bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Okadaic acid promotes epithelial‐mesenchymal transition of hepatocellular carcinoma cells by inhibiting protein phosphatase 2A
Authors: Kong Juan , Li Di , Zhang Shidong , Zhang Huixia , Fu Yuanyuan , Qian Bo , Bei Chunhua , Tan Shengkui , Zhu Xiaonian
Published: January 2020

As a specific inhibitor of serine/threonine protein phosphatases, okadaic acid (OA) has been found to be a tumor promoter. However, whether OA plays a role in metastasis of hepatocellular carcinoma (HCC) has not been well elucidated. In this study, Hep3B and HepG2 cells were treated with different doses of OA and the cell viability was determined by CCK8 test. As a result, Hep3B and HepG2 cells showed no obvious cytotoxicity after OA treatment below 20 or 25 nM for 12 or 24 hours. However, wound healing, invasion, and migration abilities of HCC cells were significantly enhanced in the OA‐treated groups than those of the control group (P < .05), measured by cell scratching and BD transwell assays. Moreover, we found that the expression of epithelial‐mesenchymal transition (EMT)‐related key factors was changed upon OA treatment in a dose‐dependent manner. In addition, the activity of protein phosphatase 2A (PP2A) in OA‐treated cells was also decreased significantly compared with the control cells (P < .05). Interfering of PP2A subunit A or C caused a similar expression change of EMT‐related key factors as the OA treatment in HCC cells. Our results suggest that OA promotes the EMT process of HCC cells by inhibiting the activity of PP2A.
Adrenal diffuse large B‐cell lymphoma with high PD‐L1 expression: Two case reports and literature review
Authors: Chen Yu , He He Sheng , Hu Qing Feng , Wang Gang
Published: January 2020

Background

Primary adrenal lymphoma (PAL) is an infrequent malignant disease and there is no consensus classification or specialized treatment for it. However, PAL has been observed to have worse prognosis compared with other extrarenal malignant lymphomas and diffuse large B‐cell lymphoma presents as the most common subtype of PAL.

Methods

The current study reported two cases of adrenal diffuse large B‐cell lymphoma with high PD‐L1 expression and discussed the clinical significance of PD‐L1 through literature review.

Key Results

The PD‐L1 expression rate of the two cases was 90% and 80%, respectively, which was significantly higher than those reported in the literature.

Conclusion

PAL is a type of non‐Hodgkin's lymphoma with low incidence and poor prognosis, and it is necessary to further explore the early use of immunological checkpoint inhibitors for patients with higher expression of PD‐L1 and with rituximab‐resistance.
Whale tear glands in the bowhead and the beluga whales: Source and function
Authors: Rehorek Susan J. , Stimmelmayr Rapahela , George John C. , Suydam Robert , McBurney Denise M. , Thewissen JGM
Published: January 2020

Orbital glands are found in many tetrapod vertebrates, and are usually separate structures, consisting of individual glands lying in the eyelids and both canthi of the orbit. In cetaceans, however, the orbital glandular units are less distinct and have been described by numerous authors as a single, periorbital mass. There are few histochemical and immunhistochemical studies to date of these structures. In this study, we examined the orbital glandular region of both the bowhead whale (Balaena mysticetus: Mysticeti) and the beluga whale (Delphinapterus leucas: Odontoceti) using histological, histochemical, and immunohistochemical techniques. Histologically, in the bowhead, three glandular areas were noted (circumorbital, including Harderian and lacrimal poles), palpebral (midway in the lower eyelid), and rim (near the edge of the eyelid). In the beluga, there was only a large, continuous mass within the eyelid itself. Histochemical investigation suggests neither sexual dimorphism nor age‐related differences, but both whales had two cell types freely intermingling with each other in all glandular masses. Large cells (cell type 1) were distended by four histochemically distinct intracellular secretory granules. Smaller cells (cell type 2) were not distended (fewer granules) and had two to three histochemically distinct intracellular secretory granules. The beluga orbital glands had additional lipid granules in cell type 1. Counterintuitively, both lipocalin and transferrin were localized to cell type 2 only. This intermingling of cell types is unusual for vertebrates in whom individual orbital glands usually have one cell type with one to two different secretory granules present. The heterogeneity of the orbital fluid produced by cetacean orbital glands implies a complex function, or series of functions, for these orbital glands and their role in producing the tear fluid.
Fibrotic changes in the infrapatellar fat pad induce new vessel formation and sensory nerve fiber endings that associate prolonged pain
Authors: Onuma Hiroaki , Tsuji Kunikazu , Hoshino Takashi , Inomata Kei , Udo Mio , Nakagawa Yusuke , Katagiri Hiroki , Miyatake Kazumasa , Watanabe Toshifumi , Sekiya Ichiro , Muneta Takeshi , Koga Hideyuki
Published: January 2020

