bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Multiplatform Social Media Event Summarization
Authors: Tiwari Akanksha , Weth Christian Von Der , Kankanhalli Mohan S.
Published: April 2018

Social media platforms are turning into important news sources since they provide real-time information from different perspectives. However, high volume, dynamism, noise, and redundancy exhibited by social media data make it difficult to comprehend the entire content. Recent works emphasize on summarizing the content of either a single social media platform or of a single modality (either textual or visual). However, each platform has its own unique characteristics and user base, which brings to light different aspects of real-world events. This makes it critical as well as challenging to combine textual and visual data from different platforms. In this article, we propose summarization of real-world events with data stemming from different platforms and multiple modalities. We present the use of a Markov Random Fields based similarity measure to link content across multiple platforms. This measure also enables the linking of content across time, which is useful for tracking the evolution of long-running events. For the final content selection, summarization is modeled as a subset selection problem. To handle the complexity of the optimal subset selection, we propose the use of submodular objectives. Facets such as coverage, novelty, and significance are modeled as submodular objectives in a multimodal social media setting. We conduct a series of quantitative and qualitative experiments to illustrate the effectiveness of our approach compared to alternative methods.
Research for practice
Authors: Schwarzkopf Malte , Bailis Peter
Published: April 2018

Expert-curated guides to the best of CS research.
SABR
Authors: Bhat Divyashri , Rizk Amr , Zink Michael , Steinmetz Ralf
Published: April 2018

State-of-the-art software-defined wide area networks (SD-WANs) provide the foundation for flexible and highly resilient networking. In this work, we design, implement, and evaluate a novel architecture (denoted as SABR) that leverages the benefits of software-defined networking (SDN) to provide network-assisted adaptive bitrate streaming. With clients retaining full control of their streaming algorithms, we clearly show that by this network assistance, both the clients and the content providers benefit significantly in terms of quality of experience (QoE) and content origin offloading. SABR utilizes information on available bandwidths per link and network cache contents to guide video streaming clients with the goal of improving the viewer’s QoE. In addition, SABR uses SDN capabilities to dynamically program flows to optimize the utilization of content delivery network caches.

Backed by our study of SDN-assisted streaming, we discuss the change in the requirements for network-to-player APIs that enables flexible video streaming. We illustrate the difficulty of the problem and the impact of SDN-assisted streaming on QoE metrics using various well-established player algorithms. We evaluate SABR together with state-of-the-art dynamic adaptive streaming over HTTP (DASH) quality adaptation algorithms through a series of experiments performed on a real-world, SDN-enabled testbed network with minimal modifications to an existing DASH client. In addition, we compare the performance of different caching strategies in combination with SABR. Our trace-based measurements show the substantial improvement in cache hit rates and QoE metrics in conjunction with SABR indicating a rich design space for jointly optimized SDN-assisted caching architectures for adaptive bitrate video streaming applications.
Canary analysis service
Authors: Davidovič Štěpán , Beyer Betsy
Published: April 2018

Automated canarying quickens development, improves production safety, and helps prevent outages.
Data acquisition in vehicular ad hoc networks
Authors: Wang Xiaonan
Published: April 2018

The data comes from multiple optimal sources in parallel, helping reduce addressing and data-acquisition latency.
Loss of myogenic potential and fusion capacity of muscle stem cells isolated from contractured muscle in children with cerebral palsy
Authors: Domenighetti Andrea A. , Mathewson Margie A. , Pichika Rajeswari , Sibley Lydia A. , Zhao Leyna , Chambers Henry G. , Lieber Richard L.
Published: April 2018

Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a nonprogressive perinatal insult to the brain. Although the brain lesion is nonprogressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles. Here we measured the myogenic potential of satellite cells isolated from contractured muscles in children with CP. When compared with typically developing (TD) children, satellite cell-derived myoblasts from CP differentiated more slowly (slope: 0.013 (SD 0.013) CP vs. 0.091 (SD 0.024) TD over 24 h, P < 0.001) and fused less (fusion index: 21.3 (SD 8.6) CP vs. 81.3 (SD 7.7) TD after 48 h, P < 0.001) after exposure to low-serum conditions that stimulated myotube formation. This impairment was associated with downregulation of several markers important for myoblast fusion and myotube formation, including DNA methylation-dependent inhibition of promyogenic integrin-β 1D (ITGB1D) protein expression levels (−50% at 42 h), and ~25% loss of integrin-mediated focal adhesion kinase phosphorylation. The cytidine analog 5-Azacytidine (5-AZA), a demethylating agent, restored ITGB1D levels and promoted myogenesis in CP cultures. Our data demonstrate that muscle contractures in CP are associated with loss of satellite cell myogenic potential that is dependent on DNA methylation patterns affecting expression of genetic programs associated with muscle stem cell differentiation and muscle fiber formation.
Three-dimensional in vitro models answer the right questions in ADPKD cystogenesis
Authors: Dixon Eryn E. , Woodward Owen M.
Published: April 2018

