bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial
Authors: Chen Fa-Ming , Gao Li-Na , Tian Bei-Min , Zhang Xi-Yu , Zhang Yong-Jie , Dong Guang-Ying , Lu Hong , Chu Qing , Xu Jie , Yu Yang , Wu Rui-Xin , Yin Yuan , Shi Songtao , Jin Yan 
Published: February 2016

Abstract
Background
Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry.

Methods
We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss®) or the Control group (treatment with GTR and Bio-oss® without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure.

Results
A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05).

Conclusions
This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size.

Trial Registration
NCT01357785 Date registered: 18 May 2011.
Functioning of drug-metabolizing microsomal cytochrome P450s: In silico probing of proteins suggests that the distal heme ‘active site’ pocket plays a relatively ‘passive role’ in some enzyme-substrate interactions
Authors: Venkatachalam Avanthika , Parashar Abhinav , Manoj Kelath Murali 
Published: February 2016

AbstractPurposeThe currently held mechanistic understanding of microsomal cytochrome P450s (CYPs) seeks that diverse drug molecules bind within the deep-seated distal heme pocket and subsequently react at the heme centre. To explain a bevy of experimental observations and meta-analyses, we indulge a hypothesis that involves a “diffusible radical mediated” mechanism. This new hypothesis posits that many substrates could also bind at alternate loci on/within the enzyme and be reacted without the pertinent moiety accessing a bonding proximity to the purported catalytic Fe-O enzyme intermediate.MethodsThrough blind and heme-distal pocket centered dockings of various substrates and non-substrates (drug molecules of diverse sizes, classes, topographies etc.) of microsomal CYPs, we explored the possibility of access of substrates via the distal channels, its binding energies, docking orientations, distance of reactive moieties (or molecule per se) to/from the heme centre, etc. We investigated specific cases like- (a) large drug molecules as substrates, (b) classical marker drug substrates, (c) class of drugs as substrates (Sartans, Statins etc.), (d) substrate preferences between related and unrelated CYPs, (e) man-made site-directed mutants’ and naturally occurring mutants’ reactivity and metabolic disposition, (f) drug-drug interactions, (g) overall affinities of drug substrate versus oxidized product, (h) meta-analysis ofin silicoversus experimental binding constants and reaction/residence times etc.ResultsIt was found that heme-centered dockings of the substrate/modulator drug molecules with the available CYP crystal structures gave poor docking geometries and distances from Fe-heme centre. In conjunction with several other arguments, the findings discount the relevance of erstwhile hypothesis in many CYP systems. Consequently, the newly proposed hypothesis is deemed a viable alternate, as it satisfies Occam’s razor.ConclusionsThe new proposal affords expanded scope for explaining the mechanism, kinetics and overall phenomenology of CYP mediated drug metabolism. It is now understood that the heme-iron and the hydrophobic distal pocket of CYPs serve primarily to stabilize the reactive intermediate (diffusible radical) and the surface or crypts of the apoprotein bind to the xenobiotic substrate (and in some cases, the heme distal pocket could also serve the latter function). Thus, CYPs enhance reaction rates and selectivity/specificity via a hitherto unrecognized modality.
Changes in extra-striatal functional connectivity in patients with schizophrenia in a psychotic episode
Authors: Peters Henning , Riedl Valentin , Manoliu Andrei , Scherr Martin , Schwerthöffer Dirk , Zimmer Claus , Förstl Hans , Bäuml Josef , Sorg Christian , Koch Kathrin 
Published: February 2016

BackgroundIn patients with schizophrenia in a psychotic episode, intra-striatal intrinsic connectivity is increased in the putamen but not ventral striatum. Furthermore, multimodal changes have been observed in the anterior insula that interact extensively with the putamen.AimsWe hypothesised that during psychosis, putamen extra-striatal functional connectivity is altered with both the anterior insula and areas normally connected with the ventral striatum (i.e. altered functional connectivity distinctiveness of putamen and ventral striatum).MethodWe acquired resting-state functional magnetic resonance images from 21 patients with schizophrenia in a psychotic episode and 42 controls.ResultsPatients had decreased functional connectivity: the putamen with right anterior insula and dorsal prefrontal cortex, the ventral striatum with left anterior insula. Decreased functional connectivity between putamen and right anterior insula was specifically associated with patients' hallucinations. Functional connectivity distinctiveness was impaired only for the putamen.ConclusionsResults indicate aberrant extra-striatal connectivity during psychosis and a relationship between reduced putamen–right anterior insula connectivity and hallucinations. Data suggest that altered intrinsic connectivity links striatal and insular pathophysiology in psychosis.
Eye movement desensitisation and reprocessing therapy v. stabilisation as usual for refugees: randomised controlled trial
Authors: ter Heide F. Jackie June , Mooren Trudy M. , van de Schoot Rens , de Jongh Ad , Kleber Rolf J. 
Published: February 2016

