bluuebunny/crossref_metadata_2025_split huggingface dataset:
Romidepsin for the Treatment of Peripheral T-Cell Lymphoma
Authors: Iyer Swaminathan P. , Foss Francine F. 
Published: June 2015

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by expert hematopathologists improves accuracy of subtyping, and referral to academic or specialty centers is recommended. Many patients, however, will receive treatment in the community, and knowledge of approved agents is key to optimizing therapeutic approaches for all patients. There is no current standard of care for patients with PTCL and no approved therapies for first-line treatment. Although many patients initially respond to induction chemotherapy, responses are often brief, and many patients relapse or become treatment refractory. For patients with relapsed or refractory PTCL, achievement of durable responses is challenging, and there are few treatment options. Romidepsin is a histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received one prior systemic therapy or more and patients with PTCL who have received one prior therapy or more. Approval of romidepsin for PTCL was based on a pivotal phase II study of patients with relapsed or refractory PTCL (n = 131) that demonstrated an objective response rate of 25% including 15% with complete response; responses lasted a median of &gt;2 years. Long-term responses to romidepsin were achieved in patients regardless of baseline characteristics, including subtype, heavy pretreatment, response to prior therapy, or advanced disease. Common adverse events included hematologic abnormalities, gastrointestinal or asthenic conditions, and infections; romidepsin was not correlated with clinically meaningful QT prolongation or electrocardiogram abnormalities.

Implications for Practice:
Due to the rarity, severity, and heterogeneous nature of peripheral T-cell lymphoma (PTCL), diagnosis by expert hematopathologists is preferred, and referral to specialty centers is recommended. Many patients, however, will receive treatment in the community, and community oncologists play a key role in the recognition and treatment of PTCL. Knowledge of approved agents is key for optimizing therapeutic approaches. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.
Confronting Therapeutic Failure: A Conversation Guide
Authors: Morgans Alicia K. , Schapira Lidia 
Published: June 2015

Abstract

We reflect on the impact of bad news on both clinician and patient in the setting of cancer treatment failure. We review the classic six-step SPIKES (setting, perception, invitation for information, knowledge, empathy, summarize and strategize) protocol for giving bad news that has been widely adopted since it was first published in this journal in 2005. The goal of such a conversation guide is to describe both the process and the tasks that constitute vital steps for clinicians and to comment on the emotional impact of the conversation on the clinician. Confronting therapeutic failure is the hardest task for oncologists. We offer practical tips derived from a thorough review of the evidence and our clinical experience.

Implications for Practice:
Discussing the failure of anticancer therapy remains a very difficult conversation for oncologists and their patients. In this article, the process of confronting this failure is broken down into various components, and practical tips are provided for clinicians following a classic protocol for breaking bad news. Also addressed are the emotions of the oncologist and the reasons why these conversations are typically so hard. These insights are based on solid research intended to deepen the therapeutic connection between physician and patient.
Hepatocellular carcinoma in eastern India, a detail analytical report from a tertiary care hospital
Authors: Mukherjee Sudeb , Dhar Kingshuk , Datta Suhana , Mukherjee Apurba Kumar 
Published: June 2015

<p class="abstract"><strong><span lang="EN-US">Background: </span></strong>Hepatocellular carcinoma is the one of the commonest tumour worldwide. A detailed clinical profile including its etiology and vast presentation is not available in Eastern India.</p><p class="abstract"><strong><span lang="EN-US">Methods: </span></strong>Retrospective chart review of 90 patients with HCCwas done. Total 90 patients (male 81, female9) fulfillingdiagnostic criteria for HCC adopted by Barcelona-2000 EASL conferencewere analyzed for clinical, etiological, biochemical and radiological profile.</p><p class="abstract"><strong><span lang="EN-US">Results: </span></strong>Underlying cirrhosis was seen in 60% cases with Hepatitis B virus being the most common (33.3%) etiologic agent followed by Alcoholism (26.6%) in cirrhotic range. In 76.7% of HCC patients have AFP level more than 500 unit and practically diagnostic of HCC. Almost all patients presented with advanced disease (96.7%). Only 3.3% of HCC patients presented with mild disease.</p><p class="abstract"><strong><span lang="EN-US">Conclusions: </span></strong>The characteristics of HCC in eastern India are somewhat different from the rest of worlds. Alcohol and HBV infection are the two most important etiology prevailing here. </p><p class="keywords"><strong><span lang="EN-US">Keywords: </span></strong>HCC (Hepatocellular carcinoma), AFP (Alpha fetoprotein), HBV (Hepatitis B virus), HCV (Hepatitis C virus)</p>
A avaliação da educação superior pelo mundo do trabalho
Authors: Moraes Gustavo Henrique , Cordazzo Taciana , Wollinger Paulo Roberto 
Published: June 2015

