bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombomodulin Functional Domains Support Osteoblast Differentiation and Bone Healing in Diabetes in Mice
Authors: Chen Chung-Hwan , Lai Chao-Han , Hong Yi-Kai , Lu Jui-Ming , Lin Sung-Yen , Lee Tien-Ching , Chang Lan-Yun , Ho Mei-Ling , Conway Edward M , Wu Hua-Lin , Cheng Tsung-Lin 
Published: April 2020

ABSTRACT
Thrombomodulin (TM) is a transmembrane glycoprotein that contains five functional domains. Soluble TM (sTM), comprising extracellular domains TMD1 (lectin-like), TMD2 (epidermal growth factor [EGF]-like repeat containing), and TMD3 (serine-threonine rich), can be shed from cells by the intramembrane protease rhomboid-like-2 (RHBDL2). TM is expressed by osteoblasts, yet its role there has not been determined. Herein we aimed to investigate the properties of TM and its domains in osteoblast function and bone repair following injury in diabetes. In response to a scratch injury of cultured osteoblast-like MG63 cells, expression of TM and RHBDL2 was enhanced, with increased release of sTM. Conditioned media from the injured cells promoted osteoblast migration, an effect that was lacking with conditioned media from MG63 cells in which TM was silenced by shRNA. Exogenous recombinant TMD1 had no effect on osteoblast activities or on bone repair in vivo. However, TM domains 2 and 3 (TMD2/3), induced MG63 cell migration, proliferation and mineralization in vitro, and when locally administered in mice, improved in vivo healing of injured calvarium. This beneficial effect of TMD2/3, mediated via fibroblast growth factor receptor (FGFR)/ERK signaling pathways, was also observed in vitro under high glucose conditions where endogenous TM expression was reduced, and in vivo in diabetic mice following tibia fracture or calvarium injury, where the osteoblastic response and healing were otherwise dampened. Taken together, osteoblast TM participates in bone healing, and recombinant TMD2/3 holds promise as a novel therapy for diabetic bone defect healing. © 2020 American Society for Bone and Mineral Research.
Abstract
We investigate the role of osteoblast thrombomodulin (TM). In response to injury stimulation, RNA released from damaged cells promotes the expression of RHBDL2 and TM in osteoblasts. RHBDL2 cleaves TM transmembrane domain to generate soluble TM (sTM). Among sTM fragments, TM domains 2 and 3 (TMD2/3) rather than the lectin-like domain (TMD1) promotes osteoblast functions and bone healing through FGFR/ERK signaling. Given that injury-enhanced TM expression and sTM production are reduced in high-glucose environments, treatment with recombinant TMD2/3 improves bone healing.
Ghrelin promotes midbrain neural stem cells differentiation to dopaminergic neurons through Wnt/β‐catenin pathway
Authors: Gong Bing , Jiao Lingling , Du Xixun , Li Yong , Bi Mingxia , Jiao Qian , Jiang Hong 
Published: April 2020

AbstractGhrelin plays a neuroprotective role in the process of dopaminergic (DAergic) neurons degeneration in Parkinson's disease (PD). However, it still largely unknown whether ghrelin could affect the midbrain neural stem cells (mbNSCs) from which DAergic neurons are originated. In the present study, we observed that ghrelin enhanced mbNSCs proliferation, and promoted neuronal differentiation especially DAergic neuron differentiation both in vitro and ex vivo. The messenger RNA levels of Wnt1, Wnt3a, and glial cell line‐derived neurotrophic factor were increased in response to the ghrelin treatment. Results showed that Wnt/β‐catenin pathway was relevant to this DAergic neuron differentiation induced by ghrelin. Our finding gave a new evidence that ghrelin may enable clinical therapies for PD by its neurogenesis role.
Shared discovery: A process to coproduce knowledge among scientists, policy makers, and stakeholders for solving nutrient pollution problems
Authors: Royer Matthew B. , Brooks Robert P. , Shortle James S. , Yetter Susan 
Published: April 2020