The infrapatellar fat pad (IFP) contains nerve fiber endings and is considered to play an important role in the perception of knee pain. However, it is unclear whether and to what degree prolonged pain influences the nociceptive role of the IFP. To answer this question, we established a novel rat model of knee pain in which inflammation is restricted to the IFP. Rats received a single intra‐IFP injection of monoiodoacetic acid (MIA) (0.2 mg/10 µL or 1.0 mg/10 µL) in the left knee and a phosphate‐buffered saline (10 µL) injection in the right knee as a control. Pain‐avoidance behavior and histological changes of the knee joint were measured at multiple time points up to 28 days after MIA injection. Histological analysis showed a transient inflammatory response in the IFP body in the 0.2‐mg model, whereas prolonged inflammation followed by fibrotic changes was observed in the 1.0‐mg model. Subtle histological alterations were observed in the articular cartilage and IFP surface regardless of the dose. The pain‐avoidance behavior test indicated the development of prolonged knee pain throughout the experimental period in the 1.0‐mg group. Histological assessments showed a significant increase in calcitonin gene‐related peptide (CGRP)‐positive nerve fiber endings inside IFPs with fibrosis in newly vascularized surrounding regions. These data suggest that irreversible fibrotic changes in the IFP induce the formation of new vessels and CGRP‐positive nerve fiber endings that associate prolonged pain in the joint.
Assessment of visual fatigue under LED tunable white light with different blue components
Authors: Zhang Yin , Tu Yan , Wang Lili , Zhang Wei
Published: January 2020

Light‐emitting diode (LED) light source has high intensity emission of blue components absent in the daylight spectra and regulates human physiology and behavior. The aim of this study was to explore the effects of LED tunable white light with different blue‐component intensities on visual fatigue based on human eye photoreceptors. The short (S)‐cone and melanopsin illuminance were about 212% and 82% higher for blue‐enriched white light than blue‐less white light, respectively. The photopic illuminance was same for these two lights. The results revealed that blue‐enriched LED tunable white light with higher illuminance of S cones had a significant effect on visual fatigue. Participants experienced more eye discomfort under blue‐enriched white light accompanied with decreased vision function and changes in the autonomic nervous system. Visual acuity and tear film stability declined, and heart rhythm changed more significantly under blue‐enriched white light than blue‐less white light. While memory performance did not decline with more severe visual fatigue, improved memory performance under blue‐enriched white light may be due to enhanced alertness or arousal associated with high melanopsin illuminance. Our results suggest that blue‐enriched white light with higher illuminance of S cones and melanopsin has beneficial effects on cognitive performance, but it can induce relatively more visual fatigue.
Inhibition of glutaminase to reverse fibrosis in iatrogenic laryngotracheal stenosis
Authors: Tsai Hsiu‐Wen , Motz Kevin M. , Ding Dacheng , Lina Ioan , Murphy Michael K. , Benner Dimitri , Feeley Michael , Hooper Jody , Hillel Alexander T.
Published: January 2020

Objectives/Hypothesis

Glutamine metabolism is a critical energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and glutaminase (GLS) is an essential enzyme converting glutamine to glutamate. We hypothesize that the GLS‐specific inhibitor BPTES will block glutaminolysis and reduce iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro.

Study Design

Test‐tube Lab Research.

Methods

Immunohistochemistry of a cricotracheal resection (n = 1) and a normal airway specimen (n = 1) were assessed for GLS expression. GLS expression was assessed in brush biopsies of subglottic/tracheal fibrosis and normal airway from patients with iLTS (n = 6). Fibroblasts were isolated and cultured from biopsies of subglottic/tracheal fibrosis (n = 6). Fibroblast were treated with BPTES and BPTES + dimethyl α‐ketoglutarate (DMK), an analogue of the downstream product of GLS. Fibroblast proliferation, gene expression, protein production, and metabolism were assessed in all treatment conditions and compared to control.

Results

GLS was overexpressed in brush biopsies of iLTS scar specimens (P = .029) compared to normal controls. In vitro, BPTES inhibited iLTS scar fibroblast proliferation (P = .007), collagen I (Col I) (P < .0001), collagen III (P = .004), and α‐smooth muscle actin (P = .0025) gene expression and protein production (P = .031). Metabolic analysis demonstrated that BPTES reduced glycolytic reserve (P = .007) but had no effects on mitochondrial oxidative phosphorylation. DMK rescued BPTES inhibition of Col I gene expression (P = .0018) and protein production (P = .021).

Conclusions

GLS is overexpressed in iLTS scar. Blockage of GLS with BPTES significantly inhibits iLTS scar fibroblasts proliferation and function, demonstrating a critical role for GLS in iLTS. Targeting GLS to inhibit glutaminolysis may be a successful strategy to reverse scar formation in the airway.

