bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower sensitivity to peripheral hypermetropic defocus due to higher order ocular aberrations
Authors: Papadogiannis Petros , Romashchenko Dmitry , Unsbo Peter , Lundström Linda
Published: February 2020

Purpose

Many myopia control interventions are designed to induce myopic relative peripheral refraction. However, myopes tend to show asymmetries in their sensitivity to defocus, seeing better with hypermetropic rather than myopic defocus. This study aims to determine the influence of chromatic aberrations (CA) and higher‐order monochromatic aberrations (HOA) in the peripheral asymmetry to defocus.

Methods

Peripheral (20° nasal visual field) low‐contrast (10%) resolution acuity of nine subjects (four myopes, four emmetropes, one hypermetrope) was evaluated under induced myopic and hypermetropic defocus between ±5 D, under four conditions: (a) Peripheral Best Sphere and Cylinder (BSC) correction in white light; (b) Peripheral BSC correction + CA elimination (green light); (c) Peripheral BSC correction + HOA correction in white light; and (d) Peripheral BSC correction + CA elimination + HOA correction. No cycloplegia was used, and all measurements were repeated three times.

Results

The slopes of the peripheral acuity as a function of positive and negative defocus differed, especially when the natural HOA and CA were present. This asymmetry was quantified as the average of the absolute sum of positive and negative defocus slopes for all subjects (AVS). The AVS was 0.081 and 0.063 logMAR/D for white and green light respectively, when the ocular HOA were present. With adaptive optics correction for HOA, the asymmetry reduced to 0.021 logMAR/D for white and 0.031 logMAR/D for green light, mainly because the sensitivity to hypermetropic defocus increased when HOA were corrected.

Conclusion

The asymmetry was only slightly affected by the elimination of the CA of the eye, whereas adaptive optics correction for HOA reduced the asymmetry. The HOA mainly affected the sensitivity to hypermetropic defocus.
Size selection of levitated aerosol particulate in an ultrasonic field
Authors: Argo Theodore F. , Zadler Brian J. , Meegan G. Douglas
Published: February 2020

The ability to characterize and manipulate micron-size aerosols and particulate is useful for applications in medicine, environmental monitoring, and chemical-biological defense. An experiment was conducted to determine the effects of ultrasonic frequency on the size-selectivity of concentration of polyglycol aerosols that are entrained in air within an ultrasonic resonator. Measurements of aerosol concentration at 4, 25, and 40 kHz were compared with theoretical predictions based on one-dimensional models for radiation pressure and asymmetric Stokes drag effects. The experimental results are shown to be consistent with theory.
Relationship Between Tethered Swimming in a Flume and Swimming Performance
Authors: Ruiz-Navarro Jesús J. , Morouço Pedro G. , Arellano Raúl
Published: February 2020

Purpose: To study the relationship between tethered swimming in a flume at different speeds and swimming performance. Methods: Sixteen regional-level swimmers performed 25-, 50-, and 100-m front-crawl trials and four 30-s tethered-swimming tests at 0, 0.926, 1.124, and 1.389 m·s−1 water-flow velocities. Average and maximum force, average and maximum impulse, and intracyclic force variation (dF) were estimated for each tethered-swimming trial. Swimming velocity and intracyclic velocity variation (dv) were obtained for each free-swimming trial. Stroke rate and rating of perceived exertion (RPE) were registered for all trials. Results: Tethered-swimming variables, both at 1.124 m·s−1 and at 1.389 m·s−1 water-flow velocities, were positively associated with 25-m swimming velocity (P < .05). Average force and maximum impulse in stationary swimming were significantly associated with 25-m swimming velocity (P < .05). A positive relationship between water-flow velocities with dF was observed. Swimming performance was not related to dF or dv. Neither stroke rate nor RPE differed between the 4 tethered conditions and mean 50-m free-swimming velocity (P > .05). Conclusions: Measuring force in a swimming flume at higher water-flow velocities is a better indicator of performance than stationary tethered swimming. It enables assessment of the ability to effectively apply force in the water.
Complete cognitive recovery in a severe case of anti-N-methyl-d-aspartate receptor encephalitis treated with electroconvulsive therapy
Authors: Leding Cæcilie , Marstrand Lisbet , Jorgensen Anders
Published: February 2020

