bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial abundance distribution of prokaryotes is associated with dissolved organic matter composition and ecosystem function
Authors: LaBrie Richard , Bélanger Simon , Benner Ronald , Maranger Roxane
Published: October 2020

Diverse prokaryotic communities consume and transform a broad suite of molecules in the dissolved organic matter (DOM) pool, which controls major biogeochemical cycles. Despite methodological advancements that provide increasingly more detailed information on the diversity of both prokaryotic communities and DOM components, understanding how these two component parts are structured to influence ecosystem functioning remains a major challenge in microbial ecology. Using empirical data collected along a gradient of productivity in the Labrador Sea, we characterized relationships among DOM compounds, metabolic processing, and prokaryotic diversity by structuring prokaryotic communities using spatial abundance distribution (SpAD) modeling. We identified strong associations of different SpAD taxonomic groups with specific organic substrates as well as with metabolic rates. Amplicon sequence variants (ASVs) with more cosmopolitan distributions (i.e. normal‐like) such as Bacteroidia were related to fresher DOM substrates such as free and combined amino acids whereas rare ASVs (i.e. logistic) like δ‐proteobacteria were associated with complex forms of organic matter. In terms of ecosystem function, rates of respiration and production were most strongly predicted by the abundance of certain SpAD taxonomic groups. Given the importance and complexity of linking environmental conditions, prokaryotic community structure, and ecosystem function, we propose a framework to bridge the gap between prokaryotic diversity, microbial ecology, and biogeochemistry among methods and across scales. Our work suggests that SpAD modeling can be used as an intermediate step to link prokaryotic community structure to both finer DOM details and larger ecosystem scale processes.
Severity‐Dependent Effects of Parkinson's Disease on Perception of Visual and Vestibular Heading
Authors: Beylergil Sinem Balta , Petersen Mikkel , Gupta Palak , Elkasaby Mohamed , Kilbane Camilla , Shaikh Aasef G.
Published: October 2020

Objectives

Parkinson's disease (PD) commonly affects visuospatial navigation causing postural instability and falls. Our overarching aim was to examine the visual and vestibular systems governing visuospatial navigation in PD. We hypothesize that PD affects vestibular and visual motion perception but to a different extent. The effects of PD on motion perception are dependent on the severity of the disease.

Methods

The two‐alternative‐forced‐choice task objectively measured the motion perception during two experiments. One experiment examined the vestibular motion perception with en bloc movement of the platform. The second experiment tested the visual motion perception using an immersive virtual reality goggle.

Results

We found that accuracy, threshold, and precision of vestibular perception were more impaired in advanced‐PD patients compared to those with a mild form of the disease. The parameters also correlated with the disease duration, overall axial motor impairment causing postural instability and falls, and subjective rating of the balance function. Such changes were present but less severe in visual motion perception.

Conclusion

We conclude that PD affects motion perception in the visual and vestibular domains in a severity‐dependent manner. The impact of the disease in the vestibular domain is more severe compared to the visual domain. © 2020 International Parkinson and Movement Disorder Society
A CPW‐fed compact square slot antenna with wideband circularly polarized for C‐band application
Authors: Felegari Nader , Zafari Sajad , Malekpour Narges , Hassani Hamid Reza
Published: October 2020

This paper presents a compact wideband circularly‐polarized square slot antenna (CPSSA). The antenna is a coplanar waveguide feed structure with three T‐stubs toward the slot center and one semi‐circle tuning stub was etched to the feed line and modified inverted L‐shaped strips around the corners of the ground. Moreover, two spiral slots were loaded in the ground plane for exciting currents in a different direction. A prototype of the designed antenna is fabricated and measured to confirm the simulation results. A reasonably good agreement between the measured and simulated results in terms of the reflection coefficient <−10 dB and axial ratio are achieved. The 3‐dB axial ratio bandwidth achieved by the combination is from 4.35 to 8.15 GHz (60%, measured). The designed CPSSA has a compact size of 0.57λₒ × 0.57λₒ × 0.0116λₒ at the center frequency and fabricated on the FR4 substrate.
Quantitative and simultaneous measurement of oxygen consumption rates in rat brain and skeletal muscle using 17O MRS imaging at 16.4T
Authors: Wiesner Hannes M. , Balla Dávid Z. , Scheffler Klaus , Uğurbil Kâmil , Zhu Xiao‐Hong , Chen Wei , Uludağ Kâmil , Pohmann Rolf
Published: October 2020

Purpose

Oxygen‐17 (17O) MRS imaging, successfully used in the brain, is extended by imaging the oxygen metabolic rate in the resting skeletal muscle and used to determine the total whole‐body oxygen metabolic rate in the rat.