O Sistema Nacional de Avaliação da Educação Superior completou dez anos em 2014, consolidando uma política pública bem-sucedida que vinculou os processos regulatórios aos resultados da avaliação, induzindo a qualidade do ensino. Essa avaliação, contudo, ainda tem pouca articulação com o mundo do trabalho, ficando mais restrita ao campo acadêmico e não superando a lógica que dissocia a universidade da sociedade. O Ministério da Educação, no enfrentamento dessa situação, firmou uma política colaborativa com os conselhos federais de regulamentação profissional, incluindo-os no processo regulatório. Os resultados dessa política que articula avaliação, ensino superior e trabalho ainda não foram explorados pela comunidade acadêmica, configurando uma lacuna na pesquisa educacional. Apresentam-se, com este artigo, a concepção, a análise e alguns resultados desse processo, valendo-se da investigação empírica do convênio celebrado junto ao Conselho Federal de Administração.
Excelência com equidade: fatores escolares para o sucesso educacional em circunstâncias desfavoráveis
Authors: Faria Ernesto Martins , Guimarães Raquel Rangel de Meireles 
Published: June 2015

São analisados os determinantes de sucesso no aprendizado de um grupo seleto de escolas públicas que atendem alunos de nível socioeconômico baixo, considerando os resultados da Prova Brasil 2011 e de seu Índice de Desenvolvimento da Educação Básica. Foca-se nos anos iniciais do ensino fundamental (1º ao 5º ano). Com base nos dados da Prova Brasil, fez-se uma análise descritiva e inferencial da diferença entre os fatores escolares das 215 escolas identificadas pelo estudo “Excelência com equidade” (chamadas de escolas tratamento) e os das escolas com características semelhantes em 2007, mas que não apresentaram o mesmo desempenho no aprendizado de seus alunos em 2011 (denominadas escolas controle). Os resultados apontam que as escolas tratamento possuem diretores mais bem avaliados pelos professores e uma grande influência do município em seu desempenho.
Para uma avaliação de larga escala multidimensional
Authors: Dalben Adilson , Almeida Luana Costa 
Published: June 2015

Inserido no projeto de pesquisa financiado pelo Observatório da Educação – Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, “A qualidade da escola pública: um estudo longitudinal para a sustentação da responsabilização compartilhada”, e partindo da observação de que a avaliação de larga escala atualmente praticada abarca um conjunto de objetivos menor do que aqueles da matriz de formação desenvolvida nas escolas, sendo esses demais objetivos também importantes para a formação dos alunos, o presente texto traz à discussão a necessidade de uma avaliação externa mais fiel ao trabalho desenvolvido nos estabelecimentos de ensino, que, para se consolidar como tal, não pode fugir à multidimensionalidade do objeto a ser avaliado. Discutem-se, assim, os processos de avaliação de larga escala, defendendo não se poder avaliar a aprendizagem dos estudantes e a qualidade ofertada pelas escolas sem a construção de uma avaliação multidimensional.
TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes
Authors: Eigenbrod Tatjana , Pelka Karin , Latz Eicke , Kreikemeyer Bernd , Dalpke Alexander H. 
Published: June 2015

