bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for a double-blind, randomised placebo-controlled trial evaluating clinical effects of platelet-rich plasma injection for acute grade-2 hamstring tear among high performance athletes
Authors: A Hamid Mohamad Shariff , Hussein Kamarul Hashimy , Helmi Salim Ahmad Munawwar , Puji Arshad , Mat Yatim Rosnah , Yong Chin Chee , Sheng Thomas Wong Yong
Published: November 2020

Introduction

Hamstring injury among athletes often results in significant morbidity. Currently, there are controversies regarding the clinical use of platelet-rich plasma (PRP) for the treatment of acute hamstring injury.

Methods and analysis

This study is a single-centre double-blind randomised placebo-controlled trial. Sixty-eight patients will be randomised to receive under ultrasound guidance either a single injection of leucocyte-rich PRP (LR-PRP) or normal saline. All patients will undergo a standardised hamstring rehabilitation programme under the supervision of a sports physiotherapist. Outcome data will be collected before intervention (baseline), and thereafter on a weekly basis. The primary outcome measure is the duration to return-to-play. It is defined as the duration (in days) from the date on which the injury occurred until the patients were pain-free, able to perform the active knee extension test and have regained hamstring muscle strength. Secondary outcome measures include assessment of pain intensity and the effect of pain on to day-to-day functions using the self-reported Brief Pain Inventory—Short Form questionnaire. Both the primary and secondary outcomes were assessed at baseline and thereafter once a week until return to play. Also, hamstring injury recurrence within the first 6 months after recovery will be monitored via telephone. The results of this study will provide insights into the effect of LR-PRP in muscle and may help to identify the best PRP application protocol for muscle injuries.

Ethics and dissemination

Ethics approval were obtained from the Medical Research Ethics Committee of the University of Malaya Medical Centre. Results of this trial will be submitted for publication in a peer-reviewed journal.

Trial registration number

ISRCTN76844299.
Cost-effectiveness of antiviral treatment in adult patients with immune-tolerant phase chronic hepatitis B
Authors: Kim Hye-Lin , Kim Gi-Ae , Park Jae-A , Kang Hye-Rim , Lee Eui-Kyung , Lim Young-Suk
Published: November 2020

Objective

The cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain.

Design

We designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase (‘treat-IT’) vs delaying the therapy until active hepatitis phase (‘untreat-IT’) in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated.

Results

From a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost.

Conclusion

Starting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.
Disentangling contributions of demographic, family, and socioeconomic factors on associations of immigration status and health in the United States
Authors: Bacong Adrian , Sohn Heeju
Published: November 2020

Background

In the United States, immigration policy is entwined with health policy, and immigrants’ legal statuses determine their access to care. Yet, policy debates rarely take into account the health needs of immigrants and potential health consequences of linking legal status to healthcare. Confounding from social and demographic differences and lack of individual-level data with sensitive immigration variables present challenges in this area of research.

Methods

This article used the restricted California Health Interview Survey (CHIS) to assess differences in self-rated health, obesity, and severe psychological distress. Between US-born citizens, naturalised citizens, lawful permanent residents (LPR), undocumented immigrants, and temporary visa holders living in California.

Results

Results show that while immigrant groups appear to have poorer health on the surface, these differences were explained predominantly by older age among naturalised citizens and by lower-income and education among LPRs and undocumented immigrants. Favourable family characteristics acted as protective factors for immigrants’ health, especially among disadvantaged immigrants.

Conclusion

Immigration policy that limits access to healthcare and family support may further widen the health disadvantage among immigrants with less legal protection.
Long-term functional decline of spontaneous intracerebral haemorrhage survivors
Authors: Pasi Marco , Casolla Barbara , Kyheng Maeva , Boulouis Grégoire , Kuchcinski Gregory , Moulin Solène , Labreuche Julien , Henon Hilde , Leys Didier , Cordonnier Charlotte
Published: November 2020

Objective

To identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline.

Methods

In a single-centre study, we prospectively included 6-month survivors with a modified Rankin Scale (mRS) score 0–3. We defined functional decline by a transition to mRS 4–5. We evaluated associations of baseline characteristics and new clinical events with functional decline, using univariate and multivariable models.

