bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalization with a VEGFR2‐binding antibody fragment leads to enhanced endothelialization of a cardiovascular stent in vitro and in vivo
Authors: Wawrzyńska Magdalena , Kraskiewicz Honorata , Paprocka Maria , Krawczenko Agnieszka , Bielawska‐Pohl Aleksandra , Biały Dariusz , Roleder Tomasz , Wojakowski Wojciech , O'Connor Iain B. , Duda Maciej , Michal Robert , Wasyluk Łukasz , Plesch Gustav , Podbielska Halina , Kopaczyńska Marta , Wall J. Gerard
Published: April 2019

Rapid endothelialization of cardiovascular stents is critical to prevent major clinical complications such as restenosis. Reconstruction of the native endothelium on the stent surface can be achieved by the capture of endothelial progenitor cells (EPCs) or neighboring endothelial cells (ECs) in vivo. In this study, stainless steel cardiovascular stents were functionalized with recombinant scFv antibody fragments specific for vascular endothelial growth factor receptor‐2 (VEGFR2) that is expressed on EPCs and ECs. Anti‐VEGFR2 scFvs were expressed in glycosylated form in Escherichia coli and covalently attached to amine‐functionalized, titania‐coated steel disks and stents. ScFv‐coated surfaces exhibited no detectable cytotoxicity to human ECs or erythrocytes in vitro and bound 15 times more VEGFR2‐positive human umbilical vein ECs than controls after as little as 3 min. Porcine coronary arteries were successfully stented with scFv‐coated stents with no adverse clinical events after 30 days. Endovascular imaging and histology revealed coverage of the anti‐VEGFR2 scFv‐coated stent with a cell layer after 5 days and the presence of a neointima layer with a minimum thickness of 80 μm after 30 days. Biofunctionalization of cardiovascular stents with endothelial cell‐capturing antibody fragments in this manner offers promise in accelerating stent endothelialization in vivo. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:213–224, 2020.
Exosomal transfer of miR‐124 inhibits normal fibroblasts to cancer‐associated fibroblasts transition by targeting sphingosine kinase 1 in ovarian cancer
Authors: Zhang Yuyang , Cai Huihua , Chen Siping , Sun Donghua , Zhang Dongmei , He Yuanli
Published: April 2019

Objective

The interaction between tumor microenvironment and tumor cells plays a key role in tumor progression. However, the mechanisms by which this interaction promotes the transdifferentiation of normal fibroblasts (NFs) to cancer‐associated fibroblasts (CAFs) are still unclear. The aim of this study was to investigate whether ovarian cancer (OvCa) cells‐derived microRNAs were involved in the transition of resident fibroblasts to CAFs, and in promoting tumorigenesis.

Methods

CAFs and NFs were isolated from the same ovarian site in OvCa and noncancerous prophylactic oophorectomy specimens. The effect of exosomes on the motility of CAFs or NFs was analyzed by wound healing and Transwell assays. The expression of CAFs marker α‐smooth muscle actin (α‐SMA) and fibroblast activated protein (FAP) were determined by quantitative real‐time PCR and Western blotting. A luciferase reporter assay was used to test the interaction between miR‐124 and sphingosine kinase 1 (SPHK1).

Results

NFs with downregulated miR‐124 displayed the characteristics of CAFs, including overexpression of α‐SMA and FAP and increased migratory and invasive ability. Overexpression of miR‐124 in CAFs reversed some traits of NFs. Human ovarian surface epithelial cells‐secreted miR‐124 could be transferred via exosomes to CAFs and resulted in decreased α‐SMA and FAP expression and attenuated cell motility. Moreover, our finding showed that the expression of SPHK1, a potential target of miR‐124, was significantly elevated in CAFs.

Conclusions

The present study provides important and novel perspective into OvCa CAF differentiation and extracellular matrix remodeling, which trigger the tumor progression.
Identification of a three‐miRNA signature as a novel potential prognostic biomarker in patients with clear cell renal cell carcinoma
Authors: Luo Yongwen , Chen Liang , Wang Gang , Xiao Yu , Ju Lingao , Wang Xinghuan
Published: April 2019

Current studies suggest that some microRNAs (miRNAs) are associated with prognosis in clear cell renal cell carcinoma (ccRCC). In this paper, we aimed to identify a miRNAs signature to improve prognostic prediction for ccRCC patients. Using ccRCC RNA‐Seq data of The Cancer Genome Atlas (TCGA) database, we identified 177 differentially expressed miRNAs between ccRCC and paracancerous tissue. Then all the ccRCC tumor samples were divided into training set and validation set randomly. Three‐miRNA signature including miR130b, miR‐18a, and miR‐223 were constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression model in training set. According to optimal cut‐off value of three‐miRNA signature risk score, all the patients could be classified into high‐risk group and low‐risk group significantly. Survival of patients was significantly different between two groups (hazard ratio, 5.58, 95% confidence interval, 3.17‐9.80; P < 0.0001), and three‐miRNA signature performed favorably prognostic and predictive accuracy. The results were further validated in the validation set and total set. Multivariate Cox regression analyses and subgroup analyses showed that three‐miRNA signature was an independent prognostic factor. Two nomograms that integrated three‐miRNA signature and three clinicopathological risk factors were constructed to predict overall survival and disease‐free survival after surgery for ccRCC patients. Functional enrichment analysis showed the possible roles of three‐miRNA signature in some cancer‐associated biological processes and pathways. In conclusion, we developed a novel three‐miRNA signature that performed reliable prognostic for patient survival with ccRCC, it might facilitate ccRCC patients counseling and individualize management.
Loss of p27kip1 suppresses the myocardial senescence caused by estrogen deficiency
Authors: Yan Yi , Miao Dengshun , Yang Zhijian , Zhang Dingguo
Published: April 2019