Abstract
Microbial nucleic acids constitute an important group of pathogen-associated molecular patterns (PAMPs) that efficiently trigger innate immune activation. In mice, TLR13 has recently been identified to sense a highly conserved region within bacterial 23S rRNA. However, TLR13 is not expressed in humans, and the identity of its human homolog remains elusive. Moreover, the contribution of bacterial RNA to the induction of innate immune responses against entire bacteria is still insufficiently defined. In the current study, we show that human monocytes respond to bacterial RNA with secretion of IL-6, TNF, and IFN-β, which is critically dependent on lysosomal maturation. Using small interfering RNA and overexpression, we unambiguously identify TLR8 as receptor for bacterial RNA in primary human monocyte-derived macrophages. We further demonstrate that the sequence motif sensed by TLR8 is clearly distinct from that recognized by TLR13. Moreover, TLR8-dependent detection of bacterial RNA was critical for triggering monocyte activation in response to infection with Streptococcus pyogenes. Bacterial RNA within streptococci was also a dominant stimulus for murine immune cells, highlighting the physiological relevance of RNA sensing in defense of infections.
Domain-Specific and Stage-Intrinsic Changes in Tcrb Conformation during Thymocyte Development
Authors: Majumder Kinjal , Rupp Levi J. , Yang-Iott Katherine S. , Koues Olivia I. , Kyle Katherine E. , Bassing Craig H. , Oltz Eugene M. 
Published: June 2015

Abstract
Considerable cross-talk exists between mechanisms controlling genome architecture and gene expression. AgR loci are excellent models for these processes because they are regulated at both conformational and transcriptional levels to facilitate their assembly by V(D)J recombination. Upon commitment to the double-negative stage of T cell development, Tcrb adopts a compact conformation that promotes long-range recombination between Vβ gene segments (Trbvs) and their DβJβ targets. Formation of a functional VβDβJβ join signals for robust proliferation of double-negative thymocytes and their differentiation into double-positive (DP) cells, where Trbv recombination is squelched (allelic exclusion). DP differentiation also is accompanied by decontraction of Tcrb, which has been thought to separate the entire Trbv cluster from DβJβ segments (spatial segregation-based model for allelic exclusion). However, DP cells also repress transcription of unrearranged Trbvs, which may contribute to allelic exclusion. We performed a more detailed study of developmental changes in Tcrb topology and found that only the most distal portion of the Trbv cluster separates from DβJβ segments in DP thymocytes, leaving most Trbvs spatially available for rearrangement. Preferential dissociation of distal Trbvs is independent of robust proliferation or changes in transcription, chromatin, or architectural factors, which are coordinately regulated across the entire Trbv cluster. Segregation of distal Trbvs also occurs on alleles harboring a functional VβDβJβ join, suggesting that this process is independent of rearrangement status and is DP intrinsic. Our finding that most Trbvs remain associated with DβJβ targets in DP cells revises allelic exclusion models from their current conformation-dominant to a transcription-dominant formulation.
Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation
Authors: McArthur Simon , Gobbetti Thomas , Kusters Dennis H. M. , Reutelingsperger Christopher P. , Flower Roderick J. , Perretti Mauro 
Published: June 2015

Abstract
Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse as atherosclerosis and Alzheimer’s disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by the protein annexin A1 (ANXA1), found in high abundance in inflammatory exudates. Using primary human blood monocytes from healthy donors, we identified ANXA1 as a potent CD14+CD16− monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed the p38 MAPK-mediated activation of a calcium independent phospholipase A2 with resultant synthesis of lysophosphatidic acid (LPA) driving chemotaxis through LPA receptor 2 and actin cytoskeletal mobilization. In vivo experiments confirmed ANXA1 as an independent phospholipase A2–dependent monocyte recruiter; congruently, monocyte recruitment was significantly impaired during ongoing zymosan-induced inflammation in AnxA1−/− or alx/fpr2/3−/− mice. Using a dorsal air-pouch model, passive transfer of apoptotic neutrophils between AnxA1−/− and wild-type mice identified effete neutrophils as the primary source of soluble ANXA1 in inflammatory resolution. Together, these data elucidate a novel proresolving network centered on ANXA1 and LPA generation and identify previously unappreciated determinants of ANXA1 and ALX/FPR2 signaling in monocytes.
Endoscopic management of Zenker’s diverticulum
Authors: Dhaliwal Harpal S. , Sinha Saroj K. , Kochhar Rakesh 
Published: June 2015

