bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update
Authors: Wolff Antonio C. , Hammond M. Elizabeth Hale , Allison Kimberly H. , Harvey Brittany E. , Mangu Pamela B. , Bartlett John M.S. , Bilous Michael , Ellis Ian O. , Fitzgibbons Patrick , Hanna Wedad , Jenkins Robert B. , Press Michael F. , Spears Patricia A. , Vance Gail H. , Viale Giuseppe , McShane Lisa M. , Dowsett Mitchell 
Published: May 2018

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not “must”) be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .
Phentolamine Reverses Epinephrine-Enhanced Skin Antinociception of Dibucaine in Rats
Authors: Chou An-Kuo , Chiu Chong-Chi , Chen Yu-Wen , Wang Jhi-Joung , Hung Ching-Hsia 
Published: May 2018

BACKGROUND:
The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture.

METHODS:
We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the “wheal” formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug–drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine.

RESULTS:
We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007–0.015] μmol) than for dibucaine (mean, 0.493 [95% CI, 0.435–0.560] μmol) (P < .01), while there were no significant differences between dibucaine and bupivacaine (mean, 0.450 [95% CI, 0.400–0.505] μmol). On the equipotent basis (75% effective dose, median effective dose, and 25% effective dose), sensory block duration provoked by epinephrine was greater (P < .01) than that provoked by dibucaine or bupivacaine. Coadministration of dibucaine with epinephrine produced a synergistic nociceptive block, whereas phentolamine blocked that synergistic block.

CONCLUSIONS:
The preclinical data indicated that there is no statistically significant difference between the potency and duration of dibucaine and bupivacaine in this model. Epinephrine synergistically enhances the effects of dibucaine, while phentolamine partially blocked those effects. α-Adrenergic receptors play an important role in controlling synergistic analgesic effect of dibucaine combined with epinephrine.
The transcription factor SOX30 is a key regulator of mouse spermiogenesis
Authors: Zhang Daoqin , Xie Dan , Lin Xiwen , Ma Longfei , Chen Jian , Zhang Daoqi , Wang Yang , Duo Shuguang , Feng Yanmin , Zheng Chunwei , Jiang Binjie , Ning Yan , Han Chunsheng 
Published: May 2018

ABSTRACT
The postmeiotic development of male germ cells, also known as spermiogenesis, features the coordinated expression of a large number of spermatid-specific genes. However, only a limited number of key transcription factors have been identified and the underlying regulatory mechanisms remain largely unknown. Here, we report that SOX30, the most-divergent member of the Sry-related high-motility group box (SOX) family of transcription factors, is essential for mouse spermiogenesis. The SOX30 protein was predominantly expressed in spermatids, while its transcription was regulated by retinoic acid and by MYBL1 before and during meiosis. Sox30 knockout mice arrested spermiogenesis at step 3 round spermatids, which underwent apoptosis and abnormal chromocenter formation. We also determined that SOX30 regulated the expression of hundreds of spermatid-specific protein-coding and long non-coding RNA genes. SOX30 bound to the proximal promoter of its own gene and activated its transcription. These results reveal SOX30 as a novel key regulator of spermiogenesis that regulates its own transcription to enforce and activate this meiotic regulatory pathway.
Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1
Authors: Lia Debora , Reyes Aurelio , de Melo Campos Julliane Tamara Araújo , Piolot Tristan , Baijer Jan , Radicella J. Pablo , Campalans Anna 
Published: May 2018

