bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol
Authors: Golla Heidrun , Nettekoven Charlotte , Bausewein Claudia , Tonn Jörg-Christian , Thon Niklas , Feddersen Berend , Schnell Oliver , Böhlke Christopher , Becker Gerhild , Rolke Roman , Clusmann Hans , Herrlinger Ulrich , Radbruch Lukas , Vatter Hartmut , Güresir Erdem , Stock Stephanie , Müller Dirk , Civello Daniele , Papachristou Irini , Hellmich Martin , Hamacher Stefanie , Voltz Raymond , Goldbrunner Roland
Published: January 2020

​Introduction

Randomised controlled trials (RCTs) have shown a positive effect of early integration of palliative care (EIPC) in various advanced cancer entities regarding patients’ quality of life (QoL), survival, mood, caregiver burden and reduction of aggressiveness of treatment near the end of life. However, RCTs investigating the positive effect of EIPC for patients suffering from glioblastoma multiforme (GBM) are lacking. After modelling work identifying the specific needs of GBM patients and their caregivers, the aim of this study is to investigate the impact of EIPC in this particular patient group.

​Methods and analysis

The recruitment period of this multicenter RCT started in May 2019. GBM patients (n=214) and their caregivers will be randomly assigned to either the intervention group (receiving proactive EIPC on a monthly basis) or the control group (receiving treatment according to international standards and additional, regular assessment of QoL (‘optimised’ standard care)).

The primary outcome is QoL assessed by subscales of the Functional Assessment of Cancer Therapy for brain tumour (FACT-Br) from baseline to 6 months of treatment. Secondary outcomes are changes in QoL after 12 (end of intervention), 18 and 24 months (end of follow-up), the full FACT-Br scale, patients’ palliative care needs, depression/anxiety, cognitive impairment, caregiver burden, healthcare use, cost-effectiveness and overall survival.

​Ethics and dissemination

The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the local ethics committees of the University Clinics of Cologne, Aachen, Bonn, Freiburg and Munich (LMU). Results of the trial will be submitted for publication in a peer-reviewed, open access journal and disseminated through presentations at conferences.

Trial registration number

German Register for Clinical Studies (DRKS) (DRKS00016066); Pre-results.
Ocular side effects of antirheumatic medications: a qualitative review
Authors: M Castillejo Becerra Clara , Ding Yue , Kenol Beatrice , Hendershot Andrew , Meara Alexa Simon
Published: January 2020

Topic

This paper reviews the ocular side effects of medications used in the treatment of rheumatological conditions.

Clinical relevance

Rheumatic diseases are inflammatory conditions that may affect the skin, blood vessels, joints, muscles and internal organs. Immunosuppressive agents are often used as treatment and while powerful, they carry side effects and toxicities that need careful monitoring. Ophthalmic complications have been reported with the use of antirheumatic medications; however, there is a lack of literature synthesising these reports. This paper addresses this gap and hopes to inform both rheumatologists and ophthalmologists as they work together on the management of patients with rheumatological conditions.

Methods

PubMed literature search was conducted from November to September 2019 searching for ocular side effects with the use of 25 rheumatological drugs.

Results

A total of 111 papers were included in this review. Adverse side effects were divided into non-infectious and infectious causes. Traditional disease-modifying antirheumatic drugs (DMARDs) were associated with pruritus, irritation and dryness of the conjunctiva while biologic DMARDS showed reports of new-onset/recurrent uveitis and demyelinating conditions. Infectious side effects included episodes of cytomegalovirus retinitis, toxoplasmic chorioretinitis and endophthalmitis. Other serious side effects were encountered and included in this review.

Conclusion

The goal of this paper is to inform healthcare providers about potential ocular side effects from rheumatological medications. Healthcare providers are encouraged to learn more about these ophthalmic complications and find relevance within their clinical practice.
Preventing critical failure. Can routinely collected data be repurposed to predict avoidable patient harm? A quantitative descriptive study
Authors: Nowotny Benjamin Michael , Davies-Tuck Miranda , Scott Belinda , Stewart Michael , Cox Elizabeth , Cusack Karen , Fletcher Martin , Saar Eva , Farrell Tanya , Anil Shirin , McKinlay Louise , Wallace Euan M
Published: January 2020

Objectives

To determine whether sharing of routinely collected health service performance data could have predicted a critical safety failure at an Australian maternity service.

Design

Observational quantitative descriptive study.

Setting

A public hospital maternity service in Victoria, Australia.

Data sources

A public health service; the Victorian state health quality and safety office—Safer Care Victoria; the Health Complaints Commission; Victorian Managed Insurance Authority; Consultative Council on Obstetric and Paediatric Mortality and Morbidity; Paediatric Infant Perinatal Emergency Retrieval; Australian Health Practitioner Regulation Agency.