BackgroundEye movement desensitisation and reprocessing (EMDR) therapy is a first-line treatment for adults with post-traumatic stress disorder (PTSD). Some clinicians argue that with refugees, directly targeting traumatic memories through EMDR may be harmful or ineffective.AimsTo determine the safety and efficacy of EMDR in adult refugees with PTSD (trial registration: ISRCTN20310201).MethodIn total, 72 refugees referred for specialised treatment were randomly assigned to 12 h of EMDR (3×60 min planning/preparation followed by 6×90 min desensitisation/reprocessing) or 12 h (12×60 min) of stabilisation. The Clinician-Administered PTSD Scale (CAPS) and Harvard Trauma Questionnaire (HTQ) were primary outcome measures.ResultsIntention-to-treat analyses found no differences in safety (one severe adverse event in the stabilisation condition only) or efficacy (effect sizes: CAPS –0.04 and HTQ 0.20) between the two conditions.ConclusionsDirectly targeting traumatic memories through 12 h of EMDR in refugee patients needing specialised treatment is safe, but is only of limited efficacy.
Mitochondrial functions of RECQL4 are required for the prevention of aerobic glycolysis-dependent cell invasion
Authors: Kumari Jyoti , Hussain Mansoor , De Siddharth , Chandra Suruchika , Modi Priyanka , Tikoo Shweta , Singh Archana , Sagar Chandrasekhar , Sepuri Naresh Babu V. , Sengupta Sagar 
Published: February 2016

ABSTRACT
Germline mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome, which is characterized by a predisposition to cancer. RECQL4 localizes to the mitochondria, where it acts as an accessory factor during mitochondrial DNA replication. To understand the specific mitochondrial functions of RECQL4, we created isogenic cell lines, in which the mitochondrial localization of the helicase was either retained or abolished. The mitochondrial integrity was affected due to the absence of RECQL4 in mitochondria, leading to a decrease in F1F0-ATP synthase activity. In cells where RECQL4 does not localize to mitochondria, the membrane potential was decreased, whereas ROS levels increased due to the presence of high levels of catalytically inactive SOD2. Inactive SOD2 accumulated owing to diminished SIRT3 activity. Lack of the mitochondrial functions of RECQL4 led to aerobic glycolysis that, in turn, led to an increased invasive capability within these cells. Together, this study demonstrates for the first time that, owing to its mitochondrial functions, the accessory mitochondrial replication helicase RECQL4 prevents the invasive step in the neoplastic transformation process.
Characterization of the mammalian family of DCN-type NEDD8 E3 ligases
Authors: Keuss Matthew J. , Thomas Yann , Mcarthur Robin , Wood Nicola T. , Knebel Axel , Kurz Thimo 
Published: February 2016

ABSTRACT
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit. DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like (DCNL) proteins but little is known about their specific functions or interaction partners. We found that DCNLs form stable stoichiometric complexes with CAND1 and cullins that can only be neddylated in the presence of a substrate adaptor. These CAND–cullin–DCNL complexes might represent ‘reserve’ CRLs that can be rapidly activated when needed. We further found that all DCNLs interact with most cullin subtypes, but that they are probably responsible for the neddylation of different subpopulations of any given cullin. This is consistent with the fact that the subcellular localization of DCNLs in tissue culture cells differs and that they show unique tissue-specific expression patterns in mice. Thus, the specificity between DCNL-type NEDD8 E3 enzymes and their cullin substrates is only apparent in well-defined physiological contexts and related to their subcellular distribution and restricted expression.
Agências, expertise e profissionalismo: o paradigma da técnica na administração pública
Authors: Moura Emerson Affonso da Costa 
Published: February 2016

A irradiação do paradigma da expertise das agências reguladoras na ação administrativa, como instrumento apto para atribuir racionalidade, eficiência e legitimidade à persecução do interesse público, é o tema em debate a partir da perspectiva da crise de governabilidade e legitimidade que marcam o Estado contemporâneo, da ascensão da sociedade informacional e da transmutação do modelo burocrático tradicional para uma gestão profissional moderna na administração pública gerencial. Investiga-se em que medida o predomínio de conhecimentos técnicos no exercício da discricionariedade administrativa e na gestão da administração pública é capaz de dotar com eficiência e economicidade o desempenho das tarefas estatais. The irradiate of the paradigm of expertise from agency to administrative process, as an instrument capable to attribute rationality, efficiency and legitimacy to public interest persecution, is the theme in debate from to perspective of crisis of governability and legitimacy that marks the contemporary state, the ascension of informational society and the transmutation of traditional burocrate model to an modern professional management in the new public management. Investigate in how measure, the predominance of technical knowledge in the exercise of administrative discretionary and the public management is capable to endow with efficiency and economist the performance of state tasks.
Discricionariedade administrativa das autoridades reguladoras e aplicação das normas punitivas
Authors: Neto Diogo de Figueiredo Moreira 
Published: February 2016

