bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative analysis of dynamic management in marine and terrestrial systems
Authors: Oestreich William K , Chapman Melissa S , Crowder Larry B
Published: July 2020

Protection of highly mobile species and shifting habitats is a practical challenge for conservation in both marine and terrestrial systems, particularly in light of the acceleration of land‐use change and climate‐driven range shifts. Static protected areas have long been a keystone of conservation but are generally insufficient for such species and habitats. Spatially and temporally dynamic management (DM) has arisen as a potential solution to this challenge. We present what we believe to be the first comparative analysis of DM across marine and terrestrial systems, focusing on the scales of DM approaches. Our results show that marine DM has largely been focused on relatively finer temporal scales, whereas terrestrial DM has focused on relatively finer spatial scales, often following the scale of available and relevant datasets. We explore not only the constraints imposed by data availability but also other drivers of DM trends and scales, highlighting areas in which exchange of approaches pioneered in each domain may be beneficial.
Numerical approximation of tempered fractional Sturm‐Liouville problem with application in fractional diffusion equation
Authors: Yadav Swati , Pandey Rajesh K. , Pandey Prashant K.
Published: July 2020

In this paper, we discuss the numerical approximation to solve regular tempered fractional Sturm‐Liouville problem (TFSLP) using finite difference method. The tempered fractional differential operators considered here are of Caputo type. The numerically obtained eigenvalues are real, and the corresponding eigenfunctions are orthogonal. The obtained eigenfunctions work as basis functions of weighted Lebesgue integrable function space (a,b). Further, the obtained eigenvalues and corresponding eigenfunctions are used to provide weak solution of the tempered fractional diffusion equation. Approximation and error bounds of the solution of the tempered fractional diffusion equation are provided.
The relationship between the chemical composition and the quality of the soybean film during peeling process
Authors: Ding Yin‐Yi , Li Juanjuan , Wu Cheng , Yang Yuexi , Gu Zhenyu
Published: July 2020

Soybean film is a traditional nonfermented soy product in China. It is a film formed on the surface of the soymilk during heating process. The nutrient components of soymilk will affect the quality of the soybean film. The results of this study showed that during the peeling process, the proportion of protein and carbohydrate in soymilk decreased, and the proportion of lipid increased. The mechanical properties (fracture extension and tensile strength) of the soybean film decreased during the peeling process. During the heating treatment, the Maillard reaction occurred and its intermediate products accumulated, which caused the change in soybean film color. White globular protein granules (<100 nm) existed on the surface of the soybean film. The lipid that was not wrapped by the protein network structure was exposed, and the evaporation of water led to the formation of black and gray holes on the skin (<500 nm). In addition, the results of correlation analysis showed that the changes in color, taste, and odor, as well as the mechanical properties of the skin, were all related to the changes in nutrients in the soybean film during peeling. This research provided a deeper understanding of the quality change in the soybean milk and the soybean film during the heating process.
The impact of Medicaid on medical utilization in a vulnerable population: Evidence from COFA migrants
Authors: Halliday Timothy J. , Akee Randall Q.
Published: July 2020

In March 2015, the State of Hawaii stopped covering the majority of migrants from countries belonging to the Compact of Free Association (COFA) in its Medicaid program. COFA migrants were required to obtain private insurance in the exchanges established under the Affordable Care Act. Using statewide hospital discharge data, we show that Medicaid‐funded hospitalizations and emergency room visits declined in this population by 31% and 19%, respectively. Utilization funded by private insurance did increase but not enough to offset the declines in Medicaid‐funded utilization. We show that the expiration of benefits increased uninsured ER visits. Finally, we exploit a feature of the policy change to provide evidence that the declines in utilization are due to higher rates of uninsured migrants rather than higher levels of cost sharing on private plans.
Improving the Efficacy of Liver Cancer Immunotherapy: The Power of Combined Preclinical and Clinical Studies
Authors: Feng Gen‐Sheng , Hanley Kaisa L. , Liang Yan , Lin Xiaoxue
Published: July 2020

Hepatocellular carcinoma (HCC) is a most deadly malignant disease worldwide, with no effective mechanism‐based therapy available. Therefore, following the “miracle” outcomes seen in a few patients at the advanced stages of melanoma or lung cancer, the immune checkpoint inhibitors (ICIs) immediately entered clinical trials for advanced HCC patients without pre‐clinical studies. Emerging data of clinical studies showed manageable toxicity and safety but limited therapeutic benefit to HCC patients, suggesting low response rate. Thus, one urgent issue is how to convert the liver tumors from cold to hot and responsive, which may rely on in‐depth mechanistic studies in animal models and large scale data analysis in human patients. One ongoing approach is to design combinatorial treatment of different ICIs with other reagents and modalities. Indeed, a phase 3 clinical trial showed that combination of atezolizumab and bevacizumab achieved better overall and progression‐free survival rates than sorafenib in unresectable HCC. This review highlights the value of animal models and the power of combining pre‐clinical and clinical studies in efforts to improve HCC immunotherapy.
Comparative analysis of Cu/blood and Cu–CuO/blood nanofluids on a peristaltic flow governed by an asymmetric channel
Authors: Bharathi V. , Vijayaragavan R. , Prakash J.
Published: July 2020