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis usually presents with prominent neuropsychiatric symptoms and many patients experience cognitive sequelae. Electroconvulsive therapy (ECT) has been suggested as a part of the treatment, particularly for catatonia, but concerns that ECT may worsen the cognitive function and long-term outcome may limit its use. We present a case of anti-NMDA receptor encephalitis with severe neuropsychiatric manifestations including refractory catatonia and behavioural change. A pre-ECT neuropsychological assessment revealed dysfunction in multiple cognitive domains in spite of intensive pharmacological treatment. Twenty days after the ninth and last ECT treatment, the patient underwent the same neuropsychological tests, which showed normalised test results within all cognitive domains and no need of rehabilitation. The case demonstrates that the use of ECT in anti-NMDA receptor encephalitis with severe pretreatment cognitive dysfunction can be associated with a highly favourable cognitive outcome.
Multicentre randomised controlled trial of balloon pulmonary angioplasty and riociguat in patients with chronic thromboembolic pulmonary hypertension: protocol for the MR BPA study
Authors: Kawakami Takashi , Matsubara Hiromi , Abe Kohtaro , Kataoka Masaharu , Kohsaka Shun , Sato Yasunori , Shinke Toshiro , Fukuda Keiichi
Published: February 2020

Introduction

Management of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remains a clinical challenge. Currently, medical treatment involving pulmonary vasodilators (such as soluble guanylate-cyclase stimulators) is recommended, primarily for ameliorating symptoms. More recently, balloon pulmonary angioplasty (BPA) has been developed as alternative treatment for inoperable CTEPH. This study aimed to compare the efficacy and safety of BPA and riociguat (a soluble guanylate-cyclase stimulator) as treatments for inoperable CTEPH.

Methods and analysis

This study is a multicentre randomised controlled trial. Subjects with inoperable CTEPH were randomised (1:1) into either a BPA or riociguat group, and observed for 12 months after initiation of treatment. The primary endpoint will be the change in mean pulmonary arterial pressure from baseline to 12 months after initiation of treatment. For primary analysis, we will estimate the least square means difference and 95% CI for the change of pulmonary arterial pressure between the groups at 12 months using the analysis of covariance adjusted for allocation factors.

Ethics and dissemination

This study and its protocols were approved by the institutional review board of Keio University School of Medicine and each participating institution. Written informed consent was obtained from all participants. Results will be disseminated at medical conferences and in journal publications.

Trial registration number

University Hospital Medical Information Network Clinical Trial Registry (UMIN000019549); Pre-results.
Mental health selection: common mental disorder and migration between multiple states of deprivation in a UK cohort
Authors: Greene Giles , Gartner Andrea , Farewell Daniel , Trefan Lazlo , Davies Alisha R , Bellis Mark A , Paranjothy Shantini
Published: February 2020

Objectives

To assess whether the direction of movement along the social gradient was associated with changes in mental health status.

Design

Longitudinal record-linkage study using a multistate model.

Setting

Caerphilly, Wales, UK between 2001 and 2015.

Participants

The analytical sample included 10 892 (60.8% female) individuals aged 18–74 years.

Primary and secondary outcome measures

Deprivation change at lower super output area level using the 2008 Welsh Index of Multiple Deprivation. Mental health was assessed in 2001 and 2008 using the Mental Health Inventory subscale of the short-form 36 V.2.

Results

Mental health selection was shown whereby individuals with common mental health disorders were less likely to move to areas of lower deprivation but more likely to move to areas of greater deprivation.

Conclusion

Poor mental health seems to drive health selection in a similar way to poor physical health. Therefore, funding targeted at areas of higher deprivation should consider the demand to be potentially higher as individuals with poor mental health may migrate into that area.
A pilot study of a neuroscience-based, harm minimisation programme in schools and youth centres in Australia
Authors: Debenham Jennifer , Birrell Louise , Champion Katrina , Askovic Mina , Newton Nicola
Published: February 2020

Objectives

The primary aim is to evaluate the feasibility of a newly developed, neuroscience-based, alcohol and other drug (AOD) use prevention programme, ‘The Illicit Project’, in Australian older adolescents. The secondary aim is to investigate the impact of the programme on students’ drug literacy levels (a combination of knowledge, attitudes and skills).

Design

A pilot study examining the feasibility of The Illicit Project in Australian schools was conducted.

Participants

Students aged 15–19 years from two secondary schools and a youth centre and 11 teachers and health professionals from various organisations in Sydney were recruited.

Intervention

The intervention consisted of three 90 min workshops delivered by trained facilitators within a month.

Primary and secondary measures

Students completed a drug literacy questionnaire before and after intervention. All participants (students, teachers and health professionals) completed an evaluation questionnaire postprogramme delivery. A paired-sample t-test and descriptive analytics were performed.

