bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of secondary structural elements in human microRNA hairpin precursors
Authors: Liu Biao , Childs-Disney Jessica L. , Znosko Brent M. , Wang Dan , Fallahi Mohammad , Gallo Steven M. , Disney Matthew D. 
Published: March 2016

Abstract
Background
MicroRNAs (miRNAs) regulate gene expression by targeting complementary mRNAs for destruction or translational repression. Aberrant expression of miRNAs has been associated with various diseases including cancer, thus making them interesting therapeutic targets. The composite of secondary structural elements that comprise miRNAs could aid the design of small molecules that modulate their function.

Results
We analyzed the secondary structural elements, or motifs, present in all human miRNA hairpin precursors and compared them to highly expressed human RNAs with known structures and other RNAs from various organisms. Amongst human miRNAs, there are 3808 are unique motifs, many residing in processing sites. Further, we identified motifs in miRNAs that are not present in other highly expressed human RNAs, desirable targets for small molecules. MiRNA motifs were incorporated into a searchable database that is freely available.
We also analyzed the most frequently occurring bulges and internal loops for each RNA class and found that the smallest loops possible prevail. However, the distribution of loops and the preferred closing base pairs were unique to each class.

Conclusions
Collectively, we have completed a broad survey of motifs found in human miRNA precursors, highly expressed human RNAs, and RNAs from other organisms. Interestingly, unique motifs were identified in human miRNA processing sites, binding to which could inhibit miRNA maturation and hence function.
Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: systematic review
Authors: Semrau Maya , Lempp Heidi , Keynejad Roxanne , Evans-Lacko Sara , Mugisha James , Raja Shoba , Lamichhane Jagannath , Alem Atalay , Thornicroft Graham , Hanlon Charlotte 
Published: March 2016

Abstract
Background
The involvement of mental health service users and their caregivers in health system policy and planning, service monitoring and research can contribute to mental health system strengthening, but as yet there have been very few efforts to do so in low- and middle-income countries (LMICs).

Methods
This systematic review examined the evidence and experience of service user and caregiver involvement in mental health system strengthening, as well as models of best practice for evaluation of capacity-building activities that facilitate their greater participation. Both the peer-reviewed and the grey literature were included in the review, which were identified through database searches (MEDLINE, Embase, PsycINFO, Web of Knowledge, Web of Science, Scopus, CINAHL, LILACS, SciELO, Google Scholar and Cochrane), as well as hand-searching of reference lists and the internet, and a snowballing process of contacting experts active in the area. This review included any kind of study design that described or evaluated service user, family or caregiver (though not community) involvement in LMICs (including service users with intellectual disabilities, dementia, or child and adolescent mental health problems) and that were relevant to mental health system strengthening across five categories. Data were extracted and summarised as a narrative review.

Results
Twenty papers matched the inclusion criteria. Overall, the review found that although there were examples of service user and caregiver involvement in mental health system strengthening in numerous countries, there was a lack of high-quality research and a weak evidence base for the work that was being conducted across countries. However, there was some emerging research on the development of policies and strategies, including advocacy work, and to a lesser extent the development of services, service monitoring and evaluation, with most service user involvement having taken place within advocacy and service delivery. Research was scarce within the other health system strengthening areas.

Conclusions
Further research on service user and caregiver involvement in mental health system strengthening in LMICs is recommended, in particular research that includes more rigorous evaluation. A series of specific recommendations are provided based on the review.
Psychological interventions for adults with bipolar disorder: systematic review and meta-analysis
Authors: Oud Matthijs , Mayo-Wilson Evan , Braidwood Ruth , Schulte Peter , Jones Steven H. , Morriss Richard , Kupka Ralph , Cuijpers Pim , Kendall Tim 
Published: March 2016