Contraction and expansion play a crucial role in biomedical applications, such as heart pumping, ovum in the feminine fallopian vessel, blood fluid transport, and so forth. Inspired by these features, the present effort concentrates on the consequences of a thermal slip in the peristalsis of Cu/blood and Cu–CuO/blood nanofluids in asymmetric flow formation. Hence, the microrotation influence of blood flow is considered here. Heat transported through the channel due to perpendicular flow buoyancy effects is also studied. The special effects of thermal radiation, nanoparticle shape, and heat source/sink parameters on the flow are studied in the proposed model. The MATLAB BVP4c condition is utilized to achieve the numerical solutions of the transformed system of nonlinear coupled differential equations. The most important outcome of the present analysis is an enhancement in the evaluation study of the Cu/blood and Cu–CuO/blood nanofluids on the axial velocity, axial spin velocity, pressure gradient, and temperature distributions in the asymmetric channel. Also, another important outcome is observed that the Cu–CuO blood nanofluid strongly has dominated the Cu/blood nanofluid in axial spin velocity.
ECB'S non‐standard monetary policy and asset price volatility: Evidence from EU‐6 economies
Authors: Ciarlone Alessio , Colabella Andrea
Published: July 2020

In this paper, we provide evidence that the effects of the different waves of asset purchase programmes implemented by the ECB from 2009 onwards have spilled over into a group of six Central and Eastern European economies belonging to the EU but not to the euro area, contributing to shield their financial markets from the negative shocks that hit international investors' degree of risk aversion in recent years. By means of a Dynamic Conditional Correlation Multivariate Generalized Autoregressive Conditional Heteroskedasticity Model, and resorting to three different proxies to describe the functioning, and measure the impact, of the ECB's programmes of asset purchase, we show that such non‐standard monetary measures have had a marked role in dampening volatility spikes in EU‐6 financial markets, likely reflecting the working of a “risk taking” and a “liquidity” channel of transmission. Results are in general robust to an extensive series of tests, including changes in the estimation methodology.
Anticipating the value of share repurchase announcements: The role of short sellers
Authors: Zheng Liyi
Published: July 2020

This study investigates whether short sellers anticipate undervaluation information before a repurchase announcement. Apart from exploring investment opportunities via searching for unfavourable information, short sellers should have the same incentive to identify favourable information to prevent potential losses. An observed significant negative relation between pre‐announcement short selling activities and announcement abnormal returns supports the informed hypothesis. This negative relation is stronger under high levels of information asymmetry, and more significant when the repurchase announcement is associated with the undervaluation.
Roles of estradiol levels on the day of human chorionic gonadotrophin administration in the live birth of patients with frozen embryo transfer
Authors: Chen Haixiao , Cai Jiali , Liu Lanlan , Sun Xiaohua
Published: July 2020

Background

Estradiol (E2) is an important hormone in women. Changes of serum E2 levels may affect the endometrial receptivity for embryo implantation and thus affect pregnancy outcomes. This study was to assess the association between serum E2 levels on the day of human chorionic gonadotrophin (HCG) administration and live‐birth rates in patients with frozen embryo transfer (FET).

Methods

Totally 2071 women receiving long protocols of long‐acting gonadotropin‐releasing hormone (GnRH) agonists were enrolled. According to the E2 levels on the day of HCG administration, these patients were divided into four groups: 676 cases of E2 ≤ 3051 pg/mL in Q1 group, 676 cases of 3051 pg/mL < E2 ≤ 4558 pg/mL in Q2 group, 675 cases of 4558 pg/mL < E2 ≤ 6718 pg/mL in Q3 group, and 674 cases of E2 > 6718 pg/mL in Q4 group. The clinical indicators including female age, body mass index (BMI), duration of infertility, infertility styles, treatment protocols, hormone levels, total antral follicle count, endometrial thickness, top‐level embryos, and live‐birth rates were analyzed, and multivariable logistic model was conducted to select significant variables.

Results

Significant differences were observed for the female age (OR = 0.965, 95% CI: 0.946‐0.985, P < .001), total antral follicle counts (OR = 1.025, 95% CI: 1.008‐1.043, P = .004), transferring what day of embryos (OR = 1.242, 95% CI: 1.137‐1.356, P < .001), endometrial thickness (OR = 1.058, 95% CI: 1.004‐1.115, P = .035), top‐level embryos (OR = 1.416, 95% CI: 1.157‐1.731, P = .001), and E2 levels on HCG day >6781 pg/mL (OR = 1.344, 95% CI: 1.069‐1.690, P = .011) between live‐birth and non‐live‐birth groups. The area under the curve (AUC) for E2 levels on HCG day was 0.558, the sensitivity was 54.75%, and the specificity was 55.10%.