Novel technologies, new understanding of the basement membrane composition, and better comprehension of the embryonic development of the mammalian kidney have led to explosive growth in the use of three-dimensional in vitro models to study a range of human disease pathologies (Clevers H. Cell 165: 1586–1597, 2016; Shamir ER, Ewald AJ. Nat Rev Mol Cell Biol 15: 647–664, 2014). The development of these effective model systems represents a new tool to study the progressive cystogenesis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a prevalent and complex monogenetic disease, characterized by the pathological formation of fluid fill cysts in renal tissue (Grantham JJ, Mulamalla S, Swenson-Fields KI. Nat Rev Nephrol 7: 556–566, 2011; Takiar V, Caplan MJ. Biochim Biophys Acta 1812: 1337–1343, 2011). ADPKD cystogenesis is attributed to loss of function mutations in either PKD1 or PKD2, which encode for two transmembrane proteins, polycystin-1 and polycystin-2, and progresses with loss of both copies of either gene through a proposed two-hit mechanism with secondary somatic mutations (Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M. Biochem Biophys Res Commun 322: 1374–1383, 2004; Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St George-Hyslop P. Am Soc Nephrol 10: 1524–1529, 1999; Wu G, D’Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H Jr, Kucherlapati R, Edelmann W, Somlo S. Cell 93: 177–188, 1998). The exaggerated consequences of large fluid filled cysts result in fibrosis and nephron injury, leading initially to functional compensation but ultimately to dysfunction (Grantham JJ. Am J Kidney Dis 28: 788–803, 1996; Norman J. Biochim Biophys Acta 1812: 1327–1336, 2011; Song CJ, Zimmerman KA, Henke SJ, Yoder BK. Results Probl Cell Differ 60: 323–344, 2017). The complicated disease progression has scattered focus and resources across the spectrum of ADPKD research.
Invariant and heritable local cortical organization as revealed by fMRI
Authors: Christova Peka , Georgopoulos Apostolos P.
Published: April 2018

Neural interactions in local cortical networks critically depend on the distance between interacting elements: the shorter the distance, the stronger the interactions. Here we quantified these interactions in six cortical areas of 854 individuals, including monozygotic and dizygotic twins, nontwin siblings, and nonrelated individuals. We found that the strength of zero-lag correlation between prewhitened, resting-state, blood level oxygenation-dependent functional magnetic resonance imaging time series decreased with distance as a power law. The rate of decrease, b, varied among individuals by ~1.9×, was highly correlated between hemispheres, but differed among areas (by ~1.2×) in a systematic fashion, becoming progressively less steep from frontal to occipital areas. With respect to twin status, b was significantly correlated between monozygotic twins, less so between dizygotic twins or nontwin siblings, and not at all in nonrelated individuals. These results quantify the lawful, distance-related cortical interactions and demonstrate, for the first time, the heritability of their power law.

NEW & NOTEWORTHY Local cortical circuitry involves orderly neuronal interactions. A key feature of these interactions is that they are stronger the closer the interacting neurons. Here we quantified this crucial dependence of neural interactions on distance with functional magnetic resonance imaging and found that the strength of interactions decreases with distance as a power law that is very similar in all cortical lobes and heritable. These findings identify an invariant and heritable property of local cortical organization.
Inhibition of BDNF signaling in the paraventricular nucleus of the hypothalamus lowers acute stress-induced pressor responses
Authors: Schaich Chris L. , Wellman Theresa L. , Einwag Zachary , Dutko Richard A. , Erdos Benedek
Published: April 2018

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during stress, and our recent studies indicate that BDNF induces sympathoexcitatory and hypertensive responses when injected acutely or overexpressed chronically in the PVN. However, it remained to be investigated whether BDNF is involved in the mediation of stress-induced cardiovascular responses. Here we tested the hypothesis that inhibition of the high-affinity BDNF receptor TrkB in the PVN diminishes acute stress-induced cardiovascular responses. Male Sprague-Dawley rats were equipped with radiotelemetric transmitters for blood pressure measurement. BDNF-TrkB signaling was selectively inhibited by viral vector-mediated bilateral PVN overexpression of a dominant-negative truncated TrkB receptor (TrkB.T1, n = 7), while control animals ( n = 7) received green fluorescent protein (GFP)-expressing vector injections. Rats were subjected to acute water and restraint stress 3–4 wk after vector injections. We found that body weight, food intake, baseline mean arterial pressure (MAP), and heart rate were unaffected by TrkB.T1 overexpression. However, peak MAP increases were significantly reduced in the TrkB.T1 group compared with GFP both during water stress (GFP: 39 ± 2 mmHg, TrkB.T1: 27 ± 4 mmHg; P < 0.05) and restraint stress (GFP: 41 ± 3 mmHg, TrkB.T1: 34 ± 2 mmHg; P < 0.05). Average MAP elevations during the poststress period were also significantly reduced after both water and restraint stress in the TrkB.T1 group compared with GFP. In contrast, heart rate elevations to both stressors remained unaffected by TrkB.T1 overexpression. Our results demonstrate that activation of BDNF high-affinity TrkB receptors within the PVN is a major contributor to acute stress-induced blood pressure elevations.

