bluuebunny/crossref_metadata_2025 huggingface dataset:
Age differences in clinical features and outcomes in patients with COVID-19, Jiangsu, China: a retrospective, multicentre cohort study
Authors: Luo Huanyuan , Liu Songqiao , Wang Yuancheng , Phillips-Howard Penelope A , Ju Shenghong , Yang Yi , Wang Duolao
Published: October 2020

Objectives

To determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China.

Design and setting

Retrospective, multicentre cohort study performed at 24 hospitals in Jiangsu, China.

Participants

625 patients with COVID-19 enrolled between 10 January and 15 March 2020.

Results

Of the 625 patients (median age, 46 years; 329 (52.6%) men), 37 (5.9%) were children (18 years or younger), 261 (41.8%) young adults (19–44 years), 248 (39.7%) middle-aged adults (45–64 years) and 79 (12.6%) elderly adults (65 years or older). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease and diabetes comorbidities increased with age (trend test, p<0.0001, p=0.0003, p<0.0001 and p<0.0001, respectively). Fever, cough and shortness of breath occurred more commonly among older patients, especially the elderly, compared with children (χ2test, p=0.0008, 0.0146 and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both p<0.0001). Older patients had many significantly different laboratory parameters from younger patients. Elderly patients had the highest proportion of severe or critically-ill cases (33.0%, χ2test p<0.0001), intensive care unit use (35.4%, χ2test p<0.0001), respiratory failure (31.6%, χ2test p<0.0001) and the longest hospital stay (median 21 days, Kruskal–Wallis test p<0.0001).

Conclusions

Elderly (≥65 years) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure and the longest hospital stay, which may be due partly to their having a higher incidence of comorbidities and poor immune responses to COVID-19.
Association between handgrip strength and the risk of new-onset metabolic syndrome: a population-based cohort study
Authors: Shen Chao , Lu Jiangting , Xu Zhijie , Xu Yuanyuan , Yang Ying
Published: October 2020

Objectives

A lower relative handgrip strength (HGS) may disrupt metabolic homeostasis and then lead to metabolic syndrome (MetS). There is a paucity of longitudinal studies to examine whether relative HGS at baseline is linked to incident MetS. Thus, the purpose of the present study was to explore the association between relative HGS and new-onset MetS.

Design

This is an observational and longitudinal research.

A nationally representative sample of population in China.

Participants

A total of 3350 subjects without MetS were selected for analysis in the present study. Data are from the China Health and Retirement Longitudinal Study (2011–2015).

Outcome measures

We calculated the relative HGS by dividing the HGS by body weight. Participants were divided into gender-specific quartiles. We estimated HRs for MetS and its components using Cox proportional hazard models according to the relative HGS categories.

Results

After multiple adjustment, the risk of MetS increased with the lower quartile of relative HGS in both sexes. Using the highest quartile (Q4) as a reference, the HR for quartile Q3–1 was 1.49 (0.95, 2.34), 1.67 (1.08, 2.59) and 1.76 (1.12, 2.78), respectively, in men, and 1.14 (0.82, 1.58), 1.30 (1.02, 1.57) and 1.28 (1.03, 1.55), respectively, in women. Additionally, we observed that relative HGS was negatively or inversely associated with the risk of abdominal obesity in both sexes.

Conclusions

The current study demonstrated that relative HGS was inversely and independently associated with an increased risk of MetS and abdominal obesity, suggesting a possible role of relative HGS as a useful and simple index for muscle strength in the prediction of occurrence of MetS.
Feasibility and effectiveness of tools that support communication and decision making in life-prolonging treatments for patients in hospital: a systematic review
Authors: Thodé Maureen , Pasman H Roeline W , van Vliet Liesbeth M , Damman Olga C , Ket Johannes C F , Francke Anneke L , Jongerden Irene P
Published: October 2020

Objective

Patients with advanced diseases and frail older adults often face decisions regarding life-prolonging treatment. Our aim was to provide an overview of the feasibility and effectiveness of tools that support communication between healthcare professionals and patients regarding decisions on life-prolonging treatments in hospital settings.

Design

Systematic review: We searched PubMed, CINAHL, PsycINFO, Embase, Cochrane Library and Google Scholar (2009–2019) to identify studies that reported feasibility or effectiveness of tools that support communication about life-prolonging treatments in adult patients with advanced diseases or frail older adults in hospital settings. The Mixed Methods Appraisal Tool was used for quality appraisal of the included studies.

