bluuebunny/crossref_metadata_2025 huggingface dataset:
3D‐Printed high‐NA catadioptric thin lens for suppression of XPM background in Stimulated Raman Scattering microscopy
Authors: Bertoncini Andrea , Laptenok Sergey P. , Genchi Luca , Rajamanickam Vijayakumar P. , Liberale Carlo
Published: July 2020

Stimulated Raman Scattering (SRS) is a fast chemical imaging technique with remarkable bioscience applications. Cross Phase Modulation (XPM) is a ubiquitous nonlinear phenomenon that can create spurious background signals that render difficult a high‐contrast imaging in SRS measurements. The XPM‐induced signal is usually suppressed using high numerical aperture (NA) microscope objectives or condensers to collect the transmitted excitation beam. However, these high NA optics feature short working distances, hence they are not compatible with stage‐top incubators, that are necessary to perform live‐cell time‐lapse experiments in controlled environments. Here, we show a 3D printed high NA compact catadioptric lens that fits inside stage‐top incubators and allows the collection of XPM‐free SRS signals. The lens delivers SRS images and spectra with a quality comparable to a signal collection with a high‐NA microscope objective. We also demonstrate the compatibility of the 3D printed lens with other nonlinear microscopies usually associated with SRS in multimodal microscopes.
Model‐Based Determination of Elotuzumab Pharmacokinetics in Japanese Patients With Multiple Myeloma Incorporating Time‐Varying M Protein
Authors: Ide Takafumi , Roy Amit , Imai Yasuhiko , Vezina Heather E.
Published: July 2020

A population pharmacokinetic model was developed to evaluate the effects of Japanese ethnicity, prior line of therapy (0 or ≥1), time‐varying M protein, and maintenance dosing regimens (10 mg/kg intravenously every 2 weeks or 20 mg/kg intravenously every 4 weeks beginning in cycle 19) on the pharmacokinetics of elotuzumab in patients with multiple myeloma treated with elotuzumab plus lenalidomide/dexamethasone. Elotuzumab pharmacokinetics were characterized by a 2‐compartment model with parallel linear (nonspecific) and Michaelis‐Menten elimination from the central compartment and target‐mediated elimination from the peripheral compartment. Asian race on nonspecific clearance (CL) and central volume of distribution, prior line of therapy on CL, and maximum target‐mediated elimination rate (Vmax) were statistically significant but not considered clinically relevant (magnitude < 20%). Time‐varying M protein on Vmax was statistically significant, and the magnitude was >20%; however, clinical implications in the setting of combination therapy were not expected. Model‐predicted steady‐state elotuzumab exposure in cycle 12 were similar in Japanese and non‐Japanese patients and in Japanese patients with 0 and ≥1 prior lines of therapy. Elotuzumab 20 mg/kg intravenously every 4 weeks beginning in cycle 19 produced time‐averaged concentrations similar to elotuzumab 10 mg/kg intravenously every 2 weeks, although maximum and minimum concentrations after elotuzumab 20 mg/kg intravenous every‐4‐week dosing were slightly higher and lower, respectively. In conclusion, the current analysis demonstrates that Japanese ethnicity, prior line of therapy, time‐varying M protein, and change in elotuzumab dosing regimen in cycle 19 have no clinically meaningful impact on elotuzumab pharmacokinetics and exposure in Japanese patients with multiple myeloma.
Estimation of Attainment of Steady‐State Conditions for Compounds With a Long Half‐Life
Authors: Krause Andreas , Lott Dominik , Dingemanse Jasper
Published: July 2020

Half‐life is a standard result reported with analysis of pharmacokinetic data. Different definitions such as noncompartmental half‐life, terminal half‐life, effective half‐life, and context‐sensitive half‐life can yield substantially different estimates of the quantity “half‐life.” Time to attainment of steady‐state conditions is generally derived from (terminal) half‐life and therefore sensitive toward the definition of half‐life. Thus, estimates of the time to attain steady state must be provided with a precise definition of steady state and the method used for estimation, particularly for drugs with long (terminal) half‐life. For clinical purposes, terminal half‐life can have limited relevance if drug concentrations in the terminal elimination phase are low. A general rule for which half‐life to use is infeasible. While limited accumulation can be negligible if a plateau in pharmacokinetics/pharmacodynamics is reached or with a wide therapeutic window (ie, exposure range), small additional drug accumulation can be highly relevant for drugs with a narrow therapeutic window. Beyond the average, estimation of individual time to attainment of steady state can add highly relevant information about the variability between subjects. Simulations from population models and the use of different definitions of steady state provide an assessment of robustness of the results. The relevance of accurate estimation of time to attainment of steady state is illustrated with cenerimod, an sphingosine‐1‐phosphate 1 receptor modulator with long half‐life currently in clinical development for which estimates of time to steady state ranged from 35 to 110 days with different calculations.
Assessment of cadmium toxicity and its possible effects on goldfish (Carassius auratus), employing microscopy and biochemical techniques
Authors: Noor Zohaib , Khan Syed Allauddin , Noor Mannal
Published: July 2020