Main outcome measures

Numbers and rates for events (activity, deaths, complaints, litigation, practitioner notifications). Correlation coefficients.

Results

Between 2000 and 2014 annual birth numbers at the index hospital more than doubled with no change in bed capacity, to be significantly busier than similar services as determined using an independent samples t-test (p<0.001). There were 36 newborn deaths, 11 of which were considered avoidable. Pearson correlations revealed a weak but significant relationship between number of births per birth suite room birth and perinatal mortality (r2=0.18, p=0.003). Independent samples t-tests demonstrated that the rates of emergency neonatal and perinatal transfer were both significantly lower than similar services (both p<0.001). Direct-to-service patient complaints increased ahead of recognised excess perinatal mortality.

Conclusion

While clinical activity data and direct-to-service patient complaints appear to offer promise as potential predictors of health service stress, complaints to regulators and medicolegal activity are less promising as predictors of system failure. Significant changes to how all data are handled would be required to progress such an approach to predicting health service failure.
Epidemiology of facial fractures: incidence, prevalence and years lived with disability estimates from the Global Burden of Disease 2017 study
Authors: Lalloo Ratilal , Lucchesi Lydia R , Bisignano Catherine , Castle Chris D , Dingels Zachary V , Fox Jack T , Hamilton Erin B , Liu Zichen , Roberts Nicholas L S , Sylte Dillon O , Alahdab Fares , Alipour Vahid , Alsharif Ubai , Arabloo Jalal , Bagherzadeh Mojtaba , Banach Maciej , Bijani Ali , Crowe Christopher Stephen , Daryani Ahmad , Do Huyen Phuc , Doan Linh Phuong , Fischer Florian , Gebremeskel Gebreamlak Gebremedhn , Haagsma Juanita A , Haj-Mirzaian Arvin , Haj-Mirzaian Arya , Hamidi Samer , Hoang Chi Linh , Irvani Seyed Sina Naghibi , Kasaeian Amir , Khader Yousef Saleh , Khalilov Rovshan , Khoja Abdullah T , Kiadaliri Aliasghar A , Majdan Marek , Manafi Navid , Manafi Ali , Massenburg Benjamin Ballard , Mohammadian-Hafshejani Abdollah , Morrison Shane Douglas , Nguyen Trang Huyen , Nguyen Son Hoang , Nguyen Cuong Tat , Olagunju Tinuke O , Otstavnov Nikita , Polinder Suzanne , Rabiee Navid , Rabiee Mohammad , Ramezanzadeh Kiana , Ranganathan Kavitha , Rezapour Aziz , Safari Saeed , Samy Abdallah M , Sanchez Riera Lidia , Shaikh Masood Ali , Tran Bach Xuan , Vahedi Parviz , Vahedian-Azimi Amir , Zhang Zhi-Jiang , Pigott David M , Hay Simon I , Mokdad Ali H , James Spencer L
Published: January 2020

Background

The Global Burden of Disease Study (GBD) has historically produced estimates of causes of injury such as falls but not the resulting types of injuries that occur. The objective of this study was to estimate the global incidence, prevalence and years lived with disability (YLDs) due to facial fractures and to estimate the leading injurious causes of facial fracture.

Methods

We obtained results from GBD 2017. First, the study estimated the incidence from each injury cause (eg, falls), and then the proportion of each cause that would result in facial fracture being the most disabling injury. Incidence, prevalence and YLDs of facial fractures are then calculated across causes.

Results

Globally, in 2017, there were 7 538 663 (95% uncertainty interval 6 116 489 to 9 493 113) new cases, 1 819 732 (1 609 419 to 2 091 618) prevalent cases, and 117 402 (73 266 to 169 689) YLDs due to facial fractures. In terms of age-standardised incidence, prevalence and YLDs, the global rates were 98 (80 to 123) per 100 000, 23 (20 to 27) per 100 000, and 2 (1 to 2) per 100 000, respectively. Facial fractures were most concentrated in Central Europe. Falls were the predominant cause in most regions.

Conclusions

Facial fractures are predominantly caused by falls and occur worldwide. Healthcare systems and public health agencies should investigate methods of all injury prevention. It is important for healthcare systems in every part of the world to ensure access to treatment resources.
Combined use of contact aspiration and the stent retriever technique versus stent retriever alone for recanalization in acute cerebral infarction: the randomized ASTER 2 study protocol
Authors: Lapergue Bertrand , Labreuche Julien , Blanc Raphaël , Marnat Gaultier , Consoli Arturo , Rodesch Georges , Saleme Suzanna , Costalat Vincent , Bracard Serge , Desal Hubert , Duhamel Alain , Mazighi Mikael , Spelle Laurent , Houdart Emmanuel , Shotar Eimad , Ben Maacha Malek , Lopez Delphine , Ferre Jean-Christophe , Prevot Claire , Gory Benjamin , Piotin Michel
Published: January 2020

Rationale

Mechanical thrombectomy (MT) using a stent retriever (SR) device is currently the recommended treatment in ischemic stroke due to anterior circulation large vessel occlusion. Combining contact aspiration (CA) with SR is a promising new treatment, although it was not found to be superior to SR alone as first-line treatment for achieving successful reperfusion.