NEW & NOTEWORTHY We have shown that inhibition of the high-affinity brain-derived neurotrophic factor receptor TrkB in the paraventricular nucleus of the hypothalamus significantly reduces blood pressure elevations to acute stress without having a significant impact on resting blood pressure, body weight, and food intake.
Common Mitochondrial Haplogroups and Cutaneous Squamous Cell Carcinoma Risk
Authors: Jorgenson Eric , Choquet Hélène , Yin Jie , Asgari Maryam M.
Published: April 2018

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in United States, and its incidence is substantially higher in men than women, but the reasons for the difference are unknown. We explored whether common mitochondrial DNA (mtDNA) haplogroups, which have been associated with cancer risk, and in particular squamous cell carcinoma risk arising in other organs, could explain this biological sex difference in cSCC susceptibility.

Methods: We performed a retrospective cohort study using data from the Genetic Epidemiology Research in Adult Health and Aging cohort composed of 67,868 non-Hispanic white subjects (7,701 cSCC cases and 60,167 controls). Genotype information on >665,000 SNPs was generated using Affymetrix Axiom arrays designed to maximize genome-wide coverage, and 102 high-quality mtDNA SNPs were used to determine mtDNA haplogroups. Associations between each mtDNA haplogroup and cSCC risk were evaluated by logistic regression analysis adjusting for age, sex, and population stratification using ancestry principal components.

Results: cSCC was more common in men (15.4% vs. 8.4% for women). Nine common mtDNA haplogroups (frequency ≥1%) were identified in addition to the most common haplogroup, H, used as the reference group. No association with cSCC risk was detected for any of the mtDNA haplogroups or overall or sex-stratified analyses.

Conclusions: Common mitochondrial variation is not associated with cSCC risk.

Impact: This well-powered study refutes the hypothesis that common mitochondrial haplogroups play a role in the differential sex predilection of cSCCs. Cancer Epidemiol Biomarkers Prev; 27(7); 838–41. ©2018 AACR.
Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinoma In Vitro and Patient-Derived Xenografts In Vivo
Authors: Song Mengqiu , Liu Xuejiao , Liu Kangdong , Zhao Ran , Huang Hai , Shi Yuanyuan , Zhang Man , Zhou Silei , Xie Hua , Chen Hanyong , Li Yin , Zheng Yan , Wu Qiong , Liu Fangfang , Li Enmin , Bode Ann M. , Dong Zigang , Lee Mee-Hyun
Published: April 2018

Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from Rabdosia rubescens, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. The role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G2–M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bims in ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling. Mol Cancer Ther; 17(7); 1540–53. ©2018 AACR.
Molecular Profile of Advanced Thyroid Carcinomas by Next-Generation Sequencing: Characterizing Tumors Beyond Diagnosis for Targeted Therapy
Authors: Chen Hui , Luthra Rajyalakshmi , Routbort Mark J. , Patel Keyur P. , Cabanillas Maria E. , Broaddus Russell R. , Williams Michelle D.
Published: April 2018

Next-generation sequencing (NGS) for molecular diagnostics allows simultaneous testing of activating oncogenes and tumor suppressor mutations in multiple signal pathways. Extended mutational profiling of advanced thyroid cancers may enhance considerations for targeted therapies. We analyzed clinically derived molecular profiling of 216 patients with advanced thyroid carcinoma using NGS (Ion Torrent Personal Genome Machine) from April 2012 to February 2014. We examined substitutions and small indels in 46 or 50 cancer-related genes using Ampliseq Cancer Hotspot panel in respect to tumor diagnosis and clinical correlations.