AbstractThere is growing recognition of the importance of involving stakeholders in solution‐oriented multidisciplinary environmental research projects. Management of nutrients to address water pollution is a wicked problem requiring multidisciplinary research and participation of stakeholders. Here, we frame participatory research as shared discovery, a deliberative, focused engagement process that serves as a directional guide for how research unfolds during the entire span of a project. We explore its application within a 5‐yr, multidisciplinary research project seeking innovative solutions to nutrient management challenges in four agriculturally influenced small watersheds in the Chesapeake Bay basin. This process involved deliberate development of a stakeholder engagement strategy and structure, which included a specific research team dedicated to implementing shared discovery throughout. Recognizing that stakeholders involved in nutrient and watershed management engage at multiple scales, we developed a biscalar approach to engage stakeholders at both a regional or state policy level and within the local study watersheds. Early collaboration allowed stakeholders to be participatory in developing research questions and shaping research design, which made research results more applicable to the identified problems. The biscalar framework for engagement was a novel approach that allowed researchers to incorporate both broader policy concepts into research and local concerns and concepts specific to the small study watersheds, allowing solutions to be tailored to local needs. Although infusing research with stakeholder engagement and input from the outset is a time‐consuming process, it bolsters research design and products and leads to greater application of research to solve nutrient pollution—a wicked problem indeed.
Influence of low‐disturbance fall liquid dairy manure application on corn silage yield, soil nitrate, and rye cover crop growth
Authors: Sherman Jessica F. , Young Eric O. , Jokela William E. , Cavadini Jason 
Published: April 2020

AbstractTillage incorporation of manure can mitigate nutrient loss but increases erosion potential and damages cover crops. More information on the effects of low‐disturbance manure application (LDMA) on corn yield, cover crop establishment, and soil properties is needed to better predict manure management practice trade‐offs. Here, corn silage (Zea mays L.) yield, winter rye (Secale cereale L.) establishment, and soil nitrate concentrations were compared for a range of manure application methods, including broadcast incorporation, broadcast/disk, fertilizer N (spring applied at 67, 134, and 202 kg N ha−1), and a no‐manure control, at the University of Wisconsin's Marshfield Agricultural Research Station from 2012 to 2015. Compared with the control, manure and fertilizer N treatments increased corn yield by an average of 1.1‐ to 1.6‐fold and 1.4‐ to 1.6‐fold, respectively. Of the LDMA treatments (sweep‐, strip till‐, and coulter‐injection; aerator/band; broadcast), corn yield was greatest for sweep injection, which did not differ from the high N fertilizer rate (P < .0001). Corn yield averaged across LDMA treatments did not differ from the 134 or 202 kg N ha−1 yields. Compared with disking, LDMA maintained more crop residue (P < .0001), with levels comparable to the control. Soil nitrate‐N at depths of 0–30 and 30–60 cm was influenced by LDMA and fertilizer N; however, leaching to 60–90 cm was comparable among treatments. Results indicate that LDMA with injection conserved more N, caused less damage to winter rye, and had similar yields to fertilizer N treatments with improved soil aggregate stability and higher total carbon content.
A pilot study of the antiviral activity of anionic and cationic polyamidoamine dendrimers against the Middle East respiratory syndrome coronavirus
Authors: Kandeel Mahmoud , Al‐Taher Abdulla , Park Byoung Kwon , Kwon Hyung‐Joo , Al‐Nazawi Mohammed 
Published: April 2020

