bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Perceived Impact of the Chronic Disease Self‐Management Program on Self‐Management Behaviors among African American Women with Lupus: A Qualitative Study
Authors: Twumasi Abena A. , Shao Anna , Dunlop‐Thomas Charmayne , Drenkard Cristina , Cooper Hannah L.
Published: February 2020

Objective

To qualitatively explore the processes through which the Chronic Disease Self‐Management Program (CDSMP)—a peer‐led, group‐based educational intervention for people with chronic conditions—affects self‐management behaviors among African American women with systemic lupus erythematosus (SLE).

Methods

Using a longitudinal pre‐ and postintervention design, we conducted two waves of one‐on‐one, semistructured interviews with 24 purposefully sampled participants. Wave 1 interviews explored self‐management behaviors at baseline; wave 2 interviews focused on changes in these behaviors postintervention. Transcripts were analyzed using thematic analysis methods.

Results

Study participants perceived the CDSMP to be a valuable resource that helped them improve fundamental self‐management behaviors, including exercise, relaxation, diet, and medication adherence. We found, with few exceptions, that in this sample, women's reported changes in self‐management behaviors did not vary by participant age, education, SLE disease severity, or depression status. Our analysis suggests that the CDSMP had the most widespread perceived effects on relaxation and exercise. Strategies that generated improvements in relaxation and exercise included goal setting, action planning, encouragement to pursue low‐impact physical activity, and introduction of mindfulness techniques to better manage SLE symptoms.

Conclusion

Our findings suggest that African American women with SLE perceived the CDSMP as an effective educational self‐management intervention. The program can potentially catalyze improvements in self‐management behaviors in this population, regardless of demographic or disease characteristics.
Adaptive control of unactuated dynamical systems through interconnections: Stability and performance guarantees
Authors: Gruenwald Benjamin C. , Yucelen Tansel , Chakravarthy Animesh
Published: February 2020

This article studies control and performance enforcement for a class of uncertain dynamical systems that consist of actuated and unactuated portions physically interconnected to each other. The proposed approach stabilizes the overall interconnected system in the presence of unknown physical interconnections as well as system uncertainties. Performance guarantees are enforced, individually, on the actuated as well as unactuated portions of the interconnected system via this approach. For enforcing these performance guarantees, a set‐theoretic model reference adaptive control approach is used, in conjunction with linear matrix inequalities, to restrict the respective system error trajectories of the actuated and unactuated dynamics inside a priori, user‐defined compact sets. The efficacy of the proposed approach is demonstrated using simulations.
Enhancement of Subcutaneously Transplanted β Cell Survival Using 3D Stem Cell Spheroids with Proangiogenic and Prosurvival Potential
Authors: Yu Chih‐Ping , Juang Jyuhn‐Huarng , Lin Yu‐Jie , Kuo Ching‐Wen , Hsieh Li‐Hung , Huang Chieh‐Cheng
Published: February 2020

Islet transplantation has been demonstrated to be a promising therapy for type 1 diabetes mellitus. Although it is a minimally invasive operating procedure and provides easy access for graft monitoring, subcutaneous transplantation of the islet only has limited therapeutic outcomes, owing to the poor capacity of skin tissue to foster revascularization in a short period. Herein, 3D cell spheroids of clinically accessible umbilical cord blood mesenchymal stem cells and human umbilical vein endothelial cells are formed and employed for codelivery with β cells subcutaneously. The 3D stem cell spheroids, which can secrete multiple proangiogenic and prosurvival growth factors, induce robust angiogenesis and prevent β cell graft death, as indicated by the results of in vivo bioluminescent tracking and histological analysis. These experimental data highlight the efficacy of the 3D stem cell spheroids that are fabricated using translationally applicable cell types in promoting the survival and function of subcutaneously transplanted β cells.
Stretchable Skin‐Like Cooling/Heating Device for Reconstruction of Artificial Thermal Sensation in Virtual Reality
Authors: Lee Jinwoo , Sul Heayoun , Lee Wonha , Pyun Kyung Rok , Ha Inho , Kim Dongkwan , Park Hyojoon , Eom Hyeonjin , Yoon Yeosang , Jung Jinwook , Lee Dongjun , Ko Seung Hwan
Published: February 2020