Mutations were common in advanced thyroid carcinomas 154 (71%) predominately in targetable MAPK pathway (146/216, 68%), and several PI3K/AKT pathway (8, 4%; six as comutations). BRAF V600E mutation associated with papillary (94/139, 68%), poorly differentiated (4/39, 10%), and anaplastic (3/12, 25%) carcinomas. NRAS mutations occurred in follicular (5/12, 42%) and poorly differentiated thyroid carcinoma (12/39, 31%). Tumor suppressor mutations (16, 7%) occurred predominantly in TP53 in Hurthle cell (2/5, 40%, the only mutation), in anaplastic (3/12, 25%) and poorly differentiated thyroid carcinoma (4/39, 10%) some as comutations and in papillary thyroid carcinoma (5/139, 4%) always a comutation. Kaplan–Meier analysis of patients with poorly differentiated thyroid carcinoma containing activating mutations who received targeted therapeutics showed improved survival compared to similarly treated patients without mutations in targetable pathways (P = 0.02). In conclusion, MAPK pathway is the predominant target for therapy in advance thyroid carcinomas; adding NGS enables the identification of comutations associated with resistance (PI3K/AKT). Within poorly differentiated thyroid carcinoma, the molecular profile may hold prognostic value in the era of targeted therapy. Mol Cancer Ther; 17(7); 1575–84. ©2018 AACR.
A Twelve-Week Moderate Exercise Programme Improved Symptoms of Depression, Insomnia, and Verbal Learning in Post-Aneurysmal Subarachnoid Haemorrhage Patients: A Comparison with Meningioma Patients and Healthy Controls
Authors: Colledge Flora , Brand Serge , Pühse Uwe , Holsboer-Trachsler Edith , Zimmerer Stefan , Schleith Ramona , Gerber Markus
Published: April 2018

Objectives: Deficits in psychological functioning, cognitive functioning, and sleep are frequently experienced by individuals who have survived aneurysmal subarachnoid haemorrhage (aSAH). Exercise has been shown to improve these domains; to date, it has never been explored in patients following aSAH. The aim of this exploratory study is to compare the effects of an exercise programme in this population with another patient group, and a group of healthy controls. Methods: The present study explored the effects of 12 weeks of moderate aerobic exercise training on 15 aSAH patients, 16 meningioma patients, and 17 healthy controls. Data on symptoms of depression, hypochondria, perceived stress, satisfaction with life, verbal learning and memory, and subjective and objective sleep, were gathered at baseline, following intervention, and at 6-month follow-up. Results: aSAH patients and meningioma patients had decreased symptoms of depression and insomnia at follow-up. While perceived stress decreased in the meningioma group, in aSAH patients it increased. Total learning performance increased in all three groups. Conclusions: An exercise programme had a positive effect on symptoms of depression, insomnia, and verbal learning in patients following aSAH. No positive changes in other domains were observed. This may be due to the cautious approach taken with regard to exercise intensity.
Serum Obestatin: A Biomarker of Cardiovascular and All-Cause Mortality in Hemodialysis Patients
Authors: Beberashvili Ilia , Katkov Anna , Sinuani Inna , Azar Ada , Shapiro Gregory , Feldman Leonid , Gorelik Oleg , Stav Kobi , Efrati Shai
Published: April 2018

Background: Recent experimental studies have suggested that obestatin, a proposed anorexigenic gut hormone and a physiological opponent of acyl-ghrelin, has protective cardiovascular effects. We tested the hypothesis that obestatin is independent of inflammatory mediators and/or acyl-ghrelin in predicting outcomes of the maintenance hemodialysis (MHD) population. Methods: It was a 6-year cohort study on 261 MHD patients. Obestatin, acyl-ghrelin, adipokines (leptin and adiponectin), markers of inflammation and nutrition, prospective all-cause and cardiovascular mortality were studied. Results: During the follow-up, 160 patients died in total, with 74 deaths due to cardiovascular causes. For each ng/mL increase in baseline obestatin level in fully adjusted models (including malnutrition-inflammation score, Interleukin-6 [IL-6], adipokines and acyl-ghrelin), the hazard for death from all causes was 0.90 (95% CI 0.81–0.99) and for cardiovascular death 0.85 (95% CI 0.73–0.99). However, these associations were more robust in the subgroup of patients aged above 71 years: 0.85 (95% CI 0.73–0.98) for all-cause death and 0.66 (95% CI 0.52–0.85) for cardiovascular death. An interaction between high IL-6 (above median) and low obestatin (below median) levels for increased risk of all-cause mortality (synergy index [SI] 5.14, p = 0.001) and cardiovascular mortality (SI 4.81, p = 0.02) emerged in the development of multivariable adjusted models. Interactions were also observed between obestatin, Tumor necrosis factor-alpha, adipokines and acyl-ghrelin, which were associated with mortality risk. Conclusion: Serum obestatin behaves as a biomarker for cardiovascular and all-cause mortality in MHD patients. The prognostic ability of obestatin in this regard is independent of inflammation, nutritional status, acyl-ghrelin’s and adipokines’ activity and is modified by age being very prominent in patients older than 71 years.
Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair
Authors: Yuan Jie , Xin Fei , Jiang Wenxue
Published: April 2018