AbstractZenker’s diverticulum (ZD) is a posterior hypopharyngeal mucosal and submucosal outpouching through an area of relative muscular weakness, known as Killian’s triangle. It is an uncommon but highly treatable cause of mechanical dysphagia in elderly patients. Diagnosis is established by esophagography and upper endoscopy. The treatment has evolved with the advancement in the understanding of underlying pathophysiology. Traditionally, the management had been open surgical exposure and cricopharyngeal myotomy, combined with diverticular excision, suspension or inversion. Peroral endoscopic techniques (rigid and flexible) have gained popularity as minimally invasive and effective therapeutic options, with lesser mortality and morbidity. Flexible endoscopic myotomy offers additional benefits over rigid endoscopic techniques, as it does not require general anesthesia and neck hyperextension. The initial results of flexible endoscopy are quite encouraging, but long-term data are not yet available. For the optimal outcome, flexible endotherapy requires a formidable endoscopic skill, sound knowledge of the neck anatomy and meticulous understanding of the electrosurgical principles. In this article, we have comprehensively reviewed the current understanding of the pathophysiology involved and various techniques used in the management of ZD, with a focus on flexible endoscopic techniques.
Pancreatic pleural effusion due to ductal disruption upstream of a tight ductal stricture in patient with chronic calcific pancreatitis: Successful management with pancreatic sphincterotomy and dilatation of ductal stricture by Guide Wire
Authors: Sharma Vishal , Prasada K. V. Raghavendra , Kancharla Harish , Sharma Ravi , Rana Surinder S. , Bhasin Deepak K. 
Published: June 2015

AbstractEndoscopic therapy has evolved as the standard of care for pancreatic pleural effusion and pancreatic ascites. Endoscopic retrograde cholangiopancreatography and bridging the disruption of ductal disruption with stent placement is the treatment of choice. However, it may not be always possible to negotiate tight pancreatic duct (PD) strictures or stricture stone complex, and endoscopic sphincterotomy alone may not be sufficient. We report a 53-year-old male who had chronic calcific pancreatitis with bilateral pancreatic pleural effusion and a tight stricture at head body junction, across which conventional endoscopic accessories could not be negotiated except for the 0.035 inch guidewire, which we kept across the stricture for 48 h for guidewire induced stricture dilation. This led to the complete resolution of symptoms and pancreatic pleural effusion. Combination of endoscopic sphincterotomy and guide wire induced stricture dilation can be used as rescue technique in cases of very tight PD strictures with complications such as pancreatic pleural effusion.
Eighty-year-old man with 10 years dysphagia
Authors: Kadla Showkat A. , Shah Nisar Ahmad , Parveen Shaheena , Khan Bilal A. , Shah Asif I. , Lone Shaheen Nazir , Sharma Sandeep 
Published: June 2015

AbstractDysphagia is a sensation of food being "stuck" up in its passage from the mouth to stomach. It is of two main types, oropharyngeal dysphagia, and esophageal dysphagia. In oropharyngeal dysphagia, there is difficulty in transferring the food from the mouth to upper esophagus. Thus, this dysphagia is also called as transfer dysphagia. It occurs within 1 st 1-2 s of the swallow. We also call this dysphagia as instant dysphagia. It is almost always associated with sinobronchial symptoms. The second type of dysphagia is esophageal dysphagia in which there is difficulty in passing the food from upper esophagus to the stomach. The two main mechanisms responsible for dysphagia are either a problem with the motor function of oropharynx or esophagus (neuromuscular causes) or mechanical narrowing of oropharynx or esophagus (mechanical dysphagia). As this dysphagia occurs a little later in the act of swallowing, we can call it delayed dysphagia. The mechanical cause of dysphagia includes benign strictures, malignancies, webs and rings, retropharyngeal abscesses, Zenker′s diverticulum, cricopharyngeal bar, and some vascular causes. We report an 80-year-old male with vascular dysphagia.
The Internationalization of Brazilian Design Firms: What do We Know?
Authors: Senra Melissa , Da Rocha Angela Maria Cavalcanti 
Published: June 2015