Along with visual and tactile sensations, thermal sensation by temperature feeling on the skin can provide rich physical information on the environment and objects. With a simple touch of objects, relative temperature can be sensed and even objects can be differentiated with different thermal properties without any visual cue. Thus, artificially reproducing accurate/controllable thermal sensation haptic signals on human epidermis will certainly be a major research area to reconstruct a more realistic virtual reality (VR) environment. In this study, for the first time, a skin‐like, highly soft and stretchable and bi‐functional (both cold and hot sensation) thermo‐haptic device is reported for wearable VR applications with a single device structure (not separate heater and cooler). The skin‐like thermo‐haptic (STH) device can actively cool down and heat up deformable skin surfaces with instantaneous and accurate adjustment of temperature based upon a feedback control algorithm to mimic desirable thermal sensation with 230% stretchability. As a proof‐of‐concept, the STH device is integrated with a finger‐motion tracking glove to provide artificial thermal sensation information to the skin in various situations such as touching cold beer bottles and hot coffee cups in virtual space. This new type of STH device can offer potential implications for next‐generation haptic devices to provide unique thermal information for a more realistic virtual‐world field and medical thermal treatment.
Engineering of the Heterointerface of Porous Carbon Nanofiber–Supported Nickel and Manganese Oxide Nanoparticle for Highly Efficient Bifunctional Oxygen Catalysis
Authors: Ji Dongxiao , Sun Jianguo , Tian Lidong , Chinnappan Amutha , Zhang Tianran , Jayathilaka Wanasinghe Arachchige Dumith Madushanka , Gosh Rituparana , Baskar Chinnappan , Zhang Qiuyu , Ramakrishna Seeram
Published: February 2020

Constructing heterointerfaces between metals and metal compounds is an attractive strategy for the fabrication of high performance electrocatalysts. However, realizing the high degree of fusion of two different metal components to form heterointerfaces remains a great challenge, since the different metal components tend to grow separately in most cases. Herein, by employing carboxyl‐modified carbon nanotubes to stabilize different metal ions, the engineering of abundant Ni|MnO heterointerfaces is achieved in porous carbon nanofibers (Ni|MnO/CNF) during the electrospinning–calcination process. Remarkably, the resulting Ni|MnO/CNF catalyst exhibits activities that are among the best reported for the catalysis of both the oxygen reduction and oxygen evolution reactions. Moreover, the catalyst also demonstrates high power density and long cycle life in Zn–air batteries. Its superior electrochemical properties are mainly ascribed to the synergy between the engineering of oxygen‐deficient Ni|MnO heterointerfaces with a strong Ni/Mn alloying interaction and the 1D porous CNF support. This facile anchoring strategy for the initiation of bimetallic heterointerfaces creates appealing opportunities for the potential use of heteronanomaterials in practical sustainable energy applications.
Signatures of Sixfold Degenerate Exotic Fermions in a Superconducting Metal PdSb2
Authors: Kumar Nitesh , Yao Mengyu , Nayak Jayita , Vergniory Maia G. , Bannies Jörn , Wang Zhijun , Schröter Niels B. M. , Strocov Vladimir N. , Müchler Lukas , Shi Wujun , Rienks Emile D. L. , Mañes J. L. , Shekhar Chandra , Parkin Stuart S. P. , Fink Jörg , Fecher Gerhard H. , Sun Yan , Bernevig B. Andrei , Felser Claudia
Published: February 2020

Multifold degenerate points in the electronic structure of metals lead to exotic behaviors. These range from twofold and fourfold degenerate Weyl and Dirac points, respectively, to sixfold and eightfold degenerate points that are predicted to give rise, under modest magnetic fields or strain, to topological semimetallic behaviors. The present study shows that the nonsymmorphic compound PdSb2 hosts six‐component fermions or sextuplets. Using angle‐resolved photoemission spectroscopy, crossing points formed by three twofold degenerate parabolic bands are directly observed at the corner of the Brillouin zone. The group theory analysis proves that under weak spin–orbit interaction, a band inversion occurs.
Cylindrical Direct‐Current Triboelectric Nanogenerator with Constant Output Current
Authors: Wang Jianlong , Li Yikang , Xie Zhijie , Xu Yuhong , Zhou Jianwen , Cheng Tinghai , Zhao Hongwei , Wang Zhong Lin
Published: February 2020

In this article, a cylindrical direct‐current triboelectric nanogenerator (DC‐TENG) that can generate an almost constant current output with a low crest factor by phase coupling is reported for the first time. Here, the influence of phases (P) and groups (G) on the DC‐TENG is investigated. Experiments show that the crest factor of current, significantly decreases as the phases increase, and the output performance significantly increases as the groups increase. One phase triboelectric power‐generating unit of the DC‐TENG with three‐phase and five‐group (3P5G) produces an open‐circuit voltage of 149.5 V, short‐circuit current 7.3 μA, and transferred charge of 56.7 nC at 600 rpm. The DC‐TENG can produce a coupling current of 21.6 μA and the average output power of 2.04 mW after each phase output is rectified and superimposed. Additionally, the crest factor of output current is reduced to 1.08, and the high‐performance characteristics of an almost constant direct‐current is achieved. The research is of considerable significance to the practical applications of TENGs in powering sensors of low consumption.
Study of reinforcement mechanism and structural elucidation of expanded graphite‐carbon black hybrid filler‐SBR nanocomposites through comprehensive analysis of mechanical properties and small angle X‐ray data
Authors: Roy Amrita , Mondal Titash , Kar Saptarshi , Naskar Kinsuk , Ghosal Ranjan , Mukhopadhyay Rabindra , Bhowmick Anil K.
Published: February 2020