Level of Evidence

NA

Laryngoscope, 2020
Spatial–temporal variations in urbanization in Kunming and their impact on urban lake water quality
Authors: Yang Kun , Luo Yi , Chen Kexin , Yang Yang , Shang Chunxue , Yu Zhenyu , Xu Jiaxin , Zhao Yisong
Published: January 2020

As a radiation centre or hub in Southeast Asia and South Asia and the only Chinese metropolis bordering other ASEAN countries, Kunming has experienced extensive urbanization since the 1980s. This type of human activity has been accompanied by environmental deterioration, especially water quality pollution, in Dianchi Lake, China's sixth largest freshwater lake. This study reveals that the urbanization process has led to land degradation over the past 30 years. First law of geography was introduced to analyze the effects of impervious surface area (ISA) expansion on the lake water environment. The results indicate that the ISA encompassed the lake and radiated outwards. Since the 1990s, approximately 35% of natural surfaces transformed to ISA, and the urban district density exploded from one in 2001 to four in 2017. The urban district area density exploded from 0.06% to 12.05% over the past 17 years. During the past 30 years, the growth rate of ISA exceeded 21 km2 a−1 and even reached 38 km2 a−1 between 2004 and 2017. The spatial pattern of lake water quality was determined by the spatial influences of ISA (G). Then the relationship between water quality indicators and G was analyzed, and the threshold between G and water quality was investigated using an exponential regression analysis method. The results of the correlation analysis indicated that a significant correlation exists between G and lake water quality; although the lake water quality showed a cyclical change, the G impact on the lake water quality was notable. This research proposed an effective method to calculate the spatial influence of the impervious surface on the water quality to reveal the effect of urbanization on the water environment quantitatively and helps us to enhance the understanding of ISA expansion impact on lake environment. Moreover, this research provides decision supports for the environmental protection and management of the lake and empirical evidence regarding urban development impacts on watershed planning.
Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice
Authors: Williams Ian M. , McClatchey P. Mason , Bracy Deanna P. , Bonner Jeffrey S. , Valenzuela Francisco A. , Wasserman David H.
Published: January 2020

Objective

The continuous endothelium of skeletal muscle (SkM) capillaries regulates insulin’s access to skeletal myocytes. Whether impaired transendothelial insulin transport (EIT) contributes to SkM insulin resistance (IR), however, is unknown.

Methods

Male and female C57/Bl6 mice were fed either chow or a high‐fat diet for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries, electron microscopy to assess endothelial ultrastructure, and glucose tracers to measure indices of glucose metabolism.

Results

Diet‐induced obesity (DIO) male mice were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT was associated with a 45% reduction in endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice still showed SkM IR indicating severe myocellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure, or SkM insulin sensitivity between lean female mice and female mice fed a high‐fat diet.

Conclusions

These results suggest that, in male mice, obesity results in ultrastructural alterations to the capillary endothelium that delay EIT. Nonetheless, the myocyte appears to exceed the endothelium as a contributor to SkM IR in DIO male mice.
Event‐triggered H∞ synchronization control for switched master‐slave systems subject to stochastic cyber attacks and quantization
Authors: Li Xianling , Liu Ziyang , Qiu Zhiqiang , Qi Yiwen , Yuan Shuo
Published: January 2020

This paper studies the event‐triggered H∞ control for synchronization of networked switched master‐slave systems under external disturbance, stochastic attacks, and quantization. With the proposed event‐triggering schemes, the communication frequency and data packets can be effectively regulated and reduced. To reduce further the burden of network transmission, the quantized control is applied. Moreover, the network transmission delay and the stochastic cyberattacks are concerned. In addition, the synchronization problem between switched master systems and switched slave systems is transformed into a stability problem of switched error systems. By adopting multiple Lyapunov functions and average dwell time method, sufficient conditions are constructed to assure the mean‐square exponential stability with H∞ performance of the switched error systems. Meanwhile, the stagger between data switching instants and triggering instants is discussed in the system in detail. Accordingly, the controller gains and event‐triggering parameters are obtained utilizing a set of linear matrix inequalities. Finally, a numerical simulation and a practical example are illustrated to demonstrate the effectiveness of the presented method.
Optimization of graphene in carbon black‐filled nitrile butadiene rubber: Constitutive modeling and verification using finite element analysis
Authors: Goswami Mohit , Mandloi Bharat Singh , Kumar Abhay , Sharma Sujit , Ghorai Sanjoy Kumar , Sarkar Kajal , Chattopadhyay Santanu
Published: January 2020