Estrogen deficiency accelerates the aging process and increases the risk of developing cardiovascular disease (CVD). Apoptosis is one of the important mechanisms of aging. p27kip1 is a cyclin‐dependent kinase inhibitor that can regulate cell cycle, apoptosis, and cell motility. p27kip1 overexpression can inhibit cell cycle and increase apoptosis so it has been considered as a marker of aging. In the present study, bilateral ovariectomy (OVX) was performed as a model for menopause in wild‐type (WT) and p27kip1 knockout (KO) mice to assess the effects of p27kip1 loss in myocardial aging caused by estrogen deficiency. We found that myocardial fibrosis and heart weight/body weight ratio of mice in the OVX group and p27kip1 KO group were significantly increased. Echocardiography showed that the left ventricular diameter and volume of the WT OVX group increased significantly and the cardiac function decreased. However, there was no significant difference in the results of echocardiography between the two p27kip1 KO groups. The aging and apoptosis indexes in OVX group were increased significantly, However, the indexes in p27kip1 KO mice were decreased. The expression of antioxidant indexes in OVX group was decreased significantly and p27kip1 KO can improve the antioxidant ability. These results provided that estrogen deficiency increased oxidative stress and apoptosis, accelerated aging of heart. p27kip1 KO can partly delay the aging and apoptosis of heart through upregulated antioxidant enzymes.
Suppression of c‐Myc using 10058‐F4 exerts caspase‐3‐dependent apoptosis and intensifies the antileukemic effect of vincristine in pre‐B acute lymphoblastic leukemia cells
Authors: Sheikh‐Zeineddini Negar , Bashash Davood , Safaroghli‐Azar Ava , Riyahi Niknam , Shabestari Rima Manafi , Janzamin Ehsan , Safa Majid
Published: April 2019

Despite an old history behind the identification of the leading role of c‐Myc in leukemogenesis, the road to constructing a therapeutic perspective for this molecule in acute lymphoblastic leukemia (ALL) is yet mesmerizing. This study was designed to provide a better outlook for the anticancer property of 10058‐F4, an appealing inhibitor of c‐Myc, in pre‐B ALL cell lines either in the context of monotherapy or in combination with chemotherapeutic drugs. Our results declared that abrogation of c‐Myc decreased the proliferative capacity of pre‐B ALL‐derived cells through halting the transition of the cells from G1 phase, and reducing the replicative potential of both REH and Nalm‐6 cells, at least partly, through c‐Myc‐mediated suppression of human telomerase reverse transcriptase. Moreover, 10058‐F4 potently induced a caspase‐3‐dependent apoptosis in pre‐B ALL cells via shifting the balance between pro‐ and anti‐apoptotic target genes. Although the inhibition of PI3Kδ using Idelalisib upregulated the messenger RNA expression of autophagy‐related genes in 10058‐F4‐treated cells, treatment with autophagy inhibitor chloroquine decreased viability of the cells, either as a single agent or in combination with Idelalisib and/or 10058‐F4; suggesting that the activation of autophagy in pre‐B ALL cells could blunt apoptotic events and attenuate anticancer effect of both c‐Myc and PI3K inhibitors. Finally, the results of our synergistic experiments delineated that 10058‐F4 produced a synergistic effect with vincristine and provided an enhanced therapeutic efficacy in ALL cells, highlighting that c‐Myc oncoprotein could be a bona fide target for the treatment of ALL.
Lentiviral delivery of a shRNA sequence analogous to miR‐4319/miR‐125‐5p induces apoptosis in NSCLC cells by arresting G2/M phase
Authors: Xu Xuebo , Lai Yueyang , Zhou Wenzhao , Hua Zichun
Published: April 2019

In this study, we explored the therapeutic potential of microRNA (miR) analogs against non–small‐cell lung cancer (NSCLC) using lentiviral delivery of short hairpin RNA (shRNA). By using A549 as a model cell line, we used analogs and mimics of miR‐4319/miR‐125‐5p to target the tumorigenic RAF1 gene. Lentiviral vectors carrying shRNA of a highly efficient miRNA analog of miR‐4319/miR‐125‐5p, Analog2, were constructed to infect A549 cells. Our results showed that, compared with the noncancerous bronchial epithelial cell line 16HBE, lentivirus delivering Analog2 shRNA induced significant G2/M arrest and subsequent apoptosis in A549 cells, but not in 16HBE cells. Western blot analysis revealed that key factors regulating cell cycle were downregulated following RAF1 inhibition. In vivo xenograft experiments showed that lentivirus carrying Analog2 shRNA markedly decreased tumor size. Therefore, lentiviral delivery of Analog2 shRNA is a valid RNA interference‐based treatment against NSCLC with high potency and specificity.
Reaction energy benchmarks of hydrocarbon combustion by Gaussian basis and plane wave basis approaches
Authors: Ishikawa Atsushi , Tateyama Yoshitaka
Published: April 2019

