bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification of spondylolytic clefts in patients with spondylolysis or isthmic spondylolisthesis using positional MRI
Authors: Niggemann Pascal , Kuchta Johannes , Hadizadeh Dariusch , Pieper Claus Christian , Schild Hans Heinz 
Published: March 2016

Background Posterior instability is a pathologic movement occurring in the spondylolytic cleft. Purpose To present a new classification system for the evaluation of spondylolytic cleft by positional magnetic resonance imaging (MRI) and determine the prevalence of the different types. Material and Methods A total of 176 segments of the lumbar spine with spondylolysis or isthmic spondylolisthesis were examined using positional MRI. Scans were obtained in neutral sitting, flexion, and extension positions. No visible movement in the cleft was defined as type A, fluid displaced into the cleft as type BI, displacement of the flava ligaments at the level of the cleft as type BII, and intraspinal cysts arising from the spondylolytic cleft as type BIII. The movements were characterized by a radiologist and a neurosurgeon experienced in positional MRI. Clinical findings were correlated with the different types of instability. Results A high agreement was found between the two observers. In total, 131 segments were characterized as type A, six as type BI, 24 as type BII, and 10 as type BIII. In five segments, the type differed between the right and the left side. Two patients had a mixed type BI/II, another two patients had a mixed type BII/III, and one patient had a mixed type BI/III. Patients with type BII and BIII instabilities suffered more often from radicular symptoms compared to patients without any instability. Conclusion The presented classification might help to better understand and study changes encountered in the spondylolytic cleft in patients with spondylolysis and isthmic spondylolisthesis using positional MRI.
Systematic Review and Patient-Level Meta-analysis of the Streamliner Multilayer Flow Modulator in the Management of Complex Thoracoabdominal Aortic Pathology
Authors: Hynes Niamh , Sultan Sherif , Elhelali Ala , Diethrich Edward B. , Kavanagh Edel P. , Sultan Mohamed , Stefanov Florian , Delassus Patrick , Morris Liam 
Published: March 2016

Purpose: To examine the safety and short-term efficacy of the Streamliner Multilayer Flow Modulator (SMFM) in the management of patients with complex thoracoabdominal aortic pathology who are unfit for alternative interventions. Methods: Biomedical databases were systematically searched for articles published between 2008 and 2015 on the SMFM. A patient-level meta-analysis was used to evaluate aneurysm-related survival. Secondary outcomes were all-cause survival, stroke, spinal cord ischemia, renal impairment, and branch vessel patency. Other considerations were the impact of compliance with the instructions for use (IFU) on clinical outcome. Mean values and Kaplan-Meier estimates are presented with the 95% confidence interval (CI). Results: Fifteen articles (3 multicenter cohort studies, 3 observational cohort studies, and 9 case reports) were included, presenting 171 patients (mean age 68.8±12.3 years; 139 men). The mean aneurysm diameter was 6.7±1.6 cm (95% CI 6.4 to 6.9 cm). Technical success reported in 15 studies was 77.2%. Aneurysm-related survival at 1 year was 78.7% (95% CI 71.7% to 84.4%). One-year all-cause survival was 53.7% (95% CI 46.0% to 61.3%). There were no reported cases of spinal cord ischemia, renal insult, or stroke. Conclusion: The SMFM can be safely utilized in some patients with complex thoracoabdominal pathologies provided operators adhere to the IFU. The SMFM is a novel technology with no long-term published data on its sustained effectiveness and a lack of comparative studies. Randomized clinical trials, registries, and continued assessment are essential before this flow-modulating technology can be widely disseminated.
Splenic marginal zone lymphoma: from genetics to management
Authors: Arcaini Luca , Rossi Davide , Paulli Marco 
Published: March 2016

AbstractSplenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.
Optimizing therapy for nodal marginal zone lymphoma
Authors: Thieblemont Catherine , Molina Thierry , Davi Frédéric 
Published: March 2016