Graphene nanoplatelet loading is varied in carbon black‐filled nitrile butadiene rubber (NBR) to form a hybrid system. The mechanical properties of the hybrid system are determined by performing tension and compression tests. It is found that graphene nanosheets are well dispersed possessing strong interfacial interaction with NBR and carbon black. There is an increment of 9% in tensile strength of the carbon black‐filled hybrid system with a graphene loading of 4 phr without hampering ultimate strain. Further addition of graphene resulted in degraded properties. Hyperelastic material models describing nonlinear mechanical behavior are fitted with experimental data to acquire material constants. Young's modulus is determined using various models, and a synergistic effect is observed with graphene loading of 4 phr. A comparison between experimental result and finite element analysis (FEA) result is presented for uniaxial tension and compression. Maximum principal stresses at break are also visualized with the help of FEA.
Enhancing UV Photopolymerization by a Red‐light Preirradiation: Kinetics and Modeling Strategies for Reduced Oxygen Inhibition
Authors: Lin Jui‐Teng , Cheng Da‐Chuan , Chen Kuo‐Ti , Chiu Yin‐Chen , Liu Hsia‐Wei
Published: January 2020

A novel strategy for red‐light‐controlled oxygen inhibition for improved UV‐light‐initiated monomer conversion is theoretically presented for the first time. The dual‐wavelength kinetic equations are derived, numerically and analytically solved for the oxygen and photoinitiator concentration profiles. The UV‐light‐initiated Type I conversion efficacy is an increasing function of its concentration (C20) and the light dose at transient state, but it is a decreasing function of the light intensity, scaled by [C20/I20]0.5, at steady state. In contrast, the red‐light‐initiated Type II efficacy is mainly dose dependent. Longer red‐light preirradiation time (TP) leads to a shorter UV‐light TID of UV‐light conversion, which is strongly red‐light dose dependent, rather than intensity dependent. The numerical new finding is also predicted by the analytic formulas showing that oxygen and monomer conversion are strongly red‐light dose dependent in a Type II mechanism. Finally, strategies for controlled initiation–inhibition switch based on two mechanisms, (a) oxygen inhibition for improved conversion and (b) radical inhibition for spatial confirmation in 3D printing, are presented. To conclude, UV‐light conversion could be improved by a red‐light preirradiation and more importantly and could be customizely tailored by the controlled induction time. UV‐light photopolymerization conversion could be improved by a red‐light preirradiation and could be customizely tailored by the controlled induction time. The UV‐light‐initiated Type I conversion efficacy is an increasing function of its concentration and the light dose at transient state, but it is a decreasing function of the light intensity at steady state. In contrast, the red‐light‐initiated Type II efficacy is mainly dose dependent. Longer red‐light preirradiation time leads to a shorter UV light. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 683–691
Ferroelectric and Piezoelectric Properties of BiFeO3‐Based Piezoelectric Ceramics
Authors: Habib Muhammad , Lee Myang Hwan , Kim Da Jeong , Choi Hai In , Kim Myong-Ho , Kim Won-Jeong , Song Tae Kwon
Published: January 2020

Bismuth ferrite‐based bulk ceramics (1–x)Bi0.97Sm0.08FeO3–xBaTiO3(BSF–xBT withx = 0.00 FC,x = 0.00 WQ,x = 0.01 WQ,x = 0.03 WQ, andx = 0.05 WQ, where FC is the furnace cooled and WQ is the water quenched) are synthesized by a conventional solid‐state reaction method followed by WQ process. The WQ procedure (compared with FC) dramatically improves the remnant polarization (Pr) ofx = 0.00 ceramic from 11 to 21 μC cm−2. BT incorporation gradually reduces the coercive field (Ec) andPrsignificantly enhances to 28.5 μC cm−2(atx = 0.03) with fully saturatedP–Ehysteresis loops. The temperature‐dependent ferroelectric properties reveal that the correspondingPrvalues improve with the rising temperature; this behavior may be related to the thermally activated domain walls motion. Symmetric and closed electromechanical strain–electric field (S–E) curves are obtained with a maximum strain ofSmax = 0.05% for an optimum composition together with high charge sensor constant (d33 = 56 pC N−1). The structural and electrical properties of the investigated ceramics are presented in detail.
Does the endometrial thickness on the day of the trigger affect the pregnancy outcomes after fresh cleaved embryo transfer in the clomiphene citrate‐based minimal stimulation cycle?
Authors: Nishihara Seiko , Fukuda Junichiro , Ezoe Kenji , Endo Masako , Nakagawa Yuko , Yamadera Rie , Kobayashi Tamotsu , Kato Keiichi
Published: January 2020

Purpose

Thin endometrium is often observed after clomiphene citrate (CC) administration for follicular development and is one of the reasons for embryo transfer (ET) cancelation or implantation failure. We retrospectively analyzed whether the endometrial thickness (EMT) on the days of the maturation trigger and ET are predictive factors of pregnancy outcomes after fresh cleaved ET in a CC‐based minimal stimulation cycle (CC‐cycle).

Methods

A total of 746 CC‐cycles in vitro fertilization (IVF), followed by fresh cleaved ET, from November 2018 to March 2019 were analyzed. Associations between the pregnancy outcomes and EMT on the days of the trigger and ET were statistically evaluated.