Results

Seven studies were included, all involving patients with advanced cancer. The overall methodological quality of the included studies was moderate to high. Five studies described question prompt lists (QPLs), either as a stand-alone tool or as part of a multifaceted programme; two studies described decision aids (DAs). All QPLs and one DA were considered feasible by both patients with advanced cancer and healthcare professionals. Two studies reported on the effectiveness of QPL use, revealing a decrease in patient anxiety and an increase in cues for discussing end-of-life care with physicians. The effectiveness of one DA was reported; it led to more understanding of the treatment in patients.

Conclusions

Use of QPLs or DAs, as a single intervention or part of a programme, may help in communicating about treatment options with patients, which is an important precondition for making informed decisions.
Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation
Authors: Bhatia Harpreet Singh , Nishimura Marin , Dickson Stephen , Adler Eric , Greenberg Barry , Thomas Isac C
Published: October 2020

Objective

Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes.

Methods

We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months.

Results

Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0–1.0 vs median 2.0, IQR 1.0–3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E’ ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group.

Conclusions

METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.
Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC
Authors: Keegan Alissa , Ricciuti Biagio , Garden Padric , Cohen Limor , Nishihara Reiko , Adeni Anika , Paweletz Cloud , Supplee Julianna , Jänne Pasi A , Severgnini Mariano , Awad Mark M , Walt David R
Published: October 2020

Background

Blood-based biomarkers of anti-solid tumor immune checkpoint blockade (ICB) response are lacking. We hypothesized that changes in systemic cytokine levels with the initial doses of programmed cell death protein 1 (PD-1) pathway inhibitors would correlate with clinical responses. New ultrasensitive ELISA technology enables quantitation of plasma proteins in sub-picogram-per-milliliter concentrations.

Methods

We measured plasma cytokines by ultrasensitive single-molecule array assays in patients with non-small-cell lung carcinoma before and during treatment with anti-PD-1 therapy. Association with best overall response and progression-free survival (PFS) was assessed by Kruskall-Wallis test and Kaplan-Meier plots with log-rank test, respectively.

Results

A decrease in interleukin 6 (IL-6) levels was associated with improved PFS (n=47 patients, median PFS: 11 vs 4 months, HR 0.45 (95% CI 0.23 to 0.89), p=0.04). The extent of change in IL-6 differed between best overall response categories (p=0.01) and correlated with changes in C reactive protein levels. We also explored plasma cytokine levels in relation to immune-related adverse effects and observed some correlation.

Conclusions

This study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP.
Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy
Authors: Rodrigues Mantuano Natalia , Natoli Marina , Zippelius Alfred , Läubli Heinz
Published: October 2020

During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans are able to inhibit anticancer immune responses by engagement of immune receptors on leukocytes. A family of immune-modulating receptors are sialic acid-binding Siglec receptors that have been recently described to inhibit antitumor activity mediated by myeloid cells, natural killer cells and T cells. Other TACA-binding receptors including selectins have been linked to cancer progression. Recent studies have shown that glycan-lectin interactions can be targeted to improve cancer immunotherapy. For example, interactions between the immune checkpoint T cell immunoglobulin and mucin-domain containing-3 and the lectin galectin-9 are targeted in clinical trials. In addition, an antibody against the lectin Siglec-15 is being tested in an early clinical trial. In this review, we summarize the previous and current efforts to target TACA and to inhibit inhibitory immune receptors binding to TACA including the Siglec-sialoglycan axis.
Characteristics and outcome of patients with COVID-19 complicated by Takotsubo cardiomyopathy: case series with literature review
Authors: Hegde Shruti , Khan Rizwan , Zordok Magdi , Maysky Michael
Published: October 2020

Background

Cardiac involvement with COVID-19 is increasingly being recognised. Clinical characteristics and outcomes of patients with COVID-19 complicated by secondary Takotsubo cardiomyopathy (TC) is poorly understood.

Methods

This retrospective case series was conducted between March and April 2020 at four hospitals of Steward Health Care Network of Massachusetts, USA. Seven patients out of 169 who had echocardiogram were identified to have features of TC. Demographic, clinical, laboratory, management and outcome were gathered from their electronic medical records. We also reviewed all the published cases of COVID-19 and TC in the literature to recognise their common clinical characteristics, risk factors and outcomes.

Results

In our series of seven patients, three typical, two inverted, one biventricular and one global TC were recognised. Three were females and four were males. The mean age was 71±11 years. In-hospital death was observed in 57% of patients. Patients who belonged to the high-risk group and had high-risk echocardiographic features in our series had a 100% mortality rate.