Abstract
Nodal marginal zone lymphoma (NMZL) is a rare form of indolent small B-cell lymphoma which has only been clearly identified in the last 2 decades and which to date remains incurable. Progress in therapeutic management has been slow, largely due to the very small number of patients treated and the heterogeneity of treatments administered; thus, standard-of-care treatment is currently nonspecific for this lymphoma entity. In this review, treatments routinely used to manage adult NMZL patients are presented, principally based on immunochemotherapy (when treatment is needed). Biological research behind the key axes of agents currently under development is described; development of novel agents is heavily based on data from gene profiling and genome-wide sequencing research, uncovering a number of critical deregulated pathways specific to NMZL tumors. These include B-cell receptor, JAK/STAT, NF-κB, NOTCH, and Toll-like receptor signaling pathways, as well as intracellular processes such as the cell cycle, chromatin remodeling, and transcriptional regulation in terms of epigenetic modifiers, histones, or transcriptional co-repressors, along with immune escape via T-cell–mediated tumor surveillance. These pathways are examined in detail and a projection of how the field may evolve in the near future for an efficient personalized treatment approach for NMZL patients is presented.
Comparison of module detection algorithms in protein networks and investigation of the biological meaning of predicted modules
Authors: Tripathi Shailesh , Moutari Salissou , Dehmer Matthias , Emmert-Streib Frank 
Published: March 2016

Abstract
Background
It is generally acknowledged that a functional understanding of a biological system can only be obtained by an understanding of the collective of molecular interactions in form of biological networks. Protein networks are one particular network type of special importance, because proteins form the functional base units of every biological cell. On a mesoscopic level of protein networks, modules are of significant importance because these building blocks may be the next elementary functional level above individual proteins allowing to gain insight into fundamental organizational principles of biological cells.

Results
In this paper, we provide a comparative analysis of five popular and four novel module detection algorithms. We study these module prediction methods for simulated benchmark networks as well as 10 biological protein interaction networks (PINs). A particular focus of our analysis is placed on the biological meaning of the predicted modules by utilizing the Gene Ontology (GO) database as gold standard for the definition of biological processes. Furthermore, we investigate the robustness of the results by perturbing the PINs simulating in this way our incomplete knowledge of protein networks.

Conclusions
Overall, our study reveals that there is a large heterogeneity among the different module prediction algorithms if one zooms-in the biological level of biological processes in the form of GO terms and all methods are severely affected by a slight perturbation of the networks. However, we also find pathways that are enriched in multiple modules, which could provide important information about the hierarchical organization of the system.
The role of neutrophils in immune dysfunction during severe inflammation
Authors: Leliefeld Pieter H. C. , Wessels Catharina M. , Leenen Luke P. H. , Koenderman Leo , Pillay Janesh 
Published: March 2016

AbstractCritically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.
Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis
Authors: Gubert Fernanda , Decotelli Ana B. , Bonacossa-Pereira Igor , Figueiredo Fernanda R. , Zaverucha-do-Valle Camila , Tovar-Moll Fernanda , Hoffmann Luísa , Urmenyi Turan P. , Santiago Marcelo F. , Mendez-Otero Rosalia 
Published: March 2016

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that selectively affects the motor neurons. The details of the mechanisms of selective motor-neuron death remain unknown and no effective therapy has been developed. We investigated the therapy with bone-marrow mononuclear cells (BMMC) in a mouse model of ALS (SOD1G93A mice).

Methods
We injected 106 BMMC into the lumbar portion of the spinal cord of SOD1G93A mice in presymptomatic (9 weeks old) and symptomatic (14 weeks old) phases. In each condition, we analyzed the progression of disease and the lifespan of the animals.

Results
We observed a mild transitory delay in the disease progression in the animals injected with BMMC in the presymptomatic phase. However, we observed no increase in the lifespan. When we injected BMMC in the symptomatic phase, we observed no difference in the animals’ lifespan or in the disease progression. Immunohistochemistry for NeuN showed a decrease in the number of motor neurons during the course of the disease, and this decrease was not affected by either treatment. Using different strategies to track the BMMC, we noted that few cells remained in the spinal cord after transplantation. This observation could explain why the BMMC therapy had only a transitory effect.