Results

Although the EMT on the day of ET was not significantly associated with the ongoing pregnancy rate (adjusted odds ratio [AOR], 1.043; P = .3251), a decreased EMT on the day of the trigger was significantly associated with a low ongoing pregnancy rate (AOR, 1.154; P = .0042). Furthermore, the clinical pregnancy rate was significantly lower when the EMT was <7 mm on the day of the trigger during the CC‐cycle.

Conclusions

These results suggest that measurement of the EMT on the day of the trigger could be effective for predicting the pregnancy outcomes after fresh cleaved ET during the CC‐cycle.
In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation
Authors: Tanimoto Yuji , Yamasaki Tomoteru , Nagoshi Narihito , Nishiyama Yuichiro , Nori Satoshi , Nishimura Soraya , Iida Tsuyoshi , Ozaki Masahiro , Tsuji Osahiko , Ji Bin , Aoki Ichio , Jinzaki Masahiro , Matsumoto Morio , Fujibayashi Yasuhisa , Zhang Ming-Rong , Nakamura Masaya , Okano Hideyuki
Published: January 2020

Transplantation of human-induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC-NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long-term observation of hiPSC-NS/PCs post-transplantation suggested some “unsafe” differentiation-resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular-functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)-positive undifferentiated neural cells in the CNS of immune-deficient (nonobese diabetic-severe combined immune-deficient) mice after hiPSC-NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC-NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC-NS/PCs-derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC-NS/PCs-derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

Significance statement Stem cell-based therapy using neural stem/progenitor cells (NS/PCs) derived from human-induced pluripotent cells (hiPSCs) provides a promising approach for treating neurodegenerative diseases and neurotrauma. However, not all transplanted cells fully differentiate into mature neurons and glial cells, even if clinically “safe” clones are used. These undifferentiated cells can trigger tumorigenic overgrowth due to their pluripotency. By utilizing the characteristic of NS/PCs to express the 18 kDa translocator protein (TSPO), positron emission tomography with TSPO ligand was able to visualize residual immature neural cells after NS/PCs transplantation into central nervous system and could potentially have critical importance in regenerative medicine.
Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population
Authors: George Mitchell J. , Prabhakara Karthik , Toledano-Furman Naama E. , Gill Brijesh S. , Wade Charles E. , Cotton Bryan A. , Cap Andrew P. , Olson Scott D. , Cox Charles S.
Published: January 2020

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect. Human MSCs from bone marrow, adipose, and amniotic tissues and freshly isolated bone marrow MNC samples were tested. TF expression and phenotype were quantified using flow cytometry. CCTs were mixed individually with trauma patients’ whole blood, assayed with thromboelastography (TEG), and compared with healthy subjects mixed with the same cell sources. Heparin was added to samples at increasing concentrations until TEG parameters normalized. Clotting time or R time in TEG decreased relative to the TF expression of the CCT treatment in a logarithmic fashion for trauma patients and healthy subjects. Nonlinear regression curves were significantly different with healthy subjects demonstrating greater relative decreases in TEG clotting time. In vitro coadministration of heparin normalized the procoagulant effect and required dose escalation based on TF expression. TF expression in human MSC and MNC has a procoagulant effect in blood from trauma patients and healthy subjects. The procoagulant effect is lower in trauma patients possibly because their clotting time is already accelerated. The procoagulant effect due to MSC/MNC TF expression could be useful in the bleeding trauma patient; however, it may emerge as a safety release criterion due to thrombotic risk. The TF procoagulant effect is reversible with heparin.

Significance statement Stem cells are currently under investigation as a treatment for sequela of trauma like brain or lung injury. However, stem cells express tissue factor (TF) that causes rapid blood clotting. It is demonstrated that stem cells make blood from trauma patients, which clot faster. A potential antidote to this effect is heparin, a common and inexpensive blood thinner. It is believed that stem cells used in trauma studies should be risk-stratified based on their TF expression.
Changing the channel: Digitization and the rise of “middle tail” strategies
Authors: Benner Mary J. , Waldfogel Joel
Published: January 2020

Research Summary

Prior research has studied whether digitization shifts demand away from mass‐appeal blockbusters toward a “long tail” of existing products. We extend this work by studying whether digitization influences the products created. Using unique data on movies, we examine whether the reduced costs of production and new digital distribution channels spur producers to create products aimed at smaller audiences. We employ a flexible, transparent, and largely graphical empirical approach to document changes unfolding with digitization. We find growth in both intended blockbuster and long tail products, but also, the rise of a “middle tail,” movies distributed via digital channels, with budgets suggesting commercial intent but well below the averages for theatrical distribution. The new middle tail is largely due to newcomers rather than major incumbents.