Pulsed electromagnetic field (PEMF) stimulation, as a prospective, noninvasive, and safe physical therapy strategy to accelerate bone repair has received tremendous attention in recent decades. Physical PEMF stimulation initiates the signaling cascades, which effectively promote osteogenesis and angiogenesis in an orchestrated spatiotemporal manner and ultimately enhance the self-repair capability of bone tissues. Considerable research progresses have been made in exploring the underlying cellular and subcellular mechanisms of PEMF promotion effect in bone repair. Moreover, the promotion effect has shown strikingly positive benefits in the treatment of various skeletal diseases. However, many preclinical and clinical efficacy evaluation studies are still needed to make PEMFs more effective and extensive in clinical application. In this review, we briefly introduce the basic knowledge of PEMFs on bone repair, systematically elaborate several key signaling pathways involved in PEMFs-induced bone repair, and then discuss the therapeutic applications of PEMFs alone or in combination with other available therapies in bone repair, and evaluate the treatment effect by analyzing and summarizing recent literature.
UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction
Authors: Lang Hongmei , Xiang Yang , Ai Zhihua , You Zhiqing , Jin Xiaolan , Wan Yong , Yang Yongjian
Published: April 2018

Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH) are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3) plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.
Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages
Authors: Chen Jianjun , Luo Yang , Zhou Yong , Qin Shaolan , Qiu Yier , Cui Ran , Yu Minhao , Qin Jun , Zhong Ming
Published: April 2018

Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.
ДОСЛІДЖЕННЯ З РОЗРОБКИ ТЕХНОЛОГІЇ НАСТОЙКИ «СТИМУФІТ», ПРИЗНАЧЕНОЇ ДЛЯ ЗАСТОСУВАННЯ ПРИ ТЕЛОГЕНОВІЙ АЛОПЕЦІЇ
Authors: Fedorovska M. I. , Polovko N. P. , Leochko N. S.
Published: April 2018

Мета роботи. Розробка технології складної настойки «Стимуфіт», призначеної для нашкірного застосування при телогеновій алопеції.Матеріали та методи. В якості лікарської рослинної сировини (ЛРС) використовували суміш листя кропиви дводомної –50 г, листя шавлії лікарської –30 г, листя каштана кінського –20 г. Для розробки технології складної настойки обирали оптимальні параметри екстрагування, а саме: концентрація етанолу (20 %, 40 %, 70 %), співвідношення сировини і готового продукту (1:5, 1:10, 1:15, 1:20), ступінь подрібнення сировини (подрібнена та непросіяна ЛРС, різні фракції), час (6 год, 1 доба, 2 доби, 3 доби, 7 діб) та метод (мацерація, ремацерація, перколяція) екстракції. Критеріями оцінки були: вихід екстрактивних речовин та кількісний вміст гідроксикоричних кислот (ГКК).Результати й обговорення. Як екстрагент обрано 40 % етанол, який добре розчиняє основні біологічно активні речовини та безпечний для нашкірного застосування. Враховуючи концентрацію сухого залишку та ГКК в самій настойці, а також у перерахунку на суху сировину (ефективність виснаження ЛРС), обґрунтовано технологію складної настойки, яку одержують із подрібненої та непросіяної суміші ЛРС у співвідношення 1:10 методом трикратної ремацерації протягом 3 діб.Висновки. Визначені оптимальні технологічні параметри виготовлення складної настойки, а саме: концентрація етанолу – 40 %, співвідношення ЛРС до готового продукту – 1:10, ступінь подрібнення сировини – подрібнена ціла ЛРС, час екстракції – не довше 3-х діб, метод екстрагування – ремацерація. Враховуючи отримані результати, розроблено технологічну схему виробництва складної настойки «Стимуфіт» у промислових умовах.
СИНТЕЗ ТА ОЦІНКА ПРОТИЗАПАЛЬНОЇ АКТИВНОСТІ ПОХІДНИХ РОДАНІНУ З 2-(2,6-ДИХЛОРОФЕНІЛАМІНО)ФЕНІЛАЦЕТАМІДНИМ ФРАГМЕНТОМ У МОЛЕКУЛАХ
Authors: Shepeta Yu. L. , Lelyukh M. I. , Zimenkovsky B. S. , Nektegayev I. O. , Lesyk R. B.
Published: April 2018