The reaction energies of 275 elementary reactions from the hydrocarbon combustion model GRI‐Mech 3.0 were evaluated by electronic structure calculations using both localized Gaussian basis and plane wave basis sets. In the Gaussian basis calculations, the d‐polarization function on C, N, and O elements reduces the mean absolute deviation (MAD) from the experimental value by 53%, a significant improvement in computational accuracy. In the plane wave basis calculation using different exchange‐correlation (XC) functionals, the MAD values were 0.316–0.426 eV when non‐hybrid type XC functionals such as RPBE, PBE, PW91, revPBE, and PBEsol were used. On the other hand, hybrid functionals like B3LYP and HSE06 reduced the MAD values significantly down to 0.182 and 0.233 eV, respectively. The B3LYP results have 49% less MAD compared to the PBE results. These demonstrated the strong advantage of the hybrid functional for calculating gas‐phase reaction energies. The present comprehensive benchmarks will be crucial for future microkinetics as well as machine learning studies on the catalytic reactions. © 2019 Wiley Periodicals, Inc.
Covering arrays for some equivalence classes of words
Authors: Cassels Joshua , Godbole Anant
Published: April 2019

Covering arrays for words of length over a ‐letter alphabet are arrays with entries from the alphabet so that for each choice of columns, each of the ‐letter words appears at least once among the rows of the selected columns. We study two schemes in which all words are not considered to be different. In the first case known as partitioning hash families, words are equivalent if they induce the same partition of a element set. In the second case, words of the same weight are equivalent. In both cases, we produce logarithmic upper bounds on the minimum size of a covering array. Definitive results for , as well as general results, are provided.
Integrated mRNA and miRNA expression profile analyses reveal the potential roles of sex‐biased miRNA–mRNA pairs in gonad tissues of the Chinese concave‐eared torrent frog (Odorrana tormota)
Authors: Shu Yilin , Zhang Huijuan , Cai Qijia , Tang Dong , Wang Gang , Liu Ting , Lv Bihua , Wu Hailong
Published: April 2019

The Chinese concave‐eared torrent frog (Odorrana tormota) is typically sexually dimorphic. Females are significantly less common than males in the wild. Until now, the molecular mechanisms of reproduction and sex differentiation of frogs remain unclear. Here, we integrated mRNA and microRNA (miRNA) expression profiles to reveal the molecular mechanisms of reproduction and sex differentiation in O. tormota. We identified 234 differentially expressed miRNAs (DEMs) and 18,551 differentially expressed transcripts. Of these, 12,053 mRNAs and 64 miRNAs were upregulated in testes, and 6,498 mRNAs and 170 miRNAs were upregulated in ovaries. Integrated analysis of the miRNA and mRNA expression profiles predicted 75,602 potential miRNA–mRNA interaction sites, with 42,065 negative miRNA–mRNA interactions. We found 36 differentially expressed genes (DEGs) related to reproduction and sex differentiation, of which 15 DEGs formed 92 negative miRNA–mRNA interactions with 34 known DEMs. Thus, miRNAs may play other important roles in O. tormota. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed reproductive‐related processes, such as the gonadotropinreleasing hormone signaling pathway and ovarian steroidogenesis. Based on functional annotation and the literature, the retinoic acid signaling pathway, the SOX9–AMH pathway, and the process of spermatogenesis may be involved in the molecular mechanisms of reproduction and sex differentiation in O. tormota, and may be regulated by miRNAs. The miRNA–mRNA pairs described may provide further understanding of the regulatory mechanisms associated with reproduction and sex differentiation, and the molecular mechanism of reproduction in O. tormota.
Access to sexual and reproductive health services for women living with HIV in Latin America and the Caribbean: systematic review of the literature
Authors: Gómez‐Suárez Marcela , Mello Maeve B , Gonzalez Mónica Alonso , Ghidinelli Massimo , Pérez Freddy
Published: April 2019

Introduction

Systematic reviews show that women living with HIV (WLHIV) have high unmet sexual and reproductive health (SRH) needs due to barriers to access sexual and reproductive health services (SRHS). In Latin America and the Caribbean (LAC), as of 2016, there were nearly one million WLHIV, but the existing evidence of their SRH needs comes from a few individual studies. This systematic review provides an overview of these women's needs to help define new and/or adapt existing public health strategies to the local context. This review synthesizes the evidence from the literature on the use of and access to SRHS related to family planning, antenatal care, abortion services and violence against WLHIV in LAC.

Methods

Using a systematic review of mixed studies, a search was performed in MEDLINE, EMBASE, LILACS, INASP, POPLINE, SCOPUS, for studies conducted in LAC, from 2004 to 2017, as well as contact with authors and hand search as needed. Two independent reviewers evaluated the quality of the studies using the Mixed Methods Appraisal Tool; inclusion was conducted according to the PRISMA flow diagram. An exploratory narrative synthesis followed by quantitative synthesis data was undertaken. Group analysis or meta‐analysis was not considered appropriate given the level of heterogeneity of the studies.

Results

A total of 18 studies in 13 LAC countries for a population of 5672 WLHIV were included. Data from individual studies reported unmet family planning needs; higher, but inconsistent use of condom as the sole contraceptive method OR=1.46 [1.26 to 1.69]; lesser use of other non‐permanent contraceptive methods OR=0.26 [0.22 to 0.31]; more unplanned pregnancies OR=1.30 [1.02 to 1.66]; more induced abortions OR=1.96 [1.60 to 2.39]; higher risk of immediate postpartum sterilization; and higher exposure to sexual and institutional violence by WLHIV when compared with women without HIV.