Aim

To determine whether endovascular treatment combining first-line use of CA and SR is more efficient than SR alone.

Methods

The ASTER 2 clinical trial is a prospective, randomized, multicenter, open-label trial with a blinded endpoint. We included patients admitted with suspected anterior circulation ischemic stroke secondary to large vessel occlusion <8 hours from symptom onset. They were randomly allocated in a 1:1 ratio to one of two treatment groups (combined CA and SR or SR alone). In the case of failure of the assigned technique after three attempts, other adjunctive techniques were applied.

Study outcome

The primary outcome is the rate of successful/complete reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score 2c/3) after the entire endovascular procedure. Secondary outcomes include reperfusion rates after the assigned first-line intervention alone and at the end of the procedure, procedural times, change in NIH Stroke Scale score at 24 hours, intracerebral hemorrhage at 24 hours, procedure-related serious adverse events, the modified Rankin Scale score, and all-cause mortality at 90 days and 1 year. The cost effectiveness of the two procedures will also be analyzed.

Discussion

This is the first head-to-head randomized trial to directly compare the efficacy of the combined use of CA and SR versus SR alone. This prospective trial aims to demonstrate the synergistic effects of CA and SR devices in first-line endovascular treatment.
Extended Higgs sector of 2HDM with real singlet facing LHC data
Authors: Arhrib A. , Benbrik R. , Kacimi M. EL , Rahili L. , Semlali S.
Published: January 2020

We study the phenomenology of the two Higgs doublet model with a real singlet scalar S (N2HDM). The model predicts three CP-even Higgses $$h_{1,2,3}$$h1,2,3, one CP-odd $$A^0$$A0 and a pair of charged Higgs. We discuss the consistency of the N2HDM with theoretical as well as with all available experimental data. In contrast with previous studies, we focus on the scenario where $$h_2$$h2 is the Standard Model (SM) 125 GeV Higgs, while $$h_1$$h1 is lighter than $$h_2$$h2 which may open a window for Higgs to Higgs decays. We perform an extensive scan into the parameter space of N2HDM of type I and explore the effect of the singlet-doublet admixture. We found that a large singlet-doublet admixture is still compatible with the recent Higgs data from LHC. Moreover, we show that $$h_1$$h1 could be quasi-fermiophobic and would decay dominantly into two photons. We also study in details the consistency of the non-detected decay of $$h_2\rightarrow h_1 h_1$$h2→h1h1 with LHC data followed by $$h_1\rightarrow \gamma \gamma $$h1→γγ which leads to four photons final state at LHC: $$pp\rightarrow h_2\rightarrow h_1 h_1\rightarrow 4\gamma $$pp→h2→h1h1→4γ. Using the results of null searches of multi-photons carried by the ATLAS collaboration, we have found that a large area of the parameter space is still allowed. We also demonstrate that various neutral Higgs of the N2HDM could have several exotic decays.
Conformally symmetric Friedmann–Robertson–Walker metric in f(R,T) gravity
Authors: Taṣer Dog̃ukan
Published: January 2020

In this paper, conformal symmetric Freidmann–Robertson–Walker (FRW) universe with perfect fluid in the framework of [Formula: see text] gravitational theory is investigated. Firstly, field equations of FRW universe with perfect fluid are obtained for [Formula: see text] modified theory of gravity. The field equations of the model have been revised to understand physical nature between matter and geometry by means of conformal symmetry in [Formula: see text] gravitational theory. The exact solutions of conformal FRW universe with perfect fluid are attained for matter part of the [Formula: see text] model in the case of [Formula: see text]. The [Formula: see text] gravitational theory is one of the acceptable modifications of General Relativity (GR) in order to expound cosmic acceleration of the universe with no needing any exotic component. Nevertheless, the obtained model indicates exotic matter distribution for the current selection of arbitrary constants. Also, different value selections of arbitrary constants for the obtained model are able to predicate expanding or contracting universe with zero deceleration. Besides, it is shown that the FRW universe under the influence of the conformal Killing vector preserves to isotropic nature. Energy conditions are investigated. Also, it is shown that the constructed model satisfies strong energy condition (SEC) in all cases.
Free Parameter Optimization of DTMDs Based on Improved Hybrid Genetic-Simulated Annealing Algorithm
Authors: Han Qiang , Zhang Xuan , Xu Kun , Du Xiuli
Published: January 2020