Conclusions

COVID-19 complicated by TC has a high mortality rate. Early identification of patients with COVID-19 who are at higher risk for developing secondary TC is important for the prevention of complications, and thus improved outcomes.
Coronary risk of patients with valvular heart disease: prospective validation of CT-Valve Score
Authors: Hasselbalch Rasmus Bo , Pries-Heje Mia Marie , Kjølhede Holle Sarah Louise , Engstrøm Thomas , Heitmann Merete , Pedersen Frants , Schou Morten , Mickley Hans , Elming Hanne , Steffensen Rolf , Koeber Lars , Iversen Kasper
Published: October 2020

Objective

To prospectively validate the CT-Valve score, a new risk score designed to identify patients with valvular heart disease at a low risk of coronary artery disease (CAD) who could benefit from multislice CT (MSCT) first instead of coronary angiography (CAG).

Methods

This was a prospective cohort study of patients referred for valve surgery in the Capital Region of Denmark and Odense University Hospital from the 1 February 2015 to the 1 February 2017. MSCT was implemented for patients with a CT-Valve score ≤7 at the referring physician’s discretion. Patients with a history of CAD or chronic kidney disease were excluded. The primary outcome was the proportion of patients needing reevaluation with CAG after MSCT and risk of CAD among the patients determined to be low to intermediate risk.

Results

In total, 1149 patients were included. The median score was 9 (IQR 3) and 339 (30%) had a score ≤7. MSCT was used for 117 patients. Of these 29 (25%) were reevaluated and 9 (7.7%) had CAD. Of the 222 patients with a score ≤7 that did not receive an MSCT, 14 (6%) had significant CAD. The estimated total cost of evaluation among patients with a score ≤7 before implementation was €132 093 compared with €79 073 after, a 40% reduction. Similarly, estimated total radiation before and after was 608 mSv and 362 mSv, a 41% reduction. Follow-up at a median of 32 months (18–48) showed no ischaemic events for patients receiving only MSCT.

Conclusion

The CT-Valve score is a valid method for determining risk of CAD among patients with valvular heart disease. Using a score ≤7 as a cut-off for the use of MSCT is safe and cost-effective.
Development of ‘speed ratio’ based level of service criteria on undivided urban streets in mixed traffic context
Authors: Pandey Ashutosh , Biswas Subhadip
Published: October 2020

Developing countries are facing challenges in sustaining urban traffic congestion due to rapid urbanization. To manage urban traffic, a traffic engineer first needs to assess the current operational condition on urban roads. Level of service (LOS) is used to define the operational traffic condition within a traffic stream in terms of service quality that a facility is providing to its user. This paper proposes a novel approach to estimate ‘speed ratio’ by considering individual free-flow speed (FFS) of different vehicle categories. This study also provides a comparison between FFS estimated using the methods given in Highway Capacity Manual 2010 and Indian-Highway Capacity Manual 2018. LOS criteria were developed using five clustering technique: K-means, K-medoids, Clustering Large Applications, Fuzzy-C Means, and Hierarchical Agglomerative Clustering. Both internal and external cluster validation indices were used to find the optimal number of clusters and suitable clustering algorithms.
A Pattern Logic for Automata with Outputs
Authors: Filiot Emmanuel , Mazzocchi Nicolas , Raskin Jean-François
Published: October 2020

We introduce a logic to express structural properties of automata with string inputs and, possibly, outputs in some monoid. In this logic, the set of predicates talking about the output values is parametric. We then consider three particular automata models (finite automata, transducers and automata weighted by integers here called sum-automata) and instantiate the generic logic for each of them. We give tight complexity results for the three logics with respect to the model-checking problem, depending on whether the formula is fixed or not. We study the expressiveness of our logics by expressing classical structural patterns characterising for instance finite ambiguity and polynomial ambiguity in the case of finite automata, determinisability and finite-valuedness in the case of transducers and sum-automata. As a consequence of our complexity results, we directly obtain that these classical properties can be decided in polynomial time.
From Two-Way Transducers to Regular Function Expressions
Authors: Baudru Nicolas , Reynier Pierre-Alain
Published: October 2020

Transducers constitute a fundamental extension of automata. The class of regular word functions has recently emerged as an important class of word-to-word functions, characterized by means of (functional, or unambiguous, or deterministic) two-way transducers, copyless streaming string transducers, and MSO-definable graph transformations. A fundamental result in language theory is Kleene’s Theorem, relating finite state automata and regular expressions. Recently, a set of regular function expressions has been introduced and used to prove a similar result for regular word functions, by showing its equivalence with copyless streaming string transducers. In this paper, we propose a direct, simplified and effective translation from unambiguous two-way transducers to regular function expressions extending the Brzozowski and McCluskey algorithm. In addition, our approach allows us to derive a subset of regular function expressions characterizing the (strict) subclass of functional sweeping transducers.
Zero-Hopf Periodic Orbits for a Rössler Differential System
Authors: Llibre Jaume , Makhlouf Ammar
Published: October 2020