Мета роботи. На основі реакцій гетероциклізації та Кньовенагеля здійснити синтез нових 5-іліденроданінів sз фрагментом диклофенаку в положенні 3 для скринінгу протизапальної активності.Матеріали і методи. Органічний синтез, спектроскопія ЯМР, елементний аналіз, фармакологічний скринінг, SAR-аналіз.Результати й обговорення. Взаємодією гідразиду 2-(2,6-дихлорофеніламіно)-фенілацетатної кислоти з тіокарбоніл-біс-тіогліколевою кислотою в середовищі етанолу синтезовано похідне роданіну з фрагментом протизапального засобу «Диклофенак» в положенні 3. Враховуючи наявність активної метиленової групи в положенні 5, проведено подальшу модифікацію отриманого роданіну в умовах реакції Кньовенагеля з різноманітними ароматичними альдегідами, похідними ізатину та цинамового альдегіду з утворенням серій відповідних 5-ариліден-, 5-ізатиніліден- та 5-(3-фенілпропен)іліденпохідних для вивчення  антиексудативної активності. Структуру синтезованих сполук підтверджено елементним аналізом та спектроскопією ПМР.Висновки. Результати дослідження протизапальної активності синтезованих сполук дозволили ідентифікувати три високоактивні сполуки, які за показником пригнічення запальної реакції (42,4-45,3%) були співмірними з еталонним нестероїдним протизапальним засобом «Диклофенак натрію».
ТЕХНОЛОГІЧНІ ПАРАМЕТРИ ВИРОБНИЦТВА ЛІПОСОМ З ОКСАЛІПЛАТИНОМ
Authors: Stadnichenko O. V. , Krasnopolsky Yu. M. , Yarnykh T. G.
Published: April 2018

Мета роботи: на основі експерименту запропонувати науково-обґрунтовану технологію виробництва ліпосомальної форми оксаліплатину. Провести аналіз проміжних продуктів, визначити контрольні точки.Матеріали і методи. Для виготовлення ліпосом використовували яєчний фосфатидилхолін виробництва Lipoid (Німеччина). Дипальмітоілфосфатидилгліцерин, холестерин і розчинники використовували виробництва фірми Sigma-Aldrich (США). Ліпідну плівку отримували на роторному випарювачі Buchi 210. Для гомогенізації використовували метод екструзії при високому тиску. Процес ліофілізації здійснювали на обладнанні Quarco (КНР).Результати й обговорення.  Розроблено дослідно-промислову технологію отримання ліпосомальної форми оксаліплатину. Створення повноцінної технології вимагало вивчення колоїдних властивостей гетерогенної лікарської наносистеми, особливо на етапі регідратації, параметрів ліофілізації, валідації методик контролю ступеня інкапсуляції оксаліплатину в ліпосоми, валідації кількісного визначення і визначення сторонніх домішок.Висновки. Запропоновано нову, оригінальну технологію отримання ліпосомальної форми оксаліплатину. Технологію апробовано на серіях препарату для проведення доклінічних досліджень.
ДОСЛІДЖЕННЯ МОЖЛИВОСТЕЙ ЕКСТЕМПОРАЛЬНОГО ВИГОТОВЛЕННЯ В УКРАЇНІ ТА ЗА КОРДОНОМ
Authors: Samborskyi O. S.
Published: April 2018

Мета роботи. Провести аналіз стану екстемпоральної рецептури у вітчизняних та закордонних аптеках і розробити на його основі рекомендації, орієнтовані на збереження екстемпорального виготовлення та розширення доступності асортименту вищезазначених засобів.Матеріали і методи. У роботі використано загальнонаукові та спеціальні методи: аналітичний і маркетингових досліджень. Інформаційну базу досліджень становили статистичні матеріали МОЗ України та інших організацій, сайти вітчизняних та закордонних аптек, публікації.Результати й обговорення. Досвід Центральної Європи показав, що європейські аптеки широко використовують можливості екстемпорального виготовлення − у деяких країнах виготовлення в умовах аптеки займає 20 % від усіх лікарських засобів, відпущених за рецептом. Аптеки Швеції, наприклад, пропонують екстемпоральні лікарські засоби для терапії в таких напрямках медицини, як онкологія, офтальмологія, педіатрія, хірургія, гематологія, догляд за новонародженими, інфекційні захворювання, препарати для операцій, для інтенсивного догляду. Виготовляють препарати для хіміотерапії, розчини антибіотиків, парентеральне харчування, а також лікарські засоби для полегшення болю. Серед асортименту екстемпоральних лікарських засобів в аптеках пропонують попередньо заповнені шприци, амбулаторні насоси та касети, що дають можливість персоналу зекономити до 1/2 години додаткового часу на кожному препараті та усунути медичні помилки. Також досліджено асортимент екстемпоральної рецептури українських аптек із погляду представлення груп екстемпоральних лікарських засобів, їх глибини та економічної доступності.Висновки. Проведений аналіз досвіду європейських країн відносно використання екстемпоральної рецептури свідчить про широкі можливості виробничих аптек за кордоном, про високий ступінь їх залучення в систему охорони здоров’я. Це дає підстави використовувати вітчизняні аптеки з можливістю екстемпорального виготовлення як повноцінну складову для забезпечення раціональної та доступної фармакотерапії. Досліджено асортимент екстемпоральної рецептури українських аптек. Ширина асортименту екстемпоральних лікарських засобів у вітчизняних аптеках варіює близько 20 груп, глибина у кожній асортиментній групі налічує у середньому від 2 до 10 позицій. Найменш представлені на ринку засоби для лікування ендокринологічних та офтальмологічних захворювань, найбільше представлені косметичні засоби та препарати для лікування оториноларингологічних захворювань. Усі групи екстемпоральних ліків показали достатню економічну доступність − зазвичай, вартість препарату не перевищує ½ − 1 середньоденної мінімальної заробітної плати українця. Таким чином, аптеки мають достатній асортимент екстемпоральної рецептури з доступними цінами, а досвід інших країн дає нові ідеї для відродження даного напряму діяльності, сприятиме розширенню асортименту ліків, розрахованих на різні категорії населення.
ПАМ'ЯТІ ГЕОРГІЄВСЬКОГО ВІКТОРА ПЕТРОВИЧА ПРИСВЯЧУЄТЬСЯ
Authors: Of Pharmaceutical Review Pharmaceutical Society of Ukraine And editorial office
Published: April 2018