Managerial Summary

Digitization has reduced the costs to create movies, while also enabling new distribution channels that avoid the high costs of theatrical distribution. With lower costs, movies no longer need to be “blockbusters” at the box office to be financially successful. In this article, we study whether digitization has spurred an increase in lower‐budget movies that are not aimed for release in theaters. We find that digitization has unleashed a large number of very low budget movies that attract little commercial attention (i.e., the “long tail”). However, we also find an increase in a new category of movies with budgets between $100,000 and $10 million, aimed at smaller audiences via new digital distribution channels. We show growth in this “middle tail” following digitization.
On the need for expanded guidance in navigating ethical learning research at science museums
Authors: McManimon Shannon K. , Causey Lauren , King Zdanna , Ronning Evelyn C. , Bequette Marjorie B.
Published: January 2020

Science learning occurs throughout people's lives, inside and outside of school, in formal, informal, and nonformal settings. While museums have long played a role in science education, learning in this and other informal settings has not been studied nor understood as deeply as in formal settings (i.e., schools and classrooms). This position paper, written by learning researchers in a science museum engaged in equity and access work, notes that while the researchers consider the ethics of their work regularly and deeply, little formal guidance exists for the ethical challenges they routinely face in studying science learning. To explore this, the paper first shares contexts of studying informal science education at the Science Museum of Minnesota, including epistemological understandings of both science and research, a commitment to justice‐based equity, and existing ethical guidance and processes. Drawing on three research projects, it explores ethical issues pertaining to (a) museum visitors and (b) museum staff and community members engaging in participatory research. First, as visitors do not generally come to a museum to be part of a research study, learning researchers must consider sampling, representation, and data collection methods, balancing these with a museum‐goer's desires for their visit. Second, when using participatory methodologies with staff, community members, and young people as co‐researchers, ethical considerations involve building relationships, redefining (unanticipated) risks, and data collection and dissemination practices that do not extend existing social inequities or work hierarchies. Ultimately, this position paper argues for expanded or revised ethical guidance that meets the needs of this work, surpasses current guidelines or institutional review board practices, draws on epistemologies outside of a supposedly neutral, individualistic Western framework, and places participants at the center of the work. Such a discussion could enhance the ethical study of science learning across settings.
Communicating about science and engineering practices and the nature of science: An exploration of American Sign Language resources
Authors: Enderle Patrick , Cohen Scott , Scott Jessica
Published: January 2020

Science classrooms have been demonstrated to be educational contexts with unique and challenging language demands. Enhanced cognitive and linguistic demands arising from an emphasis on the science and engineering practices (SEPs) and the nature of science (NOS) in the Next Generation Science Standards warrant consideration of how to support students with different language abilities. Deaf and Hard of Hearing (DHH) students must negotiate multiple languages in the science classroom, including academic science vocabulary, written English, and spoken American Sign Language (ASL). However, science‐specific ASL vocabulary is rather limited, and current development efforts mostly focus on developing signs for more traditional content vocabulary. Yet, effective science instruction for DHH students must also provide them opportunities to engage in and communicate about the NOS and the functions of the SEPs. The current study explores the availability of such ASL resources across a body of science‐specific resources available for teachers of DHH students. Reviewing a body of publicly available resources, researchers identified a small list of 21 ASL signs that are common across multiple resources. These signs, and the larger data set, were reviewed to identify trends and patterns across them and how well they communicate scientific meanings for NOS and the SEPs. Issues that emerged and classroom implications are discussed.
Subspecific identity and a comparison of genetic diversity between wild and ex situ wildebeest
Authors: Caspers Lauren M. , Ferrie Gina M. , Wolfe Kristen , Hoffman Eric A.
Published: January 2020

The original North American ex situ wildebeest population was believed to originate from the white‐bearded wildebeest (Connochaetes taurinus albojubatus), which is both morphologically distinct and geographically separated from the brindled wildebeest (C. t. taurinus). However, after an import of wildebeest into North America in 2001, managers have suspected that white‐bearded and brindled wildebeest were mixed in herds at multiple institutions. We sequenced the mitochondrial control region (d‐loop) from a portion of the managed North American population and compared our sequences with previously published sequences from wild individuals to determine the subspecific identity and genetic diversity of our ex situ population. We were able to confidently identify C. t. albojubatus as the subspecies identity of the sampled portion of our population. Within our population, haplotype and nucleotide diversity were low (0.169 and 0.001, respectively) with a single common haplotype (H1) containing 41 of the 45 individuals sequenced, while two rare haplotypes (H2 and H3) were derived from three individuals and a single individual, respectively. Nucleotide and haplotype diversity were greater overall in the wild populations compared with our managed population. However, C. t. albojubatus was found to exhibit lower nucleotide diversity in both wild and ex situ populations when compared to other wild subspecies. Though the overall goal of the North American wildebeest population is for public education and not reintroduction, maintaining genetic diversity is vital for the long‐term viability of this managed population, which may benefit from periodic supplementation of wild animals.
Validation of the scandinavian guidelines for initial management of minor and moderate head trauma in children
Authors: Sönnerqvist Caroline , Brus Ole , Olivecrona Magnus
Published: January 2020

Background

Head trauma in children is common, with a low rate of clinically important traumatic brain injury. CT scan is the reference standard for diagnosis of traumatic brain injury, of which the increasing use is alarming because of the risk of induction of lethal malignancies. Recently, the Scandinavian Neurotrauma Committee derived new guidelines for the initial management of minor and moderate head trauma. Our aim was to validate these guidelines.