The present study aimed to evaluate and compare the toxicity level of dietary and waterborne Cadmium (Cd) source on the Goldfish Carassius auratus (C. auratus) using various biochemical and microscopic shreds of evidence. C. auratus were divided into two groups based on Cadmium supplementation methods subjected to the same concentrations in the diet and water; moreover, control (Ctrl) group was set up for comparison. Dietary supplemented group (DSG) group and (Aqueous supplemented groups) ASG were supplied with 0.5% of the Cadmium. Successful completion of the study resulted in the lucrative outcomes, and we noticed significantly high concentrations of Cadmium in the gills of the ASG fish while considerably low levels in the gills of DSG. Histopathological evidence showed clear and distinct changes in the liver cells, dilated sinusoids and unusual occurrence of Kupffer cells were noticed in the AS group fish. At the same time, there were also noticeable changes in the DS group compared to CTRL. Visible changes can be seen on the outer morphology of gills, lamella of ASG and DSG both were shrunk and broken, similar changes were noticed in the muscles myoepithelium. The stress parameters were differentially expressed in both the groups; waterborne Cadmium caused a pronounced release of AST, ALT, cortisol, and glucose concentrations. Comparative mortality showed the highest death rate in the ASG fish compared to DSG fish. The present study depicts the highest toxicity of Cadmium in the soluble Addendum form moreover, administered route and time length are crucial factors.
Improved electroretinographic responses following dietary intervention in a patient with Refsum disease
Authors: Benson Matthew D. , MacDonald Ian M. , Sheehan Melissa , Jain Shailly
Published: July 2020

Refsum disease is a rare inherited metabolic disorder arising from a defect in peroxisomal metabolism. Patients lack the functional enzyme phytanoyl‐CoA hydroxylase, resulting in perturbed alpha oxidation of fatty acids. Phytanic acid accumulates in nervous and adipose tissue and leads to several disease phenotypes including early‐onset retinal degeneration, hearing loss, peripheral neuropathy, anosmia, and cerebellar ataxia, among others. Currently, restricting dietary phytanic acid is the only means of altering the chronic sequelae and the disease course. While dietary intervention has been demonstrated to improve peripheral neuropathy, ichthyosis, and ataxia, there have been no reports of improved retinal function in patients with Refsum disease. We describe the case of a 51‐year‐old patient with molecularly and biochemically confirmed Refsum disease who underwent electroretinography before and after beginning a phytanic acid‐restricted diet. His post‐intervention 30 Hz flicker electroretinogram demonstrated significantly improved waveform amplitudes and implicit times, suggesting improved retinal function. Thus, we propose that the possibility exists for some visual recovery in these patients and we highlight the utility of performing standardized electroretinography to assess treatment response in Refsum disease.
Numerical modeling and parameters extraction of novel triple hole block layer‐based organic light‐emitting diode for display
Authors: Negi Shubham , Mittal Poornima , Kumar Brijesh
Published: July 2020

Depth knowledge regarding device internal physics is very essential, and its application aids to develop innovative methods for device performance enhancement. Taking this point into cognizance, the present article introduced a novel triple hole block layer (HBL) organic light‐emitting diode (OLED) architecture and its analytical modeling based on Poisson's equation and drift diffusion equation. Compared with multilayered OLED and double HBL structure, the novel device depicted improvement of luminescence performance by 47% and 30% correspondingly, at a driving voltage of 18 V. Analytical analysis is undertaken to extract internal device parameters such as electron and hole concentration, their mobility, and current density. Analysis results revealed the reason for improved performance is higher electron concentration (2.53 * 1018), 5% increase over multilayered OLED. Additionally, it is observed that mismatch in electron and hole concentration is small in novel triple HBL OLED and compared with multilayered OLED, the mismatch is lower by 63%. Therefore, objective to achieve a balanced electron and hole concentration is achieved by utilization of triple HBL OLED without increasing the overall device dimension.
Effects of Contrast‐Enhanced Ultrasound of Indeterminate Renal Masses on Patient Clinical Management
Authors: Eisenbrey John R. , Kamaya Aya , Gummadi Sriharsha , Bird Kristen , Burrowes David , Arias Diego , Lallas Costas D. , Trabulsi Edouard J. , Lyshchik Andrej
Published: July 2020

Objectives

To investigate the long‐term impact of contrast‐enhanced ultrasound (CEUS) on the treatment of patients with indeterminate renal masses.

Methods

In this retrospective study, consecutive charts of all patients receiving renal CEUS at 1 of 2 academic medical centers between January 1, 2014, and December 31, 2018, were reviewed. Patients were included in the study if they had documented chronic renal disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2) or prior nephrectomy and received CEUS for a previously untreated renal mass.

Results

A total of 215 lesions in 157 patients were used for analysis. Contrast‐enhanced ultrasound provided a final treatment recommendation in 71.6% of lesions (154 of 215). Of these 154 lesions, 7.8% (12 of 154) were lost to follow‐up despite CEUS suggesting malignancy; 15.6% (24 of 154) went directly for surgical intervention, with malignancy confirmed by pathologic results in 87.5% (21 of 24) of these cases; and the remaining 76.6% (118 of 154) were deemed benign and required no additional follow‐up. Of the 118 lesions diagnosed by CEUS as benign and requiring no follow‐up, none showed evidence of later renal cell carcinoma development and, only 5.1% (6 of 118) of the total population was referred for further cross‐sectional imaging of the mass in question. In 28.4% of all lesions (61 of 215), CEUS resulted in a recommendation for surveillance imaging at a 6‐ to 12‐month interval, and less than 10% (6 of 61) of these underwent additional cross‐sectional imaging within the recommended 6 months after CEUS.