We study the zero-Hopf bifurcation of the Rössler differential system [Formula: see text] where the dot denotes the derivative with respect to the independent variable [Formula: see text] and [Formula: see text], [Formula: see text], [Formula: see text] are real parameters.
Chaos Detection and Optimal Control in a Cannibalistic Prey–Predator System with Harvesting
Authors: Kharbanda Harsha , Kumar Sachin
Published: October 2020

This paper deals with a stage-structured predator–prey system which incorporates cannibalism in the predator population and harvesting in both population. The predator population is categorized into two divisions; adult predator and juvenile predator. The adult predator and prey species are harvested via hypothesis of catch-per-unit-effort, whereas juveniles are safe from being harvested. Mathematically, the dynamic behavior of the system such as existing conditions of equilibria with their stability is studied. The global asymptotic stability of prey-free equilibrium point and nonzero equilibrium point, if they exist, is proved by considering respective Lyapunov functions. The system undergoes transcritical and Hopf–Andronov bifurcations. The impacts of predator harvesting rate and prey harvesting rate on the system are analyzed by taking them as bifurcation parameters. The route to chaos is discussed by showing maximum Lyapunov exponent to be positive with sensitivity dependence on the initial conditions. The chaotic behavior of the system is confirmed by positive maximum Lyapunov exponent and non-integer Kaplan–Yorke dimension. Numerical simulations are executed to probe our theoretic findings. Also, the optimal harvesting policy is studied by applying Pontryagin’s maximum principle. Harvesting effort being an emphatic control instrument is considered to protect prey–predator population, and preserve them also through an optimal level.
Global Stability and Bifurcation Analysis of a Rumor Propagation Model with Two Discrete Delays in Social Networks
Authors: Zhu Linhe , Wang Xuewei , Zhang Zhengdi , Shen Shuling
Published: October 2020

In this paper, we improve an Ignorant-Lurker-Spreader-Removal (ILSR) rumor propagation model as in [Yang et al., 2019] in social networks with consideration to Logistic growth and two discrete delays. First, we prove the existence of equilibrium points by calculating the basic reproduction number according to the next generation matrix. Regarding the two discrete delays as bifurcating parameters, the local asymptotical stability and Hopf bifurcation of the positive equilibrium point are discussed for six different scenarios by analyzing the characteristic equations of linearized systems. Applying the normal form theory and the center manifold theorem, some important conclusions about the stability and direction of bifurcating periodic solution are given when the two time delays are equal. Subsequently we study the global stability of the equilibrium points by constructing Lyapunov functions when the two delays disappear. Finally, we verify the conclusions through numerical simulations and perform sensitivity analysis on the basic reproduction numbers.
Preliminary Research of Chaotic Characteristics and Prediction of Short-Term Wind Speed Time Series
Authors: Tian Zhongda
Published: October 2020

Short-term wind speed prediction has its special significance in wind power industry. However, due to the characteristics of the wind system itself, it is not easy to predict the short-term wind speed accurately. In order to solve the problem, this paper studies the chaotic characteristics and prediction of short-term wind speed time series. The short-term wind speed data at four time scales are collected as the research object. The predictability of short-term wind speed time series is determined by the Hurst exponent. The chaotic characteristics of short-time wind speed at different time scales are analyzed by the 0–1 test method for chaos and the maximum Lyapunov exponent method. The results show that the short-term wind speed time series has chaotic characteristics at different time scales. The phase-space reconstruction technology is introduced; delay time is determined by the C–C method; embedding dimension is obtained by the G–P method. Echo state network is improved to suppress the influence of input noise on prediction performance. At the same time, an improved grey Wolf optimization algorithm is proposed to optimize the parameters of reserve pool of the echo state network. The results of a case study show that, compared with state-of-the-art methods, the proposed prediction method improves the prediction accuracy and reduces the predictive errors.
A New Time-Delay Model for Chaotic Glucose-Insulin Regulatory System
Authors: AL-Hussein Abdul-Basset A. , Rahma Fadhil , Fortuna Luigi , Bucolo Maide , Frasca Mattia , Buscarino Arturo
Published: October 2020