AbstractThe Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emerging virus that causes infection with a potentially fatal outcome. Dendrimers are highly branched molecules that can be added to antiviral preparations to improve their delivery, as well as their intrinsic antiviral activity. Studies on identifying anti‐MERS‐CoV agents are few. Three types of polyanionic dendrimers comprising the terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were used to assess their antiviral activity with the MERS‐CoV plaque inhibition assay. The hydroxyl polyanionic set showed a 17.36% to 29.75% decrease in MERS‐CoV plaque formation. The most potent inhibition of MERS‐CoV plaque formation was seen by G(1.5)‐16COONa (40.5% inhibition), followed by G(5)‐128SA (39.77% inhibition). In contrast, the cationic dendrimers were cytotoxic to Vero cells. Polyanionic dendrimers can be added to antiviral preparations to improve the delivery of antivirals, as well as the intrinsic antiviral activity.
Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience
Authors: Infantino Maria , Grossi Valentina , Lari Barbara , Bambi Riccardo , Perri Alessandro , Manneschi Matteo , Terenzi Giovanni , Liotti Irene , Ciotta Giovanni , Taddei Cristina , Benucci Maurizio , Casprini Patrizia , Veneziani Francesca , Fabbri Sergio , Pompetti Adolfo , Manfredi Mariangela 
Published: April 2020

AbstractA pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID‐19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID‐19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty‐one COVID‐19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti‐SARS CoV‐2 antibodies IgM and IgG. All COVID‐19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse‐transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti‐SARS CoV‐2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti‐SARS‐CoV‐2 antibodies profile and can be considered an excellent tool for COVID‐19 diagnostics.
Pressure‐induced insertion and transformation of N2 in the cavities of zeolitic imidazolate framework‐8: A Raman study
Authors: Chen Shuanglong , Li Xin , Lv Hang , Dong Enlai , Yang Xibao , Liu Ran , Liu Bingbing 
Published: April 2020

AbstractWe have investigated the pressure‐induced behaviors of nitrogen confined in the zero‐dimensional cavities of zeolitic imidazolate framework (ZIF)‐8 using Raman spectroscopy. Pressure forces the nitrogen molecules in the pressure‐transmitting medium (PTM) to enter the inner pores of ZIF‐8, and two Raman bands attributed to the nitrogen molecules interacting with the framework of ZIF‐8 and those approximately in the central part of the cavities surrounded by the former are observed. The confined nitrogen species transform in a different way under high pressure from those of the bulk nitrogen and the confined nitrogen in the one‐dimensional inorganic channels. Both the intermolecular interaction and the host–guest interaction jointly contribute to the transformation and a highly disordered and densely compressed state of the confined nitrogen is formed at 20 GPa. A hysteresis is found when comparing the Raman spectra at low and industrially accessible pressures after a compression and decompression cycle, suggesting that the ability of ZIF‐8 to storage nitrogen molecules increases. This study opens a new path toward understanding new behaviors of nitrogen in the nanostate and applications of ZIF‐8 for gas storage and capture.
Texture Analysis of Ultrasound Images to Differentiate Simple Fibroadenomas From Complex Fibroadenomas and Benign Phyllodes Tumors
Authors: Basara Akin Isil , Ozgul Hakan , Simsek Kursat , Altay Canan , Secil Mustafa , Balci Pinar 
Published: April 2020

ObjectivesAmerican College of Radiology Breast Imaging Reporting and Data System (BI‐RADS) category 4A lesions can be distinguished from BI‐RADS 3 lesions with main ultrasound (US) findings such as a well‐defined contour, round/oval shape, and parallel orientation with a homogeneous echo pattern. Breast Imaging Reporting and Data System 4A solid masses might be diagnosed as simple fibroadenomas (SFAs), complex fibroadenomas (CFAs), or benign phyllodes tumors (BPTs). Complex fibroadenomas have an increased risk of invasive cancer development than SFAs, and BPTs have a risk of borderline‐malignant phyllodes tumor transformation; both of them are surgically treated, whereas follow‐up procedures are applied in SFAs. It is essential to differentiate SFAs from CFAs and BPTs. Grayscale features of these lesions include a prominent overlap. Texture analyses in breast lesions have contributions in benign‐malignant lesion differentiation. In this study, we aimed to use texture analysis of US images to differentiate these benign lesions.MethodsGrayscale US features of lesions (32 SFAs, 31 CFAs, and 32 BPTs) were classified according to the BI‐RADS. Texture analysis of US images with LIFEx software (http://www.lifexsoft.org) was performed retrospectively. First‐ and second‐order histogram parameters were evaluated.ResultsIn grayscale US, the shape, orientation, and posterior acoustic characteristics had statistical significance (P < .05). In the statistical analysis, skewness, kurtosis, excess kurtosis, gray‐level co‐occurrence matrix (GLCM)‐energy, GLCM‐entropy log 2, and GLCM‐entropy log 10 revealed significant differences among all 3 groups (P < .05).ConclusionsAs grayscale US features show prominent intersections, and treatment options differ, correct diagnosis is essential in SFAs, CFAs, and BPTs. In this study, we concluded that texture analysis of US images can discriminate SFAs from CFAs and BPTs. Texture analyses of US images is a potential candidate diagnostic tool for these lesions, and accurate diagnoses will preclude patients from undergoing unnecessary biopsies.
Evaluation of Cell‐Penetrating Peptides Using Microfluidic In Vitro 3D Brain Endothelial Barrier
Authors: Chung Bohye , Kim Jaehoon , Nam Jiyoung , Kim Hyunho , Jeong Yeju , Liu Hui‐wen , Cho Youngkyu , Kim Yong Ho , Oh Hyun Jeong , Chung Seok 
Published: April 2020

