bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel insights into the function and dynamics of extracellular matrix in liver fibrosis
Authors: Karsdal Morten A. , Manon-Jensen Tina , Genovese Federica , Kristensen Jacob H. , Nielsen Mette J. , Sand Jannie Marie B. , Hansen Niels-Ulrik B. , Bay-Jensen Anne-Christine , Bager Cecilie L. , Krag Aleksander , Blanchard Andy , Krarup Henrik , Leeming Diana J. , Schuppan Detlef
Published: March 2015

Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases.
[18F]-FDG positron emission tomography—an established clinical tool opening a new window into exercise physiology
Authors: Rudroff Thorsten , Kindred John H. , Kalliokoski Kari K.
Published: March 2015

Positron emission tomography (PET) with [18F]-fluorodeoxyglucose (FDG) is an established clinical tool primarily used to diagnose and evaluate disease status in patients with cancer. PET imaging using FDG can be a highly valuable tool to investigate normal human physiology by providing a noninvasive, quantitative measure of glucose uptake into various cell types. Over the past years it has also been increasingly used in exercise physiology studies to identify changes in glucose uptake, metabolism, and muscle activity during different exercise modalities. Metabolically active cells transport FDG, an18fluorine-labeled glucose analog tracer, from the blood into the cells where it is then phosphorylated but not further metabolized. This metabolic trapping process forms the basis of this method's use during exercise. The tracer is given to a participant during an exercise task, and the actual PET imaging is performed immediately after the exercise. Provided the uptake period is of sufficient duration, and the imaging is performed shortly after the exercise; the captured image strongly reflects the metabolic activity of the cells used during the task. When combined with repeated blood sampling to determine tracer blood concentration over time, also known as the input function, glucose uptake rate of the tissues can be quantitatively calculated. This synthesis provides an accounting of studies using FDG-PET to measure acute exercise-induced skeletal muscle activity, describes the advantages and limitations of this imaging technique, and discusses its applications to the field of exercise physiology.
Coordinate Loss of MAP3K7 and CHD1 Promotes Aggressive Prostate Cancer
Authors: Rodrigues Lindsey Ulkus , Rider Leah , Nieto Cera , Romero Lina , Karimpour-Fard Anis , Loda Massimo , Lucia M. Scott , Wu Min , Shi Lihong , Cimic Adela , Sirintrapun S. Joseph , Nolley Rosalie , Pac Colton , Chen Haitao , Peehl Donna M. , Xu Jianfeng , Liu Wennuan , Costello James C. , Cramer Scott D.
Published: March 2015

Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement–negative prostate cancer has not been conducted. Here, we identified an ETS− subtype of aggressive prostate cancer (ERG−MAP3K7delCHD1del) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7–CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7–shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7–Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with dual MAP3K7–CHD1 loss also displayed neuroendocrine and neural characteristics. In addition, dual Map3k7–Chd1 suppression promoted E-cadherin loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also correlated with Gleason grade and E-cadherin loss in clinical samples. To further validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7–shCHD1 LNCaP xenografts displayed increased tumor growth and decreased survival compared with shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development. Cancer Res; 75(6); 1021–34. ©2015 AACR.
CCR 20th Anniversary Commentary: BMS-247550—Microtubule Stabilization as Successful Targeted Therapy
Authors: Pabla Navjotsingh , Sparreboom Alex
Published: March 2015

In a landmark article published in the May 1, 2001, issue of Clinical Cancer Research, Lee and colleagues reported the original preclinical studies demonstrating anticancer activity of BMS-247550 (ixabepilone) against taxane-sensitive and taxane-resistant cancers. Subsequent clinical trials established the clinical efficacy of ixabepilone, leading to its regulatory approval for the treatment of drug-resistant metastatic or locally advanced breast cancers. Clin Cancer Res; 21(6); 1237–9. ©2015 AACR.

See related article by Lee et al., Clin Cancer Res 2001;7(5) May 2001;1429–37
Endothelial Jagged1 Antagonizes Dll4 Regulation of Endothelial Branching and Promotes Vascular Maturation Downstream of Dll4/Notch1
Authors: Pedrosa Ana-Rita , Trindade Alexandre , Fernandes Ana-Carina , Carvalho Catarina , Gigante Joana , Tavares Ana Teresa , Diéguez-Hurtado Rodrigo , Yagita Hideo , Adams Ralf H. , Duarte António
Published: March 2015

Objective—

Notch signaling controls cardiovascular development and has been associated with several pathological conditions. Among its ligands, Jagged1 and Dll4 were shown to have opposing effects in developmental angiogenesis, but the underlying mechanism and the role of Jagged1/Notch signaling in adult angiogenesis remain incompletely understood. The current study addresses the importance of endothelial Jagged1-mediated Notch signaling in the context of adult physiological angiogenesis and the interactions of Jagged1 and Dll4 on angiogenic response and vascular maturation processes.