Use of hybrid fillers as a reinforcing agent for polymers is found to be critical step toward developing a high‐performance composite material. However, limited know‐how on the nature of interaction of the hybrid fillers with the polymer chains resulted in a major impediment toward large‐scale transmissibility of such a technology. Herein, we report about a strategy, wherein the polymer composite (free of curatives), comprising of hybrid filler and its gel was leveraged to effectively understand the physics involved toward reinforcement. Styrene‐butadiene random copolymer as the matrix, and combination of expanded graphite and carbon black (N220) as the model hybrid filler were selected. The hybrid filler containing composite (SG22) demonstrated significant improvement in terms of the physico‐mechanical properties such as tensile strength, modulus and so forth compared to the neat carbon black‐filled system (S22). Stress‐relaxation studies indicated that SG22 registered minimal decay in the force with time compared to S22. SG22 demonstrated a gel fraction of 68 ± 1% while 56 ± 1% was noted for S22. Further, rheometric studies like strain sweep, frequency sweep, complex viscosity of the gel fragments indicated the formation of fractal network of the hybrid fillers inside the polymer matrix. Small angle X‐ray studies corroborated the crucial role played by the expanded graphite sheets in determining the microstructure of the composite owing to their lubrication effect and segregation of carbon black agglomerates by cutting through their sharp edges resulting in a well‐distributed filler network.
Geophysical survey of the Iberian site (seventh–third centuries bc) of Masies de Sant Miquel (Catalonia, Spain). Interpretative challenges of geophysical data of an Iberian town
Authors: Sala Roger , Ortiz Helena , Sanmartí Joan , Garcia‐Garcia Ekhine , Belarte Maria Carme , Noguera Jaume , Morer Jordi , Ble Eduard , Pou Josep , Asensio David , Jornet Rafael
Published: February 2020

Geophysical surveys based on ground‐penetrating radar (GPR) and magnetic methods have recently been carried out at the Iberian site of Masies de Sant Miquel, which is dated to the Iron Age (seventh–third centuries bc). The design and execution of the survey are presented, as well as the interpretation process, which is based on the interaction between the members of the prospection team (SOT Prospection) and the archaeologists from the University of Barcelona (UB) and the Catalan Institute of Classical Archaeology (ICAC), integrating geophysical as well as archaeological data. Although the site had previously been studied during the 1980s and 1990s, excavations have been limited in scope and the settlement remained largely unknown. The new research discussed in this article makes it possible to deduce the general traits of the urban plan and the major architectural features. The results confirm the urban nature of the site, not only due to its size (several densely‐occupied hectares), but also the complexity of its architecture and urban planning.
Nonrapid eye movement sleep and risk for autism spectrum disorder in early development: A topographical electroencephalogram pilot study
Authors: Page Jessica , Lustenberger Caroline , Frӧhlich Flavio
Published: February 2020

Objective

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that emerges in the beginning years of life (12–48 months). Yet, an early diagnosis of ASD is challenging as it relies on the consistent presence of behavioral symptomatology, and thus, many children are diagnosed later in development, which prevents early interventions that could benefit cognitive and social outcomes. As a result, there is growing interest in detecting early brain markers of ASD, such as in the electroencephalogram (EEG) to elucidate divergence in early development. Here, we examine the EEG of nonrapid eye movement (NREM) sleep in the transition from infancy to toddlerhood, a period of rapid development and pronounced changes in early brain function. NREM features exhibit clear developmental trajectories, are related to social and cognitive development, and may be altered in neurodevelopmental disorders. Yet, spectral features of NREM sleep are poorly understood in infants/toddlers with or at high risk for ASD.

Methods

The present pilot study is the first to examine NREM sleep in 13‐ to 30‐month‐olds with ASD in comparison with age‐matched healthy controls (TD). EEG was recorded during a daytime nap with high‐density array EEG.

Results

We found topographically distinct decreased fast theta oscillations (5–7.25 Hz), decreased fast sigma (15–16 Hz), and increased beta oscillations (20–25 Hz) in ASD compared to TD.