AbstractIn drug delivery to the human brain, blood vessels are a significant hurdle because they restrict the entry of most solutes to protect brain. To overcome this hurdle, an in vitro 3D model for brain endothelial barrier is developed using a microfluidic device with hydrogel providing a 3D extracellular matrix scaffold. Using the model, peptides known to utilize receptor‐mediated transcytosis are verified, which has been one of the most promising mechanisms for brain‐specific penetration. The cytotoxicity and cellular damage to the peptide are investigated and the receptor‐mediated transcytosis and brain endothelial specific penetrating abilities of the peptides in a quantitative manner are demonstrated. As a preclinical test, applying the quantification assays conducted in this study are suggested, including the penetrating ability, cytotoxicity, endothelial damage, and receptor specificity. Using this microfluidic device as an in vitro platform for evaluating various brain targeting drugs and drug carrier candidates is also proposed.
Performance analysis of multicore multimode fiber for passive optical network
Authors: Goyal Shivani , Kaler Rajinder S. , Singh Hardeep 
Published: April 2020

AbstractWe demonstrate the first multicore multimode fiber (MC‐MMF) for passive optical network, efficiently utilizing the space division multiplexing to reduce the upstream traffic losses by eliminating the need of multiple feeder fibers. From the simulation results, the error‐free performance is achieved for upstream transmission over 18 modes of MC‐MMF. The differential group delay per unit length of fiber is also analyzed at different modes of MC‐MMF with attenuation per unit length of fiber, respectively.
Diabetic polyneuropathy and the risk of developing carpal tunnel syndrome: A nationwide, population‐based study
Authors: Moon Hyun Im , Shin Jaeyong , Kim Yong Wook , Chang Jee Suk , Yoon SeoYeon 
Published: April 2020

AbstractBackgroundWe investigated the risk of carpal tunnel syndrome (CTS) in diabetic polyneuropathy (DPN).MethodsThis study was conducted using records from the National Health Insurance System (NHIS). We divided patients diagnosed with diabetes mellitus (DM) into those with and without DPN. We assessed the effect of DPN on the risk of CTS using Cox proportional hazards regression analyses.ResultsDPN was associated with an increased risk of CTS (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12–1.58). In sub‐analyses, female gender (HR, 1.45; 95% CI, 1.20–1.76), presence of type 2 DM (HR, 1.36; 95% CI, 1.11–1.64), and age 35 to 64 years (HR 1.35; 95% CI, 1.11–1.64) were significantly associated with an increased risk of CTS.ConclusionsPatients with DPN had an increased risk of CTS compared with the non‐DPN group, particularly females, those with type 2 DM, and those aged 35 to 64 years.
The care of patients with Duchenne, Becker, and other muscular dystrophies in the COVID‐19 pandemic
Authors: Veerapandiyan Aravindhan , Wagner Kathryn R. , Apkon Susan , McDonald Craig M. , Mathews Katherine D. , Parsons Julie A. , Wong Brenda L. , Eichinger Katy , Shieh Perry B. , Butterfield Russell J. , Rao Vamshi K. , Smith Edward C. , Proud Crystal M. , Connolly Anne M. , Ciafaloni Emma 
Published: April 2020