Conclusion
This is the first report of intraspinal BMMC therapy in a mouse model of ALS. We conclude this cellular therapy has only a mild transitory effect when performed in the presymptomatic phase of the disease.
The complete genome sequence of Eubacterium limosum SA11, a metabolically versatile rumen acetogen
Authors: Kelly William J. , Henderson Gemma , Pacheco Diana M. , Li Dong , Reilly Kerri , Naylor Graham E. , Janssen Peter H. , Attwood Graeme T. , Altermann Eric , Leahy Sinead C. 
Published: March 2016

AbstractAcetogens are a specialized group of anaerobic bacteria able to produce acetate from CO2 and H2 via the Wood–Ljungdahl pathway. In some gut environments acetogens can compete with methanogens for H2, and as a result rumen acetogens are of interest in the development of microbial approaches for methane mitigation. The acetogen Eubacterium limosum SA11 was isolated from the rumen of a New Zealand sheep and its genome has been sequenced to examine its potential application in methane mitigation strategies, particularly in situations where hydrogenotrophic methanogens are inhibited resulting in increased H2 levels in the rumen. The 4.15 Mb chromosome of SA11 has an average G + C content of 47 %, and encodes 3805 protein-coding genes. There is a single prophage inserted in the chromosome, and several other gene clusters appear to have been acquired by horizontal transfer. These include genes for cell wall glycopolymers, a type VII secretion system, cell surface proteins and chemotaxis. SA11 is able to use a variety of organic substrates in addition to H2/CO2, with acetate and butyrate as the principal fermentation end-products, and genes involved in these metabolic pathways have been identified. An unusual feature is the presence of 39 genes encoding trimethylamine methyltransferase family proteins, more than any other bacterial genome. Overall, SA11 is a metabolically versatile organism, but its ability to grow on such a wide range of substrates suggests it may not be a suitable candidate to take the place of hydrogen-utilizing methanogens in the rumen.
Costs of the police service and mental healthcare pathways experienced by individuals with enduring mental health needs
Authors: Heslin Margaret , Callaghan Lynne , Barrett Barbara , Lea Susan , Eick Susan , Morgan John , Bolt Mark , Thornicroft Graham , Rose Diana , Healey Andrew , Patel Anita 
Published: March 2016

BackgroundSubstantial policy, communication and operational gaps exist between mental health services and the police for individuals with enduring mental health needs.AimsTo map and cost pathways through mental health and police services, and to model the cost impact of implementing key policy recommendations.MethodWithin a case-linkage study, we estimated 1-year individual-level healthcare and policing costs. Using decision modelling, we then estimated the potential impact on costs of three recommended service enhancements: street triage, Mental Health Act assessments for all Section 136 detainees and outreach custody link workers.ResultsUnder current care, average 1-year mental health and police costs were £10 812 and £4552 per individual respectively (n = 55). The cost per police incident was £522. Models suggested that each service enhancement would alter per incident costs by between −8% and +6%.ConclusionsRecommended enhancements to care pathways only marginally increase individual-level costs.
New insights into the endophenotypic status of cognition in bipolar disorder: Genetic modelling study of twins and siblings
Authors: Georgiades Anna , Rijsdijk Fruhling , Kane Fergus , Rebollo-Mesa Irene , Kalidindi Sridevi , Schulze Katja K. , Stahl Daniel , Walshe Muriel , Sahakian Barbara J. , McDonald Colm , Hall Mei-Hua , Murray Robin M. , Kravariti Eugenia 
Published: March 2016

BackgroundTwin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.AimsTo quantify the shared genetic variability between bipolar disorder and cognitive measures.MethodStructural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.ResultsUsing a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|–|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|–|1.00|), which remained significant after covarying for affective symptoms.ConclusionsVerbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.
Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk
Authors: Sun Fen , Nguyen Trinh , Jin Xin , Huang Renqi , Chen Zhenglan , Cunningham Rebecca L. , Singh Meharvan , Su Chang 
Published: March 2016

AbstractProgesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.
Scientific Basics of Methodology for Developing Innovative Training Package for School
Authors: ������  , Dronov V. 
Published: March 2016