Methods

We applied the guidelines to a population consisting of children with mild and moderate head trauma, enrolled in the study: “Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study” by Kuppermann et al. (Lancet 374(9696):1160–1170, https://doi.org/10.1016/S0140-6736(09)61558-0, 2009). We calculated the negative predictive values of the guidelines to assess their ability to distinguish children without clinically-important traumatic brain injuries and traumatic brain injuries on CT scans, for whom CT could be omitted.

Results

We analysed a population of 43,025 children. For clinically-important brain injuries among children with minimal head injuries, the negative predictive value was 99.8% and the rate was 0.15%. For traumatic findings on CT, the negative predictive value was 96.9%. Traumatic finding on CT was detected in 3.1% of children with minimal head injuries who underwent a CT examination, which accounts for 0.45% of all children in this group.

Conclusion

Children with minimal head injuries can be safely discharged with oral and written instructions. Use of the SNC-G will potentially reduce the use of CT.
Effective FE models for simulating the elasto-mechanical characteristics of forming machines
Authors: Tehel Robert , Päßler Thomas , Bergmann Markus
Published: January 2020

The elasto-mechanical characteristic of forming machines is crucial for a variety of forming processes. Numerical simulations are to be performed to understand the complex interaction between process, forming tool, and machine. The machine’s elastic fingerprint depends on its design, accuracy of the components, and mounting conditions. Models only based on data of the machine design are limited. Therefore, effective FE models are to be developed to transfer the physical structure into a digital representation. The paper presents different methods of creating effective models for the characteristics of forming machines determined by measurements. Examples and potential of using these models are presented.
Perceived impact of meteorological conditions on the use of public space in winter settlements
Authors: Larsson Agneta , Chapman David
Published: January 2020

This study aimed to assess the impact of meteorological conditions on the use of public space in Scandinavia and Canada. Between September 21 and December 18, 2017, a cross-sectional online survey ‘EAMQ-Climate: space’ was distributed via web-based platforms. Survey responses were received from 361 residents (258 people from Scandinavia and 103 from Canada). The relative impact of the meteorological determinants on the use of public space was calculated, and a factor analysis was performed. Disparities between Canada and Scandinavia as well as between the climate zones represented were analysed using ANOVA. Overall results showed that the most significant meteorological enablers for the use of outdoor public spaces in winter were solar gain, snowfall and snow-covered surfaces. The main barriers were slush-covered and icy surfaces, rainfall and darkness. Wind and cold were conditions with less influence. The impact of rain and ice, however, differed between climatic zones. It was also established that, when addressing the meteorological impact on avoiding the use of public spaces in winter, it is vital to discriminate between conditions related to a) the ground surface and b) ambient conditions, as well as the particular significance of c) snow and sun, and d) darkness. For the design of public space in winter cities, we conclude that designers need to focus on a wider range of weather conditions than sun, wind and cold, and include snow, rainfall, slushy and icy ground and poor visibility. The study suggests that winter public space has a higher climatic design requirement to be successful than streets and pathways that are mainly used for soft mobility.
Low antimicrobial resistance in general practice patients in Rotterdam, the city with the largest proportion of immigrants in the Netherlands
Authors: Honsbeek Maaike , Tjon-A-Tsien Aimée , Stobberingh Ellen , de Steenwinkel Jurriaan , Melles Damian C. , Lous Jan , Richardus Jan Hendrik , Voeten Hélène
Published: January 2020

Antimicrobial resistance (AMR) is an increasing problem. The prevalence of antimicrobial resistance in general practice patients is expected to be relatively high in Rotterdam, the Dutch city with the largest proportion non-Western immigrants. The aim of this study was to assess the prevalence of antibiotic-resistant uropathogens (Escherichia coli,Klebsiella pneumoniae, andProteus mirabilis) in general practices in Rotterdam, and to find a possible association between the prevalence of antibiotic-resistantE. coliand age, gender, and socioeconomic status (SES). A retrospective analysis was performed of urine samples from general practice patients in 2016. The prevalence of AMR in uropathogens was compared with national resistance data, as was the prevalence of highly and multidrug resistant and extended spectrum β-lactamase (ESBL) producingE. coliandK. pneumoniae.Univariate logistic regression was used to study associations between antibiotic-resistantE. coliand age, gender, and SES area score. No clinically relevant differences were observed in the prevalence of antibiotic-resistant uropathogens in Rotterdam compared with the national prevalence. ForE. coliandK. pneumoniae, the prevalence was 3.6% for ESBL production (both pathogens together), while the prevalence ranged between 4.2%–5.0% for high resistance and between 1.2%–3.3% for multidrug resistance. Ciprofloxacin-resistantE. coliwas significantly associated with higher age. Although Rotterdam has a high percentage of non-western immigrants and a low SES, AMR is low among general practice patients. This indicates that adherence to national guidelines in general practice enables maintenance of low AMR, even in high-risk populations.
Risk factors for lower limb lymphedema in gynecologic cancer patients after initial treatment
Authors: Kunitake Teruyo , Kakuma Tatsuyuki , Ushijima Kimio
Published: January 2020