Conclusion

These findings suggest a possible functional role of NREM sleep during this important developmental period and provide support for NREM sleep to be a potential early marker for ASD.
Know how to properly address situations involving potential ESA, service animal fraud
Authors: Masinter Michael R.
Published: February 2020

Occasionally, students deliberately misrepresent their pets as emotional support animals, service dogs, or both. The internet is rife with scam sites that offer ESA letters for a fee, and some students have purchased letters from those sites. Adding to the problem, students living in residence halls with already approved ESA dogs sometimes claim they have trained their dog to be a psychiatric service dog, allowing them to take it to classes and meals. These students may simply show up with their dog in classrooms or campus food services with rehearsed but fraudulent answers to the two approved Department of Justice questions.
Fine fescues: A review of the species, their improvement, production, establishment, and management
Authors: Braun Ross C. , Patton Aaron J. , Watkins Eric , Koch Paul L. , Anderson Nicole P. , Bonos Stacy A. , Brilman Leah A.
Published: February 2020

Fine fescues (FestucaL. spp.) comprise a group of five cool‐season grasses used in turfgrass systems under many conditions: strong creeping red fescue (F.rubraL. ssp.rubraGaudin), slender creeping red fescue [F.rubraL. ssp.littoralis(G. Mey.) Auquier], Chewings fescue [F.rubraL. ssp.commutataGaudin; syn.F.rubraL. ssp.fallax(Thuill.) Nyman], hard fescue (F.brevipilaTracey), and sheep fescue [F.ovinaL.; syn.F.ovinaL. ssp.hirtula(Hack.exTravis) M.J. Wilk.]. Their extensive geographic distribution is a result of adaptation to many different environmental and management conditions especially low‐input sites. This review summarizes the history, production, establishment, management, use, and availability of fine fescues; discusses strengths and shortcomings of fine fescue; identifies knowledge gaps; and provides an outlook toward further research on this group of grasses. Improved cultivars have been developed in recent years that expand the geographic distribution and uses of species but additional efforts to increase seed yield and improve abiotic and biotic stress tolerances are still needed. Expanded use of fine fescue could be achieved through increased sod production of fine fescue, though current research‐based information is limited. Research on fine fescue allelopathy and the contributions of fungal endophytes, both of which could lead to reduced pesticide requirements is important for improved pest management. Future research on fine fescues should focus on implementation and management of new cultivars that possess enhanced abiotic and biotic stress tolerance that will result in fewer inputs and improve the appeal and adoption of these low‐input grasses.
The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown
Authors: Holley Caroline L , Schroder Kate
Published: February 2020

The nod‐like receptor protein 3 (NLRP3) inflammasome drives inflammation in response to mitochondrial dysfunction. As metabolic powerhouses with prokaryotic ancestry, mitochondria are a cache for danger‐associated molecular patterns and pathogen‐associated molecular pattern‐like molecules that elicit potent innate immune responses. Persistent mitochondrial damage caused by infection, or genetic or environmental factors, can lead to inappropriate or sustained inflammasome signalling. Here, we review the features of mitochondria that drive inflammatory signalling, with a particular focus on mitochondrial activation of the NLRP3 inflammasome. Given that mitochondrial network dynamics, metabolic activity and redox state are all intricately linked to each other and to NLRP3 inflammasome activity, we highlight the importance of a holistic approach to investigations of NLRP3 activation by dysfunctional mitochondria.
Cell Image Classification: A Comparative Overview
Authors: Shifat‐E‐Rabbi Mohammad , Yin Xuwang , Fitzgerald Cailey E. , Rohde Gustavo K.
Published: February 2020

Cell image classification methods are currently being used in numerous applications in cell biology and medicine. Applications include understanding the effects of genes and drugs in screening experiments, understanding the role and subcellular localization of different proteins, as well as diagnosis and prognosis of cancer from images acquired using cytological and histological techniques. The article also reviews three main approaches for cell image classification most often used: numerical feature extraction, end‐to‐end classification with neural networks (NNs), and transport‐based morphometry (TBM). In addition, we provide comparisons on four different cell imaging datasets to highlight the relative strength of each method. The results computed using four publicly available datasets show that numerical features tend to carry the best discriminative information for most of the classification tasks. Results also show that NN‐based methods produce state‐of‐the‐art results in the dataset that contains a relatively large number of training samples. Data augmentation or the choice of a more recently reported architecture does not necessarily improve the classification performance of NNs in the datasets with limited number of training samples. If understanding and visualization are desired aspects, TBM methods can offer the ability to invert classification functions, and thus can aid in the interpretation of results. These and other comparison outcomes are discussed with the aim of clarifying the advantages and disadvantages of each method. © 2020 International Society for Advancement of Cytometry
Quality of service‐aware approaches in fog computing
Authors: Haghi Kashani Mostafa , Rahmani Amir Masoud , Jafari Navimipour Nima
Published: February 2020