Based on the forecasts of changes in the school education system, analyses of evolution of learning and teaching support and requirements of the Federal
State Educational Standard, the paper provides the guidelines of methodology for development of innovative training packages for school as the
pedagogical system. The general requirements and guidelines for development of appropriate training packages are defi ned, and proposals on how to
reorganize the correspondent editorial-and-publishing process are presented.
Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?
Authors: Vannucchi Maria Giuliana , Traini Chiara 
Published: March 2016

AbstractIn the interstitium of the connective tissue several types of cells occur. The fibroblasts, responsible for matrix formation, the mast cells, involved in local response to inflammatory stimuli, resident macrophages, plasma cells, lymphocytes, granulocytes and monocytes, all engaged in immunity responses. Recently, another type of interstitial cell, found in all organs so far examined, has been added to the previous ones, the telocytes (TC). In the gut, in addition to the cells listed above, there are also the interstitial cells of Cajal (ICC), a peculiar type of cell exclusively detected in the alimentary tract with multiple functions including pace-maker activity. The possibility that TC and ICC could correspond to a unique cell type, where the former would represent an ICC variant outside the gut, was initially considered, however, further studies have clearly shown that ICC and TC are two distinct types of cells. In the gut, while the features and the roles of the ICC are established, part of the scientific community is still disputing these ‘new’ interstitial cells to which several names such as fibroblast-like cells (FLCs), interstitial Cajal-like cells or, most recently, PDGFRα+cells have been attributed. This review will detail the main features and roles of the TC and ICC with the aim to establish their relationships and hopefully define the identity of the TC in the gut.
Microwave assisted adsorption based elution: a benign green process optimized by Box-Behnken modeling yields pure vasicine from Adhatoda vasica
Authors: Subramaniam Shankar , Sivasubramanian Aravind 
Published: March 2016

Abstract
Development of economical and rapid high yielding industrial processes for isolation of commercially important plant molecules have been in current industrial vogue. Adhatoda
vasica, a functional dietary supplemental plant, is found to harbor vasicine, a commercially important and physiologically active alkaloid. Attempts were made to increase the yields of vasicine by a viable “green” process – microwave assisted adsorption based elution (MAABE) with silica gel. Microwave (300 W) assisted extraction was done with 6% HCl/water (solid loading – 10%), which in 4 h yielded vasicine (8.8 mg/g of leaves, 0.88%). A Box-Behnken designed response surface methodology (RSM) optimized the extraction parameters to 9.31% solid loading, 6.64% HCl/water and 4.1 h, respectively. Further, adsorption based elution using silica gel and desorption with 70% ethanol/water yielded pure vasicine (1.12%) (recovery=93%, purity=95%). The adsorption isotherms studied to understand the adsorption mechanism suggested that the process followed the Langmuir theory. MAABE required less time and labor, in addition to its relative safety and as a “green” alternative process, to give high yields of commercially important vasicine.
Chiral oxazoline ligands with two different six-membered azaheteroaromatic rings – synthesis and application in the Cu-catalyzed nitroaldol reaction
Authors: Wolińska Ewa 
Published: March 2016

Abstract
Synthesis and catalytic activity of chiral ligands 5,6-diphenyl-3-{3-[(4S/R)-4-R/Ar-4,5-dihydro-1,3-oxazol-2-yl]pyridin-2-yl}amino-1,2,4-triazines 2 and their analogs 3 possessing an N-oxide function in the pyridine ring are described. The pivotal step in the synthesis of ligands 2 is the Buchwald-Hartwig Pd-catalyzed cross-coupling reaction between 3-bromo-5,6-diphenyl-1,2,4-triazine (7a) and enantiopure 3-(4,5-dihydro-1,3-oxazol-2-yl)pyridin-2-amines 6a–d. Aromatic nucleophilic substitution of chlorine in 3-chloro-5,6-diphenyl-1,2,4-triazine (7b) with 3-(4,5-dihydro-1,3-oxazol-2-yl)pyridin-2-amine 1-oxides 12 was investigated as the key reaction in the synthesis of ligands 3. Two undesired derivatives 13 or 14, resulting from unexpected reactions of 3, were isolated depending on reaction conditions. Compounds 2 and 3 as well as the side products 13 and 14 were screened as chiral ligands in the copper catalyzed enatioselective nitroaldol reaction.