Results

Of 560 patients, 174 (31%) had an mRS score 0–3 at 6 months. During a median follow-up of 9 years (IQR 8.1–9.5), 40 (23%) converted to mRS 4–5. Age, diabetes mellitus, ICH volume and higher mRS scores at 6 months were independently associated with functional decline. Among baseline MRI markers, presence of strictly lobar cerebral microbleeds (CMBs), and mixed lobar and deep CMBs were independently associated with functional decline. When new clinical events occurring during follow-up were added in multivariable models, age (cause-specific HR (CSHR): 1.07; 95% CI: 1.03 to 1.11), ICH volume (CSHR: 1.03; 95% CI: 1.01 to 1.06), mRS score at 6 months (CSHR per 1 point increase 1.61, 95% CI 1.07 to 2.43), occurrence of dementia (CSHR: 3.81, 95% CI: 1.78 to 8.16) and occurrence of any stroke (CSHR: 4.29, 95% CI: 1.80 to 10.22) remained independently associated with transition to mRS 4–5.

Interpretation

Almost one-fourth of patients with spontaneous ICH developed a functional decline over time. Age, ICH volume, higher mRS score at 6 months and new clinical events after ICH are the major determinants.
Cancer Research UK’S obesity campaign in 2018 and 2019: effective health promotion or perpetuating the stigmatisation of obesity?
Authors: Varshney Natasha
Published: November 2020

In 2018 and 2019 Cancer Research UK (CRUK) launched a controversial advertising campaign to inform the British public of obesity being a preventable cause of cancer. On each occasion the advertisements used were emotive and provoked frustration among the British public which was widely vocalised on social media. As well serving to educate the public of this association, the advertisements also had the secondary effect of acting as health promotion through social marketing, a form of advertising designed to influence behavioural changes. As CRUK delivered a public health message through its campaign, the advertisements should be held according to the ethical principles which underpin healthcare in the UK. This article evaluates whether the advertisements used by CRUK in 2018 and 2019 fulfilled the ethical principles of beneficence, autonomy, non-maleficence and justice. It is found that while providing an important message, the oversimplification of obesity as being the result of personal decisions ignored the complex aetiology and served to stigmatise the target demographic, potentially disengaging them from the message. Additionally, posting cancer as the consequence of obesity invokes feelings of fear due to its connotations of suffering and premature death. Based on available evidence, the use of fear in social marketing does not create sustained behavioural change. This essay recommends that CRUK discontinue its use of such strategies in its future social marketing endeavours.
Structural optimization of the heavy haul wagon body based on MPSO-BP algorithm
Authors: Liu Wenfei , Zhang Yongju , Liu Qitai , Zhang Bo , Fu Qiangxiao
Published: November 2020

Fatigue cracks usually occur at the welded joints of the heavy haul wagon body. To effectively limit the occurrence of such problems at the design stage, this study moves from the structural design strategy to the structural optimization method. First, when analyzing the results of the finite element simulation, the new structural design strategy not only considers the maximum stress, which can reflect the stress concentration position, but also focuses on the stress distributions at the key welded joints. Second, in order to further reduce the stress at the key positions, the study presents an optimization method that integrates an orthogonal experimental design, BP network, and MPSO algorithm. Finally, an 80 t gondola car body is optimized from the whole structure to the local area by the proposed method. Further, it is also verified that the structural optimization method of the heavy haul wagon body is reasonable and feasible.
Realizing unification in two different SO(10) models with one intermediate breaking scale
Authors: Ohlsson Tommy , Pernow Marcus , Sönnerlind Erik
Published: November 2020

We derive the threshold corrections in $$\text {SO}(10)$$

SO
(
10
)

grand unified models with the intermediate symmetry being flipped $$\,\text {SU}(5)\times \text {U}(1)$$

SU
(
5
)
×
U
(
1
)

or $$\,\text {SU}(3)\times \,\text {SU}(2)\times \text {U}(1)\times \text {U}(1)$$

SU
(
3
)
×

SU
(
2
)
×
U
(
1
)
×
U
(
1
)

, with the masses of the scalar fields set by the survival hypothesis. These models do not achieve gauge coupling unification if the matching conditions do not take threshold corrections into account. We present results showing the required size of threshold corrections for any value of the intermediate and unification scales. In particular, our results demonstrate that both of these models are disfavored since they require large threshold corrections to allow for unification with a predicted proton lifetime above current experimental bounds.
Tunneling under the influence of quantum gravity in black rings
Authors: Ali Riasat , Bamba Kazuharu , Asgher Muhammad , Shah Syed Asif Ali
Published: November 2020

We explore the Lagrangian equation in the background of generalized uncertainty principle. The tunneling radiation through the black ring horizon is observed. We investigated the tunneling radiation through the Hamilton–Jacobi method for solutions of Einstein–Maxwell-dilation gravity theory. The radiation of black ring without back reaction and self-interaction of particles are studied. Furthermore, we consider the quantum gravity effect on the stability of black ring.
Equivalent Single Layer Models in Free Vibration Analysis of Laminated Multi-Layered Plates
Authors: Kreja Ireneusz , Sabik Agnieszka
Published: November 2020