In recent years, fog computing, a novel paradigm, has emerged for location and latency‐sensitive applications. It is a powerful complement for cloud computing that enables provisioning services and resources outside the cloud near the end devices. In a fog system, the existence of several nonhomogenous devices, which are potentially mobile, led to quality of service (QoS) worries. QoS‐aware approaches are presented in various parts of the fog system, and several different QoS factors are taken into account. In spite of the importance of QoS in fog computing, no comprehensive study on QoS‐aware approaches exists in fog computing. Hence, this paper reviews the current research used to guarantee QoS in fog computing. This paper investigates the QoS‐ensuring techniques that fall into three categories: service/resource management, communication management, and application management (published between 2013 and October 2018). Regarding the selected approaches, this paper represents merits, demerits, tools, evaluation types, and QoS factors. Finally, on the basis of the reviewed studies, we suggest some open issues and challenges which are worth further studying and researching in QoS‐aware approaches in fog computing.
Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium–glucose cotransporter 2 inhibitors
Authors: Packer Milton
Published: February 2020

In five large‐scale trials involving >40 000 patients, sodium–glucose cotransporter 2 (SGLT2) inhibitors decreased the risk of serious heart failure events by 25–40%. This effect cannot be explained by control of hyperglycaemia, since it is not observed with antidiabetic drugs with greater glucose‐lowering effects. It cannot be attributed to ketogenesis, since it is not causally linked to ketone body production, and the benefit is not enhanced in patients with diabetes. The effect cannot be ascribed to a natriuretic action, since SGLT2 inhibitors decrease natriuretic peptides only modestly, and they reduce cardiovascular death, a benefit that diuretics do not possess. Although SGLT2 inhibitors increase red blood cell mass, enhanced erythropoiesis does not favourably influence the course of heart failure. By contrast, experimental studies suggest that SGLT2 inhibitors may reduce intracellular sodium, thereby preventing oxidative stress and cardiomyocyte death. Additionally, SGLT2 inhibitors induce a transcriptional paradigm that mimics nutrient and oxygen deprivation, which includes activation of adenosine monophosphate‐activated protein kinase, sirtuin‐1, and/or hypoxia‐inducible factors‐1α/2α. The interplay of these mediators stimulates autophagy, a lysosomally‐mediated degradative pathway that maintains cellular homeostasis. Autophagy‐mediated clearance of damaged organelles reduces inflammasome activation, thus mitigating cardiomyocyte dysfunction and coronary microvascular injury. Interestingly, the action of hypoxia‐inducible factors‐1α/2α to both stimulate erythropoietin and induce autophagy may explain why erythrocytosis is strongly correlated with the reduction in heart failure events. Therefore, the benefits of SGLT2 inhibitors on heart failure may be mediated by a direct cardioprotective action related to modulation of pathways responsible for cardiomyocyte homeostasis.
Inexpensive, Underwater Filming of Rare Fishes in High Definition
Authors: Ulrich Taylor L , Bonar Scott A
Published: February 2020

Generating public interest in fish and their biology is often challenging. Many aquatic species are cryptic and largely invisible to the public. Therefore, increasing public awareness of cryptic fishes and elevating their visibility to broad audiences requires innovation. Inexpensive technological advancements now provide fisheries biologists, managers, and researchers with means never before possible for documenting fish in their natural habitat via underwater videography. We investigated cost efficient and simple methods for capturing and creating high quality, high definition, and informative underwater videos that could be used by people with little or no previous experience in videography. We tested 1) a variety of filming equipment including cameras and camera recording settings, lenses, batteries, and memory cards; 2) active and passive camera deployment techniques; and 3) a variety of free and paid postproduction software and compared them for ease of use, expense, and quality of output. Highest quality footage, i.e., highest resolution, clearest, and most stable, was obtained using a GoPro action camera deployed underwater in a stationary position mounted to a metal base plate using a combination of stock and macro lenses, and filming in 4K resolution at 30 frames per second. Final production videos were created using Adobe Premiere Pro.
Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes
Authors: Weaver Michael J. , McHenry Scott A. , Sayuk Gregory S. , Gyawali C. Prakash , Davidson Nicholas O.
Published: February 2020