O artigo examina a politização das decisões econômicas no âmbito do direito administrativo. Trata da flexibilização das escolhas administrativas, que deriva da impossibilidade de a lei prever todos os aspectos a serem tratados pela administração pública. Tal fato surgiu da existência de três aberturas: conceitos jurídicos indeterminados; discricionariedade administrativa e regulação. Assim, surge a necessidade de processos decisórios abertos para atuarem como limites. This article examines the politicization of economic decisions in the administrative law. Deals with flexibility in the administrative choices, with derivates from the impossibility of law foresee all the aspects to be treated by the public administration. This fact comes from the existence of three apertures: undetermined law concepts; administrative discretion and regulation. Thus, arise the necessity of open decision-making process to actuate as limits.
Coisa julgada e controle incidental de constitucionalidade
Authors: Filho José dos Santos Carvalho 
Published: February 2016

O artigo faz considerações a respeito do controle de constitucionalidade e do instituto da coisa julgada, apresentando os efeitos decorrentes do controle incidental de constitucionalidade sobre o instituto da coisa julgada. This article raises questions about the control of constitutionality and the institute of res judicata, showing the effects of incidental control of constitutionality on the institution of res judicata.
"Monopólio" e "serviço público" nas constituições brasileiras (1891-1934)
Authors: Loureiro Gustavo Kaercher 
Published: February 2016

No presente estudo o autor procura traçar os sentidos dos termos “monopólio” e “serviço público” nas duas primeiras Constituições republicanas, em razão da importância que tiveram para a determinação dessas duas figuras em nossas Constituições seguintes. O resultado que emerge dessa análise é que — diferentemente do entendimento doutrinário atual — os serviços públicos e os monopólios não configuravam duas categorias jurídicas apartadas, mas, antes, espécies de um mesmo gênero, o das atividades reservadas. In the present article, the author intends to define the meaning of the terms “monopoly” and “public service” in the two first republican Constitutions — which should be carefully analyzed, regarding such issues, because of their influence in our subsequent Constitutions. The result that arises from such analysis is that — differently from current legal doctrine — public services and monopolies were not understood as two separate legal categories, but, rather, as species of a same gender — that of the reserved activities.
Autorregulação supervisionada pelo Estado: desenvolvimento de um sistema de corregulação para o mercado de corretagem de seguros, resseguros, capitalização e previdência complementar aberta
Authors: Santanna Luciano Portal 
Published: February 2016

A autorregulação visa atender a interesses corporativos, tais como a melhoria da imagem da categoria perante o público consumidor, a sociedade e o Estado e a inibição de práticas de concorrência desleal, mas também pode atender a interesses públicos, na medida em que colabora com o Estado no aprimoramento do sistema regulatório e na promoção da defesa dos interesses do consumidor. A autorregulação supervisionada pelo Estado induz a adoção de boas práticas de governança coorporativa, com o escopo de evitar o excesso de corporativismo, a falta de transparência e de rigor disciplinar, normalmente verificados nas demais formas de autorregulação. Esse modelo, inserido num sistema de corregulação público-privado, já é utilizado no Brasil no mercado de valores mobiliários e recentemente foi previsto na Lei Complementar no 137/2010 e pela Resolução no 233/2011 do Conselho Nacional de Seguros Privados também para o mercado de corretagem de seguros, resseguros, capitalização e previdência complementar aberta, no qual entidades autorreguladoras atuarão em auxílio e sob a supervisão da Superintendência de Seguros Privados (Susep). The self-regulation is designed to serve the corporate interests, such as the improvement of the image of the category for the consumer public, society and the State and the inhibition of practices of unfair competition, but it can also serve the public interests, to the extent that collaborates with the State in the improvement of the regulatory system and to promote the interests of consumers. The self-regulation supervised by the State induces the adoption of good corporative governance practices, with the scope of the avoidance of excessive corporate nature, the lack of transparency and disciplinary rigor, normally found in other forms of self-regulation. This model, inserted in a system of reconciling public and private sectors, is already used in Brazil in the security market and recently was laid down in Complementary Law no 137/2010 and Resolution no 233/2011 of the National Council for Private Insurance also for the market of insurance broking, reinsurance, capitalization and complementary pension open, in which self-regulation entities shall serve in aid and under the supervision of the Superintendence of Private Insurance (Susep).
A afetação de bens ao serviço público. O caso das redes
Authors: Ortiz Gaspar Ariño 
Published: February 2016

