bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability
Authors: Berry James D. , Paganoni Sabrina , Atassi Nazem , Macklin Eric A. , Goyal Namita , Rivner Michael , Simpson Ericka , Appel Stanley , Grasso Daniela L. , Mejia Nicte I. , Mateen Farrah , Gill Alan , Vieira Fernando , Tassinari Valerie , Perrin Steven 
Published: June 2017

ABSTRACTIntroductionImmune activation has been implicated in progression of amytrophic lateral sclerosis (ALS). Oral fingolimod reduces circulating lymphocytes. The objective of this phase IIa, randomized, controlled trial was to test the short‐term safety, tolerability, and target engagement of fingolimod in ALS.MethodsRandomization was 2:1 (fingolimod:placebo). Treatment duration was 4 weeks. Primary outcomes were safety and tolerability. Secondary outcomes included circulating lymphocytes and whole‐blood gene expression.ResultsThirty participants were randomized; 28 were administered a drug (fingolimod 18, placebo 10). No serious adverse events occurred. Adverse events were similar by treatment arm, as was study discontinuation (2 fingolimod vs. 0 placebo, with no statistical difference). Forced expiratory volume in 1 second (FEV1) and FEV1/slow vital capacity changes were similar in the fingolimod and placebo arms. Circulating lymphocytes decreased significantly in the fingolimod arm (P < 0.001). Nine immune‐related genes were significantly downregulated in the fingolimod arm, including forkhead box P3 (P < 0.001) and CD40 ligand (P = 0.003).DiscussionFingolimod is safe and well‐tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve 56: 1077–1084, 2017
Benign and malignant tumors in the UK myotonic dystrophy patient registry
Authors: Alsaggaf Rotana , Wang Youjin , Marini‐Bettolo Chiara , Wood Libby , Nikolenko Nikoletta , Lochmüller Hanns , Greene Mark H. , Gadalla Shahinaz M. 
Published: June 2017

ABSTRACTIntroductionIn light of recent evidence indicating that cancer is part of the myotonic dystrophy (DM) phenotype, we assessed the prevalence of benign and malignant tumors among 220 patients enrolled in the UK Myotonic Dystrophy Patient Registry and evaluated factors associated with their development.MethodsA survey was distributed to collect tumor history and lifestyle information. We used multinomial logistic regression for the analysis.ResultsThirty‐nine benign (30 patients), and 16 malignant (15 patients) tumors were reported. Increasing age (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.05–1.21, P = 0.001) and earlier age at DM diagnosis (OR = 1.06, 95% CI = 1.00–1.13, P = 0.04) were associated with benign and malignant tumors (OR = 1.20, 95% CI = 1.10–1.30, P < 0.001 and OR = 1.08, 95% CI = 1.01–1.15, P = 0.02, respectively). Female gender was associated with benign tumors only (OR = 6.43, 95% CI = 1.79–23.04, P = 0.004). No associations were observed between tumors and smoking (P = 0.24), alcohol consumption (P = 0.50), or body mass index (P = 0.21).DiscussionOur results confirm previous findings suggesting a limited role for common lifestyle factors and a potential genetic contribution in DM tumor predisposition. Muscle Nerve 57: 316–320, 2018
The “third abstraction” of the Chinese artist LaoZhu: Neural and behavioral indicators of aesthetic appreciation
Authors: Bao Yan , Yang Taoxi , Zhang Jinfan , Zhang Jiyuan , Lin Xiaoxiong , Paolini Marco , Pöppel Ernst , Silveira Sarita 
Published: June 2017

AbstractThe eminent Chinese artist LaoZhu has created a homogeneous set of abstract pictures that are referred to as the “third abstraction.” By definition, these pictures are meant to be representations of the artist's personal involvement and as such to create an internal point of view in the observer on an implicit level of processing. Aiming at investigating whether the artist's choice of a specific color is experienced in a specific way in the recipient, we assessed both explicit and implicit (i.e. neurocognitive) correlates in naive viewers of LaoZhu's pieces. The behavioral results reveal a preference of the original red paintings over color‐changed counterparts in green or black. Paradoxically and inconsistent with predictions, we found higher levels of neural activation in several brain regions (predominantly in the frontal and parietal cortices) for the color‐changed compared to the original red conditions. These observations add empirically to the complementarity of early visual pathways and higher‐order cognition as well as of explicit and implicit information processing during aesthetic appreciation. We discuss our findings in light of processing effort and top‐down control of the color‐changed paintings. With regard to the third abstraction as defined by LaoZhu, in particular to the distinction between an external and internal point of view when viewing abstract art, our results contribute to an understanding of “abstraction and empathy” as a fundamental part of aesthetic appreciations.
Robotic versus thoracoscopic thymectomy: The current evidence
Authors: Buentzel Judith , Heinz Judith , Hinterthaner Marc , Schöndube Friedrich A. , Straube Carmen , Roever Christian , Emmert Alexander 
Published: June 2017