Conclusions

This review presents evidence from LAC about the SRH unmet needs of WLHIV that must be addressed by decreasing institutional and structural barriers, facilitating services and reducing stigma, and discrimination among healthcare providers to improve access to SRHS based on human rights, so women independently of their HIV status can make their own reproductive decisions, free of violence and coercion.
Myeloid C-type lectin receptors in skin/mucoepithelial diseases and tumors
Authors: Tang Ce , Makusheva Yulia , Sun Haiyang , Han Wei , Iwakura Yoichiro
Published: April 2019

Myeloid C-type lectin receptors (CLRs), which consist of an extracellular carbohydrate recognition domain and intracellular signal transducing motif such as the immunoreceptor tyrosine-based activation motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM), are innate immune receptors primarily expressed on myeloid lineage cells such as dendritic cells (DCs) and Mϕs. CLRs play important roles in host defense against infection by fungi and bacteria by recognizing specific carbohydrate components of these pathogens. However, these immune receptors also make important contributions to immune homeostasis of mucosa and skin in mammals by recognizing components of microbiota, as well as by recognizing self-components such as alarmins from dead cells and noncanonical non-carbohydrate ligands. CLR deficiency not only induces hypersensitivity to infection, but also causes dysregulation of muco-cutaneous immune homeostasis, resulting in the development of allergy, inflammation, autoimmunity, and tumors. In this review, we introduce recent discoveries regarding the roles of myeloid CLRs in the immune system exposed to the environment, and discuss the roles of these lectin receptors in the development of colitis, asthma, psoriasis, atopic dermatitis, and cancer. Although some CLRs are suggested to be involved in the development of these diseases, the function of CLRs and their ligands still largely remain to be elucidated.
“Keep your feet on the ground”: Simulated range of motion and hind foot posture of the Middle Jurassic sauropodRhoetosaurus browneiand its implications for sauropod biology
Authors: Jannel Andréas , Nair Jay P. , Panagiotopoulou Olga , Romilio Anthony , Salisbury Steven W.
Published: April 2019

The biomechanics of the sauropod dinosaur pes is poorly understood, particularly among the earliest members of the group. To date, reasonably complete and articulated pedes in Early Middle Jurassic sauropods are rare, limited to a handful of taxa. Of these,Rhoetosaurus brownei, from eastern Australia, is currently the only one from the Gondwanan Middle Jurassic that preserves an articulated pes. UsingRhoetosaurus browneias a case exemplar, we assessed its paleobiomechanical capabilities and pedal posture. Physical and virtual manipulations of the pedal elements were undertaken to evaluate the range of motion between the pedal joints, under both bone‐to‐bone and cartilaginous scenarios. Using the results as constraints, virtual reconstructions of all possible pedal postures were generated. We show thatRhoetosaurus browneiwas capable of significant digital mobility at the osteological metatarsophalangeal and distal interphalangeal joints. We assume these movements would have been restricted by soft tissue in life but that their presence would have helped in the support of the animal. Further insights based on anatomy and theoretical mechanical constraints restricted the skeletal postures to a range encompassing digitigrade to subunguligrade stances. The approach was extended to additional sauropodomorph pedes, and some validation was provided via the bone data of an African elephant pes. Based on the resulting pedal configurations, the in‐life plantar surface of the sauropod pes is inferred to extend caudally from the digits, with a soft tissue pad supporting the elevated metatarsus. The plantar pad is inferred to play a role in the reduction of biomechanical stresses, and to aid in support and locomotion. A pedal pad may have been a key biomechanical innovation in early sauropods, ultimately resulting in a functionally plantigrade pes, which may have arisen during the Early to Middle Jurassic. Further mechanical studies are ultimately required to permit validation of this long‐standing hypothesis.
Spatio‐temporal drought patterns of multiple drought indices based on precipitation and soil moisture: A case study in South Korea
Authors: Kwon Moonhyuk , Kwon Hyun‐Han , Han Dawei
Published: April 2019

This study aims to explore the spatio‐temporal characteristics of meteorological and agricultural droughts using the standardized precipitation index (SPI) and standardized soil moisture index (SSI), respectively, as well as their relationships over the past three decades (1986–2016) in South Korea. The SSI shows less frequent droughts and longer drought duration compared to the SPI, due to the gradual decrease in the autocorrelation functions of the SSI. The strongest cross‐correlations are observed at a 1‐month lag between the SPI and SSI for most stations. Thus, the SPI could be more appropriate for defining the onset of a drought, whereas the SSI appears to be more effective for describing drought persistence. Moreover, the transition from meteorological to agricultural droughts is significantly dependent on the season, indicating that the transition between them is highly correlated with antecedent moisture conditions. The copula‐based multivariate standardized drought index (MSDI) is introduced to explicitly postulate interdependence between the SPI and SSI in the context of a multivariate probability distribution. We employ a hierarchical agglomerative clustering approach along with a quantile regression model to better understand the spatio‐temporal pattern of the MSDI. More drought episodes under moderate to severe drought conditions are observed along the southern coast of South Korea. Additionally, persistent droughts with higher severity are observed in the northern part of South Korea, which may be attributed to a significant decreasing trend (or increasing drought risk).
Multi‐Year Effect of Human Papillomavirus Vaccination on Recurrent Respiratory Papillomatosis
Authors: Matsuzaki Hiroumi , Makiyama Kiyoshi , Hirai Ryoji , Suzuki Hirotaka , Asai Ryohei , Oshima Takeshi
Published: April 2019

Objective

To examine whether human papilloma virus (HPV) vaccination in combination with surgical resection could suppress recurrence for an extended period of time in patients with recurrent respiratory papillomatosis (RRP).