Methods

During and after inhalations of 17O2 gas, dynamic 17O MRSI was performed in rats (n = 8) ventilated with N2O or N2 at 16.4 T. Time courses of the H217O concentration from regions of interest located in brain and muscle tissue were examined and used to fit an animal‐adapted 3‐phase metabolic model of oxygen consumption. CBF was determined with an independent washout method. Finally, body oxygen metabolic rate was calculated using a global steady‐state approach.

Results

Cerebral metabolic rate of oxygen consumption was 1.97 ± 0.19 μmol/g/min on average. The resting metabolic rate of oxygen consumption in skeletal muscle was 0.32 ± 0.12 μmol/g/min and >6 times lower than cerebral metabolic rate of oxygen consumption. Global oxygen consumed by the body was 24.2 ± 3.6 mL O2/kg body weight/min. CBF was estimated to be 0.28 ± 0.02 mL/g/min and 0.34 ± 0.06 mL/g/min for the N2 and N2O ventilation condition, respectively.

Conclusion

We have evaluated the feasibility of 17O MRSI for imaging and quantifying the oxygen consumption rate in low metabolizing organs such as the skeletal muscle at rest. Additionally, we have shown that CBF is slightly increased in the case of ventilation with N2O. We expect this study to be beneficial to the application of 17O MRSI to a wider range of organs, although further validation is advised.
Molecular imaging of cancer by glucosamine chemical exchange saturation transfer MRI: A preclinical study
Authors: Rivlin Michal , Navon Gil
Published: October 2020

Glucosamine (GlcN) was recently proposed as an agent with an excellent safety profile to detect cancer with the chemical exchange saturation transfer (CEST) MRI technique. Translation of the GlcN CEST method to the clinical application requires evaluation of its sensitivity to the different frequency regions of irradiation. Hence, imaging of the GlcN signal was established for the full Z spectra recorded following GlcN administration to mice bearing implanted 4T1 breast tumors. Significant CEST effects were observed at around 1.5, 3.6 and −3.4 ppm, corresponding to the hydroxyl, amine/amide exchangeable protons and for the Nuclear Overhauser Enhancement (NOE), respectively. The sources of the observed CEST effects were investigated by identifying the GlcN metabolic products as observed by13C NMR spectroscopy studies of extracts from the same tumor model following treatment with [UL‐13C] ‐GlcN·HCl. The CEST contribution can be attributed to several phosphorylated products of GlcN, including uridine diphosphate‐N‐acetylglucosamine (UDP‐GlcNAc), which is a substrate for the O‐linked and N‐linked glycosylated proteins that may be associated with the increase of the NOE signal. The observation of a significant amount of lactate among the metabolic products hints at acidification as one of the sources of the enhanced CEST effect of GlcN. The proposed method may offer a new approach for clinical molecular imaging that enables the detection of metabolically active tumors and may play a role in other diseases.
A mathematical analysis of ongoing outbreakCOVID‐19 in India through nonsingular derivative
Authors: Safare Kiran Malathesha , Betageri Virupaxappa Shekarappa , Prakasha Doddabhadrappla Gowda , Veeresha Pundikala , Kumar Sunil
Published: October 2020

Throughout the globe, mankind is in vastly infected situations due to a cruel and destructive virus called coronavirus (COVID‐19). The pivotal aim of the present investigation is to analyze and examine the evolution of COVID‐19 in India with the available data in two cases first from the beginning to 31st March and beginning to 23rd April in order to show its exponential growth in the crucial period. The present situation in India with respect to confirmed, active, recovered and deaths cases have been illustrated with the aid of available data. The species of novel virus and its stages of growth with respect some essential points are presented. The exponential growth of projected virus by the day‐to‐day base is captured in two‐dimensional plots to predict its developments and identify the needs to control its spread on mankind. Moreover, the SEIR model is considered to present some interesting consequences about COVID‐19 within the frame of fractional calculus. A newly proposed technique calledq‐Homotopy analysis transform method (q‐HATM) is hired to find the solution for the nonlinear system portraying projected model and also presented the existence and uniqueness of the obtained results with help of fixed point theory. The behavior has been captured with respect to fractional order and time. The present study exemplifies the importance of fractional operator and efficiency of the projected algorithm.
A new high‐order weighted essentially non‐oscillatory scheme for non‐linear degenerate parabolic equations
Authors: Abedian Rooholah
Published: October 2020