BackgroundPsychological interventions may be beneficial in bipolar disorder.AimsTo evaluate the efficacy of psychological interventions for adults with bipolar disorder.MethodA systematic review of randomised controlled trials was conducted. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE method.ResultsWe included 55 trials with 6010 participants. Moderate-quality evidence associated individual psychological interventions with reduced relapses at post-treatment (risk ratio (RR) = 0.66, 95% CI 0.48–0.92) and follow-up (RR = 0.74, 95% CI 0.63–0.87), and collaborative care with a reduction in hospital admissions (RR =0.68, 95% CI 0.49–0.94). Low-quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psychoeducation with reduced symptoms of depression and mania.ConclusionsThere is evidence that psychological interventions are effective for people with bipolar disorder. Much of the evidence was of low or very low quality thereby limiting our conclusions. Further research should identify the most effective (and cost-effective) interventions for each phase of this disorder.
Genomic Characterization of Primary Invasive Lobular Breast Cancer
Authors: Desmedt Christine , Zoppoli Gabriele , Gundem Gunes , Pruneri Giancarlo , Larsimont Denis , Fornili Marco , Fumagalli Debora , Brown David , Rothé Françoise , Vincent Delphine , Kheddoumi Naima , Rouas Ghizlane , Majjaj Samira , Brohée Sylvain , Van Loo Peter , Maisonneuve Patrick , Salgado Roberto , Van Brussel Thomas , Lambrechts Diether , Bose Ron , Metzger Otto , Galant Christine , Bertucci François , Piccart-Gebhart Martine , Viale Giuseppe , Biganzoli Elia , Campbell Peter J. , Sotiriou Christos 
Published: March 2016

Purpose Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. Methods From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Results Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. Conclusion This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment.
Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials
Authors: Lee Shing M. , Backenroth Daniel , Cheung Ying Kuen Ken , Hershman Dawn L. , Vulih Diana , Anderson Barry , Ivy Percy , Minasian Lori 
Published: March 2016

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials.
Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study
Authors: Majumdar Sumit R. , Josse Robert G. , Lin Mu , Eurich Dean T. 
Published: March 2016

Abstract

Context:
Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin).

Objective:
To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study.

Design, Setting, and Subjects:
A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores.

Main Outcomes:
We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up.

Results:
At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8–1.4; P = .7), although insulin (P &lt; .001), sulfonylureas (P &lt; .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk.

Conclusions:
Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures.
Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics
Authors: Csorba Zsofia , Petak Ferenc , Nevery Kitti , Tolnai Jozsef , Balogh Adam L. , Rarosi Ferenc , Fodor Gergely H. , Babik Barna 
Published: March 2016

BACKGROUND:
Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB).

METHODS:
Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt.

RESULTS:
Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and −0.57; P < 0.0001, respectively), whereas SIII correlated most strongly (P < 0.0001) with Raw (r = 0.63; P < 0.0001). CPB induced significant elevations in Raw and G and H (P < 0.0001). These adverse mechanical changes were reflected consistently in SII, SIII, and D2min, with weaker correlations with the dead-space indices (P < 0.0001). The intrapulmonary shunt expressed as the difference between the Enghoff and Bohr dead-space parameters was increased after CPB (95% ± 5% [SEM] vs 143% ± 6%; P < 0.001).

CONCLUSIONS:
In mechanically ventilated patients, the capnographic parameters from the early phase of expiration (SII and D2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.
Gestão alternativa de serviços públicos
Authors: Souto Marcos Juruena Villela 
Published: March 2016

1. Introdução - 2. Credenciamento de empresas - 3. Arrendamento de instalações - 4. Comunicação do aproveitamento de potencial de energia elétrica e de implantação de usina termoelétrica - 5 - Concessão de obra pública - 6. Venda de bilheteria - 7. Concessão de uso de bem público - 8. Contrato de prestação de serviços - 9. Contratos de risco - 10. Contratos com cooperativas - 11. Serviços reconhecidos de utilidade pública - 12. Contrato de gestão com organizações sociais- 13. Termo de parceria com Organizações da Sociedade Civil - 14. Autorização de serviços públicos - 15. Convênios e consórcios - 16. Franquia - 17. Cheque saúde e cheque educação - 18. Administração de penitenciárias - 19. Conclusões.
Comissão Parlamentar de Inquérito - Obrigação de comparecer - Direito ao silêncio
Authors: Mello Celso Antônio Bandeira de 
Published: March 2016

- Impõe-se ao paciente a obrigação de comparecer perante a Comissão Parlamentar de Inquérito e responder às perguntas, ressalvadas aquelas cuja resposta possa acarretar-lhe grave dano.- O direito ao silêncio constitui prerrogativa individual que não pode ser desconsiderada por qualquer dos Poderes da República.EMENTA: COMISSÃO PARLAMENTAR INQUÉRITO. PRIVILÉGIO CONTRA A AUTO-INCRIMINAÇÃO. DIREITO QUE ASSISTE A QUALQUER INDICIADO OU TESTEMUNHA. IMPOSSIBILIDADE DE O PODER PÚBLICO IMPOR MEDIDAS RESTRITIVAS A QUEM EXERCE, REGULARMENTE, ESSA PRERROGATIVA. MEDIDA LIMINAR CONCEDIDA.
Lei Municipal - Constituição Federal - Controle de constitucionalidade
Authors: Mello Celso Antônio Bandeira de 
Published: March 2016