The optimum design of distributed tuned mass dampers (DTMDs) is normally based on predefined restrictions, such as the location and/or mass ratio of the tuned mass dampers (TMDs). To further improve the control performance, a free parameter optimization method (FPOM) is proposed. This method only restricts the total mass of the DTMDs system and takes the installation position, mass ratio, stiffness and damping of each TMD as parameters to be optimized. An improved hybrid genetic-simulated annealing algorithm (IHGSA) is adopted to find the optimum values of the design parameters. This algorithm can solve the non-convexity and multimodality problems of the objective function and is quite effective in dealing with the large amount of computations in the free parameter optimization. A numerical benchmark model is adopted to compare the control efficiency of FPOM with conventional control scenarios, such as single TMD, multiple TMDs and DTMDs optimized through conventional methods. The results show that the DTMDs system optimized by using FPOM is superior to the other control scenarios for the same value of mass ratio.
Finitistic dimension and endomorphism algebras of 𝒲-Gorenstein modules
Authors: Wu Kaili , Wei Jiaqun
Published: January 2020

Let [Formula: see text] be an artin algebra, [Formula: see text] be a [Formula: see text]-Gorenstein [Formula: see text]-module and [Formula: see text], then [Formula: see text] is a [Formula: see text]-[Formula: see text]-bimodule. We use the restricted flat dimension of [Formula: see text] and the finitistic [Formula: see text]-dimension of [Formula: see text] to characterize the finitistic dimension of [Formula: see text], and obtain the following main result: if [Formula: see text] is [Formula: see text]-finite with [Formula: see text], then we have: (1) If [Formula: see text] or [Formula: see text], then [Formula: see text] (2) If [Formula: see text], then [Formula: see text]
Strong map-symmetry of SL(3,K) and PSL(3,K) for every finite field K
Authors: Breda d’Azevedo Antonio , Catalano Domenico A.
Published: January 2020

In this paper, we show that for any finite field [Formula: see text], any pair of map-generators (that is when one of the generators is an involution) of [Formula: see text] and [Formula: see text] has a group automorphism that inverts both generators. In the theory of maps, this corresponds to say that any regular oriented map with automorphism group [Formula: see text] or [Formula: see text] is reflexible, or equivalently, there are no chiral regular maps with automorphism group [Formula: see text] or [Formula: see text]. As remarked by Leemans and Liebeck, also [Formula: see text] and [Formula: see text] are not automorphism groups of chiral regular maps. These two results complete the work of the above authors on simples groups supporting chiral regular maps.
Unique Role of Think Tank Exchange in Promoting the China-U.S. Relationship
Authors: Yuan Youwei
Published: January 2020

Since the establishment of the China-U.S. diplomatic relationship, think tank exchange between both countries has undergone four phases, from very limited communication in the early years to a growing number of mutual visits, co-organized conferences and events, joint research projects, as well as representative offices or joint research/teaching programs set up in the past decade. China-U.S. think tank exchange plays a unique role in enhancing mutual understanding and mitigating distrust between both countries, thus contributing to bilateral strategic stability and closer cooperation. Under the Trump administration’s trade war and decoupling attempts toward China, however, bilateral think tank exchange has experienced a significant decline over the past few years, marked by increasing restrictions on each other’s visits, less willingness of some think tanks in such exchange, and more hardline policy stance on each other, especially from the American side. At this difficult time for China-U.S. relations, bilateral think tank exchange should be encouraged and strengthened so as to help bring the bilateral relationship back on track.
Clinical Implications ofPseudomonas aeruginosa: Antibiotic Resistance, Phage & Antimicrobial Peptide Therapy
Authors: Lim Wee Siang , Ho Pooi Leng , Li Sam Fong-Yau , Ow Dave Siak-Wei
Published: January 2020

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that is found ubiquitously in the environment. It is also the cause of nosocomial infections, which affects patients with cystic fibrosis (CF) and cathether-related infections. Treatment and eradication of P. aeruginosa is an uphill task as it has already developed resistance to many commonly used antibiotics. Some of the resistance mechanisms that P. aeruginosa employ are having low cell wall permeability, developing efflux system to pump antibiotics out, producing enzymes to inactivate antibiotics, modifying antibiotic targets, forming biofilm as a protection layer against antibiotics, and turning into more pathogenic small colony variant form. In addition, P. aeruginosa uses a host of signaling mechanisms, such as secretion system and quorum sensing, to aid its virulence. With numerous resistance mechanisms developed against conventional antibiotics, new strategies to treat P. aeruginosa infection are required. Bacteriophages such as natural bacteria viruses and studies have suggested that they can be used as an alternative to antibiotics for treatment against P. aeruginosa infections. However, phage therapy also shares the same problem with that of antibiotics, i.e., the development and emergence of bacteria resistance by masking or altering surface recognition features, inhibiting phage DNA injection and employing abortive infection (Abi) system. Another alternative treatment strategy is to use antimicrobial peptides, which are small cationic peptides that are naturally found in most organisms’ immune system. These peptides disrupt cell membrane and key cellular processes, which requires major gene alteration if evasion is needed. Hence, lowering likelihood of resistance development. This paper aims to review our current understanding of the clinical implications of P. aeruginosa infections, the mechanisms of antibiotic resistance, phage-inspired and antimicrobial peptide approaches for treatment of P. aeruginosa infections.
Green Technologies for the Production of Modified Lipids
Authors: Vázquez Luis , Bañares Celia , Torres Carlos F. , Reglero Guillermo
Published: January 2020