In this research, a new high‐order WENO method for solving 1D, 2D and 3D non‐linear degenerate parabolic equations which may contain discontinuous solutions has been designed. The new scheme is constructed by three polynomials of varying degrees. This new method applies the same six‐point stencil as the classic WENO procedures developed for degenerate parabolic by Liu et al. and Abedian et al. (Comput. Phys. Commun., 184 (2013), 1874–1888). The new scheme attains sixth‐order accuracy in smooth areas and second‐order accuracy near singularities. Comparing the magnitude of errors produced by Liu et al., Abedian et al. and the new scheme has shown that the new scheme performs better. The only condition for the linear weights (ideal weights) associated with this scheme is that their sum must be equal to one, while they can be any positive real number. Afterwards, the non‐oscillatory weights are calculated with the linear weights. The new proposed scheme can be easily developed to higher dimension by dimension‐by‐dimension technique. The new scheme enjoys simplicity, good performance and low computational cost. To explain the properties of the method such as accuracy and resolution, a number of classical numerical examples have been prepared.
He's frequency formulation for fractal nonlinear oscillator arising in a microgravity space
Authors: Wang KangLe
Published: October 2020

At a microgravity condition, a spaceflight might be subject to a microgravity‐induced vibration. There is no theory so far to study the effect of microgravity on the vibration property. Here we give a fractal vibration model by the two‐scale thermodynamics. The fractal oscillator in the microgravity space is modeled by using the fractal derivative, and its frequency is obtained by He's frequency formula. The variational principle of the fractal model is established by the fractal semi‐inverse method. The example shows that the proposed method is simple, efficient, and accurate. The frequency‐amplitude relationship is elucidated and the effect of the microgravity condition on vibration property is discussed.
Numerical solutions of the initial boundary value problem for the perturbed conformable time Korteweg‐de Vries equation by using the finite element method
Authors: Pedram Leila , Rostamy Davoud
Published: October 2020

In this paper, we investigate the initial‐boundary‐value problem for the nonhomogeneous Korteweg‐de Vries equation with conformable derivative on time part of it. We use the finite element method with B‐spline as the basis functions for obtaining the numerical solutions for this nonlinear equation. In addition, we prove a posteriori and a priori errors for it. These show the adaptivity and convergence of our method. Also, a posteriori error estimate concludes that the error estimate decreases as α increases. We show the accuracy of our work by comparing with the exact solution for the homogeneous KdV equation. We also bring an example for the nonhomogeneous conformable time KdV equation to demonstrate the accuracy and efficiency of the proposed method. Also, these numerical results are consistent with the result of theorems. The numerical results are given in tables and figures.
On the instability of Ekman boundary‐layer flow over a rough disk with a wavy surface profile
Authors: Alveroğlu Burhan
Published: October 2020

We apply the method of lines and the backward difference method to solve highly nonlinear governing mean flow equations of the Ekman boundary‐layer flow over a rough disk with a wavy surface profile. These equations are derived using the YHP roughness model that imposes a wavy surface profile in terms of the radial position r, assuming rotational symmetry. Our main interest is to determine the effect of roughness on the local linear convective instability of the Ekman flow, and we solve the local linear stability equations of the disturbances stationary relative to the disk using the Chebyshev polynomials. The crossflow and viscous types of instability modes, the Type I and Type II modes respectively, are analyzed. Our theoretical findings prompts that an adequately designed rough disk can be a useful tool for a passive flow‐control method for the Ekman flow. The underlying physical mechanisms are investigated applying a fundamental energy analysis.
A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26–104/RFASE in Patients with Advanced Solid Malignancies
Authors: Goedegebuure Ruben S.A. , Wentink Madelon Q. , van der Vliet Hans J. , Timmerman Peter , Griffioen Arjan W. , de Gruijl Tanja D. , Verheul Henk M.W.
Published: October 2020

Lessons Learned

The novel therapeutic vaccine hVEGF26–104/RFASE was found to be safe and well tolerated in patients with cancer. hVEGF26–104/RFASE failed to induce seroconversion against native hVEGF165 and, accordingly, neither a decrease in circulating vascular endothelial growth factor (VEGF) levels nor clinical benefit was observed. Remarkably, hVEGF26–104/RFASE induced VEGF165-neutralizing antibodies in a nonhuman primate model. The absence of seroconversion in human calls for caution in the interpretation of efficacy of human vaccines in nonhuman primates.

Background

Targeting vascular endothelial growth factor-A (VEGF) is a well-established anticancer therapy. We designed a first-in-human clinical trial to investigate the safety and immunogenicity of the novel vaccine hVEGF26–104/RFASE.

Methods

Patients with advanced solid malignancies with no standard treatment options available were eligible for this phase I study with a 3+3 dose-escalation design. On days 0, 14, and 28, patients received intramuscular hVEGF26–104, a truncated synthetic three-dimensional (3D)-structured peptide mimic covering the amino acids 26–104 of the human VEGF165 isoform, emulsified in the novel adjuvant Raffinose Fatty Acid Sulphate Ester (RFASE), a sulpholipopolysaccharide. Objectives were to determine safety, induction of VEGF-neutralizing antibodies, and the maximum tolerated dose. Blood was sampled to measure VEGF levels and antibody titers.