Results

Students (n=169) demonstrated a significant increase in drug literacy levels from preintervention to postintervention (t(169) = −13.22, p<0.0001). Of students evaluating the programme (n=252), over threequarters agreed that The Illicit Project was good or very good (76%), that the neuroscience content was interesting (76%) and relevant (81%), and that they plan to apply the concepts learnt to their own lives (80%). In addition, all teachers and health professionals (n=11) agreed that the programme was feasible and valid for schools and perceived the programme to be effective in reducing the harms and use of AOD.

Conclusions

There is evidence to suggest that The Illicit Project is credible and feasible in the school environment and there are preliminary data to suggest it may help to improve drug literacy levels in young people. A large-scale evaluation trial of the intervention will be conducted to determine the programme’s effectiveness in minimising the harms of AOD in older adolescents.
Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease
Authors: Lutgens Esther , Seijkens Tom T.P.
Published: February 2020

The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger arteries, is commonly present in cancer patients. A major concern is the adverse effect of ICI on atherosclerosis-related cardiovascular disease, resulting in cardiovascular events, such as myocardial infarction or ischaemic stroke. The effects of ICI on atherosclerosis in cancer patients are incompletely understood, but it is well known that immune checkpoint proteins orchestrate the inflammatory response underlying atherogenesis. This paper addresses the hypothesis that ICI therapy puts cancer patients at an increased risk for atherosclerosis-related cardiovascular disease, that might only become apparent years after ICI therapy. Until clinical and experimental studies have addressed this hypothesis, optimal cardiovascular risk management in ICI-treated patients is opportune to reduce the occurrence of cardiovascular disease in cancer patients and long-term cancer survivors.
Outcome of endovascular recanalization for intracranial in-stent restenosis
Authors: Kang Kaijiang , Gao Feng , Mo Dapeng , Yang Ming , Liu Yifan , Yang Bo , Chen Xing , Gu Weibin , Ma Guofeng , Zhao Xingquan , Miao Zhong-Rong , Ma Ning
Published: February 2020

Background and purpose

In-stent restenosis (ISR) is one of the long-term adverse outcomes of endovascular angioplasty and stenting for symptomatic intracranial arterial stenosis. In this study, we try to evaluate the safety and efficacy of endovascular treatment for intracranial ISR.

Methods

We retrospectively collected patients with intracranial ISR who underwent endovascular treatment from June 2012 to August 2019 at a high-volume stroke center. Successful recanalization was defined as ≤30% residual stenosis. Stroke, myocardial infarction, and death after stenting within 30 days were used to evaluate periprocedural safety. Recurrent stroke in the territory of the culprit vessel and re-ISR in patients with clinical and vascular imaging follow-up data were used to evaluate the long-term outcome.

Results

32 patients (59.6±7.2 years old) with ISR were recruited, including 22 patients (68.8%) treated with balloon dilatation, 8 patients (25%) with stenting, and 2 patients (6.3%) with failed procedures. Successful recanalization was achieved in 71.9% (23/32) of patients. There was no stroke, myocardial infarction or death within 30 days after the procedure. Recurrent stroke was found in 10.7% (3/28) of the patients, and re-ISR was found in 42.1% (8/19) of the patients. The re-ISR rate was lower in patients with stenting than in those with balloon dilatation (0% vs 57.1%, p=0.090), and in patients with successful recanalization than in those with unsuccessful recanalization (33.3% vs 75.0%, p=0.352), but with no statistically significant difference.

Conclusions

The periprocedural safety of endovascular treatment for intracranial ISR may be acceptable, but the long-term rates of recurrent stroke and re-ISR remain at high levels.
Temporal trends in respirable dust and respirable quartz concentrations within the European industrial minerals sector over a 15-year period (2002–2016)
Authors: Zilaout Hicham , Houba Remko , Kromhout Hans
Published: February 2020

Objectives

Since 2000 the European Industrial Minerals Association’s Dust Monitoring Programme (IMA-DMP) has systematically collected respirable dust and respirable quartz measurements from 35 companies producing industrial minerals. The IMA-DMP initiative allowed for estimating overall temporal trends in exposure concentrations for the years 2002–2016 and for presenting these trends by type of mineral produced, by jobs performed and by time of enrolment into the DMP.

Methods

Approximately 32 000 personal exposure measurements were collected during 29 sampling campaigns during a 15-year period (2002–2016). Temporal trends in respirable dust and respirable quartz concentrations were studied by using linear mixed effects models.

Results

Concentrations varied widely (up to three to four orders of magnitude). However, overall decreases in exposure levels were shown for the European minerals industry over the 15-year period. Statistically significant overall downward temporal trends of −9.0% and −3.9% per year were observed for respirable dust and respirable quartz, respectively. When analyses were stratified by time period, no downward trends (and even slight increasing concentrations) were observed between 2008 and 2012, most likely attributable to the recent global economic crisis. After this time period, downward trends became visible again.