ABSTRACT
Accumulation of 8-oxoguanine (8-oxoG) in mitochondrial DNA and mitochondrial dysfunction have been observed in cells deficient for the DNA glycosylase OGG1 when exposed to oxidative stress. In human cells, up to eight mRNAs for OGG1 can be generated by alternative splicing and it is still unclear which of them codes for the protein that ensures the repair of 8-oxoG in mitochondria. Here, we show that the α-OGG1 isoform, considered up to now to be exclusively nuclear, has a functional mitochondrial-targeting sequence and is imported into mitochondria. We analyse the sub-mitochondrial localisation of α-OGG1 with unprecedented resolution and show that this DNA glycosylase is associated with DNA in mitochondrial nucleoids. We show that the presence of α-OGG1 inside mitochondria and its enzymatic activity are required to preserve the mitochondrial network in cells exposed to oxidative stress. Altogether, these results unveil a new role of α-OGG1 in the mitochondria and indicate that the same isoform ensures the repair of 8-oxoG in both nuclear and mitochondrial genomes. The activity of α-OGG1 in mitochondria is sufficient for the recovery of organelle function after oxidative stress.
1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study
Authors: Moncrieff Marc D. , Gyorki David , Saw Robyn , Spillane Andrew J. , Peach Howard , Oudit Deemesh , Geh Jenny , Dziewulski Peter , Wilson Ewan , Matteucci Paolo , Pritchard-Jones Rowan , Olofsson Bagge Roger , Wright Frances C. , Crampton Nic , Cassell Oliver , Jallali Navid , Berger Adam , Kelly John , Hamilton Stephen , Durrani Amer , Lo Serigne , Paton Elizabeth , Henderson Michael A. 
Published: May 2018

Abstract

Background
There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT.

Methods
This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma > 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation.

Results
Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p < 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months’ follow-up, no differences were noted in QoL between groups.

Discussion
This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.
Metabolic profiles derived from residual blood spot samples: A longitudinal analysis
Authors: Murphy Malia S.Q. , Hawken Steven , Cheng Wei , Wilson Lindsay A. , Lamoureux Monica , Henderson Matthew , Potter Beth , Little Julian , Chakraborty Pranesh , Wilson Kumanan 
Published: May 2018

Background: Secondary use of newborn screening dried blood spot samples include use for biomedical or epidemiological research. However, the effects of storage conditions on archival samples requires further examination. The objective of this study was to determine the utility of residual newborn samples for deriving reliable metabolic gestational age estimates. Methods: Residual newborn dried blood spot samples that had been stored for 2-, 4-, 6-, or 12-months in temperature controlled (21°C) conditions were re-analyzed for the full panel of newborn screening analytes offered by a provincial newborn screening lab in Ottawa, Canada. Data from re-analyzed samples were compared to corresponding baseline newborn screening values for absolute agreement, and Pearson and intraclass correlation. Performance of a gestational age estimation algorithm originally developed from baseline newborn screening values was then validated on data derived from stored samples. Results: A total of 307 samples were used for this study. 17-hydroxyprogesterone and newborn hemoglobin profiles measured by immunoassay and high-performance liquid chromatography, respectively, were among the most stable markers across all time points of analysis. Acylcarnitines exhibited the greatest degree of variation in stability upon repeat measurement. The largest shifts in newborn analyte profiles and the poorest performance of metabolic gestational age algorithms were observed when samples were analyzed 12-months after sample collection. Conclusions: Duration of sample storage, independent of temperature and humidity, affects newborn screening profiles and gestational age estimates derived from metabolic gestational dating algorithms. When considering use of dried blood spot samples either for clinical or research purposes, care should be taken when interpreting data stemming from secondary use.
The future of non-invasive cerebral oximetry in neurosurgical procedures: A systematic review
Authors: Kim WooJin , Taw Benedict , Yokosako Suguru , Koyanagi Masaomi , Fukuda Hitoshi , Sinclair David , Sirhan Denis , Teitelbaum Jeanne , Lui Matthew W.M. , Kasuya Hidetoshi , Angle Mark , Lo Benjamin W.Y. 
Published: May 2018

Background:Cerebral hypoxia is one of the most important causes of secondary brain injury during neurosurgical procedures and in neurointensive care. In patients with brain injury, cerebrovascular reactivity may be impaired and a decrease in mean arterial pressure or cerebral perfusion pressure may lead to inadequate cerebral blood flow and secondary ischemia. There are several techniques available to measure brain oxygenation. In particular, near infrared spectroscopy (NIRS) is a non-invasive neuromonitoring technique and there has been a rapid expansion of clinical evidence that NIRS reduces perioperative neurologic complications. Methods:This systematic review synthesizes prospective and retrospective cohort studies that investigate the benefit of using NIRS in prevention of perioperative neurologic complications. The methodological quality of these studies is appraised.Results:Seven studies were included in this systematic review. The methodological quality of each study was assessed. They had representative patient populations, clear selection criteria and clear descriptions of study designs. Reproducible study protocols with ethics board approval were present. Clinical results were described in sufficient detail and were applicable to patient undergoing neurosurgical procedures and in neurointensive care. Limitations included small sample sizes and lack of reference standard.Conclusions:This systematic review synthesizes the most current evidence of non-invasive, inexpensive, and continuous measurement of cerebral oxygenation by NIRS. Results gained from these studies are clinically useful and shed light on how this neuromonitoring technique is beneficial in preventing perioperative neurological complications.
Desarmonia: uma virtude da ciência
Authors: Oliveira Francine Marcondes Castro 
Published: May 2018