Results

Eighteen of 27 enrolled patients received three immunizations in six different dose-levels up to 1,000 μg hVEGF26–104 and 40 mg RFASE. No dose-limiting toxicity was observed. Although in four patients an antibody titer against hVEGF26–104 was induced (highest titer: 2.77 10log), neither a reduction in VEGF levels nor neutralizing antibodies against native VEGF165 were detected.

Conclusion

Despite having an attractive safety profile, hVEGF26–104/RFASE was not able to elicit seroconversions against native VEGF165 and, consequently, did not decrease circulating VEGF levels. Deficient RFASE adjuvant activity, as well as dominant immunoreactivity toward neoepitopes, may have impeded hVEGF26–104/RFASE's efficacy in humans.
A Phase I Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors
Authors: Ma Yuxiang , Fang Wenfeng , Zhao Hongyun , Bathena Sai Praneeth , Tendolkar Amol , Sheng Jennifer , Zhang Li
Published: October 2020

Lessons Learned

The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified. The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

Background

This phase I, open-label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).

Methods

Of 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3-week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12-week cycle, to a maximum of 3 years or PD. Considering the co-primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose-limiting toxicities during the 42-day observation period to proceed with a new cohort of nine patients at 10 mg/kg.

Results

Ipilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti-ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).

Conclusion

Ipilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.
A case report of isolated zygomatic arch fracture by modified towel clip method
Authors: Hayashi Kamichika , Migita Masashi , Iwasaki Takahiro , Onda Takeshi , Takano Masayuki , Takaki Takashi
Published: October 2020

Fractures of the zygomatic arch may be treated with a variety of techniques. The disadvantages of these methods include the difficulty of reaching the fracture site via the intraoral approach and the high level of surgical invasiveness associated with the extraoral approach. This is a case report. A 20‐year‐old man was banged on the face. He presented at our department complaining of a change in facial shape and difficulty in mouth opening. Modified towel clip method was used to treat the zygomatic fracture which was classified into Yamamoto Class II type, and successful reduction was achieved. We believe that this method is very effective from the standpoint of minimum invasiveness and simplicity.
Aliphatic silicone‐epoxy based hybrid photopolymers applied in stereolithography 3D printing
Authors: Zhao Tingting , Yu Ran , Huang Wei , Zhao Wei , Wang Gong
Published: October 2020

3D Printing has become a powerful technology for future advanced manufacturing, however the choice of materials with good performance is still limited. In this research, a type of hybrid photopolymer resin based on silicone epoxy with high UV curing rate and low viscosity was applied in stereolithography (SLA) technology. First, aliphatic silicone epoxy was synthesized through hydrosilylation reaction, and then compounding with acrylates, cycloaliphatic epoxy and photo‐initiators, finally the hybrid photopolymer system for SLA was obtained. The features of UV curing process were studied through photo‐differential scanning calorimetry and real‐time Fourier transform infrared measurements. Scanning electron microscopy test showed interpenetrating polymer network structure was formed in 3D objects. The performances of 3D printed sample such as mechanical properties, thermal mechanical and stability properties were also investigated in detail. Moreover, the 3D printed objects with complicated structures showed high printing accuracy. This new type of hybrid photopolymer system based on aliphatic silicone epoxy was with fabrication ease, good mechanical properties, good thermal stability and high printing resolution and has great potential of applications in industrial design and models making fields.
Distinct contributions of cathelin‐related antimicrobial peptide (CRAMP) derived from epithelial cells and macrophages to colon mucosal homeostasis
Authors: Chen Keqiang , Yoshimura Teizo , Yao Xiaohong , Gong Wanghua , Huang Jiaqiang , Dzutsev Amiran K , McCulloch John , O'hUigin Colm , Bian Xiu‐wu , Trinchieri Giorgio , Wang Ji Ming
Published: October 2020

The cathelin‐related antimicrobial peptide CRAMP protects the mouse colon from inflammation, inflammation‐associated carcinogenesis, and disrupted microbiome balance, as shown in systemic Cnlp−/− mice (also known as Camp−/− mice). However, the mechanistic basis for the role and the cellular source of CRAMP in colon pathophysiology are ill defined. This study, using either epithelial or myeloid conditional Cnlp−/− mice, demonstrated that epithelial cell‐derived CRAMP played a major role in supporting normal development of colon crypts, mucus production, and repair of injured mucosa. On the other hand, myeloid cell‐derived CRAMP potently supported colon epithelial resistance to bacterial invasion during acute inflammation with exacerbated mucosal damage and higher rate of mouse mortality. Therefore, a well concerted cooperation of epithelial‐ and myeloid‐derived CRAMP is essential for colon mucosal homeostasis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Dimensionless squared jerk: An objective differential to assess experienced and novice probe movement in obstetric ultrasound
Authors: Dromey Brian P , Ahmed Shahanaz , Vasconcelos Francisco , Mazomenos Evangelos , Kunpalin Yada , Ourselin Sebastien , Deprest Jan , David Anna L , Stoyanov Danail , Peebles Donald M
Published: October 2020

Objective

Widely accepted, validated and objective measures of ultrasound competency have not been established for clinical practice. Outcomes of training curricula are often based on arbitrary thresholds, such as the number of clinical cases completed. We aimed to define metrics against which competency could be measured.