Methods

In a prospective case series, data of patients who received combination therapy comprising surgery and quadrivalent HPV vaccination (Gardasil; Merck & Co., West Point, PA) were collected. Patients were followed up for RRP from March 2012 to July 2018 in an academic tertiary care center. The patients comprised 16 adults with RRP who were observed for >12 months after HPV vaccination, and whose HPV‐DNA status was tested before and for >12 months after completion of combination therapy. The outcomes of this study were the severity score of larynx disease, tumor incidence rate, and relationship between this rate and HPV‐DNA negative conversion after therapy.

Results

The severity score of laryngeal disease significantly decreased from before combination therapy to the time of final examination (P = 0.00045). The tumor incidence rate decreased to approximately 20% during the period from 12 to 47 months after HPV vaccination. Regarding HPV‐DNA status in the final test results of each patient, 12 of 16 (75%) patients showed negative conversion; these 12 were significantly less likely to experience recurrence than patients who persistently tested positive for HPV‐DNA during the period between 12 and 47 months after vaccination.

Conclusion

HPV vaccination prevented recurrence associated with RRP surgery for 4 years in 80% of patients. This may be an effective adjuvant therapy, and HPV‐DNA negative conversion after HPV vaccination might predict prevention of recurrence.

Level of Evidence

2 Laryngoscope, 130:442–447, 2020
Effect of the T6 heat treatment on corrosion behavior of additive manufactured and gravity cast AlSi10Mg alloy
Authors: Girelli Luca , Tocci Marialaura , Conte Manuela , Giovanardi Roberto , Veronesi Paolo , Gelfi Marcello , Pola Annalisa
Published: April 2019

This study investigates the corrosion behavior of AlSi10Mg alloy produced by additive manufacturing and gravity casting before and after T6 heat treatment. Electrochemical tests showed that the additive manufactured material in as‐produced condition exhibits high corrosion resistance, due to the very fine microstructure, while immersion test allowed to identify an exfoliation‐like corrosion phenomenon, which caused a significant mass loss. In this case, T6 heat treatment was beneficial for corrosion resistance since the related change in microstructure led to a less detrimental corrosion mechanism. Therefore, the T6 heat treatment resulted necessary to use additive manufactured AlSi10Mg components in aggressive chloride‐bearing environments.
Neurorehabilitation Improves the Motor Features in Prodromal SCA2: A Randomized, Controlled Trial
Authors: Velázquez‐Pérez Luis , Rodríguez‐Diaz Julio C. , Rodríguez‐Labrada Roberto , Medrano‐Montero Jacqueline , Aguilera Cruz Annety B. , Reynaldo‐Cejas Lorenzo , Góngora‐Marrero Mariela , Estupiñán‐Rodríguez Annelié , Vázquez‐Mojena Yaimeé , Torres‐Vega Reidenis
Published: April 2019

Background

The search for early interventions is a novel approach in spinocerebellar ataxias, but there are few studies supporting this notion. This article aimed to assess the efficacy of neurorehabilitation treatment in prodromal spinocerebellar ataxia type 2.

Methods

Thirty spinocerebellar ataxia type 2 preclinical carriers were enrolled in a randomized, controlled trial using neurorehabilitation. The intervention in the treated group was 4 hours per day, 5 days per week for 12 weeks, emphasizing static balance, gait, and limb coordination. The control group did not receive rehabilitation. The primary outcome measure was the time for 5‐m tandem gait over the floor. Secondary outcomes included other timed tests with increased motor complexity, as well as the scores of the SARA and the Inventory of Non‐ataxia Symptoms.

Results

The times for 5‐m tandem gait over the floor and the mattress were significantly reduced only in the rehabilitated group. Moreover, the times upholding the tandem stance over a mattress and the seesaw were notably increased only in this group. Likewise, the finger‐nose and the heel‐shin tests were improved in the rehabilitated group alone. The SARA score and the count of nonataxia symptoms were unchanged.

Conclusions

This rehabilitation program improves the subtle gait, postural and coordinative deficits in prodromal spinocerebellar ataxia type 2, which provided novel hints about the preservation of motor learning and neural plasticity mechanisms in early disease stages, leading chances for other interventional approaches in this and other spinocerebellar ataxias. © 2019 International Parkinson and Movement Disorder Society
Without congressional action, CCBHCs will perish
Authors: Wentz Debra
Published: April 2019

The Certified Community Behavioral Health Clinic (CCBHC) federal demonstration program launched in 2017 in eight states, including New Jersey. These programs serve adults and children and provide mental health and substance use treatment, crisis services, case management, primary health care and more. Federal legislation (S. 824/H.R. 1767) was recently introduced to extend the CCBHC demonstration program for two years beyond its current expiration date of June 30, 2019.
Evaluation of short folded dipole antennas as receive elements of ultra‐high‐field human head array
Authors: Avdievich Nikolai I. , Solomakha Georgiy , Ruhm Loreen , Scheffler Klaus , Henning Anke
Published: April 2019

Purpose

To improve the receive (Rx) performance of a human head transceiver (TxRx) array at 9.4T without compromising its transmit (Tx) performance, a novel 16‐element array was developed, constructed, and tested.