Irritable bowel syndrome with diarrhea (IBS‐D) and NAFLD are both common conditions that may be influenced by shared pathways of altered bile acid (BA) signaling and homeostatic regulation. Pathophysiological links between IBS‐D and altered BA metabolism include altered signaling through the ileal enterokine and fibroblast growth factor 19 (FGF19) as well as increased circulating levels of 7α‐hydroxy‐4‐cholesten‐3‐one, a metabolic intermediate that denotes increased hepatic BA production from cholesterol. Defective production or release of FGF19 is associated with increased BA production and BA diarrhea in some IBS‐D patients. FGF19 functions as a negative regulator of hepatic cholesterol 7α‐hydroxylase; therefore, reduced serum FGF19 effectively de‐represses hepatic BA production in a subset of IBS‐D patients, causing BA diarrhea. In addition, FGF19 modulates hepatic metabolic homeostatic response signaling by means of the fibroblast growth factor receptor 4/klotho beta receptor to activate cascades involved in hepatic lipogenesis, fatty acid oxidation, and insulin sensitivity. Emerging evidence of low circulating FGF19 levels in subsets of patients with pediatric and adult NAFLD demonstrates altered enterohepatic BA homeostasis in NAFLD. Conclusion: Here we outline how understanding of shared pathways of aberrant BA homeostatic signaling may guide targeted therapies in some patients with IBS‐D and subsets of patients with NAFLD.
End of an era for erythropoiesis‐stimulating agents in oncology
Authors: Schoen Martin W. , Hoque Shamia , Witherspoon Bartlett J. , Schooley Benjamin , Sartor Oliver , Yang Y. Tony , Yarnold Paul R. , Knopf Kevin B. , Hrushesky William J.M. , Dickson Michael , Chen Brian J. , Nabhan Chadi , Bennett Charles L.
Published: February 2020

Erythropoiesis‐stimulating agents (ESAs) are available to treat chemotherapy‐induced anemia (CIA). In 2007–2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA‐treated CIA (3.2%). Darbepoetin use increased 3.9‐fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8‐fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8‐fold for darbepoetin‐treated CIA (262 in 2003 to 467 μg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002–2007, then increased 2.2‐fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety.
Maternal and perinatal outcomes related to superimposed pre‐eclampsia in a Brazilian cohort of women with chronic hypertension
Authors: Casagrande Laura , Rezende Gabriela P. , Guida José P. , Costa Raquel S. , Parpinelli Mary A. , Surita Fernanda G. , Costa Maria L.
Published: February 2020

Objective

To describe maternal and perinatal outcomes for women with chronic hypertension, comparing those with superimposed pre‐eclampsia (SPE) with those without pre‐eclampsia (NPE).

Methods

In a retrospective cohort study in a tertiary hospital in Brazil, the records of women with chronic hypertension were reviewed between January 1, 2012, and May 31, 2017, in order to compare maternal and perinatal outcomes among those with and without SPE. Poisson regression was performed to investigate factors independently associated with severe pre‐eclampsia.

Results

Of 385 women with chronic hypertension included in the study, 167 were in the SPE group and 218 in the NPE group. The majority were white, overweight (body mass index ≥30 kg/m2), with mean age around 31 years. Adverse neonatal outcomes were significantly more prevalent among women with SPE, including small for gestational age (SPE 17.46% vs NPE 9.63%, P=0.01), low birth weight (SPE 2577 g ± 938 vs NPE 3128 g ± 723, P=0.003), neonatal intensive care unit admission (SPE 44.91% vs NPE 18.34%, P=0.08), and incidence of cesarean delivery (SPE 79.64% vs NPE 62.38%, P=0.003). Fetal growth restriction (PR [prevalence ratio] 2.62, 95% confidence interval [CI] 1.39–4.94) and previous pre‐eclampsia (PR 1.96, 95% CI 1.17–3.28) were associated with severe pre‐eclampsia.

Conclusion

SPE is associated with prematurity and higher rates of admission to neonatal intensive care unit. Fetal growth restriction and previous pre‐eclampsia are factors associated with severe complications of pre‐eclampsia.
Di‐phase midway convolution and deconvolution network for brain tumor segmentation in MRI images
Authors: Chithra P. L. , Dheepa G.
Published: February 2020

A novel automatic image segmentation technique in magnetic resonance imaging (MRI) based on di‐phase midway convolution and deconvolution network is proposed. It consists of three convolutional and deconvolutional blocks for downsampling and upsampling layers respectively. In first block, each input slice is separately convolved using two paths with 3 × 3 and 7 × 7 kernels to produce different feature maps. Then the mean value of these feature maps is processed into upcoming blocks in downsampling and upsampling layers. This processed outcome is classified and segmented using softmax classification. Further, the volume, probability density distribution of tumor, and normal tissue regions are calculated using tissue‐type mapping technique. This method is extensively tested with BRATS 2012, BRATS 2013, and BRATS 2018 data sets. Our experimental results achieved higher dice similarity coefficient values of 24.3%, 27.5%, and 3.4%, respectively, for these three data sets when compared to the state‐of‐art brain tumor segmentation methods.
Circulating miRNAs as diagnostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance
Authors: Li Jia , Zhang Man , Wang Chengbin
Published: February 2020

Background

Multiple myeloma (MM) is still an incurable hematological malignancy evolved from asymptomatic monoclonal gammopathy of undetermined significance (MGUS). New evidence suggests that circulating microRNAs (miRNAs) can serve as stable diagnostic biomarkers for MM and MUGS.