Approach and Results—

The role of endothelial Jagged1 in wound healing kinetics and angiogenesis was investigated with endothelial-specific
Jag1
gain-of-function and loss-of-function mouse mutants (
eJag1
OE and
eJag1c
KO). To study the interactions between the 2 Notch ligands, genetic mouse models were combined with pharmacological inhibition of Dll4 or Jagged1, respectively. Jagged1 overexpression in endothelial cells increased vessel density, maturation, and perfusion, thus accelerating wound healing. The opposite effect was seen in e
Jag1
cKO animals. Interestingly, Dll4 blockade in these animals led to an increase in vascular density but induced a greater decrease in perivascular cell coverage. However, Jagged1 inhibition in
Dll4
gain-of-function (e
Dll4
OE) mutants, with reduced angiogenesis, further diminished angiogenic growth and hampered perivascular cell coverage. Our findings suggest that as Dll4 blocks endothelial activation through Notch1 signaling, it also induces Jagged1 expression. Jagged1 then blocks Dll4 signaling through Notch1, allowing endothelial activation by vascular endothelial growth factor and endothelial layer growth. Jagged1 also initiates maturation of the newly formed vessels, possibly by binding and activating endothelial Notch4. Importantly, mice administered with a Notch4 agonistic antibody mimicked the mural cell phenotype of e
Jag1
OE mutants without affecting angiogenic growth, which is thought to be Notch1 dependent.

Conclusions—

Endothelial Jagged1 is likely to operate downstream of Dll4/Notch1 signaling to activate Notch4 and regulate vascular maturation. Thus, Jagged1 not only counteracts Dll4/Notch in the endothelium but also generates a balance between angiogenic growth and maturation processes in vivo.
ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability
Authors: Magné Joëlle , Gustafsson Peter , Jin Hong , Maegdefessel Lars , Hultenby Kjell , Wernerson Annika , Eriksson Per , Franco-Cereceda Anders , Kovanen Petri T. , Gonçalves Isabel , Ehrenborg Ewa
Published: March 2015

Objective—

Autophagy has emerged as a cell survival mechanism critical for cellular homeostasis, which may play a protective role in atherosclerosis. ATG16L1, a protein essential for early stages of autophagy, has been implicated in the pathogenesis of Crohn’s disease. However, it is unknown whether ATG16L1 is involved in atherosclerosis. Our aim was to analyze ATG16L1 expression in carotid atherosclerotic plaques in relation to markers of plaque vulnerability.

Approach and Results—

Histological analysis of 143 endarterectomized human carotid atherosclerotic plaques revealed that ATG16L1 was expressed in areas surrounding the necrotic core and the shoulder regions. Double immunofluorescence labeling revealed that ATG16L1 was abundantly expressed in phagocytic cells (CD68), endothelial cells (CD31), and mast cells (tryptase) in human advanced plaques. ATG16L1 immunogold labeling was predominantly observed in endothelial cells and foamy smooth muscle cells of the plaques. ATG16L1 protein expression correlated with plaque content of proinflammatory cytokines and matrix metalloproteinases. Analysis of Atg16L1 at 2 distinct stages of the atherothrombotic process in a murine model of plaque vulnerability by incomplete ligation and cuff placement in carotid arteries of apolipoprotein-E-deficient mice revealed a strong colocalization of Atg16L1 and smooth muscle cells only in early atherosclerotic lesions. An increase in ATG16L1 expression and autophagy flux was observed during foam cell formation in human macrophages using oxidized-LDL.

Conclusions—

Taken together, this study shows that ATG16L1 protein expression is associated with foam cell formation and inflamed plaque phenotype and could contribute to the development of plaque vulnerability at earlier stages of the atherogenic process.
Streamlining Non-Tariff Measures in ASEAN: The Way Forward
Authors: Cadot Olivier , Munadi Ernawati , Yan Ing Lili
Published: March 2015

Findings show that the incidence of non-tariff measures (NTMs) in ASEAN is moderate in comparison with other regions of the world. The econometrically estimated ad valorem equivalents also seem comparable with other countries. The challenge is to design NTMs so as to maximize their effectiveness in responding to consumer concerns while minimizing the induced economic inefficiency and the interference from self-interested lobbies. This paper proposes that the way forward is not to follow traditional “notify-negotiate-eliminate” approaches but instead to bring the issue to the country level and imbed them in regulatory-reform agendas in the efforts to improve trade and investment climate.
Shifting Drivers of Growth: Policy Implications for ASEAN-5
Authors: Tan Kong Yam , Abeysinghe Tilak , Tan Khee Giap
Published: March 2015