This study investigates the internationalization process of Brazilian brand design firms. The following research question inspired the study: What are the characteristics of the internationalization of these firms? The study, of a technical nature, is based on secondary sources, complemented by personal interviews with specialists. The results show that the design sector in Brazil is still very fragmented, and that internationalization of design firms is incipient.
(De)compaction of porous viscoelastoplastic media: Solitary porosity waves
Authors: Yarushina Viktoriya M. , Podladchikov Yuri Y. , Connolly James A. D. 
Published: June 2015

AbstractBuoyancy‐driven flow in deformable porous media is important for understanding sedimentary compaction as well as magmatic and metamorphic differentiation processes. Here mathematical analysis of the viscoplastic compaction equations is used to develop an understanding of the porosity wave instability and its sensitivity to the choice of rheological model. The conditions of propagation, size, speed, and shape of the porosity waves depend strongly on the properties of the solid rock frame. Whereas most of the previous studies on porosity waves were focused on viscous or viscoelastic mode, here we consider the ability of a solid matrix to undergo simultaneous plastic (rate‐independent) and viscous (rate‐dependent) deformation in parallel. Plastic yielding is identified as a cause of compaction‐decompaction asymmetry in porous media—this is known to lead to a strong focusing of porous flow. Speed and amplitude of a porosity wave are given as functions of material parameters and a volume of a source region. Formulation is applicable to fluid flow in sedimentary rocks where viscous deformation is due to pressure solution as well as in deep crustal or upper mantle rocks deforming in a semibrittle regime.
Ecosystem CO2and CH4exchange in a mixed tundra and a fen within a hydrologically diverse Arctic landscape: 1. Modeling versus measurements
Authors: Grant R. F. , Humphreys E. R. , Lafleur P. M. 
Published: June 2015

AbstractCO2and CH4exchange are strongly affected by hydrology in landscapes underlain by permafrost. Hypotheses for these effects in the modelecosyswere tested by comparing modeled CO2and CH4exchange with CO2fluxes measured by eddy covariance from 2006 to 2009, and with CH4fluxes measured with surface chambers in 2008, along a topographic gradient at Daring Lake, NWT. In an upland tundra, rises in net CO2uptake in warmer years were constrained by declines in CO2influxes when vapor pressure deficits (D) exceeded 1.5 kPa and by rises in CO2effluxes with greater active layer depth. Consequently, net CO2uptake rose little with warming. In a lowland fen, CO2influxes declined less withDand CO2effluxes rose less with warming, so that rises in net CO2uptake were greater than those in the tundra. Greater declines in CO2influxes with warming in the tundra were modeled from greater soil‐plant‐atmosphere water potential gradients that developed under higherDin drained upland soil, and smaller rises in CO2effluxes with warming in the fen were modeled from O2constraints to heterotrophic and belowground autotrophic respiration from a shallow water table in poorly drained lowland soil. CH4exchange modeled during July and August indicated very small influxes in the tundra and larger effluxes characterized by afternoon emission events caused by degassing of warming soil in the fen. Emissions of CH4modeled from degassing during soil freezing in October–November contributed about one third of the annual total.
Pore‐scale mechanisms for the enhancement of mixing in unsaturated porous media and implications for chemical reactions
Authors: Jiménez‐Martínez Joaquín , Anna Pietro de , Tabuteau Hervé , Turuban Régis , Borgne Tanguy Le , Méheust Yves 
Published: June 2015

AbstractPorous media in which different fluid phases coexist are common in nature (e.g., vadose zone and gas‐oil reservoirs). In partially saturated porous media, the intricate spatial distributions of the wetting and nonwetting phases causes their flow to be focused onto preferential paths. Using a novel 2‐D experimental setup allowing pore‐scale measurement of concentration fields in a controlled unsaturated flow, we highlight mechanisms by which mixing of an invading fluid with the resident fluid is significantly enhanced when decreasing saturation. The mean scalar dissipation rate is observed to decrease slowly in time, while under saturated conditions it decays rapidly. This slow decrease is due to sustained longitudinal solute fingering, which causes concentration gradients to remain predominantly transverse to the average flow. Consequently, the effective reactivity is found to be much larger than under saturated conditions. These results provide new insights into the role that multiphase flows play on mixing/reaction in porous media.