Conclusions

Consistent and statistically significant downward trends were found for both exposure to respirable dust and respirable quartz. These downward trends became less or even reversed during the years of the global economic crisis. To our knowledge, this is the first time that analyses of long-term temporal trends point at an effect of a global economic crisis on personal exposure concentrations of workers from sites across Europe.
Nucleon’s energy–momentum tensor form factors in light-cone QCD
Authors: Azizi K. , Özdem U.
Published: February 2020

We use the energy–momentum tensor (EMT) current to compute the EMT form factors of the nucleon in the framework of the light cone QCD sum rule formalism. In the calculations, we employ the most general form of the nucleon’s interpolating field and use the distribution amplitudes (DAs) of the nucleon with two sets of the numerical values of the main input parameters entering the expressions of the DAs. The directly obtained results from the sum rules for the form factors are reliable at $$ Q^2\ge 1$$Q2≥1 GeV$$^2 $$2: to extrapolate the results to include the zero momentum transfer squared with the aim of estimation of the related static physical quantities, we use some fit functions for the form factors. The numerical computations show that the energy–momentum tensor form factors of the nucleon can be well fitted to the multipole fit form. We compare the results obtained for the form factors at $$ Q^2=0 $$Q2=0 with the existing theoretical predictions as well as experimental data on the gravitational form factor d$$_1^q(0)$$1q(0). For the form factors M$$_2^q (0)$$2q(0) and J$$^q(0)$$q(0) a consistency among the theoretical predictions is seen within the errors: our results are nicely consistent with the Lattice QCD and chiral perturbation theory predictions. However, there are large discrepancies among the theoretical predictions on d$$_1^q(0)$$1q(0). Nevertheless, our prediction is in accord with the JLab data as well as with the results of the Lattice QCD, chiral perturbation theory and KM15-fit. Our fit functions well define most of the JLab data in the interval $$ Q^2\in [0,0.4]$$Q2∈[0,0.4] GeV$$^2 $$2, while the Lattice results suffer from large uncertainties in this region. As a by-product, some mechanical properties of the nucleon like the pressure and energy density at the center of nucleon as well as its mechanical radius are also calculated and their results are compared with other existing theoretical predictions.
The shocklet transform: a decomposition method for the identification of local, mechanism-driven dynamics in sociotechnical time series
Authors: Dewhurst David Rushing , Alshaabi Thayer , Kiley Dilan , Arnold Michael V. , Minot Joshua R. , Danforth Christopher M. , Dodds Peter Sheridan
Published: February 2020

We introduce a qualitative, shape-based, timescale-independent time-domain transform used to extract local dynamics from sociotechnical time series—termed the Discrete Shocklet Transform (DST)—and an associated similarity search routine, the Shocklet Transform And Ranking (STAR) algorithm, that indicates time windows during which panels of time series display qualitatively-similar anomalous behavior. After distinguishing our algorithms from other methods used in anomaly detection and time series similarity search, such as the matrix profile, seasonal-hybrid ESD, and discrete wavelet transform-based procedures, we demonstrate the DST’s ability to identify mechanism-driven dynamics at a wide range of timescales and its relative insensitivity to functional parameterization. As an application, we analyze a sociotechnical data source (usage frequencies for a subset of words on Twitter) and highlight our algorithms’ utility by using them to extract both a typology of mechanistic local dynamics and a data-driven narrative of socially-important events as perceived by English-language Twitter.
Blocking-Aware Partitioned Real-Time Scheduling for Uniform Heterogeneous Multicore Platforms
Authors: Han Jian-Jun , Gong Sunlu , Wang Zhenjiang , Cai Wen , Zhu Dakai , Yang Laurence T.
Published: February 2020

Heterogeneous multicore processors have recently become
de facto
computing engines for state-of-the-art embedded applications. Nonetheless, very little research focuses on the scheduling of periodic (implicit-deadline) real-time tasks upon heterogeneous multicores under the requirements of task synchronization, which is stemmed from resource access conflicts and can greatly affect the schedulability of tasks. In view of partitioned Earliest Deadline First and Multiprocessor Stack Resource Policy, we first discuss the blocking-aware utilization bound for uniform heterogeneous multicores and then illustrate its non-monotonicity, where the bound may decrease with more deployed cores. Following the insights obtained from the bound analysis, taking the system heterogeneity into consideration, we propose a Synchronization-Aware Task Partitioning Algorithm for Heterogeneous Multicores (SA-TPA-HM)). Several resource-guided and heterogeneity-oriented mapping heuristics are incorporated to reduce the negative impacts of blocking interferences for better schedulability performance of tasks and balanced workload distribution across cores. The extensive simulation results show that SA-TPA-HM can obtain the schedulability ratios approximate to an Integer Non-Linear Programming--based solution, and much higher (e.g., 60% more) in contrast to the existing partitioning algorithms targeted at homogeneous multicores. The measurement results in Linux kernel further reveal the practical viability of SA-TPA-HM that can experience lower runtime overhead (e.g., 15% less) when compared to other mapping schemes.
BBB-CFI
Authors: He Wenjian , Das Sanjeev , Zhang Wei , Liu Yang
Published: February 2020