How the old saying “when the United States sneezes, the world catches a cold” holds true has been the subject of many research papers on global and country group business cycle synchronization and divergence. Instead of business cycle linkages, however, this paper examines the evolution of the dependence of ASEAN-5 and other Asian economies on their traditional and emerging growth engines (the United States, EU, Japan, China, and India). For this we use a structural vector autoregression model that yields time-varying growth multiplier effects. Although China has overtaken others as a major export destination for ASEAN-5 and despite the United States losing much of its relative economic clout in Asia, the multiplier effects show that the United States is still about 1.5 times more growth-enhancing than China for ASEAN-5. The EU has also not lost out completely to China as a growth engine. China, however, has overtaken Japan to become about 1.88 times more growth enhancing than Japan for ASEAN-5. India has yet to become a significant growth engine, although it is of increasing importance to Singapore, Malaysia, and Indonesia. These results call for new initiatives to balance the rising over-dependence on China.
In Search of a Strategy for Making Growth More Pro-Poor in the Philippines
Authors: Fuwa Nobuhiko , Balisacan Arsenio M. , Bresciani Fabrizio
Published: March 2015

Despite the large and expanding literature on pro-poor growth, quantitative studies identifying potential determinants of pro-poor growth remain scarce. This paper addresses this lacuna in the literature for the case of the Philippines. The main driver of rural poverty reduction has shifted from agricultural to non-agricultural growth in the Philippines, but agricultural investments can be still effective in areas with underdeveloped infrastructure. Non-agricultural income growth, on the other hand, can be made more pro-poor by reducing child mortality, facilitating international labor migration, investing in roads, and reducing income inequality.
Edible species of Agaricus (Agaricaceae) from Xinjiang Province (Western China)
Authors: Wang Zhuo-Ren , Parra LUIS A , CALLAC PHILIPPE , ZHOU JUN-LIANG , FU WEN-JIN , DUI SAN-HAN , HYDE KEVIN D , ZHAO RUI-LIN
Published: March 2015

Agaricus is a genus of macrofungi containing species with high edible and medicinal values. A survey of Agaricus species carried out around the Ebinur Lake, in Xinjiang Province of China, in 2012, yielded 19 collections that exhibited a red discolouration when bruised. Morphological and phylogenetic comparison with species of five sections of Agaricus possessing the red discolouration trait showed that the specimens belonged to four species. Two species, A. sinodeliciosus sp. nov. and A. bitorquis in section Bivelares and A. desjardinii sp. nov. and A. padanus in section Nigrobrunnescentes, both sections being monophyletic. The two new species proposed are described and illustrated and all species are compared with similar taxa or previous records. Agaricus padanus is reported outside Italy for the first time. All species are edible and consumed by locals, and appear to be adapted to relatively dry, cold and sandy habitats. Like A. bitorquis, A. sinodeliciosus produces large, delicious semihypogeous basidiomata in such conditions; it is therefore a good potential candidate for domestication and industrial production.
The first records of Polygala westii (Polygalaceae) for South Africa (North-West Province) and a key to the southern African Polygala species in the Section Tetrasepalae
Authors: Bester Stoffel Petrus , Paiva Jorge
Published: March 2015

The first record of Polygala westii (Polygalaceae) from the North-West Province (South Africa) is reported on here. The species is very rare and has previously only been collected in two separate gatherings. This species is characterised by having bracts and bracteoles caducous, the anterior sepals connate at least as much as half of their length and seeds pubescent and carunculate. It grows in a habitat that are severely impacted by agriculture and mining. A preliminary assessment of its conservation status is given. A key to the South African species in the subsection (Tetrasepalae) to which P. westii belong is provided. The aim of this paper is to highlight the species in order to stimulate the lookout for more material of this species.
Corrections to the nomenclature of genus Diatoma (Bacillariophyta: Fragilariaceae)
Authors: Blanco Lanza Saúl , WILLIAMS DAVID M.
Published: March 2015

Within plants, algae and fungi, the rules of nomenclature (ICN, McNeill et al. 2012) require that adjectival specific—and infraspecific—epithets agree grammatically (gender concordance) with the generic name. Epithets not conforming to this rule, although validly published, are to be corrected (ICN art. 23.5) without change of the author citation or date. Despite that the original spelling of these epithets is generally to be retained (art. 60.1), improper Latin terminations are always to be changed to accord with, among others, the mentioned art. 23.5 (art. 32.2).
Contrasting Impacts of the Arctic Oscillation on Surface Air Temperature Anomalies in Southern China between Early and Middle-to-Late Winter
Authors: Zuo Jinqing , Ren Hong-Li , Li Weijing
Published: March 2015