Conclusion

Serum E2 level on HCG day was an independent predictor of live‐birth achievement in patients with FET.
Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1
Authors: Sul Ok‐Joo , Hyun Hyo‐Jung , Rajasekaran Monisha , Suh Jae‐Hee , Choi Hye‐Seon
Published: July 2020

Loss of ovarian function results in increased fat mass, leading to the accumulation of adipose tissue macrophages that participate in chronic inflammation. We hypothesized that ovariectomy (OVX)‐induced increases in body weight and fat mass are associated with decreased adipose tissue (AT) browning due to estrogen (E2) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E2 recovered the OVX‐induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E2. E2‐induced M2 polarization occurred due to the increased expression of heme oxygenase‐1 (HO‐1) in macrophages, leading to decreased reactive oxygen species levels. Collectively, we demonstrated that E2 enhances AT browning via M2 polarization mediated by HO‐1.
Mass spectrometry imaging of latent fingerprints using titanium oxide development powder as an existing matrix
Authors: Hinners Paige , Lee Young Jin
Published: July 2020

Recent research has focused on increasing the evidentiary value of latent fingerprints through chemical analysis. Although researchers have optimized the use of organic and metal matrices for matrix‐assisted laser desorption/ionization‐mass spectrometry imaging (MALDI‐MSI) of latent fingerprints, the use of development powders as matrices has not been fully investigated. Carbon forensic powder (CFP), a common nonporous development technique, was shown to be an efficient one‐step matrix; however, a high‐resolution mass spectrometer was required in the low mass range due to carbon clusters. Titanium oxide (TiO2) is another commonly used development powder, especially for dark nonporous surfaces. Here, forensic TiO2 powder is utilized as a single‐step development and matrix technique for chemical imaging of latent fingerprints without the requirement of a high‐resolution mass spectrometer. All studied compounds were successfully detected when TiO2 was used as the matrix in positive mode, although, generally, the overall ion signals were lower than the previously studied CFP. TiO2 provided quality mass spectrometry (MS) images of endogenous and exogenous latent fingerprint compounds. The subsequent addition of traditional matrices on top of the TiO2 powder was ineffective for universal detection of latent fingerprint compounds. Forensic TiO2 development powder works as an efficient single‐step development and matrix technique for MALDI‐MSI analysis of latent fingerprints in positive mode and does not require a high‐resolution mass spectrometer for analysis.
A case of Crimean Congo hemorrhagic fever complicated with acute pulmonary embolism
Authors: Ture Zeynep , Kalin‐Unuvar Gamze
Published: July 2020

Background

Crimean‐Congo hemorrhagic fever (CCHF) is one of the common causes of tick‐borne hemorrhagic infections. The study aims to report a case of a female patient with severe CCHF with pulmonary embolism.

Case report

A 61‐year‐old woman admitted to the emergency department with complaints of high fever, nausea, and weakness. The patient was dealing with animal husbandry and had a tick bite history. At laboratory findings, bicytopenia, abnormal liver function tests, and elevated coagulation parameters were observed. Real‐time plymerase chain reaction confirmed the diagnosis of CCHF. Three sessions of plasmapheresis were performed due to continued fever and worsening in laboratory values. Pulmonary embolism was detected in computerized thorax tomography carried out due to respiratory alkalosis on the 6th day. She was successfully treated with supportive and anticoagulation therapy.

Conclusion

CCHF demonstrates different types of clinical presentations apart from fever and hemorrhage. Acute pulmonary embolism is a rare complication that has not been reported before.
Spatial distribution of spectral SST oscillations over the equatorial pacific in the period 1888–2014
Authors: Silva Carlos Batista , Silva Maria Elisa Siqueira , Ambrizzi Tércio , Patucci Natália Nunes , Lima Bruna Simões , Correa Wesley Campos
Published: July 2020

This study identified and analysed the spatial and temporal patterns of spectral oscillation ranges of the monthly sea surface temperature, SST, over the tropical Pacific region, from 1888 to 2014, through wavelet analysis. The strategic steps considered the variance analysis, obtained from the wavelet computation, for each single grid point instead of the analysis of a spatial mean variance, as is commonly done, allowing us to visualize the spatial distribution of SST variance during different time periods. The mean results indicate that lower‐frequency oscillations (2–4 and 4–8 years) over the considered area are becoming more intense while higher‐frequency oscillations (1–12 months) are becoming less intense through time, which can lead to more persistent climates around the globe. While the 1–2 year oscillations feature the highest positive trend along the equatorial belt over central and eastern locations, the 4–8 year oscillations feature the strongest signal closer to the western South American coast, and the 2–4 year oscillations present positive signals over areas closer to the continental coast and over more distant western locations intercalated by negative signals. Throughout time, the position of the highest EN signals occurs either over central or eastern areas of the equatorial Pacific. The SST variance in the Niño areas mainly oscillates within the 2–4 and 4–8 year spectral ranges. Niño1 + 2 and Niño3 regions, in opposition to Niño3 and Niño3 + 4 regions, present the highest SST variance values for the four considered spectral ranges. The strongest El Niño events present their main oscillations in the 2–4 and 4–8 year spectral ranges, especially in the Niño1 + 2 and Niño3 regions, while weaker El Niño events show more association with the 1–2 year spectral range. Although there are some patterns identified for distinct El Niño/Southern Oscillation, ENSO, intensities and the associated frequency oscillations, the distinct spatial spectral energy distribution over the equatorial areas suggests the importance of the spatial distribution of the spectral energy through time in order to better characterize the ENSO events.
Relationship between gingival bleeding and associated factors with reports of verbal bullying in adolescents
Authors: Baldo Moraes Renita , Knorst Jessica Klöckner , Brondani Bruna , Baldo Marques Beatriz , de Sousa Reis Magda , Henriqson Denise , Ardenghi Thiago Machado
Published: July 2020