Methods

Serum miRNAs in MM patients, MUGS patients, and healthy controls (HC) were performed by Agilent Bioanalyzer 2100. MicroRNAs in MM detected as promising biomarkers were validated by using quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) curve and multivariate logistic analysis were used to evaluate the diagnostic value of miRNAs for MM and MUGS.

Results

In microarray analysis, the top ten differential expressed miRNAs in MM included miR‐134‐5p, miR‐107, miR‐15a‐5p, miR‐5159‐3p, miR‐1914‐3p, miR‐4723‐3p, miR‐5588‐3p, miR‐6893‐3p, miR‐7106‐3p, and miR‐6722‐5p. Three up‐regulated miRNAs (miR‐134‐5p, miR‐107, and miR‐15a‐5p) were further validated. The elevated expression levels of miR‐134‐5p, miR‐107, and miR‐15a‐5p in qRT‐PCR were increased consistent with microarray analysis. These miRNAs distinguished MM and MUGS from HC significantly. Multivariate logistic analysis showed combination miR‐107, miR‐15a‐5p with Hb, the AUC was 0.954 (95% CI: 0.890‐1.000), sensitivity of 91.3%, and specificity of 93.7% for distinguishing MM from MUGS.

Conclusions

These data demonstrate that miR‐134‐5p, miR‐107, and miR‐15a‐5p are potential diagnostic biomarkers in MM and MUGS. Moreover, the combination miR‐107 and miR‐15a‐5p with Hb can distinguish MM from MUGS.
lncRNA HOXB‐AS3 exacerbates proliferation, migration, and invasion of lung cancer via activating the PI3K‐AKT pathway
Authors: Jiang Wenyang , Kai Jindan , Li Donghang , Wei Zhongheng , Wang Ying , Wang Wei
Published: February 2020

Lung cancer remains the leading cause of cancer‐related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB‐AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB‐AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB‐AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB‐AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB‐AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB‐AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB‐AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.
Early onset epileptic encephalopathy caused by novel compound heterozygous mutation of WWOX gene
Authors: Su Tangfeng , Yan Yu , Xu Shuang , Zhang Ke , Xu Sanqing
Published: February 2020

The human WW domain containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene. However, recent reports have demonstrated its dominant role in autosomal recessive disorders of the central nervous system, especially in early onset epileptic encephalopathy. Here, we report a Chinese case with novel compound heterozygous mutation of WWOX gene (c.229_230+2del mutation originated from her mother and c.1065dup (p.Ala356Serfs*173) variation from her father), and compare them to previously reported 59 WWOX‐related epileptic encephalopathy (WOREE). Early onset and frequent epileptic seizures in the postnatal period, hypsarrhythmia patterns in EEG background and retarded development are the most important characteristics of WOREE in infants. Although the seizures in our case can be controlled by phenobarbital and topiramate, the prognosis of WOREE is poor.
Regulation of the hypothalamic GnRH–GnIH system by putrescine in adult female rats and GT1‐7 neuronal cell line
Authors: Fernandes Joseph R. D. , Moitra Abhishek , Tsutsui Kazuyoshi , Banerjee Arnab
Published: February 2020

The gonadotropin‐releasing hormone—gonadotropin inhibitor (GnRH–GnIH) system in the hypothalamus of mammals is the key factor that controls the entire reproductive system. The aim of this study was to immunolocalize GnIH (RFRP‐3) in the hypothalamus during the estrous cycle and to study the effect of putrescine on the expression of GnRH‐I and GnIH through both in vivo and in vitro (GT1‐7 cells) approach and the circulatory levels of GnRH‐I, GnIH, and gonadotropins were also investigated. The study also aims in analyzing all the immunofluorescence images by measuring the relative pixel count of an image. This study showed the effect of putrescine on the morphology of ovary, uterus, and the expression of the steroidogenic acute regulatory protein in the ovary. This study showed GnIH expression was intense during the diestrus and moderate during proestrus and estrus, whereas mild staining during the metestrus. The study further showed that putrescine supplementation to adult female rats increased both GnRH‐I expression in the hypothalamus as well as the GnRH‐I levels in circulation. The study, for the first time, also showed that putrescine supplementation decreased the expression and release of GnIH. These effects of upregulating GnRH‐I expression and downregulating GnIH expression were confirmed by in vitro experiments using GT1‐7 cells. Putrescine supplementation also increased the gonadotropin levels in the serum. To summarize, putrescine can regulate the hypothalamic–pituitary–gonadal axis by increasing the GnRH‐I, luteinizing hormone, and follicle‐stimulating hormone levels and suppressing GnIH levels. This is the first report showing the simultaneous effects of putrescine on the regulation of both GnRH‐I and GnIH in the hypothalamus.
Hepatocellular carcinoma in an adult patient with congenital absence of the portal vein type II: A case report
Authors: Bessho Hiroki , Tanaka Satoshi , Ishihara Akio , Kato Shinya , Toshiyama Reishi , Hama Naoki , Mori Kiyoshi , Mano Masayuki , Miyamoto Atsushi , Ishida Hisashi , Hirao Motohiro , Mita Eiji
Published: February 2020