Methods

We designed and constructed a phased array, which consists of 8 TxRx surface loops placed in a single row and circumscribing a head, and 8 Rx‐only short folded dipole antennas. Dipoles were positioned along the central axis of each transceiver loop perpendicular to its surface. We evaluated the effect of Rx dipoles on the Tx efficiency of the array and maximum local specific absorption rate (SAR) as compared to the array of 8 surface loops only. We also compared the new array to a 16‐channel array of the same size consisting of 8 TxRx surface loops and 8 Rx‐only vertical loops in terms of Tx efficiency, SAR, and signal‐to‐noise ratio (SNR).

Results

The new array improves both peripheral (up to 2 times) and central (1.17 times) SNR as compared to the 16‐element array of the same geometry consisting of 8 TxRx surface loops and 8 Rx‐only vertical loops. We demonstrated that an addition of actively detuned Rx‐only dipole elements produces only a small decrease (~7%) of the transmit field and a small increase (<7%) of the maximum local SAR.

Conclusion

As a proof of concept, we developed and constructed a prototype of a 9.4T (400 MHz) head array consisting of 8 TxRx surface loops and 8 Rx‐only short optimized folded dipoles. We demonstrated that at ultra‐high field, dipoles outperformed Rx‐only vertical loops in vivo.
Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?
Authors: Graupner Oliver , Enzensberger Christian , Götte Malena , Wolter Aline , Müller Vera , Kawecki Andreea , Weber Stefanie , Degenhardt Jan , Herrmann Johannes , Axt‐Fliedner Roland
Published: April 2019

Objectives

Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices.

Methods

This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M‐mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively.

Results

Among other findings, right ventricular (RV) e’/a’ ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level‐dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e’/a’ ratio and β‐2‐microglobulin as well as α‐1‐microglobulin and potassium could be observed.

Conclusion

We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling.
Teacher attributions for children's attention‐deficit/hyperactivity disorder behaviors predict experiences with children and with classroom behavioral management in a summer program practicum
Authors: Mikami Amori Yee , Smit Sophie , Johnston Charlotte
Published: April 2019

Elementary school teachers often implement classroom behavioral management systems to address student misbehavior. Common problems targeted by these systems are the inattentive, hyperactive, and impulsive behaviors characteristic of attention‐deficit/hyperactivity disorder (ADHD). This study examined teachers' attributions for why children display ADHD behaviors, and how such attributions affect their experiences with children in the context of interventions to manage these behaviors. Participants were 32 preservice teachers undertaking a practicum in a summer program for 137 children (Grades 1–3), some of whom had ADHD. Teachers were trained to implement classroom‐wide behavioral management. Teachers' attributions for children's ADHD behaviors were assessed using a vignette measure, before teachers had met their students or begun training on intervention techniques. When controlling for attributions regarding oppositional behavior, teachers' initial attributions for ADHD behaviors as less internal/controllable predicted children reporting more positive relationships with that teacher during the summer program. Teachers' initial attributions for ADHD behaviors as less stable predicted teachers' greater satisfaction with the intervention techniques during the summer program and their greater attunement to children's social networks. Cognitions about the causes of children's ADHD behaviors held by preservice teachers may relate to their subsequent experiences with children in the context of implementing classroom behavioral management.
Nanoparticle‐enhanced bamboo‐like tubular nanofibers for active capture of particulate matter
Authors: Wu Guang , Luo Jiajun , Zhao Lingling , Liang Hongze , Liu Chaozong , Tan Hui , Li Weiping , Tang Youhong
Published: April 2019

We proposed a thought of active capture of particles by improving the interaction force between fibers and particles. Nanoparticle‐enhanced tubular nanofibers (Ag‐SPNTs) were prepared by template‐free cationic polymerization followed by surface modification. Ag‐SPNTs have coarse surface and bamboo‐like tubular structure with a diameter of approximately 80‐150 nm. Ag nanoparticles were embedded on the nanofibers surface, and the content of Ag nanoparticles in the nanofibers could be tuned by changing the concentration of [Ag(NH3)2]+ in the preparation process. f‐d curve measured by AFM showed that increasing the content of Ag nanoparticles in the nanofibers resulted in the enhanced interaction force between the nanofiber surface and particles. Particle matter capture test showed that the number of captured microscaled/naonoscaled particles on the fiber surface increased obviously for the nanoparticle‐enhanced tubular nanofibers (Ag‐SPNTs) compared to the nanofibers without nanoparticle (SPNTs), probably due to the increased interaction force and adhesion energy between fiber surface and particles. Filtration property test showed that the Ag‐SPNTs fiber films had a better filtration performance with a higher filter efficiency and QF value than that of SPNTs. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019
“It felt like unfinished business, it feels like that's finished now”: Women's experiences of decision making around contralateral prophylactic mastectomy (CPM)
Authors: Tollow Philippa , Williams Victoria Suzanne , Harcourt Diana , Paraskeva Nicole
Published: April 2019

Objective

Increasing numbers of women in the United Kingdom are choosing to have a contralateral prophylactic mastectomy (CPM) after diagnosis of breast cancer. Whilst research suggests that many experience high rates of psychological well‐being after CPM, professional guidelines suggest CPM is “not required” for the majority of unilateral breast cancer patients, and some individuals consider the surgery to be controversial. Existing research has explored patients' reasons for seeking CPM; however, little is known about their experiences of decision making. This study aimed to investigate women's experiences of decision making around CPM in the United Kingdom.