Background

Dentofacial features are related to increased bullying episodes in young people. The aim of this study was to assess the association between gingival bleeding and reports of verbal bullying among adolescents.

Methods

This is a cross‐sectional study conducted with a representative sample of 608 12‐year‐old adolescents from southern Brazil. The occurrence of verbal bullying was verified through adolescents' self‐report. Oral health measurements included the presence of gingival bleeding, dental fracture, dental fluorosis, and dental caries experience. Gingival bleeding was assessed through adolescent self‐perception by the following question: “Did you notice any bleeding in your gums?” Demographic, socioeconomic, and psychosocial variables were also evaluated. Poisson regression models with robust variance were used to evaluate the influence of gingival bleeding on the occurrence of verbal bullying. Results are presented as prevalence ratio (PR) and 95% confidence interval (95% CI).

Results

Out of 608 adolescents evaluated, 577 answered bullying questions. The prevalence of self‐reported verbal bullying was 12.8%. Adolescents who presented gingival bleeding had an 80% higher prevalence of verbal bullying than their counterparts (PR 1.80; 95% CI 1.01 ‐3.19). Dental shame, speech difficulties and influence of dental condition on studies also impacted the higher prevalence of bullying.

Conclusion

Our results suggest that the presence of gingival bleeding negatively impacts the social life of adolescents, causing more episodes of verbal bullying. These findings encourage public health policies aimed at reducing oral health inequities, thus reflecting on the well‐being and quality of life of this target population.
A hybrid stochastic model of retinal angiogenesis
Authors: Capasso Vincenzo , Wieczorek Radosław
Published: July 2020

Understanding the biological principles that govern blood vessel growth in the retina has important clinical implications, for the prevention of possible retinopathies, which may eventually lead to blindness. The availability of a realistic mathematical model of the relevant phenomenon may support the medical community in both issues, diagnosis being related to inverse problems, and therapy to optimal control strategies. The mathematical modeling of retinal angiogenesis leads to an highly complex problem, because of dimension, nonlinearity, and intrinsic randomness. In this paper, we propose a reduced model which leads to numerical simulations that somehow reproduce normal vascularization and predict possible pathologies. We call our model hybrid because it includes the coupling of a fully stochastic model for the construction of a vessel network in the retina, with continuum underlying fields describing relevant factors, such as growth factors and oxygen. We perform numerical simulations of a stochastic particle system coupled with partial differential equations (PDEs)' so to obtain images of vessel structure resembling real retina vasculatures. We then derive a possible mean field approximation of the stochastic vessel network, so to obtain a fully deterministic PDE system for the evolution of the underlying fields. Actually, in order to reproduce the geometric structure of the retina vessel network, we have to keep a stochastic model (though simplified) for its construction. Future investigations may concern the use of such a mean field approximation in the numerical simulations of the retina vasculature. Inverse and optimal control problems being the final goal of our research plan.
Stability analysis and optimal control strategies of direct and indirect transmission dynamics of conjunctivitis
Authors: Ogunmiloro Oluwatayo Michael
Published: July 2020

This article concerns theS–E–I–R(Susceptible–Exposed–Infected–Recovered) mathematical model formulation describing the dynamics of the spread of conjunctivitis predominant in human host population. The model considered possesses two equilibrium points, namely, the conjunctivitis‐free and conjunctivitis‐present equilibrium, which are dependent on the basic reproduction number (Rco). The local and global stabilities of derived model system were investigated at the equilibrium solutions, and it was found that ifRco < 1, the conjunctivitis‐free equilibrium is both locally and globally asymptotically stable. Also, ifRco > 1, the conjunctivitis‐present equilibrium is globally asymptotically stable. The sensitivity analysis ofRcois performed, and the corresponding graphical results are presented to examine the relative importance of conjunctivitis model parameters as to conjunctivitis prevalence. The model is reformulated by applying control measures of isolation and hygiene compliance to minimize conjunctivitis infection and irritants concentration as well as the cost associated with it. An optimality system is derived and numerically solved with and without controls using the forward–backward Runge–Kutta scheme via computational software MATLAB. The graphical results obtained showed that each of the control strategies has its own importance for conjunctivitis elimination. Further graphical descriptions reveal that the combination of isolation and hygiene compliance strategies are more effective in curtailing conjunctivitis prevalence in human and environmental host community.
Design and analysis of an 8‐element dipole array for passive coherent location systems
Authors: Wang Sungsik , Hur Jun , Jang Doyoung , Shim Hongsuk , Anh Junil , Choo Hosung
Published: July 2020