In the boreal winter, the Arctic Oscillation (AO) evidently acts to influence surface air temperature (SAT) anomalies in China. This study reveals a large intraseasonal variation in the relationship between the winter AO and southern China SAT anomalies. Specifically, a weak in-phase relationship occurs in December, but a significant out-of-phase relationship occurs in January and February. The authors show that the linkage between the AO and southern China SAT anomalies strongly depends on the AO-associated changes in the Middle East jet stream (MEJS) and that such an AO–MEJS relationship is characterized by a significant difference between early and middle-to-late winter. In middle-to-late winter, the Azores center of high pressure anomalies in the positive AO phase usually extends eastward and yields a significantly anomalous upper-level convergence over the Mediterranean Sea, which can excite a Rossby wave train spanning the Arabian Sea and intensify the MEJS. In early winter, however, the Azores center of the AO is apparently shifted westward and is mainly confined to the Atlantic Ocean; in this case, the associated change in the MEJS is relatively weak. Both observational diagnoses and experiments based on a linearized barotropic model suggest that the MEJS is closely linked to the AO only when the latter generates considerable upper-level convergence anomalies over the Mediterranean Sea. Therefore, the different impacts of the AO on the MEJS and the southern China SAT anomalies between early and middle-to-late winter are primarily attributed to the large intraseasonal zonal migrations of the Azores center of the AO.
Assault of Police
Authors: Bierie David M.
Published: March 2015

The assault of law enforcement officers is an important but understudied topic. To better understand this form of violence, this study drew on the National Incident–Based Reporting System—the nation’s largest data set tracking assaults against police alongside detailed information on situations surrounding attacks. Risk factors were examined within a fixed-effects logistic regression framework via a case-control method in which all incidents involving assault against police ( n = 20,140) were compared with a random sample of arrest encounters that did not involve this form of aggression ( n = 20,118). The data showed that a number of victim, offender, and situational characteristics predicted violence against officers, and the models were able to explain a substantial portion of the variance. Implications for research are discussed.
New multi-block isophorone diisocyanate-based copolymers with urethane urea hard segments
Authors: Tereshatov Vasiliy , Vnutskikh Zhanna , Slobodinyuk Alexey , Makarova Marina , Senichev Valeriy
Published: March 2015

Segmented polyurethane ureas (SPUUs) were synthesized on the base of oligopropylene oxide (PPO), oligotetramethylene oxide (PTMO), 2,4-toluene diisocyanate, isophorone diisocyanate (IDI), and methylene- o-chloroaniline. Structure of polymer chains with thermodynamically compatible PTMO and PPO soft segments (SS) was identified using data from rheokinetic studies of reactionary mixes with different diisocyanates. The significant swelling value in low-polar solvent toluene and non-elevated softening temperature indicates the formation of loose (defect) structure of the hard phase in compositions, synthesized using IDI. Thermal, thermomechanical, and physicomechanical properties of SPUU with variable compositions of hard segment and SS (blocks) were investigated. An interrelation between structure and properties of block copolymers of new type was estimated. Investigation results showed a significant increase in the strength of polyurethane urea at the equimolar ration between various hard blocks and SS on the base of PPO and PTMO. High strength values were obtained for SPUU in a wide diapason of stretching rates (0.56–0.003 s−1). Structural factors contributing to stability of strength properties of tetrablock-copolymers, namely: stronger inter-chain interaction in the soft phase and a “loose” structure of the hard phase. were revealed. The data relating to elevation of thermostability of these materials were given. New materials can be applied for various conditions of mechanical loading.
Platelet-Rich Plasma Reduces Retear Rates After Arthroscopic Repair of Small- and Medium-Sized Rotator Cuff Tears but Is Not Cost-Effective
Authors: Vavken Patrick , Sadoghi Patrick , Palmer Matthew , Rosso Claudio , Mueller Andreas M. , Szoelloesy Gregor , Valderrabano Victor
Published: March 2015

Background:

It has been suggested that platelet-rich plasma (PRP) improves healing after arthroscopic rotator cuff repair. The current literature provides ample but inconsistent data on this topic.

Purpose:

To systematically review the current in vivo evidence for the use of platelet concentrates (PRP) in the arthroscopic treatment of rotator cuff tears to assess effectiveness, safety, and cost-effectiveness.

Study Design:

Meta-analysis and cost-effectiveness analysis.