Code-reuse attack is a concrete threat to computing systems because it can evade conventional security defenses. Control flow integrity (CFI) is proposed to repel this threat. However, former implementations of CFI suffer from two major drawbacks: complex offline processing on programs and high overheads at runtime. Therefore, it is impractical for performance-constrained devices to adopt the technology, leaving them vulnerable to exploitation.

In this article, we develop a cross-layer approach named
basic-block-boundary-based control flow integrity
(BBB-CFI) to minimize the overheads of both offline analysis and runtime checking. Our approach employs basic block information inside the binary code and read-only data to enforce CFI. We identify a key binary-level property called
basic block boundary
, and based on it we propose the code-inspired method where short code sequences can endorse a control flow transition. Our solution enables quick application launching because it does not require control flow graph construction at the offline stage. We only demand a lightweight analysis on read-only data and a small amount of code of the application. According to the experiments, our approach incurs a negligible 0.11% runtime performance overhead with a minor processor extension, whereas it achieves an order of magnitude speedup in pre-preprocessing compared to a baseline approach. Without control flow analysis or recompilation, BBB-CFI still effectively reduces 90% of the attack surface in terms of gadget numbers. Besides this, we show that the Turing-completeness in the libc is unsustainable. Our approach also demonstrates high applicability to many programs, and it is capable of protecting striped binaries.
Automated Model-Based Optimization of Data-Adaptable Embedded Systems
Authors: Lizarraga Adrian , Sprinkle Jonathan , Lysecky Roman
Published: February 2020

Dynamic data-driven applications such as object tracking, surveillance, and other sensing and decision applications are largely dependent on the characteristics of the data streams on which they operate. The underlying models and algorithms of data-driven applications must continually adapt at runtime to changes in data quality and availability to meet both functional and designer-specified performance requirements. Given the dynamic nature of these applications, point solutions produced by traditional design tools cannot be expected to perform adequately across varying execution scenarios. Additionally, the increasing diversity and interdependence of application requirements complicates the design and optimization process. To assist designers of data-driven applications, we present a modeling and optimization framework that enables developers to model an application's data sources, tasks, and exchanged data tokens; specify application requirements through high-level design metrics and fuzzy logic--based optimization rules; and define an estimation framework to automatically optimize the application at runtime. We demonstrate the modeling and optimization process via an example application for video-based vehicle tracking and collision avoidance. We analyze the benefits of runtime optimization by comparing the performance of static point solutions to dynamic solutions over five distinct execution scenarios, showing improvements of up to 74% for dynamic over static configurations. Further, we show the benefits of using fuzzy logic--based rules over traditional weighted functions for the specification and evaluation of competing high-level metrics in optimization.
Gut microbiome of a porcine model of metabolic syndrome and HF-pEF
Authors: O’Donovan Aoife N. , Herisson Florence M. , Fouhy Fiona , Ryan Paul M. , Whelan Derek , Johnson Crystal N. , Cluzel Gaston , Ross R. Paul , Stanton Catherine , Caplice Noel M.
Published: February 2020

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.

NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.
Existence of Solution of Space–Time Fractional Diffusion-Wave Equation in Weighted Sobolev Space
Authors: Zhang Kangqun
Published: February 2020

In this paper, we consider Cauchy problem of space-time fractional diffusion-wave equation. Applying Laplace transform and Fourier transform, we establish the existence of solution in terms of Mittag-Leffler function and prove its uniqueness in weighted Sobolev space by use of Mikhlin multiplier theorem. The estimate of solution also shows the connections between the loss of regularity and the order of fractional derivatives in space or in time.
Amaranthus mangostanus Inhibits the Differentiation of Osteoclasts and Prevents Ovariectomy‐Induced Bone Loss
Authors: Jeong Yeon-Hui , Hur Haeng Jeon , Lee Ae Sin , Lee Sang Hee , Sung Mi Jeong
Published: February 2020