Method

We undertook a prospective, observational study of obstetric sonographers at a UK University Teaching Hospital. Participants were either experienced in fetal ultrasound (n = 10, >200 ultrasound examinations) or novice operators (n = 10, <25 ultrasound examinations). We recorded probe motion data during the performance of biometry on a commercially available mid‐trimester phantom.

Results

We report that Dimensionless squared jerk, an assessment of deliberate hand movements, independent of movement duration, extent, spurious peaks and dimension differed significantly different between groups, 19.26 (SD 3.02) for experienced and 22.08 (SD 1.05, p = 0.01) for novice operators, respectively. Experienced operator performance, was associated with a shorter time to task completion of 176.46 s (SD 47.31) compared to 666.94 s (SD 490.36, p = 0.0004) for novice operators. Probe travel was also shorter for experienced operators 521.23 mm (SD 27.41) versus 2234.82 mm (SD 188.50, p = 0.007) when compared to novice operators.

Conclusion

Our results represent progress toward an objective assessment of technical skill in obstetric ultrasound. Repeating this methodology in a clinical environment may develop insight into the generalisability of these findings into ultrasound education.
Development of novel frog‐skin peptide scaffolds with selectivity towards melanocortin receptor subtypes
Authors: Malik Uru , Chan Lai Yue , Cai Minying , Hruby Victor J. , Kaas Quentin , Daly Norelle L. , Craik David J.
Published: October 2020

Melanocortin receptors are pharmaceutically important receptors that are involved in complex physiological functions. They have been associated with various diseases including obesity, erectile dysfunction, acne, and skin cancer. It has been challenging to transform nonselective endogenous agonist and antagonist ligands into selective and potent ligands. In this study, we investigated naturally occurring peptides derived from frog skin secretions for selectivity and activity toward melanocortin receptors. Three peptides (ORB, ORB2K and ranacyclin‐T) were found to have selectivity towards the melanocortin receptor 5 (MC5R). ORB and ORB2K had partial binding affinity at nanomolar concentrations, whereas ranacyclin‐T had 57% binding efficiency at 1.6 μM. Backbone cyclization of ORB and ORB2K altered the binding efficiency to melanocortin receptors. Our results suggest that these frog‐skin peptides could be modified for developing melanocortin‐specific ligands and potentially future therapeutics.
Different physiotherapy protocols after coronary artery bypass graft surgery: A randomized controlled trial
Authors: Ribeiro Breno Caldas , Poça Jadson José Guimarães da , Rocha Amanda Martins Cavalcante , Cunha Clícia Naeli Silva da , Cunha Katiane da Costa , Falcão Luiz Fábio Magno , Torres Daniel da Costa , Rocha Larissa Salgado de Oliveira , Rocha Rodrigo Santiago Barbosa
Published: October 2020

Background and purpose

The aim of this study was to investigate the influence of different physiotherapy protocols on heart rate variability (HRV) and hospital length of stay in older adults undergoing coronary artery bypass graft (CABG).

Methods

Randomized controlled trial with allocation and researcher blinding and intention‐to‐treat analysis. Forty‐eight patients undergoing CABG were randomly assigned to a control group (CG), early mobilization group (EMG), or virtual reality group (VRG). CG performed respiratory physiotherapy and metabolic exercises, the EMG performed cycle ergometer exercises and ambulation, and the VRG performed the same activities as the EMG, with the addition of two Nintendo Wii games during 3 postoperative days. The variables of heart rate variability on preoperative and fourth postoperative day, and time of discharge of hospital was analyzed.

Results

The VRG presented a shorter hospital length of stay (p = 0.03). The CG showed a decline in HRV from the preoperative period to fourth postoperative day on square root of the mean of the squared differences between successive RR intervals (33.18 ± 9.89–9.74 ± 6.88, p < 0.05), standard deviation of all RR intervals (25.48 ± 7.50–15.23 ± 11.27, p < 0.05), and dispersion of points perpendicular to identity line (28.26 ± 21.6–2.73 ± 1.31, p < 0.05). The EMG and VRG presented a higher cardiac autonomic modulation compared to the CG (p < 0.05), with improved parasympathetic activity.