AbstractThe coronavirus disease 2019 (COVID‐19) pandemic has resulted in the reorganization of health‐care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID‐19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic. We address issues surrounding corticosteroid and exon‐skipping treatments, cardiac medications, hydroxychloroquine use, emergency/respiratory care, rehabilitation management, and the conduct of clinical trials. We highlight the importance of collaborative treatment decisions between the patient, family, and health‐care provider, considering any geographic or institution‐specific policies and precautions for COVID‐19. We advocate for continuing multidisciplinary care for these patients using telehealth.
Potential effects of a high CO2 future on leguminous species
Authors: Singer Stacy D. , Chatterton Syama , Soolanayakanahally Raju Y. , Subedi Udaya , Chen Guanqun , Acharya Surya N. 
Published: April 2020

Why this research MattersLegumes provide an important source of food and feed due to their high protein levels and many health benefits, and also impart environmental and agronomic advantages as a consequence of their ability to fix nitrogen through their symbiotic relationship with rhizobia. As a result of our growing population, the demand for products derived from legumes will likely expand considerably in coming years. Since there is little scope for increasing production area, improving the productivity of such crops in the face of climate change will be essential. While a growing number of studies have assessed the effects of climate change on legume yield, there is a paucity of information regarding the direct impact of elevated CO2 concentration (e[CO2]) itself, which is a main driver of climate change and has a substantial physiological effect on plants. In this review, we discuss current knowledge regarding the influence of e[CO2] on the photosynthetic process, as well as biomass production, seed yield, quality, and stress tolerance in legumes, and examine how these responses differ from those observed in non‐nodulating plants. Although these relationships are proving to be extremely complex, mounting evidence suggests that under limiting conditions, overall declines in many of these parameters could ensue. While further research will be required to unravel precise mechanisms underlying e[CO2] responses of legumes, it is clear that integrating such knowledge into legume breeding programs will be indispensable for achieving yield gains by harnessing the potential positive effects, and minimizing the detrimental impacts, of CO2 in the future.
Using collaborative logic analysis evaluation to test the program theory of an intensive interdisciplinary pain treatment for youth with pain‐related disability
Authors: Hurtubise Karen , Brousselle Astrid , Camden Chantal 
Published: April 2020

AbstractIntensive interdisciplinary pain treatment (IIPT) involves multiple stakeholders. Mapping the program components to its anticipated outcomes (ie, its theory) can be difficult and requires stakeholder engagement. Evidence is lacking, however, on how best to engage them. Logic analysis, a theory‐based evaluation, that tests the coherence of a program theory using scientific evidence and experiential knowledge may hold some promise. Its use is rare in pediatric pain interventions, and few methodological details are available. This article provides a description of a collaborative logic analysis methodology used to test the theoretical plausibility of an IIPT designed for youth with pain‐related disability. A 3‐step direct logic analysis process was used. A 13‐member expert panel, composed of clinicians, teachers, managers, youth with pain‐related disability, and their parents, were engaged in each step. First, a logic model was constructed through document analysis, expert panel surveys, and focus‐group discussions. Then, a scoping review, focused on pediatric self‐management, building self‐efficacy, and fostering participation, helped create a conceptual framework. An examination of the logic model against the conceptual framework by the expert panel followed, and recommendations were formulated. Overall, the collaborative logic analysis process helped raiseawareness of clinicians’ assumptions about the program causal mechanisms, identified program components most valued by youth and their parents, recognized the program features supported by scientific and experiential knowledge, detected gaps, and highlighted emerging trends. In addition to providing a consumer‐focused program evaluation option, collaborative logic analysis methodology holds promise as a strategy to engage stakeholders and to translate pediatric pain rehabilitation evaluation research knowledge to key stakeholders.