Mathematical modeling is very helpful for noninvasive investigation of glucose-insulin interaction. In this paper, a new time-delay mathematical model is proposed for glucose-insulin endocrine metabolic regulatory feedback system incorporating the [Formula: see text]-cell dynamic and function for regulating and maintaining bloodstream insulin level. The model includes the insulin degradation due to glucose interaction. The dynamical behavior of the model is analyzed and two-dimensional bifurcation diagrams with respect to two essential parameters of the model are obtained. The results show that the time-delay in insulin secretion in response to blood glucose level, and the delay in glucose drop due to increased insulin concentration, can give rise to complex dynamics, such as periodic oscillation. These dynamics are consistent with the biological findings and period doubling cascade and chaotic state which represent metabolic disorder that may lead to diabetes mellitus.
Tumor Stabilization Induced by T-Cell Recruitment Fluctuations
Authors: Bashkirtseva Irina , Ryashko Lev , López Álvaro G. , Seoane Jesús M. , Sanjuán Miguel A. F.
Published: October 2020

The influence of random fluctuations on the recruitment of effector cells towards a tumor is studied by means of a stochastic mathematical model. Aggressively growing tumors are confronted against varying intensities of the cell-mediated immune response for which chaotic and periodic oscillations coexist together with stable tumor dynamics. A thorough parametric analysis of the noise-induced transition from this oscillatory regime to complete tumor dominance is carried out. A hysteresis phenomenon is uncovered, which stabilizes the tumor at its carrying capacity and drives the healthy and the immune cell populations to their extinction. Furthermore, it is shown that near a crisis bifurcation, such transitions occur under weak noise intensities. Finally, the corresponding noise-induced chaos-order transformation is analyzed and discussed in detail.
Hopf Bifurcation of Limit Cycles in Some Piecewise Smooth Liénard Systems
Authors: Xu Weijiao , Han Maoan
Published: October 2020

In this paper, we consider some piecewise smooth Liénard systems and study the Hopf bifurcation of limit cycles from the origin after a perturbation. We define the cyclicity [Formula: see text] of the piecewise smooth Liénard systems at the origin and denote [Formula: see text] for fixing [Formula: see text]. Then we obtain [Formula: see text] [Formula: see text]; [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text].
ECONOMIC FLUCTUATIONS AND THE SHADOW ECONOMY: A GLOBAL STUDY
Authors: NGUYEN CANH P. , SCHINCKUS CHRISTOPHE , THANH DINH SU
Published: October 2020

The recent economic crisis re-emphasizes the importance of the economic fluctuations. This study investigates the role of shadow economy in combination with economic factors on the economic instability for 133 economies between 1991 and 2015. Using the system-GMM estimations, this paper shows that a larger shadow economy increases the fluctuations of GDP growth rate in relation to the size and the volatility of shadow economy. Notably, the shadow economy presents an inverted-U relationship with economic instability and this relationship is strongest for low- and lower-middle income economies. Our results identify two categories of drivers for economic fluctuations: the stabilizing factors (the labor force and the TFP) and the enhancing factors (capital investment, consumption, government spending, trade, and FDI inflows). Interestingly, exports increase economic fluctuations while imports decrease them. Finally, we discuss the differences in the determinants of economic instability across low, middle and high incomes countries. This study documented that shadow economy influences the economic fluctuations — our results actually confirm our hypothesis and the impact of shadow economy on the effectiveness of macroeconomic policies. The contribution of this paper is to show the extent to which the impact can affect the economic activities and how institutions can smooth this effect.
China’s Strategies and Policies for Regional Development During the Period of the 14th Five-Year Plan
Authors: WEI Houkai , NIAN Meng , LI Le
Published: October 2020

During the 13th Five-Year Plan period, China’s regional development strategies and policies have positively contributed to the economic transformation and upgrading in the eastern China, sound economic growth momentum in the central and western China, faster economic growth in old revolutionary areas, ethnic minority areas, border areas, and poor areas, and more coordinated development among regions. Despite its remarkable achievements, China’s coordinated regional development still faces problems such as unbalanced economic growth between the southern and northern China, great gaps in innovation capacity among regions, difficulties in ensuring equitable access to basic public services, and slow growth of Blue Economy. To pursue regional development in China, the most important task at present is to promote coordinated and high-quality regional development and create a new pattern that can help such development become better in terms of quality, efficiency, fairness, and sustainability. The shift from questing for coordinated regional development to high-quality coordinated regional development not only reflects the transformation of regional development concept but also adapts to the requirement for regional development transformation in today’s China. During the 14th Five-Year Plan period, to promote high-quality coordinated regional development, China should continue to make overall planning for the four major regions and coordinate the development of belts and zones with the four major regions as the basis and the key belts and zones as the framework. It should continue to deepen and improve the “[Formula: see text]” master strategy for regional development and facilitate the formation of a national system for regional development strategies. It should further improve the governance system for China’s national space, with an emphasis on creating the main framework for the development of national space that consists of three horizontal axes and three vertical axes, stretches over the eastern, central and western regions, and connects the northern region with the southern region, setting up a network of growth poles mainly supported by city clusters and metropolitan areas, and putting in place a negative list system for national space development. Besides, China should continue to accelerate the development of C-shaped open economic belts in border areas, further strengthen the opening up of inland, and spare no effort to foster the three major marine economic zones, thus working toward all-around opening up that coordinates land and marine development as well as the development of China’s coastal, border and inland areas. On that basis, China should also actively steer the northeastern region out of difficulty and help it develop vigorously, redouble efforts to cultivate advanced manufacturing centers in the central and western regions, formulate and implement support policies for relatively poor areas, and expedite the integration of modern infrastructure.
From Bypass Transition to Flow Control and Data-Driven Turbulence Modeling: An Input–Output Viewpoint
Authors: Jovanović Mihailo R.
Published: October 2020