Conclusions

Different protocols of physiotherapy intervention affected autonomic modulation of the heart rate and hospital length of stay in patients undergoing CABG.
Resampling‐based stepwise multiple testing procedures with applications to clinical trial data
Authors: He Jiwei , Li Feng , Gao Yan , Rothmann Mark
Published: October 2020

Endpoints in clinical trials are often highly correlated. However, the commonly used multiple testing procedures in clinical trials either do not take into consideration the correlations among test statistics or can only exploit known correlations. Westfall and Young constructed a resampling‐based stepdown method that implicitly utilizes the correlation structure of test statistics in situations with unknown correlations. However, their method requires a “subset pivotality” assumption. Romano and Wolf proposed a more general stepdown method, which does not require such an assumption. There is at present little experience with the application of such methods in analyzing clinical trial data. We advocate the application of resampling‐based multiple testing procedures to clinical trials data when appropriate. We have conjectured that the resampling‐based stepdown methods can be extended to a stepup procedure under appropriate assumptions and examined the performance of both stepdown and stepup methods under a variety of correlation structures and distribution types. Results from our simulation studies support the use of the resampling‐based methods under various scenarios, including binary data and small samples, with strong control of Family wise type I error rate (FWER). Under positive dependence and for binary data even under independence, the resampling‐based methods are more powerful than the Holm and Hochberg methods. Last, we illustrate the advantage of the resampling‐based stepwise methods with two clinical trial data examples: a cardiovascular outcome trial and an oncology trial.
Resveratrol inhibits bile acid‐induced gastric intestinal metaplasia via the PI3K/AKT/p‐FoxO4 signalling pathway
Authors: Lu Wenquan , Ni Zhen , Jiang Shuqin , Tong Mingfu , Zhang Jian , Zhao Jing , Feng Chenchen , Jia Qiaoyu , Wang Jingyun , Yao Tingting , Ning Hanbing , Shi Yongquan
Published: October 2020

Gastric intestinal metaplasia (GIM) is the essential pre‐malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal‐related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti‐tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid‐induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time‐ and dose‐dependent manner in gastric cell lines. A Cignal Finder 45‐Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin‐immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho‐FoxO4 nucleus trans‐location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up‐regulate FoxO4 phosphorylation and suppress CDCA‐induced GIM marker expression. Finally, we found a reverse correlation between p‐FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid‐induced GIM through the PI3K/AKT/p‐FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.
Insight into the X‐ray absorption spectra of Cu‐porphyrazines from electronic structure theory
Authors: Boydas Esma Birsen , Winter Bernd , Batchelor David , Roemelt Michael
Published: October 2020

Transition metal porphyrazines are a widely used class of compounds with applications in catalysis, organic solar cells, photodynamic therapy, and nonlinear optics. The most prominent members of that family of compounds are metallophtalocyanines, which have been the subject of numerous spectroscopic and theoretical studies. In this work, the electronic structure and X‐ray absorption characteristics of three Cu‐porphyrazine derivatives are investigated by means of modern electronic structure theory. More precisely, the experimentally observed N K‐edge and Cu L‐edge features are presented and reproduced by time‐dependent density functional theory, restricted open‐shell configuration interaction, and a restricted active space approach. Where possible, the calculations are used to interpret the observed spectroscopic features in terms of electronic transitions and, furthermore, to connect spectral differences to chemical variations. Part of the discussion of the computational results concerns the impact of various parameters and approximations that are used for the calculations, for example, the choice of active space.
Simultaneous screening of dietary supplements for 25 anti‐hyperlipidemic substances using ultra‐performance liquid chromatography and liquid chromatography/electrospray ionization tandem mass spectrometry
Authors: Kim Nam Sook , Lim Na Young , Choi Hwan Seong , Lee Ji Hyun , Moon Sun Hee , Kim Hyungil , Baek Sun Young
Published: October 2020

Rationale

Recently, illegal dietary supplements containing unauthorized compounds have been seized and internationally publicized with a warning to avoid their consumption. This adulteration can be a serious threat to public health because of insufficient and reliable safety data as well as their undesirable side effects. It is, therefore, essential to rapidly and accurately develop and simultaneously validate analytical methods for these unauthorized anti‐hyperlipidemic substances.

Methods

Dietary supplements were screened simultaneously for 25 anti‐hyperlipidemic drugs using an ultra‐high‐performance liquid chromatography (UPLC) system with a photodiode array (PDA) detector and LC/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS). The method validation, according to ICH guidelines, considered specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effects, and stability for solid and liquid blank samples. The established UPLC‐PDA and LC/ESI‐MS/MS methods were applied to screen 103 dietary supplements for 25 anti‐hyperlipidemic substances.