Conclusions

These findings highlight the impact of CEUS on clinical treatment of indeterminate renal masses, including reducing the use of the potentially nephrotoxic contrast agents and providing a direct pathway to transplant.
Dermal Fat Grafting to Reconstruct the Parotidectomy Defect Normalizes Facial Attention
Authors: Anderies Barrett J. , Dey Jacob K. , Gruszczynski Nelson R. , Price Daniel L. , Moore Eric J. , Janus Jeffrey R.
Published: July 2020

Objectives/Hypothesis

Use validated eye‐tracking technology to objectively measure 1) the attentional distraction of facial contour defects after superficial and total parotidectomy and 2) changes in attentional distraction with abdominal dermal fat graft reconstruction.

Methods

Standardized frontal and oblique facial images of 16 patients who had undergone superficial or total parotidectomy with or without fat graft reconstruction; four normal controls were obtained. One hundred casual observers were recruited to view these images, and gaze data were collected using a Tobii Pro eye‐tracking system. Gaze durations for predefined facial areas of interest were analyzed using mixed‐effects linear regression to test study hypotheses.

Results

For frontal images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (92 milliseconds, 95% confidence interval [CI]: 48‐138 milliseconds, P < .001). Fat grafting normalized the attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .414). For oblique images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (658 milliseconds, 95% CI: 463‐854 milliseconds, P < .001). Fat grafting normalized this attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .504). In both views, superficial parotidectomy demonstrated no significant attentional distractions, with or without fat grafting.

Conclusions

This eye‐tracking study objectively demonstrates that total parotidectomy results in a facial contour deformity that is distracting to observers, whereas superficial parotidectomy does not. For total parotidectomy, this attentional distraction can be normalized with dermal fat graft reconstruction.

Level of Evidence

3b Laryngoscope, 131:E124–E131, 2021
Fractional Cauchy problem with memory effects
Authors: Abadias Luciano , Alvarez Edgardo
Published: July 2020

We give an original representation integral formula for the resolvent families associated to the fractional Cauchy equation with memory effects
where and A is a sectorial operator on a Banach space X. Moreover, we get spatial bounds for the resolvent families in order to study global or blow up mild solutions when the nonlinearity f satisfies a locally Lipschitz condition. The case of critical nonlinearities is also treated.
Online advance selling or not: Pricing strategy of new product entry in a supply chain
Authors: Zhang Yawen , Li Bo , Chen Xue , Wu Shuang
Published: July 2020

Considering consumers' strategic behavior and loss averseness of the deposit, this paper establishes a two‐period Stackelberg game model in a supply chain system, in which a manufacturer cooperates with an e‐retailer to perform advance selling to consumers. The optimal pricing decisions are obtained, and the impacts of the e‐retailer's advance selling activities on the profits of both parties are discussed. Studies have shown that advance selling activities always benefit the manufacturer, but they can hurt the e‐retailer. Within some specific conditions, the advance selling model can achieve Pareto improvement to both parties and benefit the performance of the supply chain.
Therapeutic antisense oligonucleotides for movement disorders
Authors: Doxakis Epaminondas
Published: July 2020

Movement disorders are a group of neurological conditions characterized by abnormalities of movement and posture. They are broadly divided into akinetic and hyperkinetic syndromes. Until now, no effective symptomatic or disease‐modifying therapies have been available. However, since many of these disorders are monogenic or have some well‐defined genetic component, they represent strong candidates for antisense oligonucleotide (ASO) therapies. ASO therapies are based on the use of short synthetic single‐stranded ASOs that bind to disease‐related target RNAs via Watson–Crick base‐pairing and pleiotropically modulate their function. With information arising from the RNA sequence alone, it is possible to design ASOs that not only alter the expression levels but also the splicing defects of any protein, far exceeding the intervention repertoire of traditional small molecule approaches. Following the regulatory approval of ASO therapies for spinal muscular atrophy and Duchenne muscular dystrophy in 2016, there has been tremendous momentum in testing such therapies for other neurological disorders. This review article initially focuses on the chemical modifications aimed at improving ASO effectiveness, the mechanisms by which ASOs can interfere with RNA function, delivery systems and pharmacokinetics, and the common set of toxicities associated with their application. It, then, describes the pathophysiology and the latest information on preclinical and clinical trials utilizing ASOs for the treatment of Parkinson′s disease, Huntington′s disease, and ataxias 1, 2, 3, and 7. It concludes with issues that require special attention to realize the full potential of ASO‐based therapies.
When does attrition lead to biased estimates of alcohol consumption? Bias analysis for loss to follow‐up in 30 longitudinal cohorts
Authors: Keyes Katherine M. , Jager Justin , Platt Jonathan , Rutherford Caroline , Patrick Megan E. , Kloska Deborah D. , Schulenberg John
Published: July 2020

Objectives

Survey nonresponse has increased across decades, making the amount of attrition a focus in generating inferences from longitudinal data. Use of inverse probability weights [IPWs] and other statistical approaches are common, but residual bias remains a threat. Quantitative bias analysis for nonrandom attrition as an adjunct to IPW may yield more robust inference.

Methods

Data were drawn from the Monitoring the Future panel studies [twelfth grade, base‐year: 1976–2005; age 29/30 follow‐up: 1987–2017, N = 73,298]. We then applied IPW imputation in increasing percentages, assuming varying risk differences [RDs] among nonresponders. Measurements included past‐two‐week binge drinking at base‐year and every follow‐up. Demographic and other correlates of binge drinking contributed to IPW estimation.