This article deals with a design and analysis of an 8‐element dipole array for passive coherent location (PCL) systems. The array is composed of eight identical dipole elements that are arranged at a radius of 0.5λ0 from the center to the elements. To verify the performance for the PCL system, the array is fabricated and measured in an outdoor test site. Array performances such as the antenna gain, peak to side lobe ratio (PSLR), half‐power beam width (HPBW), null width, and null depth are then analyzed. The results demonstrate that the proposed array has beam pattern characteristics suitable for PCL systems.
Design of antennas using artificial magnetic conductor layer to improve gain, flexibility, and specific absorption rate
Authors: Hazarika Bidisha , Basu Banani , Nandi Arnab
Published: July 2020

In this article, two miniaturized, dual‐band, enhanced gain, flexible, low specific absorption rate (SAR) artificial magnetic conductor (AMC) integrated antennas operating at 2.4 GHz ISM and 3.9 GHz WiMAX bands have been proposed. Two compact monopoles with defected stepped ground structures have been used to improve the radiation characteristics while integrated with a common AMC surface. Defected dumbbell shaped unit‐cell has been designed to obtain zero reflection phase and modify the material features. The capacitive effect of the AMC along with the defected stepped ground structures of the monopoles have excited two resonating bands and miniaturized the antennas. Proposed AMC has compensated the out‐of‐phase radiation toward main beam direction to increase the gain up to 8.6 dB, which is 85% more than that of the only monopole. The AMC has enhanced the reflectance exploiting the double‐negative property and made the emitted radiation more directives. The integrated antennas have bestowed robust impedance matching in various bent condition by virtue of in phase reflection property. SAR values have been suppressed significantly up to 0.021 W/kg at a distance 5 mm from the human body, which is 99.5% better than that of the monopole alone
An active learning tool for quantitative genetics instruction using R and shiny
Authors: Neyhart Jeffrey L. , Watkins Eric
Published: July 2020

Basic quantitative and population genetics topics are typically taught in introductory plant breeding courses and are critical for success in upper‐level study. Active learning, including simulations and games, may be useful for instruction of these concepts, which rely heavily on theory and may be more challenging for students. The statistical computing language R is now routinely used in the analysis of plant breeding experiments, but the command‐line interface of the language may be unsuitable for an introductory course. Here we describe qgshiny (quantitative genetics in shiny), an interactive application for performing simulations to understand basic theory in quantitative and population genetics. The initial version of the application includes modules on three core topics in quantitative genetics: randomly mating populations, genetic variance, and response to selection. Students can specify parameters and initiate simulations to assess their impact on responses such as allele frequency, genetic variance, and genetic gain, which together can be used to reinforce more general learning objectives. Feedback collected from students after engaging with the application suggests this tool can have a positive impact on student learning. The application is bundled in an R package, qgshiny, which is available through the Comprehensive R Archive Network (CRAN), on GitHub (https://github.com/neyhartj/qgshiny), or interactively through the shinyapps.io platform (http://neyhartj.shinyapps.io/qgshiny).
Synthesis and chemical modification of crystalline nanocellulose to reinforce natural rubber composites
Authors: Singh Shiva , Dhakar Gopal L. , Kapgate Bharat P. , Maji Pradip K. , Verma Chhavi , Chhajed Monika , Rajkumar Kasilingam , Das Chayan
Published: July 2020

Potential of crystalline nanocellulose (CNC), as green reinforcing filler, has been evaluated for the preparation of natural rubber (NR) composites. CNC is derived from a natural source (ramie fiber) and its surface is modified with different organosilanes to strengthen the rubber‐filler interaction at the interface. It is found that, although at 2.5 phr (parts per hundred parts of rubber) loading of CNC the mechanical property of the NR composites is improved, it deteriorates at 5 phr loading. Surface modification of CNC by organosilanes is found very useful to overcome this issue. The modulus values at low strain become almost 1.5 to 2 times higher while tensile strength becomes 2.5 times higher for the modified CNC filled composites relative to those of CNC filled composites at 5 phr loading. These results are corroborated with a morphological study, where a very good state of dispersion of CNC particles is found in the surface‐modified CNC filled composites. Moreover, the particle size of CNC becomes almost half, in respect to that of unmodified CNC particles, upon surface modification by organosilane. The reinforcement effect delivered by CNC and surface‐modified CNC is also reflected by a small positive shift in Glass Transition Temperature (Tg) in differential scanning calorimetry study.
ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling
Authors: Li Bingjue , Zhu Chaohong , Dong Lihua , Qin Jing , Xiang Wenyu , Davidson Alan J , Feng Shi , Wang Yucheng , Shen Xiujin , Weng Chunhua , Wang Cuili , Zhu Tingting , Teng Lisha , Wang Junwen , Englert Christoph , Chen Jianghua , Jiang Hong
Published: July 2020