Bone homeostasis is dynamically balanced between bone forming osteoblasts and bone resorbing osteoclasts. Osteoclasts play an important role in bone destruction and osteoporosis, and they are derived from monocyte/macrophages in response to macrophage colony‐stimulating factor (M‐CSF) and receptor activator of nuclear factor κB (NF‐κB) ligand (RANKL). Amaranthus mangostanus L. (AM) is a plant with powerful antioxidant and other biological activities including anti‐inflammatory, antidiabetic, and antihyperlipidemic effects. However, its effects on bone health are unknown. In this study, we explored whether AM could affect RANK‐mediated osteoclastogenesis. AM significantly suppressed RANKL‐induced osteoclast differentiation and expression of osteoclast‐specific genes, TRAP, cathepsin K, NF‐activated T‐cells (NFATc1), and Dc‐stamp in RAW 264.7 cells. Moreover, AM significantly inhibited extracellular signal‐regulated kinase (ERK), Akt, and NF‐κB signaling pathways in RAW 264.7 cells. In addition, AM preserved ovariectomy‐induced bone loss in mice. Taken together, our results suggest that AM might be a potential candidate for the treatment of postmenopausal osteoporosis.
Analysis of Failures and Influence Factors of Critical Infrastructures: A Case of Metro
Authors: Deng Yongliang , Song Liangliang , Zhou Jianliang , Xu Na , Ni Guodong , Wang Linxiu
Published: February 2020

Metro plays an indispensable role in promoting social and economic development of the big cities. However, the safety operation of the metro system is believed to be an arduous work for its operation being susceptible to various factors, especially equipment failure, which could bring about delay, interruption, and even accidents. In consideration of the seriousness of metro accident, it is becoming more and more crucial to conduct proactive, targeted, and effective risk management to reduce failures. Firstly, based on the FMECA and influence diagram theory, this paper proposes a new analytical framework to study metro equipment failure in accordance with system decomposition. Furthermore, a case study is implemented to verify the feasibility and availability of this framework in evaluating criticality of failure modes and assessing its influence factors based on the collected data from metro operation company. As indicated by the research results, wheel damage is the most serious failure mode in the bogie system, and its most paramount influence factor is the shortage of professional skills. Finally, a discussion about the research methods and results is carried out, and several recommendations are put forward to improve safety management on the basis of research findings. This study has the potential to offer suggestions in regard to metro equipment design, operation, and maintenance for raising the safety level in metro operation.
Heat Shock Lipolysis: Radiofrequency Combined with Cryolipolysis for the Reduction of Localized Subcutaneous Fat
Authors: Abboud S. , Hachem J. P.
Published: February 2020

Introduction. Noninvasive procedures such as cryolipolysis, noncontact selective radiofrequency (RF), and laser selective fat heating have been shown to be safe and effective for the reduction of localized subcutaneous fat. Material and Methods. In this retrospective study, we describe the safety and efficacy of combining RF with cryolipolysis for localized unwanted fat after one single session. 69 patients, 61 females, and 8 males for a total of 75 treatments were included in this study. All patients underwent RF prior to and following cryolipolysis. Pictures (n = 24), taken before and after treatment, were used to clinically assess the physician Global Aesthetic Improvement Scale (PhGAIS). In parallel, patients were asked to subjectively evaluate the efficacy of the treatment using the same scale (PaGIAS). Results. PhGIAS showed an improvement in 18 patients (73.46%), 5 (22.44%) were unchanged, and 1 (4.08%) worsened their appearance after treatment. The mean PaGIAS scored as “good improvement.” Conclusion. In conclusion, combining RF with cryolipolysis in one single session is safe and effective.
Prediction of Pleural Invasion in Challenging Non-Small-Cell Lung Cancer Patients Using Serum and Imaging Markers
Authors: Zhu Kaibin , Chen Lantao , He Changjun , Lang Yaoguo , Kong Xianglong , Qu Changfa , Xu Shidong
Published: February 2020