Background

Most studies on lower limb lymphedema have been conducted in gynecologic cancer patients who underwent surgery for gynecologic malignancy. This study aimed to evaluate the risk factors for lower limb lymphedema development in gynecologic cancer patients who underwent initial treatment.

Methods

A retrospective cohort design was used to follow 903 gynecologic cancer patients who underwent treatment at Kurume University Hospital between January 1, 2013 and December 31, 2015. Data analyses were performed in 356 patients, and the patients were followed up until December 31, 2017. The model comprised two components to facilitate statistical model construction. Specifically, a discrete survival time model was constructed, and a complementary log–log link model was fitted to estimate the hazard ratio. Associations between risk factors were estimated using generalized structural models.

Results

The median follow-up period was 1083 (range 3–1819) days, and 54 patients (15.2%) developed lower limb lymphedema, with a median onset period of 240 (range 3–1415) days. Furthermore, 38.9% of these 54 patients developed lower limb lymphedema within 6 months and 85.2% within 2 years. International Federation of Gynecology and Obstetrics stage, radiotherapy, and number of lymph node dissections (≥ 28) were significant risk factors.

Conclusion

Simultaneous examination of the relationship between lower limb lymphedema and risk factors, and analysis among the risk factors using generalized structural models, enabled us to construct a clinical model of lower limb lymphedema for use in clinical settings to alleviate this condition and improve quality of life.
Grand challenges in model-driven engineering: an analysis of the state of the research
Authors: Bucchiarone Antonio , Cabot Jordi , Paige Richard F. , Pierantonio Alfonso
Published: January 2020

In 2017 and 2018, two events were held—in Marburg, Germany, and San Vigilio di Marebbe, Italy, respectively—focusing on an analysis of the state of research, state of practice, and state of the art in model-driven engineering (MDE). The events brought together experts from industry, academia, and the open-source community to assess what has changed in research in MDE over the last 10 years, what challenges remain, and what new challenges have arisen. This article reports on the results of those meetings, and presents a set of grand challenges that emerged from discussions and synthesis. These challenges could lead to research initiatives for the community going forward.
Perfect date—the review of current research into molecular bases of mammalian fertilization
Authors: Trebichalská Zuzana , Holubcová Zuzana
Published: January 2020

Fertilization is a multistep process during which two terminally differentiated haploid cells, an egg and a sperm, combine to produce a totipotent diploid zygote. In the early 1950s, it became possible to fertilize mammalian eggs in vitro and study the sequence of cellular and molecular events leading to embryo development. Despite all the achievements of assisted reproduction in the last four decades, remarkably little is known about the molecular aspects of human conception. Current fertility research in animal models is casting more light on the complexity of the process all our lives start with. This review article provides an update on the investigation of mammalian fertilization and highlights the practical implications of scientific discoveries in the context of human reproduction and reproductive medicine.
Hydrogen-bonded porous frameworks constructed by rigid π-conjugated molecules with carboxy groups
Authors: Hisaki Ichiro
Published: January 2020

This review covers construction and properties of porous molecular crystals (PMCs) constructed through hydrogen-bonding ofC3-symmetric, rigid, π-conjugated molecular building blocks possessing carboxyaryl groups, which was reported in the last 5 years by the author’s group. PMCs with well-defined, self-standing pores have been attracted attention due to various functionalities provided by selective and reversible inclusion of certain chemical species into the pores. However, it has been recognized for long time that construction of PMCs with permanent porosity is not easy due to weakness of noncovalent intermolecular interactions. Systematic construction of PMCs have been limited so far. To overcome this problem, the author has proposed a unique molecular design concept based onC3-symmetric π-conjugated molecules (C3PIs) possessingo-bis(4-carboxyphenyl)benzene moieties in their periphery and demonstrated that C3PIs systematically yielded hydrogen-bonded organic frameworks (HOFs) composed of H-bonded 2D hexagonal networks (H-HexNets) or interpenetrated 3Dpcu-networks, which exhibit permanent porosity, significant thermal stability, polar solvent durability, robustness/flexibility, and/or multifunctionality.