The performance of selected equivalent single-layer (ESL) models is evaluated within several classical benchmark tests for small amplitude free vibration analysis of multi-layered plates. The authors elaborated their own Finite Element software based on the first-order shear deformation (FOSD) theory with some modifications incorporated including a correction of the transverse shear stiffness and an application of zigzag type functions. Seven different ESL models were considered in the study; beside the classical FOSD model, there were three FOSD models with various transverse shear corrections and three ESL models enhanced by the application of zigzag functions and based on Reissner’s Mixed Variational Theorem.
Time Response Stress Analysis of Solid and Reinforced Thin-Walled Structures by Component-Wise Models
Authors: Azzara R. , Carrera E. , Filippi M. , Pagani A.
Published: November 2020

This paper deals with the evaluation of time response analyses of typical aerospace metallic structures. Attention is focussed on detailed stress state distributions over time by using the Carrera Unified Formulation (CUF) for modeling thin-walled reinforced shell structures. In detail, the already established component-wise (CW) approach is extended to dynamic time response by mode superposition and Newmark direct integration scheme. CW is a CUF-based modeling technique which allows to model multi-component structures by using the same refined finite element for each structural component, e.g. stringers, panels, ribs. Component coupling is realized by imposing displacement continuity without the need of mathematical artifices in the CW approach, so the stress state is consistent in the entire structural domain. The numerical results discussed include thin-walled open and closed section beams, wing boxes and a benchmark wing subjected to gust loading. They show that the proposed modeling technique is effective. In particular, as CW provides reach modal bases, mode superposition can be significantly efficient, even in the case of complex stress states.
Real-time embedded TSR using MDEffNet: An efficient compact DNN on varied multi-resolution images across multiple databases
Authors: Sanyal Banhi , Mohapatra Ramesh Kumar , Dash Ratnakar
Published: November 2020

Deep Learning in Traffic Sign Recognition (TSR) System is rapidly developing. Still, not much work has been reported in the literature on architectures that can work efficiently on multiple (more than two) databases across different countries. Each of these databases incorporates images of varied resolutions. Here, a Deep Neural Network called Multiple Database Efficient Network (MDEffNet) has been proposed for TSR. Batch normalization layers have been introduced to reduce the internal co-variant shift, and further, data augmentation has been carried out to achieve high efficiency with reasonable training time. Results at each step of the proposed architecture have been provided. The proposed model is compared with some state-of-the-art methods based on single or two databases, and solo works done in multiple (three) databases originating from different countries. The comparisons prove the high effectiveness of the proposed model. The achieved efficiency is much higher than all of them, including the average human ability. Deep learning techniques often suffer from increased memory and computational requirements. MDEffNet has only 1.36 million parameters ([Formula: see text] 26 times lower than the state-of-art methods) with 130 s per epoch, which is relatively low. Hence, it is also suitable for real-time embedded TSR systems.
Gauge field theories and propagators in curved space-time
Authors: Niardi Roberto
Published: November 2020

In this paper, DeWitt’s formalism for field theories is presented; it provides a framework in which the quantization of fields possessing infinite-dimensional invariance groups may be carried out in a manifestly covariant (non-Hamiltonian) fashion, even in curved space-time. Another important virtue of DeWitt’s approach is that it emphasizes the common features of apparently very different theories such as Yang–Mills theories and General Relativity; moreover, it makes it possible to classify all gauge theories in three categories characterized in a purely geometrical way, i.e. by the algebra which the generators of the gauge group obey; the geometry of such theories is the fundamental reason underlying the emergence of ghost fields in the corresponding quantum theories, too. These “tricky extra particles”, as Feynman called them in 1964, contribute to a physical observable such as the stress-energy tensor, which can be expressed in terms of Feynman’s Green function itself. Therefore, an entire section is devoted to the study of the Green functions of the neutron scalar meson: in flat space-time, the choice of a particular Green’s function is the choice of an integration contour in the “momentum” space; in curved space-time the momentum space is no longer available, and the definition of the different Green functions requires a careful discussion itself. After the necessary introduction of bitensors, world function and parallel displacement tensor, an expansion for the Feynman propagator in curved space-time is obtained. Most calculations are explicitly shown.
Holographic naturalness and topological phase transitions
Authors: Addazi Andrea
Published: November 2020