DOI:10.12957/emconstrucao.2017.28130FEYERABEND, Paul K. Ciência, um Monstro: lições trentinas. Tradução de Rogério Bettoni. Belo Horizonte: Autêntica, 2016.
REDES DE SABERES: PENSAMENTO INTERDISCIPLINAR
Authors: Cavalcanti Marcus 
Published: May 2018

RESUMO A importância de estruturar diferentes ciências sob a perspectiva de redes mostra que saberes teóricos e práticos podem conviver em um mesmo ambiente, se influenciando mutuamente. O fenômeno que a princípio parece objeto de estudo de apenas uma ciência também pode ser estudado por outras. Modificações e influências mútuas ocorrem quando diferentes modalidades de conhecimentos convivem em um mesmo trabalho. É marcante na educação contemporânea a presença do saber compartimentado. Não se estabelece conexão entre as disciplinas e essas são apresentadas aos estudantes como conhecimentos apartados uns dos outros, criando barreiras para uma concepção do conhecimento como um todo. A educação interdisciplinar tem sido a medida de maior recorrência para superar essa fragmentação do saber. A crítica à fragmentação das ciências contemporâneas traz várias discussões epistemológicas acerca da complexidade e dos paradigmas do conhecimento e, nessa perspectiva, busca expor as implicações de uma tentativa de se derivar um pensamento a partir da filosofia de Deleuze, que se configura como uma prática rizomática, em contraponto ao modelo epistemológico arbóreo cartesiano.
Geopolítica dos Recursos Naturais na América do Sul: um panorama dos recursos hídricos sob a ótica da Segurança Internacional | Geopolitics of Natural Resources in South America: a panorama of water resources under the view
Authors: Fuccille Luís Alexandre , Bragatti Milton Carlos , Leite Maria Luísa Telarolli de Almeida 
Published: May 2018

A questão ambiental e dos recursos naturais, pela mudança climática em curso, crescente escassez e aumento populacional global, se tornou motivo de preocupação e de segurança internacional. A América do Sul se insere nesse contexto devido à sua riqueza natural e hídrica, o que desperta interesse internacional e torna latente a necessidade de marcos regulatórios para essas questões. O presente artigo tem como objetivo traçar um panorama dos recursos naturais sul-americanos, especialmente da água, buscando não apenas ressaltar como esse tema ganha espaço no cenário internacional e no âmbito da segurança, mas evidenciando a necessidade premente de ações compartilhadas entre os Estados sul-americanos na construção de diretrizes para o manejo e defesa dessa riqueza natural da região, algo que envolve inclusive interesses globais. ABSTRACTThe environmental and natural resources issues, because of the ongoing climate change, the growing scarcity, and the global population growth have become a cause of concern and international security. South America is inserted in this context due to its natural and water richness, which attracts international interest and makes latent the need for regulatory frameworks in this area. The objective of this article is draw a scenery of the South American natural resources, especially water, not only to highlight how this issue gains space in the international scene and in the area of international security, but highlighting the urgent need of shared actions among the southern americans states on the construction of guidelines for the management and the defense of this natural wealth of the region, something that involves global interests.Palavras-Chave: Recursos Naturais; América do Sul; Recursos Hídricos; Segurança Internacional; Meio AmbienteKeywords: Natural Resources; South America; Water Resources; International Security; Environment Recebido em 30 de Janeiro de 2018 | Aceito em 24 de março de 2018.Received on January 30, 2018 | Accepted on March 24, 2018.
Políticas migratórias na UE: entre a estratégia do poder soberano e a cooperação compartilhada | Migration policies in the EU: between the sovereign power strategy and shared cooperation
Authors: Rodriguez Leite Ana Paula Moreira , Santos Thauan , Mendes Cintiene Sandes Monfredo 
Published: May 2018