In recent years, the use of green solvents in enzyme catalysis of lipophilic compounds is achieving increasing interest from different perspectives. Conducting reactions under supercritical fluids, ionic liquids, deep eutectic solvents, and other green solvents affords opportunities to overcome problems associated with the lack of solubility of lipids in conventional solvents and the poor miscibility of substrates. Research on the biocatalytic production of modified lipids in the framework of green chemistry is conducted to improve the efficiency of obtaining the desired products as well as the selectivity, stability, and activity of the enzymatic systems. This overview describes the fundamentals and characteristics of several types of green solvents, the main variables involved in enzymatic processes, and examples and applications in the field of lipid modification.
Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII
Authors: Jesus Itamar Couto Guedes , Mesquita Thássio Ricardo Ribeiro , Monteiro André Luís Lima , Parreira Amanda Borges , Santos Anderson Kenedy , Coelho Elizeu Lucas Xavier , Silva Mário Morais , Souza Lucas A. C. , Campagnole-Santos Maria José , Santos Robson Souza , Guatimosim Silvia
Published: January 2020

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.
Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4
Authors: Wu Shuai , Chen Han , Zuo Ling , Jiang Hai , Yan Hongtao
Published: January 2020

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.
Airway epithelial-targeted nanoparticles for asthma therapy
Authors: Kan Stanislav , Hariyadi Dewi Melani , Grainge Christopher , Knight Darryl A. , Bartlett Nathan W. , Liang Mingtao
Published: January 2020

Asthma is a common chronic inflammatory disease associated with intermittent airflow obstruction caused by airway inflammation, mucus overproduction, and bronchial hyperresponsiveness. Despite current treatment and management options, a large number of patients with asthma still have poorly controlled disease and are susceptible to acute exacerbations, usually caused by a respiratory virus infection. As a result, there remains a need for novel therapies to achieve better control and prevent/treat exacerbations. Nanoparticles (NPs), including extracellular vesicles (EV) and their synthetic counterparts, have been developed for drug delivery in respiratory diseases. In the case of asthma, where airway epithelium dysfunction, including dysregulated differentiation of epithelial cells, impaired barrier, and immune response, is a driver of disease, targeting airway epithelial cells with NPs may offer opportunities to repair or reverse these dysfunctions with therapeutic interventions. EVs possess multiple advantages for airway epithelial targeting, such as their natural intrinsic cell-targeting properties and low immunogenicity. Synthetic NPs can be coated with muco-inert polymers to overcome biological barriers such as mucus and the phagocytic response of immune cells. Targeting ligands could be also added to enhance targeting specificity to epithelial cells. The review presents current understanding and advances in NP-mediated drug delivery to airway epithelium for asthma therapy. Future perspectives in this therapeutic strategy will also be discussed, including the development of novel formulations and physiologically relevant preclinical models.
Airway smooth muscle adapting in dynamic conditions is refractory to the bronchodilator effect of a deep inspiration
Authors: Gazzola Morgan , Khadangi Fatemeh , Clisson Marine , Beaudoin Jonathan , Clavel Marie-Annick , Bossé Ynuk
Published: January 2020

Airway smooth muscle (ASM) is continuously strained during breathing at tidal volume. Whether this tidal strain influences the magnitude of the bronchodilator response to a deep inspiration (DI) is not clearly defined. The present in vitro study examines the effect of tidal strain on the bronchodilator effect of DIs. ASM strips from sheep tracheas were mounted in organ baths and then subjected to stretches (30% strain), simulating DIs at varying time intervals. In between simulated DIs, the strips were either held at a fixed length (isometric) or oscillated continuously by 6% (length oscillations) to simulate tidal strain. The contractile state of the strips was also controlled by adding either methacholine or isoproterenol to activate or relax ASM, respectively. Although the time-dependent gain in force caused by methacholine was attenuated by length oscillations, part of the acquired force in the oscillating condition was preserved postsimulated DIs, which was not the case in the isometric condition. Consequently, the bronchodilator effect of simulated DIs (i.e., the decline in force postsimulated versus presimulated DIs) was attenuated in oscillating versus isometric conditions. These findings suggest that an ASM operating in a dynamic environment acquired adaptations that make it refractory to the decline in contractility inflicted by a larger strain simulating a DI.
Patterns of muscle activation and modulation of ankle intrinsic stiffness in different postural operating conditions
Authors: Amiri Pouya , Kearney Robert E.
Published: January 2020