Transient growth and resolvent analyses are routinely used to assess nonasymptotic properties of fluid flows. In particular, resolvent analysis can be interpreted as a special case of viewing flow dynamics as an open system in which free-stream turbulence, surface roughness, and other irregularities provide sources of input forcing. We offer a comprehensive summary of the tools that can be employed to probe the dynamics of fluctuations around a laminar or turbulent base flow in the presence of such stochastic or deterministic input forcing and describe how input–output techniques enhance resolvent analysis. Specifically, physical insights that may remain hidden in the resolvent analysis are gained by detailed examination of input–output responses between spatially localized body forces and selected linear combinations of state variables. This differentiating feature plays a key role in quantifying the importance of different mechanisms for bypass transition in wall-bounded shear flows and in explaining how turbulent jets generate noise. We highlight the utility of a stochastic framework, with white or colored inputs, in addressing a variety of open challenges including transition in complex fluids, flow control, and physics-aware data-driven turbulence modeling. Applications with temporally or spatially periodic base flows are discussed and future research directions are outlined.
In Pursuit of Designing Multicellular Engineered Living Systems: A Fluid Mechanical Perspective
Authors: Serrano Jean Carlos , Gupta Satish Kumar , Kamm Roger D. , Guo Ming
Published: October 2020

From intracellular protein signaling to embryonic symmetry-breaking, fluid transport ubiquitously drives biological events in living systems. We provide an overview of the fundamental fluid mechanics and transport phenomena across a range of length scales in cellular systems, with emphasis on how cellular functions are influenced by fluid transport. We also highlight how understanding the physical basis of these fluid dynamic phenomena can be implemented to engineer increasingly complex multicellular systems that recapitulate tissue-level functions. Examples discussed include the manipulation of intracellular fluid volume to achieve cell differentiation/dedifferentiation and the use of microfluidic systems to control the spatial and temporal distribution of morphogens and fluid forces to generate vascularized organoids.
Pharmacologic Approach to Sinoatrial Node Dysfunction
Authors: Mesirca Pietro , Fedorov Vadim V. , Hund Thomas J. , Torrente Angelo G. , Bidaud Isabelle , Mohler Peter J. , Mangoni Matteo E.
Published: October 2020

The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the heart's inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. However, other forms of SND exist, including idiopathic primary SND, which is genetic, and forms that are secondary to cardiovascular or systemic disease. The incidence of SND in the general population is expected to increase over the next half century, boosting the need to implant electronic pacemakers. During the last two decades, our knowledge of sino-atrial node physiology and of the pathophysiological mechanisms underlying SND has advanced considerably. This review summarizes the current knowledge about SND mechanisms and discusses the possibility of introducing new pharmacologic therapies for treating SND.
Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes
Authors: Wang Biao , Xu Yajuan , Zhang Miao , Zhang Jingzhe , Hou Xiaofeng , Li Jingjing , Cai Yanjun , Sun Zongzong , Ban Yanjie , Wang Wentao
Published: October 2020

The purpose of this study was to explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy. In this study, oral and intestinal microbial composition was surveyed by using the 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features by using the quantitative real-time PCR (qPCR) approach in 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes. The 16S rRNA results showed that the relative abundances of Gammaproteobacteria were higher in pregnant women in the hypothyroidism group than in those in the control group, whereas the levels of Firmicutes were higher in the control group than in the hypothyroidism group. The serum C-reactive protein level, the weight gain during pregnancy, and the incidence of fetal distress were higher in the hypothyroidism group than in the control group. The QPCR results also showed the same changes of the intestinal microbiota in the two groups. There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.
Loss of CTRP4 alters adiposity and food intake behaviors in obese mice
Authors: Sarver Dylan C. , Stewart Ashley N. , Rodriguez Susana , Little Hannah C. , Aja Susan , Wong G. William
Published: October 2020