We show that our Universe lives in a topological and non-perturbative vacuum state full of a large amount of hidden quantum hairs, the hairons. We will discuss and elaborate on theoretical evidences that the quantum hairs are related to the gravitational topological winding number in vacuo. Thus, hairons are originated from topological degrees of freedom, holographically stored in the de Sitter area. The hierarchy of the Planck scale over the Cosmological Constant (CC) is understood as an effect of a Topological Memory intrinsically stored in the space-time geometry. Any UV quantum destabilizations of the CC are re-interpreted as Topological Phase Transitions, related to the disappearance of a large ensamble of topological hairs. This process is entropically suppressed, as a tunneling probability from the [Formula: see text]- to the 0-states. Therefore, the tiny CC in our Universe is a manifestation of the rich topological structure of the space-time. In this portrait, a tiny neutrino mass can be generated by quantum gravity anomalies and accommodated into a large [Formula: see text]-vacuum state. We will re-interpret the CC stabilization from the point of view of Topological Quantum Computing. An exponential degeneracy of topological hairs non-locally protects the space-time memory from quantum fluctuations as in Topological Quantum Computers.
In Vitro and In Vivo Antitumor Activity of Silver Nanoparticles on B16 Melanoma
Authors: Gao Hongkun , Fan Ping , Xu Qizhen , Li Yiting , Wang Jianxin , Weng Jie , Zhou Jie , Feng Bo
Published: November 2020

Melanoma, one of the most malignant tumors, is difficult to treat due to its high drug resistance. Silver nanoparticles (AgNPs) are widely used as antimicrobial agents in biomedical fields. In this study, the spherical AgNPs with average sizes of 5[Formula: see text]nm were prepared using a dopamine reduction method. The in vitro study shows that AgNPs with the concentrations of 0.5[Formula: see text][Formula: see text]g/mL and 1[Formula: see text][Formula: see text]g/mL exhibit good biocompatibility to 3T3L1 fibroblast cells. AgNPs with the same concentrations significantly inhibited the growth of B16 melanoma cells. In culture with B16 cells, AgNPs induced intracellular oxidative stress by generating the reactive oxygen species and reducing the superoxide dismutase, which further reduces the mitochondrial membrane potential. Moreover, the damage in mitochondria could activate mitochondrion-mediated cell apoptosis. The B16 cells apoptosis was analyzed by FITC-Annexin V/propidium iodide double staining assay, which confirms that AgNPs caused the abundance of apoptotic cells in different stages. Thus, AgNPs displayed the antitumor activity in vitro. Then, the therapeutic efficacy in vivo was evaluated in mice-bearing B16 melanoma tumors. The obtained results show the antitumor ability of AgNPs and provide a potential strategy for cancer treatment.
Wrist Contracture Caused by Adhesion of the Extensor Carpi Radialis Tendon after Distal Radius Fracture: A Case Report
Authors: Nishimura Ken , Morizaki Yutaka , Uehara Kosuke , Tabira Yoshihiko , Tanaka Sakae
Published: November 2020

Although distal radius fractures are common, wrist contracture caused by an extra-articular lesion after a distal radius fracture is seldom reported. We report a rare case of wrist contracture caused by adhesion of extensor carpi radialis brevis (ECRB) tendon after distal radius fracture. The patient was successfully treated with tenolysis of the ECRB tendon.
Attributed Collaboration Network Embedding for Academic Relationship Mining
Authors: Wang Wei , Liu Jiaying , Tang Tao , Tuarob Suppawong , Xia Feng , Gong Zhiguo , King Irwin
Published: November 2020

Finding both efficient and effective quantitative representations for scholars in scientific digital libraries has been a focal point of research. The unprecedented amounts of scholarly datasets, combined with contemporary machine learning and big data techniques, have enabled intelligent and automatic profiling of scholars from this vast and ever-increasing pool of scholarly data. Meanwhile, recent advance in network embedding techniques enables us to mitigate the challenges of large scale and sparsity of academic collaboration networks. In real-world academic social networks, scholars are accompanied with various attributes or features, such as co-authorship and publication records, which result in attributed collaboration networks. It has been observed that both network topology and scholar attributes are important in academic relationship mining. However, previous studies mainly focus on network topology, whereas scholar attributes are overlooked. Moreover, the influence of different scholar attributes are unclear. To bridge this gap, in this work, we present a novel framework of Attributed Collaboration Network Embedding (ACNE) for academic relationship mining. ACNE extracts four types of scholar attributes based on the proposed scholar profiling model, including demographics, research, influence, and sociability. ACNE can learn a low-dimensional representation of scholars considering both scholar attributes and network topology simultaneously. We demonstrate the effectiveness and potentials of ACNE in academic relationship mining by performing collaborator recommendation on two real-world datasets and the contribution and importance of each scholar attribute on scientific collaborator recommendation is investigated. Our work may shed light on academic relationship mining by taking advantage of attributed collaboration network embedding.
Principles of KLM-style Defeasible Description Logics
Authors: Britz Katarina , Casini Giovanni , Meyer Thomas , Moodley Kody , Sattler Uli , Varzinczak Ivan
Published: November 2020