Intrinsic stiffness describes the dynamic relationship between imposed angular perturbations to a joint and the resulting torque response, due to intrinsic mechanical properties of muscles and joint, and inertia of the limbs. Recently, we showed that ankle intrinsic stiffness changes substantially with sway in normal standing. In the present study, we documented how ankle intrinsic stiffness changes with postural operating conditions. Subjects stood on an apparatus while subjected to ankle position perturbations in five conditions: normal standing, toe-up and toe-down standing, and backward and forward lean. In each condition, ankle intrinsic stiffness was estimated while its modulation with sway was accounted for. The results demonstrated that ankle intrinsic stiffness varies widely, from 0.08 to 0.75 of critical stiffness, across postural operating conditions; however, it is always smaller than the critical stiffness. Therefore, other contributions are necessary to ensure stable standing. The mean intrinsic stiffness was highest in forward lean and lowest in backward lean. Moreover, within each operating condition, the intrinsic stiffness changed with center-of-pressure position in one of three ways, each associated with a distinct muscle activation pattern; these include 1) monotonically increasing stiffness-center of pressure relation, associated with a progressive increase in triceps surae activation, 2) decreasing-increasing stiffness-center of pressure relation, associated with initial activation of tibialis anterior and later activation of triceps surae, and 3) monotonically decreasing stiffness-center of pressure relation, associated with decreasing activation of tibialis anterior. Thus intrinsic stiffness varies greatly within and across postural operating conditions, and a correct understanding of postural control requires accounting for such variations.

NEW & NOTEWORTHY Ankle intrinsic stiffness changes with sway in normal standing. We quantified such changes in different postural operating conditions and demonstrated that the intrinsic stiffness changes in a manner associated with different activation patterns of ankle plantarflexors and dorsiflexors, emerging in different operating conditions. Large modulations of the intrinsic stiffness within and across postural operating conditions show that the stiffness importance and contribution change and must be accounted for in the study of postural control.
Next‐Generation Sequencing Panel Analysis of Clinically Relevant Mutations in Circulating Cell‐Free DNA from Patients with Gestational Trophoblastic Neoplasia: A Pilot Study
Authors: Luo Lingxiao , Lin Ling , Zhang Xiaoyan , Cai Qingqing , Zhao Hongbo , Xu Congjian , Cong Qing
Published: January 2020

Gestational trophoblastic neoplasia (GTN) originates from placental tissue and exhibits the potential for invasion and metastasis. Gene alterations in GTN have not been extensively studied because of a lack of qualified tumor specimens after chemotherapy. GTN has a rapid growth rate and is highly metastatic, which makes circulating tumor DNA (ctDNA) sequencing a promising modality for gene profiling. Accordingly, in this study, we performed targeted next‐generation sequencing (NGS) of 559 tumor‐associated genes using circulating cell‐free DNA (cfDNA) collected prior to chemotherapy from 11 patients with GTN. All sequenced genes were associated with oncogenesis, progression, and targeted therapy. The average cfDNA level was 0.43 ± 0.22 ng/μL. Significant correlations were found between cfDNA concentration and maximum lesion diameter (r = 0.625, p = 0.040) and time for human chorionic gonadotropin beta subunit (β‐HCG) recovering to normal level (r = 0.609, p = 0.047). There were no significant correlations between cfDNA concentrations and β‐HCG expression level or lung metastasis. ctDNA mutations were detected in all patients, and 73 mutant genes were detected in 11 patients. BMPR1A (27.3%), LRP1B (27.3%), ERCC4 (18.2%), FGF14 (18.2%), HSP90AA1 (18.2%), KAT6A (18.2%), KMT2D (18.2%), MAP3K1 (18.2%), RANBP2 (18.2%), and ZNF217 (18.2%) mutations were detected as overlapping mutations. The mRNA and protein levels of bone morphogenetic protein receptor type 1A were significantly downregulated in human JAR and JEG‐3 choriocarcinoma cells (p < 0.0001), whereas mRNA and protein levels of mitogen‐activated protein kinase kinase kinase 1 were upregulated in these two cell lines (p = 0.0128, p = 0.0012, respectively). These genes may play important roles in GTN initiation and progression and may be candidate targets for GTN treatment. These findings suggested that cfDNA levels could provide potential assessment value in disease severity of GTN and that ctDNA sequencing was a promising approach for identifying gene mutations in GTN.
Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis
Authors: Zhang Yixi , Luo Xiaojing , Lin Jianwei , Fu Shunjun , Feng Pei , Su Hongjun , He Xiangjun , Liang Xue , Liu Kunpeng , Deng Wen
Published: January 2020