Disturbed intrauterine development increases the risk of renal disease. Various studies have reported that Notch signalling plays a significant role in kidney development and kidney diseases. A disintegrin and metalloproteinase domain 10 (ADAM10), an upstream protease of the Notch pathway, is also reportedly involved in renal fibrosis. However, how ADAM10 interacts with the Notch pathway and causes renal fibrosis is not fully understood. In this study, using a prenatal chlorpyrifos (CPF) exposure mouse model, we investigated the role of the ADAM10/Notch axis in kidney development and fibrosis. We found that prenatal CPF‐exposure mice presented overexpression of Adam10, Notch1 and Notch2, and led to premature depletion of Six2+ nephron progenitors and ectopic formation of proximal tubules (PTs) in the embryonic kidney. These abnormal phenotypic changes persisted in mature kidneys due to the continuous activation of ADAM10/Notch and showed aggravated renal fibrosis in adults. Finally, both ADAM10 and NOTCH2 expression were positively correlated with the degree of renal interstitial fibrosis in IgA nephropathy patients, and increased ADAM10 expression was negatively correlated with decreased kidney function evaluated by serum creatinine, cystatin C, and estimated glomerular filtration rate. Regression analysis also indicated that ADAM10 expression was an independent risk factor for fibrosis in IgAN. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Isolated echogenic intracardiac foci and the role of cell‐free fetal DNA: A cost‐effectiveness analysis
Authors: Hacker Francis M , Hersh Alyssa R , Shaffer Brian L , Caughey Aaron B
Published: July 2020

Objectives

Cell‐free fetal DNA (cfDNA) has been increasingly incorporated into prenatal aneuploidy screening paradigms given its relatively high sensitivity for Down syndrome (DS). This is often the case when fetal ultrasonographic soft markers are present, such as the relatively common echogenic intracardiac focus (EIF). We sought to evaluate the cost‐effectiveness of a screening strategy that included cfDNA screening when an isolated EIF is identified in a low‐risk population with prior aneuploidy screening.

Methods

A decision‐analytic model was constructed using TreeAge software with probabilities derived from the literature. Our model compared cfDNA screening following isolated EIF detection in women less than 35 years with prior reassuring first trimester screen compared to a strategy of no further aneuploidy screening. Strategies were compared to generate an incremental cost‐effectiveness ratio with a threshold of $100 000/quality‐adjusted life year (QALY) and applied to a theoretical cohort.

Results

The cfDNA strategy resulted in 21 fewer DS births and 52 additional QALYs, however, increased costs by $51.3 million. This yielded an incremental cost‐effectiveness ratio of $986 503; therefore, it was not a cost‐effective strategy.

Conclusion

In a low‐risk population with prior reassuring aneuploidy screening, it is not cost effective to offer cfDNA after identification of an isolated EIF.
Spasticity Management in Persons with Disorders of Consciousness
Authors: Zhang Bei , Karri Jay , O'Brien Katherine , DiTommaso Craig , Kothari Sunil , Li Sheng
Published: July 2020

Introduction

Spasticity is one of the most frequent neurological impairments affecting persons with disorders of consciousness (DoC). If left untreated, it can mask signs of consciousness by inhibiting one's ability to interact with the environment. The lack of information about spasticity specific to patients with DoC may result in insufficient or even inappropriate treatment.

Objective

To report spasticity characteristics and management in a large dedicated DoC rehabilitation program.

Design

Retrospective chart review.

Setting

An inpatient rehabilitation hospital.

Participants

Patients admitted to the DoC rehabilitation program from 1 January 2014 to 31 October 2018.

Main Outcome Measurements

Spasticity characteristics; impact of interventions on spasticity as well as other clinical measures.

Results

A total of 146 patients were included, of whom 95.2% were affected by spasticity; 52.7% had spasticity affecting all four limbs. The most commonly affected muscle groups were shoulder internal rotators (72.6%) in the upper extremity and ankle plantar flexors (59.8%) in the lower extremity. The more commonly affected muscle groups were also more spastic (R = 0.993 and 0.989 in the upper and lower extremity, respectively; P < .01). Atypical posture patterns were also commonly observed, making positioning difficult. Chemoneurolytic injections (botulinum toxin and/or phenol) were performed in over 69.9% patients, and 26.7% had intrathecal baclofen (ITB) pump placement. All patients received individualized physical modalities and therapies. With focal managements, systemic spasmolytic medications, including enteral baclofen, were reduced by at least 50.0%, which appeared to be associated with improvements in the level of consciousness.

Conclusions

Almost all DoC patients were affected by spasticity, often to a moderate or severe degree. Extensive use of focal spasticity interventions allowed for weaning of systemic spasmolytic medications, which seemed to result in improvements in the level of consciousness.
Operationalizing patient‐centered cancer care: A systematic review and synthesis of the qualitative literature on cancer patients' needs, values, and preferences
Authors: Mitchell Kerri‐Anne R. , Brassil Kelly J. , Rodriguez Serena A. , Tsai Edward , Fujimoto Kayo , Krause Kate J. , Shay L. Aubree , Springer Andrew E.
Published: July 2020

Objective

Efficiently addressing patient priorities and concerns remains a challenge in oncology. Systematic operationalization of patient‐centered care (PCC) can support improved assessment and practice of PCC in this unique care setting. This review aimed to synthesize the qualitative empirical literature exploring the National Academy of Medicine (NAM)'s PCC constructs of values, needs, and preferences among patients' during their cancer treatment experiences.