The past 25 years have seen many attempts to introduce defeasible-reasoning capabilities into a description logic setting. Many, if not most, of these attempts are based on preferential extensions of description logics, with a significant number of these, in turn, following the so-called KLM approach to defeasible reasoning initially advocated for propositional logic by Kraus, Lehmann, and Magidor. Each of these attempts has its own aim of investigating particular constructions and variants of the (KLM-style) preferential approach. Here our aim is to provide a comprehensive study of the formal foundations of preferential defeasible reasoning for description logics in the KLM tradition.

We start by investigating a notion ofdefeasible subsumptionin the spirit of defeasible conditionals as studied by Kraus, Lehmann, and Magidor in the propositional case. In particular, we consider a natural and intuitive semantics for defeasible subsumption, and we investigate KLM-style syntactic properties for bothpreferentialandrationalsubsumption. Our contribution includes two representation results linking our semantic constructions to the set of preferential and rational properties considered. Besides showing that our semantics is appropriate, these results pave the way for more effective decision procedures for defeasible reasoning in description logics. Indeed, we also analyse the problem of non-monotonic reasoning in description logics at the level ofentailmentand present an algorithm for the computation ofrational closureof a defeasible knowledge base. Importantly, our algorithm relies completely on classical entailment and shows that the computational complexity of reasoning over defeasible knowledge bases is no worse than that of reasoning in the underlying classical DLALC.
Energy-efficient Dual-codebook–based Backscatter Communications for Wireless Powered Networks
Authors: Zhang Yufan , Li Ertao , Zhu Yi-Hua
Published: November 2020

The common backscatter communications (ComBC), widely applied in wireless powered networks such as the RFID systems, exhibit the shortcoming that only a few bits are backscattered at a time due to energy limitation. It is significant to improve energy efficiency in backscatter communications so more data can be delivered within one backscatter. In this article, the energy-efficient dual-codebook based backscatter communications (DBBC) is proposed, which adopts two prefix codebooks shared by the sender and the receiver over a backscatter communication link. With the DBBC, the sender backscatters codewords from which the receiver decodes the original data. Using Energy Consumption Disparity (ECD) between backscattering bits 1 and 0 in the existing backscatter communications, we formulate the optimization problem minimizing energy consumption over the link for the DBBC. Mapping a prefix codebook into a binary tree and performing pruning and expanding operation (PEO) on binary trees, we obtain the solution to the optimization problem, which includes the two energy-efficient codebooks and the other two key parameters for the DBBC. The experiments on wireless identification sensing platform (WISP) show that, under the proposed DBBC, the sender can backscatter data 83% more than the ComBC with the same energy without sacrificing throughput.
The Weisfeiler-Leman algorithm
Authors: Kiefer Sandra
Published: November 2020

More than half a century after its first formulation, the Weisfeiler-Leman (WL) algorithm is still an important combinatorial technique whenever graphs or other relational structures are to be classified. However, despite its simple algebraic description and its variety of applications, we still lack a precise understanding of the expressive power of the algorithm.

This column introduces the reader to the basic concepts of the WL algorithm and discusses its dimension as a parameter to capture the structural complexity of an input graph. Specifically, I present a survey of work regarding the WL dimension conducted with my co-authors. First, I outline the proof that the 3-dimensional WL algorithm (3-WL) is able to identify every planar graph. The proof version presented here relies on strong insights about the ability of 2-WL to decompose graphs. Afterwards, I highlight the most important ingredients of the generalisation of our bound to graphs that are parameterised by their Euler genus.