- Não cabe exame concentrado de constitucionalidade de lei municipal em face da Constituição Federal.- O único controle de lei ou ato normativo municipal em face da Constituição Federal é o controle difuso de constitucionalidade.EMENTA: CONTROLE ABSTRATO DE CONSTITUCIONALIDADE. AÇÃO DIRETA. IMPOSSIBILIDADE JURÍDICA DE FISCALIZAÇÃO NORMA TIV A ABSTRATA DE LEI MUNICIPAL CONTESTADA EM FACE DA CONSTITUIÇÃO FEDERAL. AÇÃO DIRETA DE QUE NÃO SE CONHECE.
Comissão Parlamentar de Inquérito - Escritório de advocacia - Sigilo profissional
Authors: Mello Celso Antônio Bandeira de 
Published: March 2016

- Busca e apreensão por iniciativa de Comissão Parlamentar de Inquérito de dados existentes em escritório de advocacia dependem de prévia autorização judicial.- A violação do sigilo profissional não se presume devendo ser efetiva ou iminente possa admitir proteção judicial.EMENTA: COMISSÃO PARLAMENTAR DE INQUÉRITO. ESCRITÓRIO DE ADVOCACIA. ARQUIVOS DADOS, CORRESPONDÊNCIA E COMUNICAÇÕES. INVIOLABILIDADE. BUSCA E APREENSÃO. ORDEM JUDICIAL (LEI Nº 8.906/94 ART. 7º, II). CONCEITO CONSTITUCIONAL DE DOMICÍLIO. RESERVA DE JURISDIÇÃO.
Invalidação de atos administrativos
Authors: Vitta Heraldo Garcia 
Published: March 2016

1 - Introdução. 2 - Conceito de Ato Administrativo. 3 - Perfeição, Validade e Eficácia do Ato. 4 - Extinção dos Atos Administrativos. 5- Invalidade dos Atos Administrativos. 5.1 - Conceito de invalidação. 5.2 - Classificação das invalidades. 5-2. 1 - Atos Inexistentes. 5.2.2 - Atos Nulos e Anuláveis. 5.2.3 - Atos irregulares. 5-3 - Os Efeitos dos Atos Inválidos. 6 - Os Elementos ou Requisitos do Ato Administrativo e a Invalidação. 7 - Conclusões. 8 - Bibliografia.
Servidor inativo - Contribuição previdenciária - Não incidência
Authors: Brindeiro Geraldo 
Published: March 2016

I. Contribuição previdenciária: incidência sobre proventos da inatividade e pensões de servidores públicos (Lei estadual 13.309/99, do Rio de Janeiro): densa plausibilidade da argüição da sua inconstitucionalidade, sob a EC 20/98, já afirmada pelo Tribunal (AdnMC 2.0/0,29.9.99).1. Reservado para outra oportunidade o exame mais detido de outros argumentos, é inequívoca, ao menos, a plausibilidade da argüição de inconstitucionalidade da norma local questionada, derivada da combinação, na redação da EC 20/98, do novo art. 40, § 12 e com o art. 195, II, da Constituição Federal, e reforçada pela análise do processo legislativo da recente reforma previdenciária, no qual reiteradamente derrotada, na Câmara dos Deputados, a proposta de sujeição de aposentados e pensionistas do setor público à contribuição previdenciária. 2. O art. 195, § 4°, parece não legitimar a instituição de contribuições sociais sobre fontes que a Constituição mesma tornara imunes à incidência delas; de qualquer sorte, se o autorizasse, no mínimo, sua criação só se poderia fazer por lei complementar.3. Aplica-se aos Estados e Municípios a afirmação da plausibilidade da argüição questionada: análise e evolução do problema.
Da expressão da oferta de energia elétrica emergencial e o adicional tarifário
Authors: Mattos Mauro Roberto Gomes de 
Published: March 2016