AbstractBackgroundThe purpose of this study was to analyze all relevant comparative studies comparing robot‐assisted minimally invasive thymectomy (RATS) and video‐assisted thoracic surgery thymectomy (VATS) in terms of surgical and short‐term outcomes.MethodsA systematic search for articles describing robot‐assisted and video‐assisted thymectomy and addressing surgical outcomes, operation time, length of hospitalization, intra‐operative blood loss, conversion to sternotomy and post‐operative complications was performed using the medical databases.ResultsOf the 478 studies from preliminary screening, five articles were included. By pooling these studies, we found no significant differences between the RATS and VATS (odds ratio 1.24 (95% CI 0.51, 3.03; p = 0.63)).There were no significant differences in comparison of conversion rates, operation time (26.29 min (95% CI –2.57, 55.35; p = 0.07)) and length of hospitalization (–1.58 days (95% CI –4.78, 1.62; p = 0.33)). There was a slightly higher blood loss in the RATS group.ConclusionOur meta‐analysis did not detect any statistically significant differences in surgery outcomes between the two groups.
A qualitative study of DevOps usage in practice
Authors: Erich F. M. A. , Amrit C. , Daneva M. 
Published: June 2017

AbstractOrganizations are introducing agile and lean software development techniques in operations to increase the pace of their software development process and to improve the quality of their software. They use the term DevOps, a portmanteau of development and operations, as an umbrella term to describe their efforts. In this paper, we describe the ways in which organizations implement DevOps and the outcomes they experience. We first summarize the results of a systematic literature review that we performed to discover what researchers have written about DevOps. We then describe the results of an exploratory interview‐based study involving 6 organizations of various sizes that are active in various industries. As part of our findings, we observed that all organizations were positive about their experiences and only minor problems were encountered while adopting DevOps.
Forward reachable sets: Analytically derived properties of connected components for dynamic networks
Authors: ARMBRUSTER BENJAMIN , WANG LI , MORRIS MARTINA 
Published: June 2017

AbstractFormal analysis of the emergent structural properties of dynamic networks is largely uncharted territory. We focus here on the properties of forward reachable sets (FRS) as a function of the underlying degree distribution and edge duration. FRS are defined as the set of nodes that can be reached from an initial seed via a path of temporally ordered edges; a natural extension of connected component measures to dynamic networks. Working in a stochastic framework, we derive closed-form expressions for the mean and variance of the exponential growth rate of the FRS for temporal networks with both edge and node dynamics. For networks with node dynamics, we calculate thresholds for the growth of the FRS. The effects of finite population size are explored via simulation and approximation. We examine how these properties vary by edge duration and different cross-sectional degree distributions that characterize a range of scientifically interesting normative outcomes (Poisson and Bernoulli). The size of the forward reachable set gives an upper bound for the epidemic size in disease transmission network models, relating this work to epidemic modeling (Ferguson, 2000; Eames, 2004).
PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk
Authors: Rifkin Samara B. , Shrubsole Martha J. , Cai Qiuyin , Smalley Walter E. , Ness Reid M. , Swift Larry L. , Zheng Wei , Murff Harvey J. 
Published: June 2017

AbstractDietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case–control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62,Ptrend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (Ptrend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.
Association of providing/receiving support on the mortality of older adults with different living arrangements in Taiwan: a longitudinal study on ageing
Authors: LIAO MIAO-YU , YEH CHIH-JUNG , LEE SHU-HSIN , LIAO CHUN-CHENG , LEE MENG-CHIH 
Published: June 2017

ABSTRACTThis longitudinal study evaluated the direct effects of providing/receiving family support on mortality in older adults with different living arrangements in Taiwan. All data analysed were obtained from the Taiwan Longitudinal Study on Aging, 1996–2007, of residents aged ⩾67 years (1,492 men and 1,177 women) and Taiwan's National Death Register. Living arrangements were divided into living alone, living only with spouse, living with family and living with others. Support was mainly defined as family support divided into two categories: providing and receiving. The effect of providing/receiving family support on the mortality of older adults was evaluated using Cox regression analysed by living arrangement. Participants living with their families had lower educational levels (illiterate or elementary school) and more disability in both activities of daily living and instrumental activities of daily living. However, they provided more family support than those in other living arrangements. After adjusting for several potentially confounding variables, including background characteristics, economic status and various health status measures, results showed that older adults living with their families and providing support had an 11 per cent lower mortality rate (Hazard ratio = 0.89; 95 per cent confidence interval = 0.83–0.96; p = 0.0018). In conclusion, we found that, when living with family, the lives of older adults can be extended by providing support, clearly supporting the old adage ‘it is more blessing to give than to receive’. Older adults wanting to extend their lives can be encouraged to provide more help to their families.
The Squire Law Library at Cambridge: the Historical Development and Current Status of the International Law Collections
Authors: Dingle Lesley 
Published: June 2017