Further details as well as a study of other aspects of the WL algorithm can be found in my dissertation [Kiefer 2020].
The Hippo Pathway in Liver Homeostasis and Pathophysiology
Authors: Driskill Jordan H. , Pan Duojia
Published: November 2020

Studies of the regenerative capacity of the liver have converged on the Hippo pathway, a serine/threonine kinase cascade discovered in Drosophila and conserved from unicellular organisms to mammals. Genetic studies of mouse and rat livers have revealed that the Hippo pathway is a key regulator of liver size, regeneration, development, metabolism, and homeostasis and that perturbations in the Hippo pathway can lead to the development of common liver diseases, such as fatty liver disease and liver cancer. In turn, pharmacological targeting of the Hippo pathway may be utilized to boost regeneration and to prevent the development and progression of liver diseases. We review current insights provided by the Hippo pathway into liver pathophysiology. Furthermore, we present a path forward for future studies to understand how newly identified components of the Hippo pathway may control liver physiology and how the Hippo pathway is regulated in the liver.
Mathematical Modeling of High-Temperature Multiphase Solid/Molten Carbonate Membranes for CO2 Capture
Authors: Li Xin , Huang Kevin , Jin Xinfang
Published: November 2020

High-temperature solid/molten-carbonate composite represent an emerging class of CO2 transport membranes to capture CO2 from flue gas with advantages in flux density and selectivity over conventional solvent/sorbent- and polymer-based counterparts. While significant technical progress in these membranes has been made in the past years, a deeper fundamental understanding of CO2 transport mechanisms is still limited. Aimed to bridge this gap, we here report a theoretical study on flux performances of four types of solid/molten-carbonate CO2 transport membranes by analytical and numerical modeling. We found that analytical and numerical results are virtually identical for solids with single charge carrier. However, for mixed conducting solids, numerical methods are preferred since analytical methods cannot solve the nonlinear local concentrations of charge carriers. Application of numerical method to a new three-phase membrane containing a mixed conducting solid, a pure electron conducting solid and molten-carbonate reveals a ∼90% increase in CO2 flux compared to the two-phase (mixed conducting solid and molten-carbonate) counterpart. The models presented here are expected to provide better fundamental insights and guidance for designing next-generation high-performance CO2 transport membranes.
COVID-19 endocrinopathy with hindsight from SARS
Authors: Kothandaraman Narasimhan , Rengaraj Anantharaj , Xue Bo , Yew Wen Shan , Velan S. Sendhil , Karnani Neerja , Leow Melvin Khee Shing
Published: November 2020

The current COVID-19 pandemic is probably the worst the world has ever faced since the start of the new millennium. Although the respiratory system is the most prominent target of SARS-CoV-2 (the contagion of COVID-19), extrapulmonary involvement are emerging as important contributors of its morbidity and lethality. This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We, hereby, summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone, and reproductive system aberrations so that clinicians armed with such insights can potentially benefit patients with COVID-19 at the bedside.
Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs
Authors: Yakah William , Singh Pratibha , Brown Joanne , Stoll Barbara , Burrin Doug , Premkumar Muralidhar H. , Otu Hasan H. , Gu Xuesong , Dillon Simon T. , Libermann Towia A. , Freedman Steven D. , Martin Camilia R.
Published: November 2020

Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.
Sarcopenia in chronic liver disease: mechanisms and countermeasures
Authors: Allen Sophie L. , Quinlan Jonathan I. , Dhaliwal Amritpal , Armstrong Matthew J. , Elsharkawy Ahmed M. , Greig Carolyn A. , Lord Janet M. , Lavery Gareth G. , Breen Leigh
Published: November 2020

Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.
The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress
Authors: Guerrina Necola , Aloufi Noof , Shi Fangyi , Prasade Kashmira , Mehrotra Caitlin , Traboulsi Hussein , Matthews Jason , Eidelman David H. , Hamid Qutayba , Baglole Carolyn J.
Published: November 2020

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose physiological function is poorly understood. The AhR is highly expressed in barrier organs such as the skin, intestine, and lung. The lungs are continuously exposed to environmental pollutants such as cigarette smoke (CS) that can induce cell death mechanisms such as apoptosis, autophagy, and endoplasmic reticulum (ER) stress. CS also contains toxicants that are AhR ligands. We have previously shown that the AhR protects against apoptosis, but whether the AhR also protects against autophagy or ER stress is not known. Using cigarette smoke extract (CSE) as our in vitro surrogate of environmental tobacco exposure, we first assessed the conversion of LC3I to LC3II, a classic feature of both autophagic and ER stress-mediated cell death pathways. LC3II was elevated in CSE-exposed lung structural cells [mouse lung fibroblasts (MLFs), MLE12 and A549 cells] when AhR was absent. However, this heightened LC3II expression could not be explained by increased expression of key autophagy genes ( Gabarapl1, Becn1, Map1lc3b), upregulation of upstream autophagic machinery (Atg5–12, Atg3), or impaired autophagic flux, suggesting that LC3II may be autophagy independent. This was further supported by the absence of autophagosomes in Ahr−/− lung cells. However, Ahr−/− lung cells had widespread ER dilation, elevated expression of the ER stress markers CHOP and GADD34, and an accumulation of ubiquitinated proteins. These findings collectively illustrate a novel role for the AhR in attenuating ER stress by a mechanism that may be autophagy independent.
Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies
Authors: Pathangey Girish , Fadadu Priyal P. , Hospodar Alexandra R. , Abbas Amr E.
Published: November 2020