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, P<0.001) and DFS (HR = 1.744, 95% CI = 1.205–2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.
The Effects of Secretory IgA in the Mucosal Immune System
Authors: Li Yue , Jin Liang , Chen Tongxin
Published: January 2020

Immunoglobulin A (IgA) is the most abundant antibody isotype in the mucosal immune system. Structurally, IgA in the mucosal surface is a polymeric structure, while serum IgA is monomeric. Secretory IgA (sIgA) is one of the polymeric IgAs composed of dimeric IgA, J chain, and secretory component (SC). Most of sIgAs were generated by gut and have effects in situ. Besides the function of “immune exclusion,” a nonspecific immune role, recent studies found it also played an important role in the specific immunity and immunoregulation. Thanks to the critical role of sIgA during the mucosal immune system homeostasis between commensal microorganisms and pathogens; it has been an important field exploring the relationship between sIgA and commensal microorganisms.
Regular and Irregular Vegetation Pattern Formation in Semiarid Regions: A Study on Discrete Klausmeier Model
Authors: Zhang Huayong , Huang Tousheng , Dai Liming , Pan Ge , Liu Zhao , Gao Zichun , Zhang Xiumin
Published: January 2020

The research on regular and irregular vegetation pattern formation in semiarid regions is an important field in ecology. Applying the framework of coupled map lattice, a novel nonlinear space- and time-discrete model is developed based on discretizing the classical Klausmeier model and the vegetation pattern formation in semiarid regions is restudied in this research. Through analysis of Turing-type instability for the discrete model, the conditions for vegetation pattern formation are determined. The discrete model is verified by Klausmeier’s results with the same parametric data, and shows advantages in quantitatively describing diverse vegetation patterns in semiarid regions, such as the patterns of regular mosaicirregular patches, stripes, fractured stripesspots, and stripes-spots, in comparing with former theoretical models. Moreover, the discrete model predicts variations of rainfall and vegetation types can cause transitions of vegetation patterns. This research demonstrates that the nonlinear mechanism of the discrete model better captures the diversity and complexity of vegetation pattern formation in semiarid regions.
Game Modelling and Strategy Research on Trilateral Evolution for Coal-Mine Operational Safety Production System: A Simulation Approach
Authors: Li Yan , Zhang Yan , Dai Haifeng , Zhao Ziyan
Published: January 2020

In view of the particularity and high risk of coal mining industry, the decision-making behavior of multiple agents inside the coal-mine enterprise plays a very important role in ensuring the safety and sustainable development of coal mining industry. The existing literature studies on coal-mine safety production focus mainly on statically analyzing the game among the external entities such as the government, the enterprises themselves, and the employees inside the enterprise from a macro perspective,are short of research on revealing the dynamic interactions among the actors directly involved in the coal-mine accidents and also on proposals for effective interactions that will lead to improved safety outcomes. Therefore, this paper explores the use of evolutionary game theory to describe the interactions among the stakeholders in China’s coal-mine safety production system, which includes the organization, the first-line miners, and the first-line managers. Moreover, the paper also explores dynamic simulations of the evolutionary game model to analyze the stability of stakeholder interactions and to identify equilibrium solutions. The simulation results show that when certain conditions are met, the decision-making behavior of the organization, miners, and managers can evolve into the unique ideal steady state (1, 1, 1). In addition, the strategy portfolio with a relatively high initial proportion of three agents converges more quickly to an ideal state than a relatively low strategy portfolio. Moreover, the stable state and equilibrium values are not affected by the initial value changes. Finally, we find that the combination of positive incentive policies and strict penalties policies can make the evolutionary game system converge to desired stability faster. The application of the evolutionary game and numerical simulation when simulating the multiplayer game process of coal-mine safety production is an effective way, which provides a more effective solution to the safety and sustainable development of coal mining industry.
The Tonoplast Intrinsic Protein Gene KvTIP3 is Responsive to Different Abiotic Stresses in Kosteletzkya virginica
Authors: Liu Xiaohua , Cheng Jieshan , Jiang Fudong , Liang Meixia , Han Junjie , Zhang Juan , Zhang Hongxia , Tang Xiaoli
Published: January 2020