Methods

Semistructured qualitative interviews were conducted with 27 women, recruited through breast cancer support charities. All participants had CPM in the United Kingdom after a diagnosis of unilateral breast cancer, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma. Data were analysed using thematic analysis.

Results

Two main themes were generated from the analytic process: “sanity check” (“battling for CPM,” “feeling stigmatised,” “seeking similar others”) and “reclaiming the body” (“being true to self,” “moving forward”). Women described defending their decision to have CPM, concerns that their thoughts about surgery may be considered “abnormal,” and seeking support from peers. The decision to have CPM was discussed in terms of their future relationship with their body and moving forward after cancer.

Conclusions

This study highlights the importance of interactions with health care professionals in the decision‐making experience, the role of peer support, and the need to fully understand the potentially complex and multifaceted nature of each woman's decision to seek CPM.
Reference values for spirometric parameters in healthy children living in a Colombian city located at 2640 m altitude
Authors: Aristizabal‐Duque Ricardo , Castiblanco Edwin , Rodriguez Ingrid , Sossa‐Briceño Monica P. , Rodriguez‐Martinez Carlos E.
Published: April 2019

Objectives

To identify the spirometric equations that are most appropriate for use in children and adolescents living in Bogota, Colombia after evaluating a set of relevant previously‐developed equations, including the Global Lung Function Initiative (GLI) 2012 spirometry reference equations.

Methods

Healthy children aged between 6 and 17 years that were attending two randomly‐selected schools in Bogota were invited to participate in the study, from January 2017 to January 2018. All participants underwent spirometry, following the procedures recommended by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To identify the model or group of models that best predict each spirometric parameter in our population, we performed extensive residuals analyses and constructed Bland‐Altman plots.

Results

Three hundred twenty‐six spirometric tests (149 boys, 177 girls) formed the reference data set. Knudson and GLI‐2012 spirometry reference equations proved to be the most accurate in predicting the majority of spirometry parameters in both sexes and both age groups, each providing the lowest median prediction error in the residual analyses or the narrowest limits of agreement in the Bland‐Altman plots in approximately one‐third of the spirometry parameters analyzed.

Conclusion

For the majority of spirometry parameters, we recommend the use of Knudson and GLI‐2012 spirometry reference equations for evaluating the respiratory function of children living in Bogota, Colombia, a city located at an altitude of 2640 m. Future investigations should target additional spirometric equations from Latin American populations living at moderate to high altitude to improve the GLI‐2012 equations.
Optimizing live‐animal bioluminescence imaging prediction of tumor burden in human prostate cancer xenograft models in SCID‐NSG mice
Authors: Kim Sangyub , Zhang Yong , Tang Suni , Qin Chongtao , Karelia Deepkamal , Sharma Arati , Jiang Cheng , Lu Junxuan
Published: April 2019

Background

Noninvasive live‐animal longitudinal monitoring of xenograft tumor growth and metastasis by bioluminescent imaging (BLI) has been widely reported in cancer biology and preclinical therapy literature, mainly in athymic nude mice. Our own experience at calibrating BLI readout with tumor weight/volume in human prostate cancer xenograft models in haired, SCID‐NSG mice through intraprostatic (orthotopic) and subcutaneous (SC) inoculations revealed either nonexistent or poor correlation (coefficient of determination, R
2 = ~0.01‐0.3). The present work examined several technical and biological factors to improve BLI utility.

Methods

After ruling out promoter‐luciferase (luc) specificity and luc gene loss in the cell inoculum with LNCaP‐AR‐luc cells expressing an androgen receptor (AR) and tagged with AR‐responsive probasin promoter‐luc gene, we evaluated different routes of d‐luciferin administration, imaging time during the day, charge‐coupled device camera image acquisition settings, and hair removal methods to improve the imaging protocol. For most imaging sessions, BLI was carried out within the same day of tumor volume measurement. After necropsy, histological and immunohistochemical (IHC) analyses were performed on the tumors to evaluate necrosis and expression of luciferase and AR, respectively.

Results

Injection of d‐luciferin by SC route, robust image‐capture setting (30 000 counts and autoexposure), imaging in the morning and thorough hair removal resulted in a substantial improvement of R2 to ~0.6. Histological analyses confirmed the lack of BLI signal in necrotic tumor masses consistent with luciferase‐mediated light emission only in oxygenated adenosine triphosphate‐producing viable cells. IHC staining detected heterogeneous expression of luciferase tracking generally with AR expression in nonnecrotic tumor tissues.

Conclusions

Our body of work highlighted a framework to validate imaging protocols to ensure the acquisition of interpretable BLI data as an indicator of xenograft tumor burden. The vast tissue heterogeneity in prostate tumor xenografts and variable luciferase expression constrained this technology from achieving a high correlation.
Circulating microRNAs in plasma among men with low‐grade and high‐grade prostate cancer at prostate biopsy
Authors: McDonald Alicia C. , Vira Manish , Walter Vonn , Shen Jing , Raman Jay D. , Sanda Martin G. , Patil Dattatraya , Taioli Emanuela
Published: April 2019

Background

MicroRNAs (miRNAs or miR‐) have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence and metastasis. We investigated whether circulating miRNAs in plasma could be used as diagnostic biomarkers for more aggressive prostate cancer at prostate biopsy.