Results

Attrition increased: 31.14%, base‐year 1976; 61.33%, base‐year 2005. The magnitude of bias depended not on attrition rate but on prevalence of binge drinking and RD among nonrespondents. The probable range of binge drinking among nonresponders was 12–45%. In every scenario, base‐year and follow‐up binge drinking were associated. The likely range of true RDs was 0.14 [95% CI: 0.11–0.17] to 0.28 [95% CI: 0.25–0.31].

Conclusions

When attrition is present, the amount of attrition alone is insufficient to understand contribution to effect estimates. We recommend including bias analysis in longitudinal analyses.
An analytical model for temperature and crystalline evolution analysis of carbon fiber reinforced polymer composites during cooling
Authors: Fang Haidong , Gu Junfeng , Li Zheng , Ruan Shilun , Shen Changyu
Published: July 2020

An analytical model for analyzing the temperature and crystalline evolution of short carbon fiber reinforced polymer composites during cooling was established, and the model was firstly verified by calculating the crystallization kinetics of a short carbon fiber reinforced polypropylene (SCFRPP) plate during isothermal and nonisothermal crystallization. Then the model was extended to calculate the temperature and crystalline evolution of two numerical examples of SCFRPP parts during cooling with different temperature boundaries, and the effects of cooling rate and short carbon fiber (SCF) content were analyzed and compared. According to the results, SCF increases the onset crystallization temperature and accelerates the crystallization rate due to the formation of transcrystal. During the cooling stage, SCF changes the evolution of crystalline and temperature complicatedly, and the changes are more significant under lower cooling rate.
Development of a method to screen and isolate lipoxidase inhibitors from Radix Saposhnikoviae via ultrafiltration liquid chromatography combined with metablism in vitro
Authors: Huang Yu , Yu Min , Wu Tong , Hou Wanchao , Liu Chunming , Li Sainan
Published: July 2020

Introduction

Radix Saposhnikoviae is an excellent source of chromones, the consumption of which has been shown to positively affect human health, such as anti‐inflammatory and antioxidant activities in vivo, and it also has been used to treat headache, inflammation, and cancer as a herbal medicine or functional soup.

Objective

Isolation and screening of lipoxidase (LOX) inhibitors from Radix Saposhnikoviae. As a result, the metabolism of the active ingredients in cytochrome P450 (CYP450) in vitro was identified.

Methods

Screen and identify the LOX inhibitors from Radix Saposhnikoviae by ultrafiltration‐liquid chromatography‐mass spectrometry (UF‐LC–MS). Then take the isolation and purification of the inhibitors by high‐speed counter‐current chromatography (HSCCC) and semi‐preparative high‐performance liquid chromatography (HPLC). Furthermore, the active ingredients were used to study the metabolism in vitro in CYP450.

Results

Subsequently, the specific binding ligands, prim‐O‐glucosylcimifugin, cimifugin, and 5‐O‐methylvisamminol (with purities of 95.28, 92.33%, and 97.89, respectively) were separated by HSCCC. Semi‐preparative HPLC was applied to separate the four major compounds in Radix Saposhnikoviae and identify them as prim‐O‐glucosylcimifugin, 5‐O‐methylvisamminol, sec‐O‐glucosylhamaudol, and hamaudol, which were obtained with relatively high purity. Furthermore, the three chromone possible metabolism pathways were obtained.

Conclusion

The results demonstrated that UF‐LC–MS combined with HSCCC and semi‐preparative HPLC is not only a powerful tool for screening and isolating LOX inhibitors in complex samples, but also a useful platform for discovering bioactive compounds for anti‐inflammatory activity. This study provides information regarding the active ingredients of chromones in Radix Saposhnikoviae and a framework for anti‐inflammatory activity treatment.
Solar cell efficiency tables (version 56)
Authors: Green Martin A. , Dunlop Ewan D. , Hohl‐Ebinger Jochen , Yoshita Masahiro , Kopidakis Nikos , Hao Xiaojing
Published: July 2020

Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined, and new entries since January 2020 are reviewed.
Trend of depression and its association with sociodemographic and clinical factors among multiple myeloma hospitalizations: A Portuguese nationwide study from 2000 to 2015
Authors: Ribeiro‐Carvalho Francisco , Gonçalves‐Pinho Manuel , Bergantim Rui , Freitas Alberto , Fernandes Lia
Published: July 2020

Objective

Patients hospitalized with multiple myeloma (MM) are particularly vulnerable to depression. The present study aims to determine the frequency of depression among MM hospitalized patients, in order to assess the possible differences between those with and without depression in relation to sociodemographic and clinical variables and to measure the impact of depression on hospitalization outcomes.

Methods

An observational retrospective study was performed using an administrative data set of all hospitalizations with a primary diagnosis of MM between 2000 and 2015 in Portuguese mainland public hospitals. Codes related to depressive disorders were grouped to generate the dichotomous variable of depression (yes/no). A multivariate analysis was conducted and adjusted odd ratios (aOR) calculated between different variables and depression.

Results

Of a total of 14.575 MM hospitalizations studied, a concurrent code of depression was registered in 666 patients (4.6%). A greater odds of depression was observed in female patients (aOR = 2.26; 95%CI = 1.91‐2.66), transplanted patients (aOR = 1.78; 95%CI = 1.44‐2.20), patients with plasma cell leukemia (aOR = 1.79; 95%CI = 1.22‐2.64) and patients with a higher Charlson Comorbidity Index (CCI) (aOR = 1.10; 95%CI = 1.05‐1.15). Length of stay was longer in patients with a registered diagnosis of depression (aOR = 1.01; 95%CI = 1.01‐1.02) while the odds of in‐hospital mortality were lower in these patients (aOR = 0.53; 95%CI = 0.41‐0.68).