Central and peripheral mechanisms are both required for proper control of energy homeostasis. Among circulating plasma proteins, C1q/TNF-related proteins (CTRPs) have recently emerged as important regulators of sugar and fat metabolism. CTRP4, expressed in brain and adipose tissue, is unique among the family members in having two tandem globular C1q domains. We previously showed that central administration of recombinant CTRP4 suppresses food intake, suggesting a central nervous system role in regulating ingestive physiology. Whether this effect is pharmacological or physiological remains unclear. We used a loss-of-function knockout (KO) mouse model to clarify the physiological role of CTRP4. Under basal conditions, CTRP4 deficiency increased serum cholesterol levels and impaired glucose tolerance in male but not female mice fed a control low-fat diet. When challenged with a high-fat diet, male and female KO mice responded differently to weight gain and had different food intake patterns. On an obesogenic diet, male KO mice had similar weight gain as wild-type littermates. When fed ad libitum, KO male mice had greater meal number, shorter intermeal interval, and reduced satiety ratio. Female KO mice, in contrast, had lower body weight and adiposity. In the refeeding period following food deprivation, female KO mice had significantly higher food intake due to longer meal duration and reduced satiety ratio. Collectively, our data provide genetic evidence for a sex-dependent physiological role of CTRP4 in modulating food intake patterns and systemic energy metabolism.
A Novel Global Energy and Local Energy-Based Legendre Polynomial Approximation for Image Segmentation
Authors: Hu Feng , Zhang Mengyun , Chen Bo
Published: October 2020

Active contour model (ACM) is a powerful segmentation method based on differential equation. This paper proposes a novel adaptive ACM to segment those intensity inhomogeneity images. Firstly, a novel signed pressure force function is presented with Legendre polynomials to control curve contraction. Legendre polynomials can approximate regional intensities corresponding to evolving curve. Secondly, global term of our model characterizes difference of Legendre coefficients, and local energy term characterizes fitting evolution curve of interested region. Final contour evolution will minimize the energy function. Thirdly, a correction term is employed to improve the performance of curve evolution according to the initial contour position, so wherever the initial contour being in the image, the object boundaries can be detected. Fourthly, our model combines the advantages of two classical models such as good topological changes and computational simplicity. The new model can classify regions with similar intensity values. Compared with traditional models, experimental results show effectiveness and efficiently of the new model.
Anemia and Kidney Function Decline among the Middle‐Aged and Elderly in China: A Population‐Based National Longitudinal Study
Authors: Yang Chao , Meng Qinqin , Wang Huaiyu , Wang Yafeng , Su Zaiming , Liu Lili , Liu Wenwen , Kong Guilan , Zhang Luxia , Zhao Yaohui , Zhao Ming-Hui
Published: October 2020

Chronic kidney disease (CKD) is a public health burden, and anemia is common among patients with CKD. However, less is known regarding the longitudinal association between anemia and deterioration of kidney function among the general population. The China Health and Retirement Longitudinal Study is a nationally representative survey for households with members aged ≥ 45 years. Participants without creatinine and demographic data in 2011 and 2015 were excluded. Anemia was defined according to definitions of the World Health Organization. Rapid decline in kidney function was defined as a ≥16.9% (quartile 3) decline in estimated glomerular filtration rate (eGFR), calculated using the CKD‐EPI equation during 2011‐2015. Multivariate logistic regression and restricted cubic splines were used to explore their relationship. Altogether, 7210 eligible participants were included in the analysis, with a mean age of 58.6 ± 8.8 years. Rapid decline in kidney function occurred among 1802 (25.0%) participants. Those with kidney function decline were more likely to be older, male, and have anemia, lower eGFRs, hypertension, and cardiovascular disease (P < 0.05). Anemia, or hemoglobin, was independently associated with rapid decline in kidney function after adjusting for potential confounding factors (OR = 1.64, 95% CI, 1.32‐2.04; OR = 0.90, 95% CI, 0.87‐0.94, respectively). Restricted cubic splines showed a nonlinear relationship between hemoglobin and rapid decline in kidney function, especially for men with anemia (P < 0.05). In conclusion, anemia is an independent risk factor for progression of kidney function among the middle‐aged and elderly population. Attentive management and intervention strategies targeting anemia could be effective to reduce the risk of kidney failure and improve the prognosis of the general population.
Atypical EEG Responses to Nonverbal Emotionally Charged Stimuli in Children with ASD
Authors: Portnova Galina V. , Maslennikova Aleksandra V.
Published: October 2020