Methods:

Published evidence from controlled, human trials of rotator cuff repair augmented with platelet concentrates was systematically gathered, and data on retear rates were extracted. Mathematical and clinical heterogeneity was evaluated, and fixed-effect meta-analysis was performed to calculate the risk ratio (RR) of retears and the number needed to treat (NNT). Subgroup analyses were made for small/medium tears (n = 404) and large/massive tears (n = 374). Cost-effectiveness was assessed using data from this meta-analysis and using cost data from the literature, including extensive sensitivity analyses, to calculate the incremental cost-effectiveness ratio (ICER).

Results:

Thirteen studies published between 2010 and 2014 were identified for analysis. The RR for retear for all patients was 0.87 (95% CI, 0.67-1.12; P = .286). For small- and medium-sized tears (<3 cm), the RR for retear was 0.60 (95% CI, 0.37-0.97), consistent with a significant difference in favor of PRP use ( P = .038). This translated into an NNT of 14 (95% CI, 7-125). However, at an ICER of US$127,893 per quality-adjusted life year gained, assuming a 5% revision rate, the use of PRP was not cost-effective for small- and medium-sized tears.

Conclusion:

In large tears, even with double-row repair, the beneficial effects of PRP alone are insufficient to compensate the progressed tissue damage. The study data suggest that PRP may promote healing of small- and medium-sized tears to reduce retear rates. However, despite the substantial biological effect, at current cost, the use of PRP is not cost-effective in arthroscopic repair of small- and medium-sized tears.
Social-Emotional Learning Program to Reduce Bullying, Fighting, and Victimization Among Middle School Students With Disabilities
Authors: Espelage Dorothy L. , Rose Chad A. , Polanin Joshua R.
Published: March 2015

Results of a 3-year randomized clinical trial of Second Step: Student Success Through Prevention (SS-SSTP) Middle School Program on reducing bullying, physical aggression, and peer victimization among students with disabilities are presented. Teachers implemented 41 lessons of a sixth- to eighth-grade curriculum that focused on social-emotional learning (SEL) skills, including empathy, bully prevention, communication skills, and emotion regulation. Two school districts in a larger clinical trial provided disability information. All sixth-grade students ( N = 123) with a disability were included in these analyses, including intervention ( n = 47) and control ( n = 76) conditions. Linear growth models indicated a significant intervention effect for bully perpetration; compared with students in the control condition, intervention students’ bullying perpetration scale scores significantly decreased across the 3-year study (δ = −.20, 95% confidence interval = [−.38, −.03]). SEL offers promise in reducing bully perpetration among students with disabilities.
Brain Science and Illness Beliefs
Authors: Wright Lorraine M.
Published: March 2015

Paradigm families and paradigm practice moments have shown me that therapeutic conversations between nurses and families can profoundly and positively change illness beliefs in family members and nurses and contribute to healing from serious illness. The integration of brain science into nursing practice offers further understanding of the importance of illness beliefs and the role they may play in helping individual and family healing. Brain science offers explanations that connect how certain family nursing interventions that soften suffering and challenge constraining illness beliefs may result in changes in brain structure and functioning. New illness beliefs may result in new neural pathways in the brain, and therefore, possibilities for a new way of being in relationship with illness and in relationship with others can also develop. Newly acquired practice skills and interventions that have emerged from an understanding of brain science plus the reemphasis of other interventions utilized in the Illness Beliefs Model are offered to enhance our care of families suffering with illness.
A Diagnosis of Insomnia Is Associated With Differential Expression of Sleep-Regulating Genes in Military Personnel
Authors: Gill Jessica M. , Lee Hyunhwa , Baxter Tristin , Reddy Swarnalatha Y. , Barr Taura , Kim Hyung-suk , Wang Dan , Mysliwiec Vincent
Published: March 2015

Sleep disturbance is a common and disturbing symptom in military personnel, with many individuals progressing to the development of insomnia, which is characterized by increased arousals, wakefulness after sleep onset, and distorted sleep architecture. The molecular mechanisms underlying insomnia remain elusive, limiting future therapeutic development to address this critical issue. We examined whole gene expression profiles associated with insomnia. We compared subjects with insomnia ( n = 25) to controls ( n = 13) without insomnia using microarray gene expression profiles obtained from peripheral samples of whole blood obtained from military personnel. Compared to controls, participants with insomnia had differential expression of 44 transcripts from 43 identified genes. Among the identified genes, urotensin 2 was downregulated by more than 6 times in insomnia participants, and the fold-change remained significant after controlling for depression, posttraumatic stress disorder, and medication use. Urotensin 2 is involved in regulation of orexin A and B activity and rapid eye movement during sleep. These findings suggest that differential expression of these sleep-regulating genes contributes to symptoms of insomnia and, specifically, that switching between rapid eye movement and nonrapid eye movement sleep stages underlies insomnia symptoms. Future work to identify therapeutic agents that are able to regulate these pathways may provide novel treatments for insomnia.
The role of epidemiology in MS research: Past successes, current challenges and future potential
Authors: Simpson Steve , Taylor Bruce V , van der Mei Ingrid
Published: March 2015