Conclusions

These results may help identify MM inpatients at higher risk of presenting depression (female gender, younger age, high CCI, plasma cell leukemia, transplant procedure). This will enable timely psychological assessment and treatment to prevent worse outcomes and higher healthcare costs associated with depression.
A central role for apathy in the effectiveness of interventions for cancer‐related fatigue
Authors: Lacourt Tamara E. , Heijnen Cobi J. , Manzullo Ellen F. , Escalante Carmen
Published: July 2020

Objective

Cancer‐related fatigue (CRF) affects a substantial number of cancer patients and survivors. Recommendations for CRF treatments are largely based on results of randomized controlled trials. The interpretability of such results is limited to patients eligible and willing to participate in these trials. We aimed to address this limitation in a retrospective study of patients seen at a CRF clinic in a comprehensive cancer center. The objectives were to (a) determine the effectiveness of clinician‐initiated interventions for CRF and identify their mediators and (b) describe the frequency and effectiveness of patient‐initiated physical activity (PA) behavior for alleviating CRF and identify determinants of this PA.

Methods

Data (patient‐reported somatic and mood symptoms; clinical data; clinician‐documented changes in medication and behavior) from n = 213 patients collected as part of the clinic's standard of care at initial clinical consult and follow‐up 4 to 11 weeks later were included. Effects of clinician‐initiated interventions and patient‐initiated PA on change in fatigue were analyzed using linear models.

Results

Of all clinician‐initiated interventions, only psychostimulant start was recorded frequent enough for further investigation and was associated with reduced fatigue; this association was mediated by a reduction in apathy. PA was also associated with reduced fatigue severity. PA initiation/increase after consult was associated with lower apathy at consult.

Conclusions

These results demonstrate a major role for patient apathy in the effectiveness and initiation of CRF‐targeting interventions. Behavioral therapies focusing on reduction in apathy should be considered as initial treatment of CRF in those with substantial apathy.
Adding nebulized corticosteroids to systemic corticosteroids for acute asthma in children: A systematic review with meta‐analysis
Authors: Castro‐Rodriguez Jose A. , Pincheira Mauricio A. , Escobar‐Serna Diana P. , Sossa‐Briceño Monica P. , Rodriguez‐Martinez Carlos E.
Published: July 2020

International guidelines have recommended the use of inhaled beta‐2 agonists and systemic corticosteroids (SCs) as the first‐line treatment for acute asthma.

Objective

To evaluate the evidence for the efficacy of inhaled corticosteroids (ICSs) in addition to SCs compared to SCs alone in children with acute asthma in the emergency department (ED) or during hospitalization.

Data Sources

Five electronic databases were searched.

Study Selection

All randomized clinical trials that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction.

Data Extraction

Two reviewers independently reviewed all the studies. The primary outcomes were hospital admission and hospital length of stay (LOS), and secondary outcomes were readmissions during follow‐up, ED‐LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates.

Results

Nine studies (n = 1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than 1 day (MD = −29.08 hours [−39.9 to −18.3]; I2 = 0%, P = < .00001). Moreover, adding budesonide significantly improved the acute asthma severity score among patients at ED.

Conclusions

Compared to SC alone, adding budesonide to SC does not affect the hospitalization rate, but decreases the LOS and improves the acute asthma score in children in an ED setting.
Prostate cancer‐specific mortality burden by risk group among men with localized disease: Implications for research and clinical trial priorities
Authors: Dee Edward Christopher , Nezolosky Michelle D. , Chipidza Fallon E. , Arega Melaku A. , Butler Santino S. , Sha Sybil T. , Mahal Brandon A. , Nguyen Paul L. , Yang David D. , Muralidhar Vinayak
Published: July 2020

Objective

To estimate contemporary population‐based patterns of the relative burden of prostate cancer‐specific mortality (PCSM) attributable to each N0M0 prostate cancer risk‐group, that may guide prioritization in research, trial design, and clinical practice.

Methods

We categorized 2004‐2015 Surveillance, Epidemiology, and End Results database patients by risk group (low, favorable intermediate, unfavorable intermediate, high, and very highrisk). Using the Fine‐Gray method, we calculated the relative burden of 10‐year PCSM attributable to each risk group.

Results

Among N = 337 162 men (6.8‐year median follow‐up; median age 65 years), the relative proportion of low‐, favorable intermediate‐, unfavorable intermediate‐, high‐, and very high‐risk diagnoses were 29.9% (N = 100 969), 31.1% (N = 104 696), 17.9% (N = 60 360), 18.1% (N = 61 023), and 3.0% (N = 10 114). Within 10 years of diagnosis, among patients who died of prostate cancer (N = 15 064), 5.0% (N = 746) had low‐risk, 13.7% (N = 2060) had favorable intermediate‐risk, 16.1% (N = 2429) had unfavorable intermediate‐risk, 47.8% (N = 7196) had high‐risk, and 17.5% (N = 2633) had very high‐risk disease at diagnosis. Patients aged 65 and older accounted for 51.9% of all diagnoses and 72.3% of 10‐year PCSM. Although black patients accounted for 15.0% of low‐risk diagnoses, they accounted for 20.6% of 10‐year PCSM. White patients accounted for 80.3% of low‐risk diagnoses and 75.7% of 10‐year PCSM.