This study focused on auditory emotional perception in children with low-functioning autism and investigated the children’s response to emotionally charged nonverbal sounds which regularly induced emotional response in typically developing (TD) peers. An EEG was conducted, and emotional reactions were assessed using analog scales and images of presented sounds with additional images during the presentation of emotional stimuli. The results showed that EEG and emotional responses to the fearful sounds were similar in TD children and children with autism spectrum disorders (ASD). Both groups of children showed an increase in peak alpha frequency and power of alpha2-band and a decrease in low-frequency bands. Sounds of crying and laughter induced an atypical EEG response in children with ASD, with no change in alpha-band’s power and frequency observed in them; this was contrary to the observation in TD children. The decrease in the fractal dimension detected in children with ASD only for sounds of crying and laughter correlated with the accuracy of assessment of these stimuli.
Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells
Authors: Lee Seong-Ho , Lee Jihye , Herald Thomas , Cox Sarah , Noronha Leela , Perumal Ramasamy , Lee Hee-Seop , Smolensky Dmitriy
Published: October 2020

Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.
Patterns of Integrative Korean Medicine Practice for Anxiety Disorders: A Survey among Korean Medicine Doctors (KMDs) in Korea
Authors: Seo Sang-Il , Choi Sung-Youl , Kim Eun-Jung , Koo Byung-Soo , Won-Jung Hyo , Lee Gun-Hee , Kim Geun-Woo
Published: October 2020

Anxiety disorder is known as the most common disease among psychiatric disorders. However, many studies have not been conducted in the Korean medicine area. This study explores the current state of anxiety disorder treatments of Korean medicine through a survey research. The survey for Korean medicine doctors (KMDs) on Korean medicine (KM) diagnosis and treatments for anxiety disorder was conducted online from December 21, 2016, to December 29, 2016. The results were divided into two groups, KMDs and Korean medicine neuropsychiatric specialists (KMNPS), and comparatively analyzed. Self‐evaluation and counseling were the most common in both diagnostic methods and evaluation of treatment effects, and KMNPS tended to make extensive use of objective indicators. There was no difference in the rate of psychiatric medication use among the patients between KMD and KMNPS. The main reason for patients wanting KM treatment was the tapering cessation of psychiatric medications. The most common treatments were acupuncture, herbal medicine, and moxibustion, in addition to dry cupping in KMD and psychotherapy in KMNPS. The most important factor for treatment was herbal medicine treatment, followed by rapport formation in KMD and patient’s temperament in KMNPS. Opinions on various items were presented as treatment barriers, and KMNPS tended to think more importantly about the patient’s family problems. For the items to be additionally trained in the future, KMD chose the diagnostic tools and KMNPS chose psychotherapies. This study is the first study to analyze the clinical patterns for anxiety disorder in KMDs. KMD and KMNPS showed similar patterns in the perception, diagnosis, and treatment of anxiety disorders, but KMNPS tended to use objective indicators and psychotherapy more actively. Further clinical studies for the development of clinical guidelines should be additionally required.
Shen-Hong-Tong-Luo Formula Attenuates Macrophage Inflammation and Lipid Accumulation through the Activation of the PPAR-γ/LXR-α/ABCA1 Pathway
Authors: Zhang Zepeng , Zhai Lu , Lu Jing , Sun Sanmiao , Wang Dandan , Zhao Daqing , Sun Liwei , Zhao Weimin , Li Xiangyan , Chen Ying
Published: October 2020

Atherosclerosis (AS) is the killer of human health and longevity, which is majorly caused by oxidized lipoproteins that attack macrophages in the endarterium. The Shen-Hong-Tong-Luo (SHTL) formula has shown great clinical efficacy and vascular protective effect for over 30 years in China, to attenuate AS progression. However, its pharmacological mechanism needs more investigation. In this study, we first investigated the chemical composition of SHTL by fingerprint analysis using high-performance liquid chromatography. In primary mouse peritoneal macrophages induced by lipopolysaccharide (LPS), we found that SHTL pretreatment suppressed reactive oxygen species accumulation and reversed the increases of the inflammatory factors, TNF-α and IL-6. Moreover, lipid accumulation induced by oxidized low-density lipoprotein (Ox-LDL) in macrophages was inhibited by SHTL. Additionally, network pharmacology was used to predict the potential targets of SHTL as the PPAR-γ/LXR-α/ABCA1 signaling pathway, which was validated in macrophages and ApoE-/- mice by histopathological staining, qPCR, and Western blot analysis. Importantly, the protective effect of SHTL in the LPS- and Ox-LDL-induced macrophages against inflammation and lipid accumulation was attenuated by GW9662, a PPAR-γ antagonist, which confirmed the prediction results of network pharmacology. In summary, these results indicated that SHTL pretreatment reduced inflammation and lipid accumulation of macrophages by activating the PPAR-γ/LXR-α/ABCA1 pathway, which may provide a new insight into the mechanism of SHTL in the suppression of AS progression.