O presente trabalho aborda o princípio da afetação de bens ao serviço público, a partir do caso das redes. Discute as especificidades do uso de redes virtuais e sua regulação como bem público. O tema assume relevância para o direito público nacional, haja vista os inúmeros casos envolvendo o compartilhamento de bens reversíveis afetados por serviço público concedido ao setor privado e regulado por entidades independentes. The present work discusses the affectation principle of goods to public service from the case of networks. Discusses the specificities of the use of virtual networks and their regulation as a public good. The theme is relevant to the national public law given the numerous cases involving the sharing of reversible goods affected by public service to the private sector and regulated by independent entities.
Democracia e contrapoderes
Authors: Neto Diogo de Figueiredo Moreira 
Published: February 2016

Este artigo contextualiza as atuais manifestações sociais que desafiam a ordem pública em diversos países. Por mais avançada que seja determinada ordem jurídica, ela só será suficiente para prevenir desordens sociais se estiver dotada dos adequados meios democráticos. Tais meios devem assegurar o emprego de permanentes e eficientes canais de comunicação institucionais abertos aos cidadãos, de modo a levarem os seus interesses aos órgãos do Estado para que lhes deem resposta. Tais como garantir ao cidadão liberdade de acesso aberto e dialógico com órgãos de decisão. Esta é a pergunta que se impõe à teoria constitucional contemporânea. This article is contextualized by the current social disorder that threatens public policy in many countries. Though a legal system is advanced it will never be enough to prevent political manifestations if it does not have the adequate democratic means. Such means must assure the use of permanent and efficient institutional channels open to citizens, so that they may be able to communicate their interests and demand a response from the State. How to guarantee the citizen open access to a dialogue with the decision-making authorities is a question that must be examined by contemporary constitutional theory.
A análise da (in)constitucionalidade no processo administrativo fiscal
Authors: Lukic Melina Rocha 
Published: February 2016

Apesar da Constituição Federal de 1988 garantir o acesso e a ampla defesa em processo administrativo fiscal para a discussão de créditos tributários, os órgãos designados para tal fim têm se eximido da apreciação da constitucionalidade de leis e atos normativos infralegais sob a alegação de que tal atribuição é exclusiva do Poder Judiciário. O objetivo do presente artigo é, portanto, fixar premissas para a análise da questão verificando: a) se a administração pública pode exercer atividade jurisdicional, b) se os julgadores administrativos podem efetuar o controle difuso de constitucionalidade e c) se podem aplicar e interpretar o ordenamento jurídico de forma parcial, sem considerar os ditames da Constituição Federal. Although the Federal Constitution of 1988 ensure the access in an administrative fiscal process to discuss the tax credit, the bodies designated for this purpose have been exempted from the examination of the constitutionality of laws and other normative acts. The aim of this paper is to analyze: a) if the administration can exercise judicial activity, b) if the administrative judges can make the diffuse control of constitutionality and c) if they can apply and interpret the laws partially, regardless of the dictates of the Constitution.
Interpretações administrativas aderem à lei?
Authors: Sundfeld Carlos Ari , Souza Rodrigo Pagani de , Jurksaitis Guilherme Jardim 
Published: February 2016

O artigo analisa como a literatura do direito administrativo vem, ao longo do tempo, tratando a discussão sobre se os costumes (as práticas administrativas) são fonte de direito. Além disso, defende a tese de que a interpretação consolidada pela prática tem de ser considerada parte da própria lei interpretada, para fins da análise da validade dos atos, contratos e processos produzidos durante a vigência da interpretação consolidada. Por fim, o artigo sustenta que, embora, em tese, interpretações consolidadas possam ser revistas para os casos futuros, o intérprete que pretenda alterá-las tem um ônus argumentativo suplementar: o de analisar empiricamente as consequências das interpretações consolidadas, provando de modo forte que, no mundo real, essas consequências são negativas. Assim, a motivação que pode levar a uma nova interpretação, contrária à consolidada, não pode ser de caráter exclusivamente abstrato. The article analyses how administrative law theory has been, throughout the times, treating the discussion about whether custom (or administrative practices) is a source of law. Moreover, it defends the thesis that a longstanding statutory interpretation, consolidated by administrative practices, must be considered as a part of the interpreted statute, for the purpose of analyzing the validity of acts, contracts and processes produced while the longstanding interpretation was in force. Finally, the article argues that, although in theory longstanding interpretations can be revised for future cases, the interpreter who intends to revise them has a supplemental argumentative burden: the one of empirically analyzing the consequences of the longstanding interpretation, proving in a strong way that, in the real world, those consequences are, or have been, negative. In this manner, the motivation that can lead to a new, opposing interpretation to the longstanding one, cannot be of an exclusively abstract character.