Conclusion

Although high‐risk and very high‐risk disease account for one‐fifth of diagnoses, they account for two‐thirds of 10‐year PCSM. Older patients and black patients with low‐risk disease accounted for a disproportionately large proportion of deaths. These findings support targeting research toward high‐risk disease and ensuring adequate representation of older and black men in clinical trials.
Theoretical calculation of positron annihilation spectrum using positron‐electron correlation‐polarization potential
Authors: Sugiura Yutaro , Takayanagi Toshiyuki , Tachikawa Masanori
Published: July 2020

The positron‐electron correlation‐polarization potential model is used to calculate annihilation spectra of carbon disulfide and benzene. We assume that the positron is captured in the vibrationally excited states of the target molecule through vibrational Feshbach resonances. Using the standard normal mode representation, we calculated the resonance energies and widths for each vibrational mode. The resonance widths were calculated with Fermi's Golden Rule approximation, where the time‐dependent wave packet approach has been applied. We found that vibrational resonances of infrared‐active modes play a dominant role in resonant annihilation; however, infrared‐inactive modes also contribute to the annihilation spectrum through polarizability changes along normal mode coordinates.
Sequential thermal dissolution of two low‐rank coals and characterization of their structures by high‐performance liquid chromatography/time‐of‐flight mass spectrometry and gas chromatography/mass spectrometry
Authors: Cao Xiao‐Hui , Fan Xing , Xia Jun‐Liu , Mo Wen‐Long , Nulahong Aisha , Zhao Yun‐Peng , Zhao Wei , Ma Feng‐Yun , Wei Xian‐Yong
Published: July 2020

Rationale

Gas chromatography/mass spectrometry (GC/MS) and high‐performance liquid chromatography/time‐of‐flight mass spectrometry (HPLC/TOF‐MS) were used to separate and reveal the molecular characteristics of organic matter in low‐rank coals.

Methods

Six soluble portions (SPs) were obtained by sequential thermal dissolution (TD) of two low‐rank coals in the order of cyclohexane, acetone and methanol solvents at 300°C. Organic matter with different molecular characteristics were enriched in eachTD extract, which was further separated and analyzed by GC/MS and HPLC/TOF‐MS using an electrospray ionization source in positive mode to obtain a comprehensive understanding of the structural composition of coals.

Results

Low polarity compounds like alkanes and arenes have a better solubility in cyclohexane. Phorone has the highest relative abundance in the acetone SPs, and the main compounds detected in the methanol SPs are alcohols and phenols. According to the data from HPLC/TOF‐MS, most of the oxygen atoms are in the form of carbonyl and alkoxy groups. The nitrogen‐containing compounds in SPs are mainly saturated aliphatic amines and pyridines. The sulfur‐containing compounds mainly exist in the form of thioalkanes and thiophenes.

Conclusions

Non‐destructive methods were used to obtain soluble matter from coals, and different chromatographic and mass spectrometric techniques were used to separate and analyze the organic matter in coals. Detailed molecular structural information was obtained for the efficient and clean utilization of low‐rank coals.
Practical stability analysis of sampled‐data switched systems with quantization and delay
Authors: Yan Jingjing , Wang Xinjing , Xia Yuanqing , Yang Hongjiu
Published: July 2020

This article is addressed with the problem of stabilizing a switched linear system using the sampled and quantized state feedback under the influence of time‐varying delay. The switching is supposed to be slow enough in the sense of dwell time, and each individual mode is assumed to be stabilizable. By expanding the approach of attractor set from an earlier result on the delay‐free case, we establish the relationship between the state and the adjacent sampling state by introducing a monotonically increasing sequence, and analyze the mismatch time with classification. On the basis of this, the increment rate of the Lyapunov function and the total mismatch time are combined to achieve the practical stability with an attractor set.
Multi‐Step Phase Transitions of Mn3O4 During Galvanostatic Lithiation: An In Situ Transmission Electron Microscopic Investigation
Authors: Xu Guoguang , Zhang Xinyi , Liu Meinan , Li Hongfei , Zhao Meizhen , Li Qingwen , Zhang Jinping , Zhang Yuegang
Published: July 2020

For study of electrochemical reaction mechanisms at nanoscale, in situ electrochemical transmission electron microscopy (EC‐TEM) exceeds many other methods due to its high temporal and spatial resolution. However, the limited amount of active materials used in previous in situ TEM studies prevents the model EC cells to operate in the constant‐current (galvanostatic) charge/discharge mode that is required for accurate control of electrochemical processes. Herein, a new in situ EC‐TEM technique is developed to investigate multi‐step phase transitions of Mn3O4 electrodes under the galvanostatic charge/discharge mode and constant‐voltage discharge mode. In galvanostatic mode, the lithiation of Mn3O4 undergoes multi‐step phase transitions following a reaction pathway of Mn3O4 + Li+ → LiMn3O4 + Li+ → MnO + Li2O → Mn + Li2O. It is also found that lithium ions prefer to enter Mn3O4 along the {101} direction to form LiMn3O4 with the help of transitional boundary phase of LixMn3O4. These results are in sharp contrast to that obtained under a constant‐voltage discharge mode, where only a single‐step lithiation process of Mn3O4 + Li+ → Mn + Li2O is observed.
Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK
Authors: Kang Mi‐Ae , Lee Jongsung , Park See‐Hyoung
Published: July 2020