Стаття-спогад про видатну особистість Георгієвського Віктора Петровича, доктора фармацевтичних наук, член-кореспондента НАН України (аналітична хімія), заслуженого діяча науки і техніки та кращого винахідника НАНУ, професіонала та патріота української фармації.
Misdiagnosis of Cerebral Vein Thrombosis in the Emergency Department
Authors: Liberman Ava L. , Gialdini Gino , Bakradze Ekaterina , Chatterjee Abhinaba , Kamel Hooman , Merkler Alexander E.
Published: April 2018

Background and Purpose—

Rates of cerebral venous thrombosis (CVT) misdiagnosis in the emergency department and outcomes associated with misdiagnosis have been underexplored.

Methods—

Using administrative data, we identified adults with CVT at New York, California, and Florida hospitals from 2005 to 2013. Our primary outcome was probable misdiagnosis of CVT, defined as a treat-and-release emergency department visit for headache or seizure within 14 days before CVT. In addition, logistic regression was used to compare rates of clinical outcomes in patients with and without probable CVT misdiagnosis. We performed a confirmatory study at 2 tertiary care centers.

Results—

We identified 5966 patients with CVT in whom 216 (3.6%; 95% confidence interval [CI], 1.1%–4.1%) had a probable misdiagnosis of CVT. After adjusting for demographics, risk factors for CVT, and the Elixhauser comorbidity index, probable CVT misdiagnosis was not associated with in-hospital mortality (odds ratio, 0.14; 95% CI, 0.02–1.05), intracerebral hemorrhage (odds ratio, 0.97; 95% CI, 0.57–1.65), or unfavorable discharge disposition (odds ratio, 0.90; 95% CI, 0.61–1.32); a longer length of hospital stay was seen among misdiagnosed patients with CVT (odds ratio, 1.62; 95% CI, 1.04–2.50). In our confirmatory cohort, probable CVT misdiagnosis occurred in 8 of 134 patients with CVT (6.0%; 95% CI, 2.6%–11.4%).

Conclusions—

In a large, heterogeneous multistate cohort, probable misdiagnosis of CVT occurred in 1 of 30 patients but was not associated with the adverse clinical outcomes included in our study.
Encoding of Novel Verbal Instructions for Prospective Action in the Lateral Prefrontal Cortex: Evidence from Univariate and Multivariate Functional Magnetic Resonance Imaging Analysis
Authors: Bourguignon Nicolas J. , Braem Senne , Hartstra Egbert , De Houwer Jan , Brass Marcel
Published: April 2018

Verbal instructions are central to humans' capacity to learn new behaviors with minimal training, but the neurocognitive mechanisms involved in verbally instructed behaviors remain puzzling. Recent functional magnetic resonance imaging (fMRI) evidence suggests that the right middle frontal gyrus and dorsal premotor cortex (rMFG-dPMC) supports the translation of symbolic stimulus–response mappings into sensorimotor representations. Here, we set out to (1) replicate this finding, (2) investigate whether this region's involvement is specific to novel (vs. trained) instructions, and (3) study whether rMFG-dPMC also shows differences in its (voxel) pattern response indicative of general cognitive processes of instruction implementation. Participants were shown instructions, which they either had to perform later or merely memorize. Orthogonal to this manipulation, the instructions were either entirely novel or had been trained before the fMRI session. Results replicate higher rMFG-dPMC activation levels during instruction implementation versus memorization and show how this difference is restricted to novel, but not trained, instruction presentations. Pattern similarity analyses at the voxel level further reveal more consistent neural pattern responses in rMFG-dPMC during the implementation of novel versus trained instructions. In fact, this more consistent neural pattern response seemed to be specific to the first instruction presentation and disappeared after the instruction had been applied once. These results further support a role of rMFG-dPMC in the implementation of novel task instructions and highlight potentially important differences in studying this region's gross activation levels versus (the consistency of) its response patterns.
The Next-Generation Goddard Convective–Stratiform Heating Algorithm: New Tropical and Warm-Season Retrievals for GPM
Authors: Lang Stephen E. , Tao Wei-Kuo
Published: April 2018