Results

Using the validated methods, the screened samples were found to contain peaks with similar retention times and PDA spectra. By comparing the calculated precursor‐product ion ratios with those of standards, lovastatin and lovastatin acid were detected at concentrations from LOQ to 4.12 mg/g and LOQ to 9.65 mg/g, respectively.

Conclusions

The developed UPLC‐PDA and LC/ESI‐MS/MS analytical methods were applied to 103 real samples, of which 13 samples were found to contain lovastatin and lovastatin acid. In view of the increasing demand for dietary supplements in the treatment of hyperlipidemic diseases, widespread use of these methods will contribute to consumer health by ensuring the safety of dietary supplements.
Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration
Authors: MacMillan Mia , Roy Bapti , McLaren Sally , Nowak Anna K. , Thomas Rajesh , Lee Y. C. Gary
Published: October 2020

We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70‐year‐old woman. She first presented with a hydropneumothorax and subsequent workup, including video‐assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)‐avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non‐resolving pulmonary infiltrates in patients with MPM.
A limit inferior ‐dependent average dwell time approach for stability analysis of switched systems
Authors: Yu Qiang , Zhai Guisheng
Published: October 2020

A novel concept of limit inferior‐dependent average dwell time (LDADT) is first proposed, which is a generalization of various existing concepts of dwell time. Based on the LDADT scheme and the multiple Lyapunov function approach, some new sufficient conditions for stability and stabilization of switched systems are established by introducing some inequalities. Those criteria acquired contain most of the established ones based on ADT, limiting ADT, mode‐dependent ADT,‐dependent ADT, etc. Specifically, the stability and stabilization criteria for switched linear systems are listed as linear matrix inequalities that can be examined and calculated easily by the LMI toolbox in Matlab. At last, three typical numerical examples are presented for illustrating the effectiveness and validity of the LDADT scheme presented in this paper.
Complementary dimension reduction
Authors: Cui Na , Hu Jianjun , Liang Feng
Published: October 2020

The goal of supervised dimension reduction (SDR) is to find a compact yet informative representation of the feature vector. Most SDR algorithms are formulated to solve sequential optimization problems with objective functions being linear functions of the L2 norm of the data, for example, the well‐known Fisher's discriminant analysis (FDA). A drawback of such objective functions is that they favor directions that result in large between‐class distances; however, if the large between‐class distance is mainly from classes that have already been well separated by prior directions, the new direction leads to a negligible improvement over classification accuracy. To address this issue, we introduce an objective function that directly quantifies classification accuracy, and present an efficient algorithm that retrieves directions sequentially from this nonlinear objective function. A key feature of our algorithm is that each sequentially added direction works complementarily with the previous sequentially‐solved directions to boost the discriminative power of the reduced space as a whole. So we name our new algorithm “Complementary Dimension Analysis” (CDA). We have further generalized CDA to retrieve sparse directions that involve only a small fraction of the features. Finally we demonstrate the utility of our algorithms on several simulated and real datasets.
Assessing consistency in clinical trials with two subgroups and binary endpoints: A new test within the logistic regression model
Authors: Grill Susann , Ring Arne , Brannath Werner , Scharpenberg Martin
Published: October 2020

In late stage drug development, the experimental drug is tested in a diverse study population within the relevant indication. In order to receive marketing authorization, robust evidence for the therapeutic efficacy is crucial requiring investigation of treatment effects in well‐defined subgroups. Conventionally, consistency analyses in subgroups have been performed by means of interaction tests. However, the interaction test can only reject the null hypothesis of equivalence and not confirm consistency. Simulation studies suggest that the interaction test has low power but can also be oversensitive depending on sample size—leading in combination with the actually ill‐posed null hypothesis to findings regardless of clinical relevance. In order to overcome these disadvantages in the setup of binary endpoints, we propose to use a consistency test based on the interval inclusion principle, which is able to reject heterogeneity and confirm consistency of subgroup‐specific treatment effects while controlling the type I error. This homogeneity test is based upon the deviation between overall treatment effect and subgroup‐specific effects on the odds ratio scale and is compared with an equivalence test based on the ratio of both subgroup‐specific effects. Performance of these consistency tests is assessed in a simulation study. In addition, the consistency tests are outlined for the relative risk regression. The proposed homogeneity test reaches sufficient power in realistic scenarios with small interactions. As expected, power decreases for unbalanced subgroups, lower sample sizes, and narrower margins. Severe interactions are covered by the null hypothesis and are more likely to be rejected the stronger they are.
A framework for considering the risk‐benefit trade‐off in designing noninferiority trials using composite outcome approaches
Authors: Montepiedra Grace , Ramchandani Ritesh , Miyahara Sachiko , Kim Soyeon
Published: October 2020