On March 11, 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19) a pandemic, and the reality of the situation has finally caught up to the widespread reach of the disease. The presentation of the disease is highly variable, ranging from asymptomatic carriers to critical COVID-19. The availability of angiotensin-converting enzyme 2 (ACE2) receptors may reportedly increase the susceptibility and/or disease progression of COVID-19. Comorbidities and risk factors have also been noted to increase COVID-19 susceptibility. In this paper, we hereby review the evidence pertaining to ACE2’s relationship to common comorbidities, risk factors, and therapies associated with the susceptibility and severity of COVID-19. We also highlight gaps of knowledge that require further investigation. The primary comorbidities of respiratory disease, cardiovascular disease, renal disease, diabetes, obesity, and hypertension had strong evidence. The secondary risk factors of age, sex, and race/genetics had limited-to-moderate evidence. The tertiary factors of ACE inhibitors and angiotensin II receptor blockers had limited-to-moderate evidence. Ibuprofen and thiazolidinediones had limited evidence.
Immunoglobulin deficiency as an indicator of disease severity in patients with COVID-19
Authors: Husain-Syed Faeq , Vadász István , Wilhelm Jochen , Walmrath Hans-Dieter , Seeger Werner , Birk Horst-Walter , Jennert Birgit , Dietrich Hartmut , Herold Susanne , Trauth Janina , Tello Khodr , Sander Michael , Morty Rory E. , Slanina Heiko , Schüttler Christian G. , Ziebuhr John , Kassoumeh Shadi , Ronco Claudio , Ferrari Fiorenza , Warnatz Klaus , Stahl Klaus , Seeliger Benjamin , Hoeper Marius M. , Welte Tobias , David Sascha
Published: November 2020

Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.6% male, median age: 61 yr). Thirteen (21.0%) of the patients displayed IgG deficiency (IgG < 7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). Patients who were IgG-deficient had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of [Formula: see text] to [Formula: see text], higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio, and serum creatinine). Patients who were IgG-deficient were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, patients who were IgG-deficient compared with those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; P = 0.001) and death (46.2% vs. 14.3%; P = 0.012), longer ICU [28 (6–48) vs. 12 (3–18) days; P = 0.012] and hospital length of stay [30 (22–50) vs. 18 (9–24) days; P = 0.004]. Univariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (odds ratio 5.14, 95% confidence interval 1.3–19.9; P = 0.018). IgG deficiency might be common in patients with COVID-19 who are critically ill, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.
On the origin of ultraslow spontaneous Na+ fluctuations in neurons of the neonatal forebrain
Authors: Perez Carlos , Felix Lisa , Durry Simone , Rose Christine R. , Ullah Ghanim
Published: November 2020

Spontaneous activity in the neonate forebrain plays a key role in cell maturation and brain development. We report spontaneous, ultraslow, asynchronous fluctuations in the intracellular Na+ concentration of neurons and astrocytes. We show that this activity is not correlated with the previously reported synchronous neuronal population bursting or Ca2+ oscillations, both of which occur at much faster timescales. Furthermore, extracellular K+ concentration remains nearly constant. The spontaneous Na+ fluctuations disappear after the first postnatal week.
The Effect of Strontium Ranelate on Fracture Healing: An Animal Study
Authors: Koukou Ourania I. , Pappas Lampros D. , Chloropoulou Pelagia , Kouroupi Maria A. , Koukos Konstantinos I. , Karpathiou Georgia , Galanos Antonios A. , Drosos Georgios I. , Magnisalis Evaggelos , Giatromanolaki Alexandra N. , Verettas Dionysios Alexandros
Published: November 2020