The Goddard convective–stratiform heating (CSH) algorithm, used to estimate cloud heating in support of the Tropical Rainfall Measuring Mission (TRMM), is upgraded in support of the Global Precipitation Measurement (GPM) mission. The algorithm’s lookup tables (LUTs) are revised using new and additional cloud-resolving model (CRM) simulations from the Goddard Cumulus Ensemble (GCE) model, producing smoother heating patterns that span a wider range of intensities because of the increased sampling and finer GPM product grid. Low-level stratiform cooling rates are reduced in the land LUTs for a given rain intensity because of the rain evaporation correction in the new four-class ice (4ICE) scheme. Additional criteria, namely, echo-top heights and low-level reflectivity gradients, are tested for the selection of heating profiles. Those resulting LUTs show greater and more precise variation in their depth of heating as well as a tendency for stronger cooling and heating rates when low-level dBZ values decrease toward the surface. Comparisons versus TRMM for a 3-month period show much more low-level heating in the GPM retrievals because of increased detection of shallow convection, while upper-level heating patterns remain similar. The use of echo tops and low-level reflectivity gradients greatly reduces midlevel heating from ~2 to 5 km in the mean GPM heating profile, resulting in a more top-heavy profile like TRMM versus a more bottom-heavy profile with much more midlevel heating. Integrated latent heating rates are much better balanced versus surface rainfall for the GPM retrievals using the additional selection criteria with an overall bias of +4.3%.
Teacher education for gender, sexuality, diversity and globalization policies
Authors: Fortunato Ivan , Mena Juanjo , Sorainen Antu
Published: April 2018

This is the opening paper of a special issue that focuses on certain cultural tendencies that have emerged as topical issues in the school curricula, in both flourishing and struggling against their social frames, namely: gender, sexuality and diversity. At the same time, new approaches to teacher education have ranged from varieties of feminism to critical race theories, postcolonial studies and queer theories. So, the first reaction from our collection of papers points out that teacher educators are the ones who share the responsibility to know, use and endorse these pedagogies of learning as reference frameworks for practice. Therefore, we offer this collection for the wider international audience interested or invested in the field, for a further reflection on the topical issues and provocative questions of our very challenging times in education and educating.
Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy
Authors: Noh Sun Up , Lee Won-Young , Kim Won-Serk , Lee Yong-Taek , Yoon Kyung Jae
Published: April 2018

Background

Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy.

Methods

Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot.

Results

As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly, small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal.

Conclusions

Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.
A new generalized cycle ergometry equation for predicting maximal oxygen uptake: The Fitness Registry and the Importance of Exercise National Database (FRIEND)
Authors: Kokkinos Peter , Kaminsky Leonard A , Arena Ross , Zhang Jiajia , Myers Jonathan
Published: April 2018

Background

To develop a clinically applicable equation derived from direct assessment of maximal oxygen uptake (VO2max) to predict VO2max assessed indirectly during cycle ergometry.

Design

VO2max was assessed by open-circuit spirometry during a graded maximal exercise test using cycle ergometry. Multivariable linear regression analysis was applied to identify the most relevant variables and construct the best prediction model for VO2max using a random sample of 70% from each of the following age categories: <40, 40–50, 50–70 and >70 years; the remaining 30% was used for validation. Work rate (Watts*6.12/kg of body weight) and gender were considered in the final regression model as predictors of measured VO2max and the resulting equation was compared to the traditional American College of Sports Medicine (ACSM) equation.

Methods

Participants were part of the Fitness Registry and the Importance of Exercise National Database (FRIEND), a multi-institutional initiative with the primary objective of establishing normative VO2max values across the adult lifespan. The final cohort consisted of 5100 (3378 men; mean age 35.9 ± 12.1 years and 1722 women; mean age 47.5 ± 14.0 years).

Results

The following equation was generated: VO2max in ml O2·kg–1·min–1 = 1.74* (Watts*6.12/kg of body weight) + 3.5. The derived FRIEND-ergometry equation predicted VO2max with an overall relative bias of 0.51% ± 0.11 compared to a 15.46% ± 0.13 associated with the traditional ACSM equations ( P < 0.001). This predictive value was independent of gender, race, cardiac risk factors and cardiac, antihypertensive, metabolic and/or lipid-lowering medication.

Conclusion

The FRIEND-ergometry equation is considerably more precise than the traditional ACSM equation with an overall error over 30 times lower than that associated with the ACSM equation.