Methods

Men, aged 40 years and above, newly diagnosed with prostate cancer were categorized into two risk groups, low‐grade (Gleason score, 6 or 7 [3 + 4] and serum prostate‐specific antigen [PSA], <20 ng/mL) and high‐grade (Gleason score, ≥7 (4 + 3) and serum PSA, ≥20 ng/mL) prostate cancers. The limma R package was used to compare the expression of miRNAs in plasma between the two risk groups, adjusting for age.

Results

There were 66 men, aged 46‐86 years, included: 40 men with low‐grade and 26 men with high‐grade prostate cancers. There were lower expressions of miR‐28, miR‐100, miR‐942, and miR‐28‐3p, and higher expressions of miR‐708, miR‐1298, miR‐886‐3p, miR‐374, miR‐376c, miR‐202, miR‐128a, and miR‐185 in high‐grade compared to low‐grade prostate cancer cases at biopsy, after adjusting for age (P < 0.05). These differences were no longer statistically significant after adjusting the P values for multiple comparisons.

Conclusion

There was no circulating miRNA associated with high‐grade prostate cancer at biopsy after adjusting for age and multiple comparisons. Nevertheless, relationships between these circulating miRNAs and high‐grade prostate cancer were observed, which suggest them as promising prostate cancer biomarkers. Further investigation in a larger cohort may provide insight into their diagnostic potential for aggressive prostate cancer.
NMR characterization of conformational fluctuations and noncovalent interactions of SUMO protein from Drosophila melanogaster (dSmt3)
Authors: Kaur Anupreet , Gourav  , Kumar Sandeep , Jaiswal Nancy , Vashisht Ashutosh , Kumar Dinesh , Gahlay Gagandeep K. , Mithu Venus S.
Published: April 2019

Structural heterogeneity in the native‐state ensemble of dSmt3, the only small ubiquitin‐like modifier (SUMO) in Drosophila melanogaster, was investigated and compared with its human homologue SUMO1. Temperature dependence of amide proton's chemical shift was studied to identify amino acids possessing alternative structural conformations in the native state. Effect of small concentration of denaturant (1M urea) on this population was also monitored to assess the ruggedness of near‐native energy landscape. Owing to presence of many such amino acids, especially in the β2‐loop‐α region, the native state of dSmt3 seems more flexible in comparison to SUMO1. Information about backbone dynamics in ns‐ps timescale was quantified from the measurement of 15N‐relaxation experiments. Furthermore, the noncovalent interaction of dSmt3 and SUMO1 with Daxx12 (Daxx729DPEEIIVLSDSD740), a [V/I]‐X‐[V/I]‐[V/I]‐based SUMO interaction motif, was characterized using Bio‐layer Interferometery and NMR spectroscopy. Daxx12 fits itself in the groove formed by β2‐loop‐α structural region in both dSmt3 and SUMO1, but the binding is stronger with the former. Flexibility of β2‐loop‐α region in dSmt3 is suspected to assist its interaction with Daxx12. Our results highlight the role of native‐state flexibility in assisting noncovalent interactions of SUMO proteins especially in organisms where a single SUMO isoform has to tackle multiple substrates single handedly.
Levodopa‐carbidopa intestinal gel high concentration formulation is clinically bioequivalent to commercial formulation
Authors: Rosebraugh Matthew , Kalluri Hari V. , Liu Wei , Locke Charles , Sidhu Dilraj , Han Jian‐Hwa , Benesh Janet
Published: April 2019

A new levodopa‐carbidopa intestinal gel (LCIG) system featuring a higher levodopa/carbidopa (LD/CD) concentration and viscosity, LCIG‐HV, is being developed to reduce the intrajejunal volume of LD/CD that is administered as compared to the current commercial formulation, LCIG‐LV. This study characterizes the LCIG‐HV formulation and compares it to the LCIG‐LV formulation via dissolution testing and a clinical pharmacokinetic bioequivalence study. In vitro release profiles of LD/CD were determined using a USP Dissolution Apparatus 2 with 500 mL of phosphate buffer (pH 4.5) operating at 25 RPM. A single dose, open‐label study was conducted according to a two‐period, randomized, crossover design in 28 healthy subjects. The point estimate (PE) of the levodopa Cmax geometric mean for the LCIG‐HV formulation was 4% higher than that of the LCIG‐LV formulation. PEs of levodopa AUCt and AUCinf geometric means were comparable for both formulations. PEs of carbidopa Cmax, AUCt and AUCinf geometric means for the LCIG‐HV formulation were 3%‐5% higher than those of the LCIG‐LV formulation. For both formulations, the median Tmax for levodopa was 1.0 and 3.0 hours for carbidopa. The levodopa half‐life harmonic mean was 1.6 hour for both formulations. The carbidopa half‐life harmonic mean was 1.9 and 2.0 hour, respectively, for the LCIG‐HV and LCIG‐LV formulations. Cmax, AUCt and AUCinf of LD/CD carbidopa were comparable for both formulations. The current study demonstrates that the LCIG‐LV and LCIG‐HV formulations are clinically bioequivalent for LD/CD according to FDA guidance. However, the dissolution method was over discriminatory of formulation differences.