high setting (DLIR-H). The CT value and standard deviation (SD) of hepatic parenchyma, spleen, paraspinal muscle and lesion were measured. The overall image quality includes subjective noise, sharpness, artifacts and diagnostic confidence were assessed by two radiologists blindly using a 5-point scale (1, unacceptable and 5, excellent). Dose between AP and DP was compared, and image quality among different reconstructions were compared using SPSS20.0.

Results:
Compared to AP, DP significantly reduced radiation dose by 76% (0.76 ± 0.09 mSv vs 3.18 ± 0.48 mSv), DLIR-H DP images had lower image noise (14.08 ± 2.89 HU vs 16.67 ± 3.74 HU, p &lt; 0.001) but similar overall image quality score as the ASIR-V50% AP images (3.88 ± 0.34 vs 4.05 ± 0.44, p &gt; 0.05). For the DP images, DLIR-H significantly reduced image noise in hepatic parenchyma, spleen, muscle and lesion to (14.77 ± 2.61 HU, 14.26 ± 2.67 HU, 14.08 ± 2.89 HU and 16.25 ± 4.42 HU) from (24.95 ± 4.32 HU, 25.42 ± 4.99 HU, 23.99 ± 5.26 HU and 27.01 ± 7.11) with ASIR-V50%, respectively (all p &lt; 0.001) and improved image quality score (3.88 ± 0.34 vs 2.87 ± 0.53; p &lt; 0.05).

Conclusion:
DLIR-H significantly reduces image noise and generates images with clinically acceptable quality and diagnostic confidence with 76% dose reduction.

Advances in knowledge:
(1) DLIR-H yielded a significantly lower image noise, higher CNR and higher overall image quality score and diagnostic confidence than the ASIR-V50% under low signal conditions. (2) Our study demonstrated that at 76% lower radiation dose, the DLIR-H DP images had similar overall image quality to the routine-dose ASIR-V50% AP images.