Methods

A systematic review of qualitative studies published between 2002 and 2018 addressing adult patient values, needs, and preferences during cancer treatment was conducted. Medline, EMBASE, PsycINFO, and SCOPUS databases were searched on September 10, 2018. Methodological rigor was assessed using a modified version of the Evaluation Tool for Qualitative Studies. Included study findings were analyzed using line‐by‐line coding; and the emergent themes were compared to the National Academy of Medicine (NAM)'s PCC dimensions.

Results

Twenty‐nine primary studies were included in the synthesis. Descriptive themes for values (autonomy, being involved, family, hope, normality, and sincerity), needs (care coordination, information, privacy, support of physical well‐being, emotional support (family/friends, peer, provider), and self‐support), and preferences (care coordination, decision‐making, information delivery, source of social support, and treatment) were identified. “Cancer care context” emerged as an important domain in which these constructs are operationalized. This thematic framework outlines PCC attributes that oncology care stakeholders can evaluate to improve patient experiences.

Conclusions

These findings build on previous PCC research and may contribute to the systematic assessment of patient priorities and the improvement of oncology care quality from the patient perspective.
A systematic review of the clinical and genetic characteristics of Chinese patients with cystic fibrosis
Authors: Shi Ruihe , Wang Xiufang , Lu Xiaojing , Zhu Zhijie , Xu Qingrong , Wang Haoran , Song Li , Zhu Changlian
Published: July 2020

Objectives

To investigate and summarize the clinical and genetic characteristics of Chinese cystic fibrosis (CF) patients to improve clinicians’ understanding and decrease the rates of misdiagnosis and missed diagnoses in China.

Methods

The EMBASE, Cochrane Library, PubMed and SinoMed databases were searched for studies involving Chinese CF patients from January 1975 to August 2019.

Results

In total, 113 Chinese patients, including 53 males and 60 females, were reported. Nineteen patients had a family history of CF. The median age at diagnosis was 8.7 years. Among Chinese CF patients, 70.8% had bronchiectasis, 9.7% had a hemoptysis history, 33.6% had clubbed fingers, 17.7% had allergic bronchopulmonary aspergillosis, and 29.2% had chronic diarrhea; the incidence of malnutrition was 52.2%. Five patients had jaundice, 26 patients had hepatomegaly, and 9 patients had meconium ileus in the neonatal period, and the incidence of liver cirrhosis was 5.3%. The predominant organism in airways was Pseudomonas aeruginosa, followed by Staphylococcus aureus. Seventy‐nine patients underwent the sweat test, and all of them were positive, with an average chloride ion level of 122.2 mmol/L. Eighty‐eight Chinese CF patients underwent genetic testing, and 74 CF transmembrane conductance regulator (CFTR) gene mutations were reported. The most common gene mutation was c.2909G→A. One Phe508del gene mutation was observed.

Conclusion

The common clinical manifestations and CFTR gene mutations in Chinese CF patients are different from those in Caucasian patients. The age at CF diagnosis in China is relatively old, suggesting that the CF incidence in China may be seriously underestimated.
Acute antioxidant and cytoprotective effects of sulforaphane in brain endothelial cells and astrocytes during inflammation and excitotoxicity
Authors: Liu Jianxiong , Chandaka Giri K. , Zhang Rong , Parfenova Helena
Published: July 2020

Sulforaphane (SFN), a bioactive phytochemical isothiocyanate, has a wide spectrum of cytoprotective effects that involve induction of antioxidant genes. Nongenomic antioxidant effects of SFN have not been investigated. Brain oxidative stress during inflammation and excitotoxicity leads to neurovascular injury. We tested the hypothesis that SNF exhibits acute antioxidant effects and prevents neurovascular injury during oxidative stress. In primary cultures of cerebral microvascular endothelial cells (CMVEC) and cortical astrocytes from the newborn pig brain, a pro‐inflammatory cytokine TNF‐α and an excitotoxic glutamate elevate reactive oxygen species (ROS) and cause cell death by apoptosis. Nox4 NADPH oxidase is the main Nox isoform in CMVEC and cortical astrocytes that is acutely activated by TNF‐α and glutamate leading to ROS‐mediated cell death by apoptosis. The Nox4 inhibitor GKT137831 blocked NADPH oxidase activity and overall ROS elevation, and prevented apoptosis of CMVEC and astrocytes exposed to TNF‐α and glutamate, supporting the leading role of Nox4 in the neurovascular injury. Synthetic SFN (10−11‐10−6 mol/L) inhibited NADPH oxidase activity and reduced overall ROS production in CMVEC and astrocytes within 1‐hour exposure to TNF‐α and glutamate. Furthermore, in the presence of SFN, the ability of TNF‐α and glutamate to produce apoptosis in CMVEC and cortical astrocytes was completely prevented. Overall, SFN at low concentrations exhibits antioxidant and antiapoptotic effects in cerebral endothelial cells and cortical astrocytes via a via a nongenomic mechanism that involves inhibition of Nox4 NADPH oxidase activity. SFN may prevent cerebrovascular injury during brain oxidative stress caused by inflammation and glutamate excitotoxicity.
Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID‐19 patients
Authors: Hendry Bruce M. , Stafford Nina , Arnold Ahran D. , Sangwaiya Arvind , Manglam Vijay , Rosen Stuart D. , Arnold Jayantha
Published: July 2020