Multiple sclerosis (MS) is a multifaceted condition, with a range of environmental, behavioural and genetic factors implicated in its aetiology and clinical course. Successes in advancing our appreciation of the roles of Epstein-Barr virus, vitamin D/UV and the HLA-DRB1 locus; and our greater understanding of these and related factors’ modes of action in MS and other conditions, can be attributed in no small part to the work of generations of epidemiologists. Hardly content to rest on our laurels, however, there are yet a range of unsolved conundrums in MS, including some changes in epidemiological characteristics (e.g. increasing incidence and sex ratio), to say nothing of the unresolved parts regarding what underlies MS risk and its clinical course. There is evidence that epidemiology will continue to play a crucial role in unravelling the architecture of MS causation and clinical course. While classic epidemiological methods are ongoing, novel avenues for research include gene-environment interaction studies, the world of ‘-omic’ research, and the utilisation of mobile and social media tools to both access and track study populations, which means that the epidemiological discoveries of the past century may be but a glimpse of our understanding in the next few decades.
Point-of-care monitoring of warfarin treatment in community dwelling elderly – A randomised controlled study
Authors: Davidson Thomas , Lindelöf Ann , Wallén Torbjörn , Lindahl Tomas L , Hallert Claes
Published: March 2015

The objective of this study was to assess clinical effectiveness and costs of launching point-of-care monitoring of warfarin treatment in community dwelling frail elderly patients. A prospective multicentre controlled randomised study over 12 months comparing a point-of-care strategy with usual monitoring routines was carried out in primary healthcare centres and anticoagulation clinics in southeast Sweden. The subjects were community dwelling elderly across rural southeast Sweden on chronic warfarin treatment. Main outcome measures were time in therapeutic range (TTR), rate of treatment-related adverse events and costs. The study comprised 103 elderly people (61% women) mean age 86 yrs (range 75--98) treated with warfarin for median 9 yrs (range 1--18). Patients randomised to start point-of-care monitoring (n = 55) showed 75.9% in TTR before trial vs. 72.6% during trial (ns). The patients randomised to continue on usual monitoring routines (n = 48) showed 75.2% in TTR prior to trial vs. 72.9% during trial (ns). The point-of-care monitoring showed potential savings of SEK 624 per patient annually (based partly on effects that were not statistically significant). The study shows that point-of-care monitoring of warfarin treatment in community dwelling elderly in rural areas is as effective as usual monitoring routines and that it may offer savings to society.
Governance, management and accountability: The experience of the school system in the English-speaking Caribbean countries
Authors: Hutton Disraeli M.
Published: March 2015

This paper seeks to explore the implementation of three of the critical elements required to improve performance in the education system: governance, accountability and management. The paper examines the education reform processes conducted by five Caribbean countries: Jamaica, Cayman Islands, Guyana, Belize, Trinidad and Tobago, along with those represented by the Organization of Eastern Caribbean States. The individual countries along with the Organization of Eastern Caribbean States have all embraced and implemented at some level the elements of governance, accountability and management as a part of their strategic planning arrangements between 1990 and 2010. The review shows that clear efforts were made by these countries to address the issue of governance, accountability and management although with varying levels of success. The most notable achievement was that the democratization and decentralization of the education process in these countries seemed to be a central strategy being used to strengthen governance, management and accountability. However, the implementation needs to be deepened so that stakeholders, especially at the school level, can have a greater say and make a more worthwhile and meaningful contribution to the process.
Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus
Authors: Oliveira Alexandra P , Calderon Iracema MP , Costa Roberto AA , Roscani Meliza G , Magalhães Claudia G , Borges Vera TM
Published: March 2015

Background:

The main manifestation of hyperglycaemia during pregnancy is gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its deleterious long-term effects, such as hypertension and cardiovascular disease. The aim of this study was to assess diastolic function in women with gestational diabetes mellitus, one of the first signs of future cardiovascular disease.

Methods:

A total of 21 women with gestational diabetes mellitus and 23 healthy pregnant women (control group) between 34 and 37 weeks of gestation underwent echocardiographic assessment. The diagnosis of gestational diabetes mellitus was made in agreement with the American Diabetes Association criteria. Echocardiographic images obtained were analysed according to the criteria of the American Society of Echocardiography. Data were analysed using Pearson correlation coefficient, analysis of variance and Student’s t-test.