Introduction. Preoperative detection of pleural invasion in lung cancer patients is key to curative surgical treatment. We tried to predict pleural invasion in non-small-cell lung cancer patients with <100 ml pleural fluid. Methods. Patients admitted from August 1, 2011, to December 31, 2018, were retrospectively retrieved. Records of serum and imaging markers were analyzed. Results. Among 7004 patients who received surgery, 43 cases with <100 ml pleural fluid who had pleural invasion were included, and another 108 cases without pleural invasion were enrolled as controls. There were no differences in squamous cell carcinoma antigen (SCC) or neuron-specific enolase (NSE) values between the pleural invasion and noninvasion groups (p=0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p<0.01 and 0.01, respectively). There were significant differences in the location of original lung cancer (right mid lobe, p=0.01), maximum lung lesion diameter (p<0.01), volume of pleural fluid (nondetectable vs. detectable fluid, p<0.01), pleural sign (p=0.03), and positron emission tomography/computed tomography- (PET/CT-) predicted pleural invasion (p=0.02) between the pleural invasion and noninvasion groups. The maximum Area-Under-the-Curve in the Receiver Operating Characteristic curve analysis was achieved with the combination of CEA, CYFRA21-1, detectable pleural fluid, PET/CT prediction, pleural sign, and location of the lung lesion. Conclusions. Serum CEA and CYFRA21-1, location of original lung cancer (right mid lobe), maximum diameter, CT-detectable pleural fluid, pleural sign by CT, and PET/CT-predicted pleural invasion were good markers for the prediction of pleural invasion in non-small-cell lung cancer patients.
Moraxella catarrhalis: A Cause of Concern with Emerging Resistance and Presence of BRO Beta-Lactamase Gene—Report from a Tertiary Care Hospital in South India
Authors: Raveendran Savitha , Kumar Gauri , Sivanandan R. N. , Dias Mary
Published: February 2020

Background. Found as a commensal in the upper respiratory tract, Gram-negative diplococcus Moraxella catarrhalis did not hold much importance as an infectious agent for long. The emergence of the first antibiotic-resistant strain of M. catarrhalis was noted in 1977 in Sweden. This has gradually spread worldwide over the years to more than 95% of the strains showing resistance to penicillin now. Penicillin resistance is mediated by the production of beta-lactamases encoded by bro-1 and bro-2 genes that code for beta-lactamases BRO-1 and BRO-2, respectively. The purpose of this study was to explore the trends of antibiotic resistance, the presence of bro genes, and clinical correlation of these findings with the rise in M. catarrhalis infections worldwide. Methods. Strains of M. catarrhalis were isolated from the respiratory samples submitted to the microbiology laboratory. Preliminary identification was done using standard microbiological techniques, and antibiotic sensitivity was determined by minimum inhibitory concentration assessed using the E-test. Further, the genes associated with the development of resistance to penicillin (beta-lactamase enzyme) were detected using polymerase chain reaction technique. Results. Fourteen strains of M. catarrhalis were isolated during the study period. Majority of the strains were isolated from patients between 40 and 60 years of age and from males. Seasonality was observed with most strains being isolated during the winter season. The most important predisposing factors identified were advanced age with a history of smoking and chronic obstructive pulmonary disease. The antibiotic susceptibility pattern showed resistance to most antibiotics commonly used for the treatment of respiratory tract infections. Finally, all the strains were beta-lactamase producers, confirmed by the detection of bro-1 beta-lactamase gene in them. Conclusion. The increase in antibiotic resistance and beta-lactamase production in M. catarrhalis is a cause of concern. The emerging resistance pattern emphasises the need for an appropriate antibiotic stewardship program in clinical practice. Importance should be given to the monitoring of the trends of antibiotic susceptibility and their usage to prevent the emergence of outbreaks with resistant strains and treatment failures.
A Case Report with Severe Thrombocytopenia Induced by Axitinib
Authors: Koksal Ulkuhan I. , Goffin Janeiro Valle , Lewis Brian , Sartor Oliver A. , Belyaeva Elizaveta , Socola Francisco , Barata Pedro C.
Published: February 2020

Axitinib is an oral, second-generation tyrosine kinase inhibitor that is selective for vascular endothelial growth factor receptors (VEGFR). This agent is approved as monotherapy or in combination with immune checkpoint inhibitors for the treatment of metastatic renal cell carcinoma. Axitinib is associated with a safety profile very similar to other anti-VEGFR inhibitors but usually with fewer hematologic adverse events, due to the selectivity for VEGF. In this report, we presented a rare case of grade 4 axitinib-induced thrombocytopenia, not observed with other antiangiogenic therapies. We discuss the differential diagnostic work-up, the necessary multidisciplinary approach, and the successful management of the case.
Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial
Authors: Reardon David A. , Desjardins Annick , Vredenburgh James J. , O'Rourke Donald M. , Tran David D. , Fink Karen L. , Nabors Louis B. , Li Gordon , Bota Daniela A. , Lukas Rimas V. , Ashby Lynn S. , Duic J. Paul , Mrugala Maciej M. , Cruickshank Scott , Vitale Laura , He Yi , Green Jennifer A. , Yellin Michael J. , Turner Christopher D. , Keler Tibor , Davis Thomas A. , Sampson John H.
Published: February 2020

Purpose:

Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma.

Patients and Methods:

In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2.

Results:

Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P < 0.0001).

Conclusions:

Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.