When a new treatment regimen is expected to have comparable or slightly worse efficacy to that of the control regimen but has benefits in other domains such as safety and tolerability, a noninferiority (NI) trial may be appropriate but is fraught with difficulty in justifying an acceptable NI margin that is based on both clinical and statistical input. To overcome this, we propose to utilize composite risk‐benefit outcomes that combine elements from domains of importance (eg, efficacy, safety, and tolerability). The composite outcome itself may be analyzed using a superiority framework, or it can be used as a tool at the design stage of a NI trial for selecting an NI margin for efficacy that balances changes in risks and benefits. In the latter case, the choice of NI margin may be based on a novel quantity called the maximum allowable decrease in efficacy (MADE), defined as the marginal difference in efficacy between arms that would yield a null treatment effect for the composite outcome given an assumed distribution for the composite outcome. We observe that MADE: (1) is larger when the safety improvement for the experimental arm is larger, (2) depends on the association between the efficacy and safety outcomes, and (3) depends on the control arm efficacy rate. We use a numerical example for power comparisons between a superiority test for the composite outcome vs a noninferiority test for efficacy using the MADE as the NI margin, and apply the methods to a TB treatment trial.
Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells
Authors: Ye Sunjie , Azad Arsalan A. , Chambers Joseph E. , Beckett Alison J. , Roach Lucien , Moorcroft Samuel C. T. , Aslam Zabeada , Prior Ian A. , Markham Alexander F. , Coletta P. Louise , Marciniak Stefan J. , Evans Stephen D.
Published: October 2020

The generation of effective and safe nanoagents for biological applications requires their physicochemical characteristics to be tunable, and their cellular interactions to be well characterized. Here, the controlled synthesis is developed for preparing high‐aspect ratio gold nanotubes (AuNTs) with tailorable wall thickness, microstructure, composition, and optical characteristics. The modulation of optical properties generates AuNTs with strong near infrared absorption. Surface modification enhances dispersibility of AuNTs in aqueous media and results in low cytotoxicity. The uptake and trafficking of these AuNTs by primary mesothelioma cells demonstrate their accumulation in a perinuclear distribution where they are confined initially in membrane‐bound vesicles from which they ultimately escape to the cytosol. This represents the first study of the cellular interactions of high‐aspect ratio 1D metal nanomaterials and will facilitate the rational design of plasmonic nanoconstructs as cytosolic nanoagents for potential diagnosis and therapeutic applications.
A simple high‐performance liquid chromatography method development for Carbidopa and Levodopa impurities: Evaluation of risk assessment before method validation by Quality by Design approach
Authors: Subramanian Velusamy B. , Konduru Naresh , Katari Naresh Kumar , Dongala Thirupathi , Gundla Rambabu
Published: October 2020

The current study is to develop a simple high‐performance liquid chromatography method for Carbidopa and Levodopa impurities' simultaneous determination with the combination of Entacapone in solid oral dosage forms. The estimation of impurities are critical in a combination product due to the more number of impurities. The presence of impurities in drug products affects quality and bio‐efficacy. The quality by design approach allows the assessment of various analytical parameters and their effects with the minimum number of experiments. The current high‐performance liquid chromatography method was developed using a kromasil column with gradient mobile phase. The detection was made 220 nm; the flow rate was 1.0 mL/min, and the column's temperature was 25°C. The analytical curves presented a coefficient of correlation of >0.99, and detection and quantification limits were evaluated for all impurities. Excellent precision and accuracy were obtained for carbidopa and levodopa impurities. Intra‐ and interday precisions RSD were lower than 10.0, and recoveries of impurities varied between 91.2 and 108.2%. The results reveal the method's successful applicability for estimating Carbidopa and Levodopa with their process and degradation impurities from its marketed formulation.
Leader humor effectiveness—The divergent dynamics of leader humor over time in East Asia and North America
Authors: Yang Inju , Horak Sven , Chi Shu‐Cheng Steve
Published: October 2020

Management research on humor, which has mainly been conducted in Anglo‐Saxon regions, generally tends to assume that the use of humor by a leader toward his or her subordinates has positive effects. However, despite the popularity of such studies in Anglo‐Saxon regions, less attention has so far been paid to the aspects of the cultural context of leader humor, particularly with regard to time. We argue that leader humor is not so effective in East Asia because of different preferences in relation to communication style and divergent expectations and value sets during early phase leader–member interactions. On the other hand, however, we also argue that leader humor may become equally if not more effective in the mature phase of leader–member interactions. While cultural differences, along with the current popularity of positive emotions, including humor, at work, are much more apparent at the early stage of a relationship, our exploration uncovers areas that are important for effective cross‐cultural communication training and the development of managers for global assignments.