Results:

Women with gestational diabetes mellitus had higher posterior wall and interventricular septum thickness, increased left ventricular mass and left ventricular mass index, lower early diastolic annular velocity and early diastolic annular velocity/late diastolic annular velocity ratio. There was a positive correlation between left ventricular mass index and fasting glucose and pregnancy body mass index.

Conclusion:

Patients with gestational diabetes mellitus seem to have a different diastolic profile as well as a mildly dysfunctional pattern on echocardiogram, which may show a need for greater glycaemic control.
Study of heat-setting treatment for biomedical polydioxanone stents
Authors: Li Gang , Li Yi , Lan Ping , He Xiao-Wen , Zhao Zheng , Li Zhi , Hu Hong
Published: March 2015

This paper presents a study of heat-setting treatment on tubular polydioxanone stents which can be used as intestinal implants. Two PDO monofilaments with linear densities of 100 ± 2 and 150 ± 2 tex respectively were used for producing a set of weft-knitted tubular stents using a small-diameter, circular weft knitting machine. The heat-setting treatment was used for the stents to restore a tubular shape. The physical, mechanical and thermal properties of the stents were examined before and after the heat-setting treatment. The results of mechanical testing illustrated that the prototype stents in this work could achieve higher radial forces than Wall stents and Z stents on the market. The heat setting with temperature of 80℃ and time of 5 min were found to be more appropriate for the stents. In conclusion, the stents were successfully developed and have potential application for the treatment of intestinal stenosis or obstruction.
Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium
Authors: Li Jun , Zhu Kai , Yang Shan , Wang Yulin , Guo Changfa , Yin Kanhua , Wang Chunsheng , Lai Hao
Published: March 2015

Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury.
Hydrothermal-assisted exfoliation of Y/Tb/Eu ternary layered rare-earth hydroxides into tens of micron-sized unilamellar nanosheets for highly oriented and color-tunable nano-phosphor films
Authors: Zhu Qi , Xu Zhixin , Li Ji-Guang , Li Xiaodong , Qi Yang , Sun Xudong
Published: March 2015

Efficient exfoliation of well-crystallized (Y0.96Tb
x
Eu0.04-x
)2(OH)5NO3 · nH2O (0 ≤ x ≤ 0.04) layered rare-earth hydroxide (LRH) crystals into tens of micron-sized unilamellar nanosheets has been successfully achieved by inserting water insoluble oleate anions (C17H33COO−) into the interlayer of the LRH via hydrothermal anion exchange at 120°C, followed by delaminating in toluene. The intercalation of oleate anions led to extremely expanded interlayer distances (up to approximately 5.2 nm) of the LRH crystals and accordingly disordered stacking of the ab planes along the c-axis and also weakened interlayer interactions, without significantly damaging the ab plane. As a consequence, the thickness of the LRH crystals increased from approximately 1 to 10 μm, exhibiting a behavior similar to that observed from the smectite clay in water. Highly [111]-oriented and approximately 100-nm thick oxide films of (Y0.96Tb
x
Eu0.04-x

)
2O3 (0 ≤ x ≤ 0.04) have been obtained through spin-coating of the exfoliated colloidal nanosheets on quartz substrate, followed by annealing at 800°C. Upon UV excitation at 266 nm, the oxide transparent films exhibit bright luminescence, with the color-tunable emission from red to orange, yellow, and then green by increasing the Tb3+ content from x = 0 to 0.04.
Quality of life in patients with retinitis pigmentosa submitted to intravitreal use of bone marrow-derived stem cells (Reticell -clinical trial)
Authors: Siqueira Rubens C , Messias Andre , Messias Katharina , Arcieri Rafael S , Ruiz Milton A , Souza Neiglene F , Martins Lia C , Jorge Rodrigo
Published: March 2015

Introduction

Retinitis pigmentosa (RP) is a severe neurodegenerative disease of the retina that can lead to blindness. Even without treatment, a clinical study with the use of stem cells is currently underway and the results are being evaluated. In the present report we assess the vision-related quality of life in patients with RP submitted to intravitreal use of bone marrow-derived stem cells.

Method

The study included 20 patients with RP submitted to intravitreal use of bone marrow-derived stem cells. We evaluate the vision-related quality of life (VRQOL) of patients using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Patients were scheduled to answer the questionnaire before treatment and 3 and 12 months after treatment.

Results

All patients completed the survey as scheduled.