In this study, we report the potential of cannabidiol, one of the major cannabis constituents, for enhancing osteoblastic differentiation in U2OS and MG‐63 cells. Cannabidiol increased the expression of Angiopoietin1 and the enzyme activity of alkaline phosphatase in U2OS and MG‐63. Invasion and migration assay results indicated that the cell mobility was activated by cannabidiol in U2OS and MG‐63. Western blotting analysis showed that the expression of tight junction related proteins such as Claudin1, Claudin4, Occuludin1, and ZO1 was increased by cannabidiol in U2OS and MG‐63. Alizarin Red S staining analysis showed that calcium deposition and mineralization was enhanced by cannabidiol in U2OS and MG‐63. Western blotting analysis indicated that the expression of osteoblast differentiation related proteins such as distal‐less homeobox 5, bone sialoprotein, osteocalcin, type I collagen, Runt‐related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase was time dependently upregulated by cannabidiol in U2OS and MG‐63. Mechanistically, cannabidiol‐regulated osteoblastic differentiation in U2OS and MG‐63 by strengthen the protein‐protein interaction among RUNX2, OSX, or the phosphorylated p38 mitogen‐activated protein kinase (MAPK). In conclusion, cannabidiol increased Angiopoietin1 expression and p38 MAPK activation for osteoblastic differentiation in U2OS and MG‐63 suggesting that cannabidiol might provide a novel therapeutic option for the bone regeneration.
The multifaceted role of PARP1 in RNA biogenesis
Authors: Eleazer Rebekah , Fondufe‐Mittendorf Yvonne N.
Published: July 2020

Poly(ADP‐ribose) polymerases (PARPs) are abundant nuclear proteins that synthesize ADP ribose polymers (pADPr) and catalyze the addition of (p)ADPr to target biomolecules. PARP1, the most abundant and well‐studied PARP, is a multifunctional enzyme that participates in numerous critical cellular processes. A considerable amount of PARP research has focused on PARP1's role in DNA damage. However, an increasing body of evidence outlines more routine roles for PARP and PARylation in nearly every step of RNA biogenesis and metabolism. PARP1's involvement in these RNA processes is pleiotropic and has been ascribed to PARP1's unique flexible domain structures. PARP1 domains are modular self‐arranged enabling it to recognize structurally diverse substrates and to act simultaneously through multiple discrete mechanisms. These mechanisms include direct PARP1‐protein binding, PARP1‐nucleic acid binding, covalent PARylation of target molecules, covalent autoPARylation, and induction of noncovalent interactions with PAR molecules. A combination of these mechanisms has been implicated in PARP1's context‐specific regulation of RNA biogenesis and metabolism. We examine the mechanisms of PARP1 regulation in transcription initiation, elongation and termination, co‐transcriptional splicing, RNA export, and post‐transcriptional RNA processing. Finally, we consider promising new investigative avenues for PARP1 involvement in these processes with an emphasis on PARP1 regulation of subcellular condensates.

This article is categorized under:

RNA Processing > Splicing Regulation/Alternative Splicing
Computer assisted solution of systems of two variable linear functional equations
Authors: Borus Gergő Gyula , Gilányi Attila
Published: July 2020

In the present paper, a general class of linear functional equations is considered and a computer program is described, which determines the exact solutions of systems of equations belonging to this class.
Factors determining the surface oil concentration of encapsulated lipid particles: impact of the emulsion oil droplet size
Authors: Linke Annika , Weiss Jochen , Kohlus Reinhard
Published: July 2020

Microencapsulation of oxidation sensitive oils aims to separate lipids from the environmental oxygen by embedding oil droplets in a solid matrix, which builds a physical barrier. Some oil droplets are not fully incorporated and are in contact with the powder surface generating surface oil. It is proposed that the probability of oil droplets being in contact with the particle surface increases with the oil droplet size. The aim of the study is to investigate the impact of the oil droplet size on the encapsulation efficiency (EE). Two sets of feed emulsions differing in the applied homogenization pressure and in the protein to oil ratio were spray dried using a pilot plant spray dryer. The oil droplet size of the emulsion was determined by static light scattering (SLS). In addition, nuclear magnetic resonance (NMR) was used to measure the d3,2 of oil droplets in the emulsion and in the powder before and after surface oil removal. Encapsulates were analyzed regarding aw, moisture content, particle size, oil load and EE. The oil droplet size in the emulsion decreased with increasing protein to oil ratio as well as with the homogenization pressure. Large oil droplets and in particular droplet clusters resulted in more non-encapsulated oil. The experimentally determined EE was in accordance with the theoretical one, calculated based on the droplet and particle diameter. For emulsions with a diameter > 1 µm, the d3,2 decreased in the powder and further by removing the surface oil, which was related to the deformation of oil droplets contributing to the non-encapsulated oil.
Exploring contrast-enhanced MRI findings of the clinically non-inflamed symptomatic pediatric wrist
Authors: Verkuil Floris , van Gulik E. Charlotte , Nusman Charlotte M. , Barendregt Anouk M. , Nassar-Sheikh Rashid Amara , Schonenberg-Meinema Dieneke , Dolman Koert M. , Maas Mario , Kuijpers Taco W. , van den Berg J. Merlijn , Hemke Robert
Published: July 2020

Background

Knowledge of the synovial and tenosynovial appearance of the clinically non-arthritic symptomatic juvenile wrist using contrast-enhanced magnetic resonance imaging (MRI) is sparse.

Objectives

To analyze contrast-enhanced MRI findings of the clinically non-inflamed symptomatic pediatric wrist, focusing on the enhancing synovial and tenosynovial membrane. To evaluate the coexistent presence of (teno)synovial enhancement, joint fluid, bony depressions and medullary changes suggestive of bone marrow edema.