I - Introdução. II - Da tarifa e a cobrança do seu adicional. III - Responsabilidade da ANEEL pela falta de regulação retirando do consumidor a obrigação de reparar o que não deu causa. IV - Indenização não pode ser repassada ao consumidor como adicional tarifário. V - Conclusão.
Medidas Provisórias pelos Municípios
Authors: Pedra Anderson Sant'Ana 
Published: March 2016

Trata de análise quanto à possibilidade de adoção de medidas provisórias pelos Municípios, considerando para tanto, a oportunidade do instituto e a sua inserção no ordenamento jurídico pátrio que contempla os princípios da separação dos poderes e o da autonomia municipal, este como derivação dos princípios fundamentais da república e da federação.
Poder normativo de entes reguladores
Authors: Bacellar Filho Romeu Felipe 
Published: March 2016

I - A Constituição Federal de 1988 e o direito fundamental ao serviço público adequado - II - Administração pública e serviços públicos - III - ReguLação e princípios do sen1iço público - IV - Participação dos cidadãos na atividade dos entes reguladores.
Recursos administrativos no direito comparado: brasileiro e argentino
Authors: Majadas Marcia Fratari 
Published: March 2016

1. Introdução - 2. Considerações sobre a Lei 9.784/99 - 3. Apreciação sobre as leis da Argetina - 4. Importância da Lei 9.784/99 no direito comparado Argentino - 5. Recursos: Revisão total ou parcial de atos administrativos - 6. Fundamentos do direito comparado no recurso administrativo - 7. Classificação dos recursos segundo a Lei 9.784/99 - 7.1 Modalidades- 7.1.1. Representação- 7.1.2. Reclamação- 7.1.3. Pedido de Reconsideração - 8. Procedimentos dos recursos administrativos no direito argentino - 8. I Recurso de Recollsideração - 8.2. Recurso Hierárquico - 8.3. Recurso de Alçada - 8.4. Recurso Extraordinário de Revisão - 8.5. Recurso de Revisâo - 8.6. Outras Vias Administrativas - 8.6.1. Queixa - 8.6.2. Retificação de Erros Materiais - 8.6.3. Aclaratória - 9. Efeito do recurso no direito comparado - 9. I. Efeitos Gerais no Recurso - 9.2. Tutela Preventiva - 10. Requisitos dos recursos no direito comparado - 10.1. Requisito Formal - 10.2. Requisito Material - 11. Prazos do recurso - 11.1. A Legitimação Recursal no Direito Comparado - 11.2. Revisão Ex Officio na Lei Federal 9.784/99 - 11.3. Recurso - Revogação na Lei Federal 9.784/99 - 12. PRAZOS PARA INTERPOSIÇÃO DE RECURSO - 12.1. Prazos Processuais no Direito Brasileiro - 12.2. Prazos no Direito Argentino - 13. Conclusões - 14. Referências bibliográficas.
Legitimidade constitucional
Authors: Moreira Neto Diogo de Figueiredo 
Published: March 2016

1. O tema da legitimidade e a Constituição - 2. Breves notas sobre a evolução da tipologia constitucional - 3. A carta política brasileira de 1988 como último modelo extremado de texto analítico dirigente - 4. FLexibilidade e adaptabilidade programáticas, como pressupostos da estabilidade constitucional- 5. Esboço de uma simples tipologia das reformas constitucionais - 6. Porque aperfeiçoar os mecanismos existentes da emenda e da mutação jurisprudencial e institucionalizar uma revisão periódica - 7. Como institucionalizar a revisão periódica - 8. Conclusão: A legitimação permanente.
Rediscutindo a estabilização, pelo decurso temporal, dos atos administrativos supostamente viciados
Authors: Leite Fabio Barbalho 
Published: March 2016

1. ALGUMAS CONSIDERAÇÕES DE ORDEM TE6RICA, 2. OS NÓS; 3. PANORAMA DAS POSIÇÕES DOUTRINÁRIAS E JURISPRUDENCIAIS ACERCA DO TEMA; 4. DESCONSTRUINDO PARA CONSTRUIR; 5. PARA UMA TENTATIVA DE SISTEMATIZAÇÃO DAS SOLUÇÕES OFERTÁVEIS AO PROBLEMA EM FOCO: a) A estabilização dos atos administrativos viciados se dá com a operação da prescrição: primeiro fundamento; b) A estabilização dos atos administrativos viciados se dá com a operação da prescrição: segundo fundamento; c) Competência legislativa da União Federal e correlações com as competências legislativas do demais entes federativos; d) Os prazos; 6. ENFIM...