See related commentary by Wick and Wagener, p. 1535
Routine Plasma-Based Genotyping to Comprehensively Detect Germline, Somatic, and ReversionBRCAMutations among Patients with Advanced Solid Tumors
Authors: Vidula Neelima , Rich Thereasa A. , Sartor Oliver , Yen Jennifer , Hardin Aaron , Nance Tracy , Lilly Michael B. , Nezami Mohammad Amin , Patel Sandip P. , Carneiro Benedito A. , Fan Alice C. , Brufsky Adam M. , Parker Barbara A. , Bridges Benjamin B. , Agarwal Neeraj , Maughan Benjamin L. , Raymond Victoria M. , Fairclough Stephen R. , Lanman Richard B. , Bardia Aditya , Cristofanilli Massimo
Published: February 2020

Purpose:

PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) BRCA1/2 mutations. Acquired reversions can restore BRCA1/2 function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, and/or reversion mutations in BRCA1/2 has not been established. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) provides a platform to identify these three types of BRCA1/2 mutations.

Experimental Design:

Patients with advanced breast, ovarian, prostate, or pancreatic cancer were tested using a clinically validated 73-gene cfDNA assay that evaluates single-nucleotide variants and insertion–deletion mutations (indels) in BRCA1/2, and distinguishes somatic/reversion from germline mutations with high accuracy.

Results:

Among 828 patients, one or more deleterious BRCA1/2 mutations were detected in 60 (7.2%) patients, including germline (n = 42) and somatic (n = 18) mutations. Common coexisting mutations included TP53 (61.6%), MYC (30%), PIK3CA (26.6%), BRAF (15%), and ESR1 (11.5%). Polyclonal reversion mutations (median, 5) were detected in 9 of 42 (21.4%) germline BRCA1/2-mutant patients, the majority (77.7%) of whom had prior PARPi exposure (median duration, 10 months). Serial cfDNA demonstrated emergence of reversion BRCA mutations under therapeutic pressure from initial PARPi exposure, which contributed to subsequent resistance to PARPi and platinum therapy.

Conclusions:

cfDNA NGS identified high rates of therapeutically relevant mutations without foreknowledge of germline or tissue-based testing results, including deleterious somatic BRCA1/2 mutations missed by germline testing and reversion mutations that can have important treatment implications. Further research is needed to confirm clinical utility of these findings to guide precision medicine approaches for patients with advanced malignancies.
Elimination of Hepatitis C in Portugal: An Urban Legend?
Authors: Velosa José , Macedo Guilherme
Published: February 2020

The burden of hepatitis C virus infection remains very high despite huge progress in the cure of the infection. The high prevalence of hepatitis C, especially in vulnerable groups and particularly drug users, may compromise the achievement of the 2030 WHO targets with a 90% reduction in new infections and a 65% reduction in mortality. Therapy with the latest pangenotypic direct-acting antivirals provides cure rates in the order of 97% with short-term oral treatment (8–12 weeks) and with an excellent safety and tolerability profile. Curing the infection causes significant health gains derived from preventing complications from cirrhosis, especially hepatocellular carcinoma, and from liver transplantation. Elimination of hepatitis seems feasible with the implementation of a massive therapy program, focusing particularly on vulnerable populations, through micro-elimination strategies, and in the general population with age-based screening. The reduction of the virus reservoir (humans are the only reservoir) is a determining factor in eradicating the virus.
The Relevance of Typology for Pattern Replication
Authors: Meyer Robin
Published: February 2020

Structuralists and generativists have insisted for a long time that the elements and structures one language could borrow from another are constrained by typological compatibility, naturalness, and other factors (cf. Thomason and Kaufman 1988: 13–34). Such constraints are still thought to apply to structural interference, or pattern replication in the terms of Matras and Sakel (2007), and the often concomitant contact-induced grammaticalisation of non-native structures.

This paper suggests that a priori there are no typological constraints against pattern replication in general. It is proposed that typological differences between model and replica pattern are only of relevance during the grammaticalisation and maintenance of such patterns in the replica language; in other words, typological constraints do not apply at the stage of pattern replication. It will be argued that typology, in the form of system pressure, interacts with pattern frequency and socio-historical factors, which together determine retention, adaptation, or loss of a replicated pattern.

This argument is illustrated on the basis of three short studies of partial alignment change in Old Aramaic, Classical Armenian, and North-Eastern Neo-Aramaic, all of which have been in contact with Iranian languages for extended periods. In each case, Iranian ergative alignment patterns have been replicated, adapted, grammaticalised to varying degrees, and finally ousted in favour of nominative-accusative alignment. The loss of the replica pattern in each case is shown to be dependent on both typology, extent of bilingualism, and pattern frequency.