Materials and methods

We included 20 children (15 girls; age range: 7.5–17.6 years) who underwent contrast-enhanced MRI of the wrist, based on initial clinical indication, and eventually turned out to be unaffected by arthritic or orthopedic disorders. Various imaging characteristics of the synovium, tenosynovium, joint fluid, bone tissue and bone marrow were evaluated using existing MRI scoring systems.

Results

In 3/20 (15%) children, mild or moderate-severe synovial enhancement was observed and 2/20 (10%) children showed mild tenosynovial enhancement/thickening. Joint fluid (11/20 children; 55%), bony depressions (20/20 children; 100%) and medullary changes suggestive of bone marrow edema (6/20; 30%) were found in a substantial percentage of children. The most frequently observed combination of coexisting imaging characteristics was bony depressions with ≥2 mm joint fluid, which was found in 7/20 (35%) children. Simultaneous presence of synovial and tenosynovial enhancement/thickening, bony depressions and medullary changes suggestive of bone marrow edema was observed in one child.

Conclusion

Several juvenile idiopathic arthritis-relevant MRI characteristics can be observed in the clinically non-inflamed symptomatic pediatric wrist.
Impact of lordotic cages in the restoration of spinopelvic parameters after dorsal lumbar interbody fusion: a retrospective case control study
Authors: Oikonomidis Stavros , Heck Vincent , Bantle Sonja , Scheyerer Max Joseph , Hofstetter Christoph , Budde Stefan , Eysel Peer , Bredow Jan
Published: July 2020

Purpose

Aim of this study was to compare the reconstruction of radiological sagittal spinopelvic parameters between lordotic (10°) and normal cages (0°) after dorsal lumbar spondylodesis.

Methods

This retrospective monocentric study included patients who received dorsal lumbar spondylodesis between January 2014 and December 2018. Inclusion criteria were degenerative lumbar diseases and mono- or bi-segmental fusions in the middle and lower lumbar region. Exclusion criteria were long-distance fusions (3 segments and more) and infectious and tumour-related diseases. The sagittal spinopelvine parameters (lumbar lordosis, segmental lordosis, sacral slope, pelvic incidence, and pelvic tilt) were measured pre- and post-operatively by two examiners at two different times. The patients were divided into 2 groups (group 1: lordotic cage, group 2: normal cage).

Results

One hundred thirty-eight patients (77 female, 61 male) with an average age of 66.6 ± 11.2 years (min.: 26, max.: 90) were included in the study based on the inclusion criteria. Ninety-two patients (66.7%) received 0° cages and 46 (33.3%) lordotic cages (10°). Segmental lordosis was increased by 4.2° on average in group 1 and by 6.5° in group 2 (p = 0.074). Average lumbar lordosis was increased by 2.1° in group 1 and by 0.6° in group 2 (p = 0.378). There was no significant difference in the correction of sagittal spinopelvic parameters. Inter- and inter-class reliability was between 0.887 and 0.956.

Conclusion

According to the results of our study, no advantages regarding sagittal radiological parameters for the implantation of a lordotic cage could be demonstrated.
Development and validation of a classification algorithm to diagnose and differentiate spontaneous episodic vertigo syndromes: results from the DizzyReg patient registry
Authors: Groezinger Michael , Huppert Doreen , Strobl Ralf , Grill Eva
Published: July 2020

Background

Spontaneous episodic vertigo syndromes, namely vestibular migraine (VM) and Menière’s disease (MD), are difficult to differentiate, even for an experienced clinician. In the presence of complex diagnostic information, automated systems can support human decision making. Recent developments in machine learning might facilitate bedside diagnosis of VM and MD.

Methods

Data of this study originate from the prospective patient registry of the German Centre for Vertigo and Balance Disorders, a specialized tertiary treatment center at the University Hospital Munich. The classification task was to differentiate cases of VM, MD from other vestibular disease entities. Deep Neural Networks (DNN) and Boosted Decision Trees (BDT) were used for classification.

Results

A total of 1357 patients were included (mean age 52.9, SD 15.9, 54.7% female), 9.9% with MD and 15.6% with VM. DNN models yielded an accuracy of 98.4 ± 0.5%, a precision of 96.3 ± 3.9%, and a sensitivity of 85.4 ± 3.9% for VM, and an accuracy of 98.0 ± 1.0%, a precision of 90.4 ± 6.2% and a sensitivity of 89.9 ± 4.6% for MD. BDT yielded an accuracy of 84.5 ± 0.5%, precision of 51.8 ± 6.1%, sensitivity of 16.9 ± 1.7% for VM, and an accuracy of 93.3 ± 0.7%, precision 76.0 ± 6.7%, sensitivity 41.7 ± 2.9% for MD.

Conclusion

The correct diagnosis of spontaneous episodic vestibular syndromes is challenging in clinical practice. Modern machine learning methods might be the basis for developing systems that assist practitioners and clinicians in their daily treatment decisions.
Tools for the construction and analysis of systems
Authors: Beyer Dirk , Huisman Marieke
Published: July 2020

In order to develop reliable software and systems, we depend on practical techniques for the construction and analysis of such software and systems. This special issue of Software Tools for Technology Transfer presents various tool-supported techniques that can help with the construction and analysis of such reliable software and systems. The papers in this special issue are extended versions of selected conference papers from the proceedings of the 24th International Conference on Tools and Algorithms for the Construction and Analysis of Systems (TACAS 2018).