In higher plants, aquaporin proteins (AQPs) play important roles in the uptake of water across cell membranes. However, their functions in halophytes are still largely unknown. In this work, we isolated, cloned, and identified KvTIP3, a tonoplast intrinsic protein gene from Kosteletzkya virginica. Bioinformatic analyses demonstrated that KvTIP3 encoded a tonoplast protein with the common properties of AQPs. Further multiple sequence alignment and phylogenetic analyses showed that KvTIP3 shared 65%–82% homology with other AQPs from Arabidopsis, cotton, polar, and cocoa. Quantitative real‐time PCR (qPCR) analyses revealed that KvTIP3 was ubiquitously expressed in various tissues such as leaves, stems, and roots, with a predominant expression in roots. In addition, KvTIP3 transcript was strongly induced by NaCl, low temperature, and ABA in K. virginica. Our findings suggest that KvTIP3 encodes a new AQP possibly involved in multiple abiotic stress responses in K. virginica, and KvTIP3 could be used as a potential candidate gene for the improvement of plants resistant to various abiotic stresses.
Postprocessing Study for the Controllable Structures of Ceramic Green Parts Realized by a Flexible Binder Jetting Printing (BJP) Solution
Authors: Cao Shu , Xie Fangxia , He Xueming , Zhang Chaofeng , Wu Meiping
Published: January 2020

For indirect ceramic additive manufacturing (AM), green parts’ initial densities are low, limiting the postprocessing strengthening under atmospheric pressure. This study employed binder jetting printing (BJP) based on the polycondensation curing of urea‐formaldehyde resin to produce series of Al2O3 green specimens with controllable structures. Further, an integrated postprocessing procedure, including the sequential stages of presintering, ceramic slurry infiltration, and final sintering, was conducted on these green specimens with designed structural characteristics for verifying strengthening mechanism. Using a self‐developed BJP machine system and the related material which are flexible in process, this study printed green specimens with strong bonding (flexural strength above 6.84 MPa), additionally can regulate their initial densities within the wide range between 21.7%∼43.9%. Infiltrated with ceramic slurry, low‐density green specimens were significantly strengthened via final sintering, realizing final densities, flexural strength, and compressive strength of 73.2%, 43.15 MPa, and 331.17 MPa, respectively. In comparison, high‐density specimens performing poor infiltration obtained limited density increment after final sintering, but better mechanical properties and surface strengthening were realized, exhibiting final densities, flexural strength, comprehensive strength, surface roughness Ra, and Vickers hardness of 70.1%, 63.22 MPa, 450.18 MPa, 9.73 μm, and 4.58 GPa, respectively. In summary, this study is helpful to provide the technical reference for custom AM ceramic green parts and the postprocessing optimization.
Aflatoxins in Uganda: An Encyclopedic Review of the Etiology, Epidemiology, Detection, Quantification, Exposure Assessment, Reduction, and Control
Authors: Omara Timothy , Nassazi Winfred , Omute Tom , Awath Aburu , Laker Fortunate , Kalukusu Raymond , Musau Bashir , Nakabuye Brenda Victoria , Kagoya Sarah , Otim George , Adupa Eddie
Published: January 2020

Uganda is an agrarian country where farming employs more than 60% of the population. Aflatoxins remain a scourge in the country, unprecedentedly reducing the nutritional and economic value of agricultural foods. This review was sought to synthetize the country’s major findings in relation to the mycotoxins’ etiology, epidemiology, detection, quantification, exposure assessment, control, and reduction in different matrices. Electronic results indicate that aflatoxins in Uganda are produced byAspergillus flavusandA. parasiticusand have been reported in maize, sorghum, sesame, beans, sunflower, millet, peanuts, and cassava. The causes and proliferation of aflatoxigenic contamination of Ugandan foods have been largely due to poor pre-, peri-, and postharvest activities, poor government legislation, lack of awareness, and low levels of education among farmers, entrepreneurs, and consumers on this plague. Little diet diversity has exacerbated the risk of exposure to aflatoxins in Uganda because most of the staple foods are aflatoxin-prone. On the detection and control, these are still marginal, though some devoted scholars have devised and validated a sensitive portable device for on-site aflatoxin detection in maize and shown that starter cultures used for making some cereal-based beverages have the potential to bind aflatoxins. More efforts should be geared towards awareness creation and vaccination against hepatitis B and hepatitis A to reduce the risk of development of liver cancer among the populace.
Cardiac Syncope with Anoxic Seizure Activity
Authors: Talibi Samed , Douglas Craig , Pope Benjamin
Published: January 2020

This is a case report, which explores the presentation to the emergency department of a fit and well female with a known ventricular bigeminy. She presented with convulsive episodes. The working differential diagnosis was of possible cardiac syncope with anoxic seizure activity or neurogenically mediated arrhythmia secondary to subarachnoid haemorrhage. On further collateral history, the patient was on citalopram. The ECGs demonstrated PVCs of multiple morphologies that were transiently bidirectional, raising the possibility of catecholaminergic polymorphic ventricular tachycardia. The presentation of a young fit patient with syncope and seizure-like episodes should always raise concern for the admitting emergency medicine clinician of an underlying cardiac pathology.
General Anesthetic‐Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies
Authors: Luo Ailin , Tang Xiaole , Zhao Yilin , Zhou Zhiqiang , Yan Jing , Li Shiyong
Published: January 2020

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long‐term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.