Background. Strontium ranelate (StR) is an antiosteoporotic agent previously utilized for the enhancement of fracture union. We investigated the effects of StR on fracture healing using a rabbit model. Methods. Forty adult female rabbits were included in the study and were divided in 2 equal groups, according to StR treatment or untreated controls. All animals were subjected to osteotomy of the ulna, while the contralateral ulna remained intact and served as a control for the biomechanical assessment of fracture healing. Animals in the study group received 600 mg/kg/day of StR orally. All animals received ordinary food. At 2 and 4 weeks, all animals were euthanatized and the osteotomy sites were evaluated for healing through radiological, biomechanical, and histopathological studies. Results. The treatment group presented statistically significant higher callus diameter, total callus area, percentage of fibrous tissue (p < 0.001), vessels/mm2, number of total vessels, and lower osteoclast number/mm2 (p < 0.05) than the control group at 2 weeks. Additionally, the treatment group presented significantly higher percentages of new trabecular bone, vessels/mm2, osteoclast number/mm2, and lower values for callus diameter, as well as total callus area (p < 0.05), than the control group at 4 weeks. At 4 weeks, in the treatment group, force applied (p = 0.003), energy at failure (p = 0.004), and load at failure (p = 0.003) were all significantly higher in the forearm specimens with the osteotomized ulnae compared to those without. Radiological bone union was demonstrated for animals receiving StR at 4 weeks compared with controls (p = 0.045). Conclusion. StR appears to enhance fracture healing but further studies are warranted in order to better elucidate the mechanisms and benefits of StR treatment.
GCN2 Deficiency Enhances Protective Effects of Exercise on Hepatic Steatosis
Authors: Luo Xueting , Shi Xiaowei , Sun Zhongguang , Xiao Jing , Song Hui , Lu Guo , Xu Xin
Published: November 2020

Background. Combined aerobic and resistance training has been demonstrated to benefit glycemic control and reverse nonalcoholic fatty liver disease in childhood obesity. General control nonderepressible 2 (GCN2) deficiency has been reported to attenuate hepatic steatosis and insulin resistance. However, whether GCN2 impacts the positive effects of combined aerobic and resistance exercise remains unknown. Objectives. To investigate whether combined aerobic and resistance exercise improves hepatic steatosis and glucose intolerance and the role GCN2 plays in mediating the metabolic regulation of exercise. Methods. Wild‐type (WT) and GCN2 knockout (GCN2KO) mice were fed a high‐fat diet (HFD) for 25 weeks. The WT and GCN2KO mice performed exercise (treadmill running + ladder climbing) during the last eight weeks. Their body and liver weights, their triglyceride content, and their levels of aspartate transaminase (AST), alanine transaminase (ALT), and blood glucose were measured, and the expressions of proteins involved in the GCN2/eIF2α/ATF4 pathway and the glucolipid metabolism‐related proteins (e.g., p‐AMPK, SIRT1, PPARα, PGC‐1α, GLUT4, and p‐GSK‐3β) were determined. Results. The body weight of WT and GCN2KO mice continued to increase until the end of the experiment. The liver weights, hepatic triglyceride content, and AST and ALT levels of the exercised mice were significantly reduced compared to those of the sedentary mice. Exercise improved blood glucose levels and glucose clearance ability in the WT mice, but the glucose intolerance of GCN2KO mice was not improved. Exercise increased PGC‐1α, GLUT4, and p‐GSK‐3β expressions in the WT rather than the GCN2KO mice. Interestingly however, exercise‐trained GCN2KO mice were better protected against hepatic steatosis with downregulated expressions of p‐eIF2α and ATF4, upregulated expressions of p‐AMPK and SIRT1, and the presence of PPARα in the liver, compared to the exercised WT mice. Conclusion. Combined aerobic and resistance exercise had positive effects on hepatic steatosis and the control of glucose intolerance. GCN2 was found to be necessary for exercise‐induced improved glucose intolerance. However, the better efficacy in improving hepatic steatosis by exercise in the GCN2‐deficient mice enhanced liver lipid metabolism, at least partially, via the AMPK/SIRT1/PPARα pathway.
Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta‐Analysis of Randomized Controlled Trials
Authors: Ling Tao , Li Jiao Jiao , Xu Rui-Juan , Wang Bin , Ge Wei-Hong
Published: November 2020

This study was performed to assess the efficacy and safety of a topical diclofenac solution in patients with knee osteoarthritis (OA). PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases were searched for randomized controlled trials until June 2020. The WOMAC pain, stiffness, physical function subscales, pain on walking, and the occurrence of adverse events were pooled to comprehensively analyse the efficacy and safety of topical diclofenac solution. All statistical analyses were conducted using Review Manager 5.3 software. Five RCTs were included, which provided high‐quality evidence. In comparison to the vehicle control, the mean differences for WOMAC pain, stiffness, and physical function subscales, as well as pain on walking, were all statistically significant in favor of topical diclofenac solution. The safety of topical diclofenac solution was similar to the vehicle control, apart from adverse events involving application‐site skin reactions. Topical diclofenac solution is effective and safe for use in patients with knee OA, but may cause minor skin reactions.