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID‐19. Pentoxifylline is an immunomodulator with anti‐inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor‐mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS‐CoV‐2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre‐clinical data support pentoxifylline as effective in cytokine‐driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine‐induced lung damage in humans are positive and consistent with anti‐inflammatory efficacy. Pentoxifylline is a readily available, off‐patent and inexpensive drug, suitable for large‐scale use including in resource‐limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID‐19 as a complementary approach to target the host responses.
Antimicrobial activity and secondary structure of a novel peptide derived from ovalbumin
Authors: Tan Ao , Suzuki Rio , Yokoyama Chikako , Yano Shigekazu , Konno Hiroyuki
Published: July 2020

A novel antimicrobial peptide derived from ovalbumin has been discovered. First, the peptide fragment RKIKVYLPRMK (TK9.1) was identified based on computerized predictions of the secondary structure of peptides in a protein data bank. Using HeliQuest, the sequence was developed into RKIKRYLRRMI (TK9.1.3), which was synthesized using Fmoc‐solid phase peptide synthesis, and found to have strongly antimicrobial activity against Gram‐positive and Gram‐negative bacteria, and fungi but not cytotoxic to HeLa cells and hemolysis in mouse red blood cells. Although ovalbumin itself does not have an antibacterial activity, our results suggest that it may supply the organisms that consume it with antimicrobial peptides, in support of their immunodefence.
High‐Resolution On‐Demand Nanostructures
Authors: Schneider Norbert , Kolew Alexander , Schneider Marc , Worgull Matthias , Gspann Thurid , Leuthold Juerg
Published: July 2020

By embedding a film of highly aligned carbon nanotubes (CNTs) into a shape memory polymer (SMP), a fourfold increase in resolution of nanostructures raised on demand with a simple laser pointer is achieved. In the design of nanostructured compounds for micro‐optic and microfluidic lab‐on‐chip and security applications, the SMP's imprinted surface modifications act as the active part, while the CNT film aids their fabrication as an efficient broadband absorber converting light into thermal energy and initializing the polymer's shape memory effect. Due to its extraordinarily high thermal conductivity, the CNT film further acts as a highly efficient heat sink dissipating excess heat before it can blur the boundaries of the raised nanostructures’ region. A low‐cost fabrication method of those CNT–SMP compounds is presented and how the programming and recovery properties enable the production of nanoscale surface modifications with unprecedented simplicity, flexibility, and resolution is shown.
Regional consistency and sample size considerations in a multiregional equivalence trial
Authors: Wu Si‐Cheng , Xu Jin‐Fang , Zhang Xin‐Ji , Li Zhi‐Wei , He Jia
Published: July 2020

The main objective of a confirmatory multiregional clinical trial (MRCT) is to demonstrate the overall efficacy of test drugs in all participating regions as well as to evaluate the possibility of extrapolating the overall results to each region. With the emergence of the demands of biosimilar drugs development, some guidelines recommended using equivalence design to demonstrate the comparability of efficacy between biosimilar and reference drugs. Previous discussions about assessing regional consistency in MRCT are mainly focused on superiority or non‐inferiority designs, while the extensions to equivalence designs were limited. In this work, we proposed a flexible regional consistency criterion for the MRCT with equivalence design. Based on this criterion, sample size determination and sample allocation were also discussed.
Nonfragile fault‐tolerant control of suspension systems subject to input quantization and actuator fault
Authors: Xiong Jun , Chang Xiao‐Heng , Park Ju H. , Li Zhi‐Min
Published: July 2020

This study addresses the quantized nonfragile feedback control problem for active suspension systems with and without actuator faults. By considering the input quantization, a class of dynamic quantizers is adopted. The multiplicative controller gain variation is used to describe the actuator parameter perturbation or uncertainty. Apart from the ride comfort, the road holding ability and the hard constraints on suspension deflection and actuator force are also taken into account, which can be treated as a multi‐objective control problem. The redundancy of input quantization error is used to formulate the quantized closed‐loop system via the descriptor representation approach, then a novel quantized control strategy based on state feedback by separately designing dynamic quantizer and controller is proposed for the closed‐loop system with and without actuator faults. The design strategy is a unified and simple one, then can be easily extended to the case of static output feedback, as only part of the variables measured by sensors are available, which avoids some equality constraints in existing works. Finally, some simulation results are presented to validate the feasibility and effectiveness of the developed control strategies.