There was a statistically significant improvement (P <0.05) in the quality of life of patients 3 months after treatment, whereas by the 12th month there was no statistically significant difference from baseline.

Conclusions

Cell therapy with intravitreal use of bone marrow-derived stem cells can improve the quality of life of patients with RP, although the improvement is lost with time. A larger number of cases will be necessary to evaluate the repercussions of this therapy on the quality of life of these patients.

Trial registration

Clinicaltrials.gov: NCT01560715. Registered March 19, 2012.
Transplantation of mouse embryonic stem cell-derived oligodendrocytes in the murine model of globoid cell leukodystrophy
Authors: Kuai Xiao Ling , Ni Run Zhou , Zhou Guo Xiong , Mao Zheng Biao , Zhang Jian Feng , Yi Nan , Liu Zhao Xiu , Shao Nan , Ni Wen Kai , Wang Zhi Wei
Published: March 2015

Introduction

Globoid cell leukodystrophy (GLD) is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. Cell-based therapies are highly promising strategies for GLD. In this study, G-Olig2 mouse embryonic stem cells (ESCs) were induced into oligodendrocyte progenitor cells (OPCs) and were implanted into the brains of twitcher mice, an animal model of GLD, to explore the therapeutic potential of the cells.

Methods

The G-Olig2 ESCs were induced into OPCs by using cytokines and a multi-step differentiation procedure. Oligodendrocyte markers were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. The toxicity of psychosine to OPCs was determined by a cell proliferation assay kit. The GALC level of OPCs was also examined. OPCs were labeled with Dir and transplanted into the brains of twitcher mice. The transplanted cells were detected by in-Vivo Multispectral Imaging System and real-time PCR. The physiological effects of twitcher mice were assessed.

Results

Oligodendrocyte markers were expressed in OPCs, and 76% ± 5.76% of the OPCs were enhanced green fluorescent protein (eGFP)-positive, eGFP was driven by the Olig2 promoter. The effect of psychosine on cell viability indicated that OPCs were more resistant to psychosine toxicity. The GALC level of OPCs was 10.0 ± 1.23 nmol/hour per mg protein, which was significantly higher than other cells. Dir-labeled OPCs were injected into the forebrain of post-natal day 10 twitcher mice. The transplanted OPCs were myelin basic protein (MBP)-positive and remained along the injection tract as observed by fluorescent microscopy. The level of the Dir fluorescent signal and eGFP mRNA significantly decreased at days 10 and 20 after injection, as indicated by in-Vivo Multispectral Imaging System and real-time PCR. Because of poor cell survival and limited migration ability, there was no significant improvement in brain GALC activity, MBP level, life span, body weight, and behavioral deficits of twitcher mice.

Conclusions

ESC-derived OPC transplantation was not sufficient to reverse the clinical course of GLD in twitcher mice.
Selective pruning in pineapple plants as means to reduce heterogeneity in fruit quality
Authors: Fassinou Hotegni V Nicodème , Lommen Willemien J M , Agbossou Euloge K , Struik Paul C
Published: March 2015

Heterogeneity in fruit quality (size and taste) is a major problem in pineapple production chains. The possibilities were investigated of reducing the heterogeneity in pineapple in the field by pruning slips on selected plants, in order to promote the fruit growth on these plants. Slips are side shoots that develop just below the pineapple fruit during fruit development. Two on-farm experiments were carried out in commercial fields in Benin with a cultivar locally known as Sugarloaf, to determine (a) the effect of slip pruning on fruit quality; (b) whether the effect of slip pruning depends on the pruning time; and (c) whether slip pruning from the plants with the smallest infructescences results in more uniformity in fruit quality. A split-plot design was used with pruning time (2 or 3 months after inflorescence emergence) as main factor and fraction of pruned plants (no plants pruned (control); pruning on the one-third plants with the smallest infructescences; pruning on the two-thirds plants with the smallest infructescences; pruning on all plants) as sub-factor. Fruit quality characteristics measured at harvest were the fruit (infructescence + crown) weight and length, the infructescence weight and length, the crown weight and length, the ratio crown length: infructescence length, the total soluble solids, the juice pH and the flesh translucency. Results indicated that pruning of slips of any fraction of the plants at 2 or 3 months after inflorescence emergence did not lead to a consistent improvement in quality or uniformity. Consequently it is not recommended to farmers in Benin to prune the slips.
Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation
Authors: Dapunt Ulrike , Giese Thomas , Maurer Susanne , Stegmaier Sabine , Prior Birgit , Hänsch G Maria , Gaida Matthias M
Published: March 2015

Bone infections of patients with joint replacement by endoprosthesis (so called “periprosthetic joint infection”) pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.