Congenital absence of the portal vein (CAPV) is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. CAPV is classified into two types based on the absence (type I) or presence (type II) of portal venous flow into the hepatic parenchyma and is associated with multiple other anomalies such as usually benign hepatic tumors. There have been only two case reports describing hepatocellular carcinoma (HCC) in patients with CAPV type II to date. We report the third such patient. A 50‐year‐old woman was referred to our hospital for management of a giant hepatic tumor. Contrast‐enhanced computed tomography (CECT) indicated a huge mass occupying the right lobe of the liver; the radiological diagnosis was HCC. CECT also demonstrated that the superior mesenteric vein (SMV) and the splenic vein (SpV) joined to form a shunt draining into the left renal vein and that a hypoplastic portal vein branched from the confluence of the SMV and SpV and drained into the liver, indicating that the CAPV was type II. Liver resection was successfully performed to treat the HCC, and the pathological diagnosis was well‐differentiated HCC. Seven months after the operation, a recurrent small HCC was detected and treated with radiofrequency ablation without complications. The patient has been carefully followed for 6 months to date without any evidence of further recurrence. Patients with CAPV are predisposed to developing HCC and require close surveillance.
The role of SLITRK6 in the pathogenesis of Tourette syndrome: From the conclusion of a family‐based study in the Chinese Han population
Authors: Liu Wenmiao , Zhang Xuzhan , Deng Ziwen , Li Guixia , Zhang Ru , Yang Zongjun , Che Fengyuan , Liu Shiguo , Li Hui
Published: February 2020

Background

Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family‐based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population.

Methods

We genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype‐based haplotype relative risk (HHRR) methods.

Results

The TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association.

Conclusions

Despite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations.
Fast Imaging for Hyperpolarized MR Metabolic Imaging
Authors: Gordon Jeremy W. , Chen Hsin‐Yu , Dwork Nicholas , Tang Shuyu , Larson Peder E. Z.
Published: February 2020

MRI with hyperpolarized carbon‐13 agents has created a new type of noninvasive, in vivo metabolic imaging that can be applied in cell, animal, and human studies. The use of 13C‐labeled agents, primarily [1‐13C]pyruvate, enables monitoring of key metabolic pathways with the ability to image substrate and products based on their chemical shift. Over 10 sites worldwide are now performing human studies with this new approach for studies of cancer, heart disease, liver disease, and kidney disease. Hyperpolarized metabolic imaging studies must be performed within several minutes following creation of the hyperpolarized agent due to irreversible decay of the net magnetization back to equilibrium, so fast imaging methods are critical. The imaging methods must include multiple metabolites, separated based on their chemical shift, which are also undergoing rapid metabolic conversion (via label exchange), further exacerbating the challenges of fast imaging. This review describes the state‐of‐the‐art in fast imaging methods for hyperpolarized metabolic imaging. This includes the approach and tradeoffs between three major categories of fast imaging methods—fast spectroscopic imaging, model‐based strategies, and metabolite specific imaging—as well additional options of parallel imaging, compressed sensing, tailored RF flip angles, refocused imaging methods, and calibration methods that can improve the scan coverage, speed, signal‐to‐noise ratio (SNR), resolution, and/or robustness of these studies. To date, these approaches have produced extremely promising initial human imaging results. Improvements to fast hyperpolarized metabolic imaging methods will provide better coverage, SNR, resolution, and reproducibility for future human imaging studies.

Level of Evidence

5

Technical Efficacy Stage

1
A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats
Authors: He Yang , Wang Yimin , Liu Shu , Pi Zifeng , Liu Zhiqiang , Xing Junpeng , Zhou Hui
Published: February 2020

As a well‐known traditional Chinese medicine formula, Ding‐Zhi‐Xiao‐Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding‐Zhi‐Xiao‐Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding‐Zhi‐Xiao‐Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25‐35 was injected into the bilateral hippocampus of Sprague–Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding‐Zhi‐Xiao‐Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding‐Zhi‐Xiao‐Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding‐Zhi‐Xiao‐Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.