As políticas migratórias da UE são caracterizadas como estratégicas, nas quais os interesses securitários da Comunidade são priorizados. A lógica de tais políticas consiste na regulação a partir das fronteiras sob dois mecanismos dispostos em normativas comunitárias: o Acordo de Schengen e o Tratado de Amsterdã. No decorrer da Primavera Árabe, em especial, o fluxo de refugiados somou-se ao de imigrantes irregulares, denunciando as lacunas existentes na gestão das fronteiras europeias em termos estratégicos e também humanitários. O aporte metodológico utilizado da análise comparada nos permite identificar as distorções entre documento e prática no que se refere ao Tratado de Amsterdã e o Acordo de Schengen na gestão de fronteiras. Nossa hipótese é de que o aumento do fluxo de refugiados geraria uma crise institucional na qual o poder soberano se sobreporia ao poder supranacional.Abstract: EU migration policies are characterized as strategic, in which the securitization interests of the Community are prioritized. The logic of such policies is to regulate from the borders under two mechanisms set out in Community legislation: the Schengen Agreement and the Treaty of Amsterdam. During the Arab Spring, in particular, the influx of refugees added to irregular migrants, stressing the shortcomings in the management of European borders in strategic and humanitarian terms. The methodological approach used in the comparative analysis allows us to identify the distortions between document and practice regarding the Treaty of Amsterdam and the Schengen Agreement on border management. Our hypothesis is that increasing the flow of refugees would create an institutional crisis in which sovereign power would replace supranational power.Palavras-chave: União Europeia, fluxo de refugiados, gestão de fronteiras.Keywords: European Union, Refugee flows, border management. Recebido em 30 de Janeiro de 2018 | Aceito em 05 de Maio de 2018.Received on January 30, 2018 | Accepted on May 5, 2018.
A metodologia estrutural comparativa e sua contribuição às Relações Internacionais | The comparative structural methodology and its contribution to the International Relations discipline
Authors: Barbosa de Souza Pimenta Marilia Carolina 
Published: May 2018

O artigo reflete sobre o potencial da chamada Metodologia Estrutural Comparativa para distintas agendas de pesquisa em Relações Internacionais. Este método propõe um deslocamento do modelo para se concentrar na solidez das variáveis, a fim de que a teoria possa ser continuamente aprimorada. Apresenta-se como estudos de caso a sua aplicação para o mapeamento das chamadas áreas não governadas ou black spots no sistema internacional, como uma alternativa à sua utilização tradicional: a análise cognitiva de lideranças; ambas propostas por Margaret Hermann. Conclui-se assim que esta metodologia, embora ainda pouco utilizada, torna-se valiosa para observar questões e temas variados dentro da disciplina de Relações Internacionais.ABSTRACTThe article reflects on the potential of the so-called Comparative Structural Method for research agendas on International Relations. This method proposes a shift to focus on the strength of variables instead of the model itself, so that the theory could continually be improved. It presents as Study Case its application on ungoverned areas or the so-called black spots in the international system, as an alternative to its traditional usage: the cognitive foreign policy analysis, both proposed by Margaret Hermann. It is concluded that this methodology, although still shortly used, becomes valuable to look at various issues and topics related to the International Relations discipline. Palavras-Chave: Metodologia Estrutural Comparativa- Relações Internacionais- MétodoKeywords: Comparative Structural Methodology-International Relations-MethodRecebido em 03 de março de 2018 | Received on March 3, 2018.Aceito em 14 de Abril de 2018 | Accepted on April 14, 2018.
Feed and Bleed Bipolar Membrane Electrodialysis Process
Authors: ABA Mohamed Amine BEN ALI , El-Sayed Wessam N. 
Published: May 2018

In this study, a bipolar membrane electrodialysis process (BPMED) is applied to regenerate nitric acid and ammonia by splitting ammonium nitrate. Firstly, we have proved the process feasibility in batch mode. Secondly, using the same operating conditions, we have proposed to extend the study to a continuous (feed and bleed) operating mode. Forecast calculations, derived from the balance material equations, and using the batch mode results, allowed the estimation of the continuous functioning parameters for both acid and salt.Â There is a good agreement between the performances of the two functioning modes. The acid and ammonia current efficiencies reached respectively 85 and 83 % in batch processing, and 83 and 80 % in continuous processing.