AbstractIn this paper Lesley Dingle provides a detailed account of the historical development of the public international law collections at the Squire Law Library in Cambridge. She explains the close involvement of the academic lawyers and the librarians, past and present, in developing an important collection which reflects the significance of the subject at Cambridge's Faculty of Law. Finally, she brings things up-to-date by detailing the extent of the electronic provision which benefits the modern scholar in this discipline.
An Exploration into the Information Searching Behaviours of Young Barristers in Ireland
Authors: Fay Ruth 
Published: June 2017

AbstractBarristers need information. They need it to defend their clients by presenting their case in court. Some of the information they need is to be found in a book; some is to be found on a database. Choices made by the barristers and the rationale for these choices form the basis for what is to follow, as Ruth Fay explains. In this piece of research, a lack of a control group meant that no firm conclusions could be drawn. However, some interesting findings emerged in terms of how the library was used. A number of recommendations were proposed. For the most part, they centred on practical and immediate rethinks with encouragement towards the ushering in of a new culture.
Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint
Authors: Hu Xiangjing , Shen Bin , Liao Shangying , Ning Yan , Ma Longfei , Chen Jian , Lin Xiwen , Zhang Daoqin , Li Zhen , Zheng Chunwei , Feng Yanmin , Huang Xingxu , Han Chunsheng 
Published: June 2017

AbstractZMYM3, a member of the MYM-type zinc finger protein family and a component of a LSD1-containing transcription repressor complex, is predominantly expressed in the mouse brain and testis. Here, we show that ZMYM3 in the mouse testis is expressed in somatic cells and germ cells until pachytene spermatocytes. Knockout (KO) of Zmym3 in mice using the CRISPR-Cas9 system resulted in adult male infertility. Spermatogenesis of the KO mice was arrested at the metaphase of the first meiotic division (MI). ZMYM3 co-immunoprecipitated with LSD1 in spermatogonial stem cells, but its KO did not change the levels of LSD1 or H3K4me1/2 or H3K9me2. However, Zmym3 KO resulted in elevated numbers of apoptotic germ cells and of MI spermatocytes that are positive for BUB3, which is a key player in spindle assembly checkpoint. Zmym3 KO also resulted in up-regulated expression of meiotic genes in spermatogonia. These results show that ZMYM3 has an essential role in metaphase to anaphase transition during mouse spermatogenesis by regulating the expression of diverse families of genes.
The role of MAP2 kinases and p38 kinase in acute murine liver injury models
Authors: Zhang Jun , Min Robert W M , Le Khanh , Zhou Sheng , Aghajan Mariam , Than Tin A , Win Sanda , Kaplowitz Neil 
Published: June 2017

Abstractc-Jun N-terminal kinase (JNK) mediates hepatotoxicity through interaction of its phospho-activated form with a mitochondrial outer membrane protein, Sh3bp5 or Sab, leading to dephosphorylation of intermembrane Src and consequent impaired mitochondrial respiration and enhanced ROS release. ROS production from mitochondria activates MAP3 kinases, such as MLK3 and ASK1, which continue to activate a pathway to sustain JNK activation, and amplifies the toxic effect of acetaminophen (APAP) and TNF/galactosamine (TNF/GalN). Downstream of MAP3K, in various contexts MKK4 activates both JNK and p38 kinases and MKK7 activates only JNK. The relative role of MKK4 versus 7 in liver injury is largely unexplored, as is the potential role of p38 kinase, which might be a key mediator of toxicity in addition to JNK. Antisense oligonucleotides (ASO) to MKK4, MKK7 and p38 (versus scrambled control) were used for in vivo knockdown, and in some experiments PMH were used after in vivo knockdown. Mice were treated with APAP or TNF/GalN and injury assessed. MKK4 and MKK7 were expressed in liver and each was efficiently knocked down with two different ASOs. Massive liver injury and ALT elevation were abrogated by MKK4 but not MKK7 ASO pretreatment in both injury models. The protection was confirmed in PMH. Knockdown of MKK4 completely inhibited basal P-p38 in both cytoplasm and mitochondria. However, ALT levels and histologic injury in APAP-treated mice were not altered with p38 knockdown versus scrambled control. p38 knockdown significantly increased P-JNK levels in cytoplasm but not mitochondria after APAP treatment. In conclusion, MKK4 is the major MAP2K, which activates JNK in acute liver injury. p38, the other downstream target of MKK4, does not contribute to liver injury from APAP or TNF/galactosamine.
Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis
Authors: Wu Fan , Tian Fuju , Zeng Weihong , Liu Xiaorui , Fan Jianxia , Lin Yi , Zhang Yan 
Published: June 2017

AbstractPeroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal–fetal interface has not been clarified yet. In this study, significantly lower Prdx2 expression was found in the first-trimester villous cytotrophoblasts of patients with recurrent miscarriage (RM) than in cytotrophoblasts from healthy controls. Further, Prdx2 knockdown inhibited proliferation and increased apoptosis of trophoblast cells. The reason for this may be an increase in the level of cellular ROS after knockdown of Prdx2, which may subsequently lead to an increase in the expression of phosphorylated p53 (p-p53) and p38-MAPK/p21. Prdx2 knockdown also impaired the fusion of BeWo cells induced by forskolin. Bioinformatics analysis identified a c-Myc-binding site in the Prdx2 promoter region, and chromatin immunoprecipitation verified that c-Myc directly bound to a site in this locus. Suppression and overexpression of c-Myc resulted in reduction and increase of Prdx2 expression respectively. Furthermore, we demonstrated that c-Myc was downregulated in the first-trimester cytotrophoblasts of patients with RM, and its downregulation is also related with inhibited cell proliferation, increased apoptosis, as well as upregulated p21 expression and p-p53/p53 ratio. Our findings indicate that Prdx2 might have an important role in the regulation of trophoblast proliferation and apoptosis during early pregnancy, and that its expression is mediated by c-Myc. Thus, these two proteins may be involved in the pathogenesis of RM and may represent potential therapeutic targets.
Ochratoxin A-induced autophagy in vitro and in vivo promotes porcine circovirus type 2 replication
Authors: Qian Gang , Liu Dandan , Hu Junfa , Gan Fang , Hou Lili , Chen Xingxiang , Huang Kehe 
Published: June 2017

AbstractOchratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. Recently, we reported that low doses of OTA promoted PCV2 replication in vitro and in vivo, but the underlying mechanism needed further investigation. The present studies further confirmed OTA-induced PCV2 replication promotion as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. Our studies also showed that OTA induced autophagy in PK-15 cells, as assessed by the markedly increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, autophagy-related protein 5 (ATG5), and Beclin-1 and the accumulation of green fluorescent protein (GFP)-LC3 dots. OTA induced complete autophagic flux, which was detected by monitoring p62 degradation and LC3-II turnover using immunoblotting. Inhibition of autophagy by 3-methylademine (3-MA) and chloroquine (CQ) significantly attenuated OTA-induced PCV2 replication promotion. The observed phenomenon was further confirmed by the knock-down of ATG5 or Beclin-1 by specific siRNA. Further studies showed that N-acetyl-L-cysteine (NAC), an ROS scavenger could block autophagy induced by OTA, indicating that ROS may be involved in the regulation of OTA-induced autophagy. Furthermore, we observed significant increases in OTA concentrations in lung, spleen, kidney, liver and inguinal lymph nodes (ILN) and bronchial lymph nodes (BLN) of pigs fed 75 and 150 μg/kg OTA compared with controls in vivo. Administration of 75 μg/kg OTA significantly increased PCV2 replication and autophagy in the lung, spleen, kidney and BLN of pigs. Taken together, it could be concluded that OTA-induced autophagy in vitro and in vivo promotes PCV2 replication.
Oxygen consumption of gastrocnemius medialis muscle during submaximal voluntary isometric contractions with and without preceding stretch
Authors: Paternoster F. K. , Hahn D. , Stöcker F. , Schwirtz A. , Seiberl W. 
Published: June 2017

AbstractAfter an active muscle stretch, maintaining a certain amount of force in the following isometric phase is accompanied by less muscle activation compared to an isometric contraction without preceding active stretch at the corresponding muscle length. This reduced muscle activation might be related to reduced metabolic costs, such as the oxidative metabolism. Hence, the aim of this study was to clarify if mechanisms associated with stretch-induced activation reduction (AR) also influence oxygen consumption of voluntary activated human muscles after active stretch. Plantarflexion torque of 20 subjects was measured during 1) purely isometric and 2) active stretch contractions (26°, 60°/s), at a submaximal torque level of 30% MVC. Oxygen consumption (m$$\dot{\rm{V}}$$

V

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O2) of gastrocnemius medialis (GM) was estimated by near-infrared spectroscopy while applying arterial occlusion. Since the overall group did not show AR at GM after active stretch (p > 0.19), a subgroup was defined (n = 10) showing AR of 13.0 ± 10.3% (p = 0.00). However, for both purely isometric and active contractions m$$\dot{\rm{V}}$$

V

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O2 was the same (p = 0.32). Therefore, AR triggered by active stretch did not affect m$$\dot{\rm{V}}$$

V

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O2 of active human muscle.