bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field practice study of half‐dose sorafenib treatment on safety and efficacy for hepatocellular carcinoma: A propensity score analysis
Authors: Morimoto Manabu , Numata Kazushi , Kondo Masaaki , Kobayashi Satoshi , Ohkawa Shinichi , Hidaka Hisashi , Nakazawa Takahide , Okuwaki Yusuke , Okuse Chiaki , Matsunaga Kotaro , Suzuki Michihiro , Morita Satoshi , Taguri Masataka , Tanaka Katsuaki 
Published: May 2014

AimPatients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full‐ to half‐dose sorafenib.MethodsWe reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full‐dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score‐matching analysis was used to adjust for potential bias.ResultsMultivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half‐dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05–1.15; P < 0.001). Fifty‐eight patients each in the half‐dose and full‐dose groups were selected for propensity score matching. The incidence of grade 3–4 severe adverse effects was lower in the half‐dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression‐free survival (PFS) and overall survival (OS) rates were not significantly different (half‐dose group, 3.8 and 10.2 months; full‐dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively).ConclusionPropensity score‐matched analyses indicate that initial half‐dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.
Construction and Contestation: Toward a Unifying Methodology for Borderlands History
Authors: Orsi Jared 
Published: May 2014

AbstractBorderlands history is a burgeoning field that churns out dozens of important monographs every year. Despite their individual insights, these works collectively lack conceptual glue to hold them together as a field. Using US‐Mexican border historiography as a case study, this article synthesizes recent scholarship to extract an emerging but as yet not fully articulated methodology that unites much of the field's scholarship of the last decade. Regardless of their individual time, place, or subject matter emphases, the works considered here share common starting questions that inquire what borders are present in any historical context and what their origins and consequences are. The keystone of the methodology is a dialect through which borderlands historians understand borders to be constructed, contested, reconstructed, and ultimately unfinished and unstable. Borderlands historians extend their analysis to include the mental categories with which people have historically made sense of their worlds, and they employ innovative narrative structures that integrate large and small spatial and geographical scales into coherent stories. As a research field seeking to explain the origins and evolution of national and other borders, borderlands history explores one of the most important developments of modern history. As a teaching field that introduces students to the history of boundary making and crossing, borderlands history helps prepare them for twenty‐first‐century world citizenship.
Canadian Political History and Ideas: Intersections and Influences
Authors: Anderson Kevin 
Published: May 2014

AbstractOver the last two decades, traditionally minded historians have argued that the rise of social and cultural history has fragmented Canadian history and caused the decline of Canadian political history. Despite these claims, current Canadian political history is proving to be a dynamic field that embraces the methodological and theoretical innovations of social and cultural history by incorporating gender, class, race and ethnicity as categories of analysis to create a “new political history.” However, the “new political history” in Canada has neglected to integrate the history of ideas. Studying the history of ideas in Canadian political history could expand the discipline beyond the current trends that include highly individualised political biography and studies emphasising politics, the state and ideology within Ian McKay's potentially reductive liberal order framework. Supplementing the “new political history” with the history of ideas, influenced by the work of Michael Freeden, would allow innovative analyses of institutional and popular politics to accompany the voices of elite political figures.
Telegraphy and Journalism in Colonial India, c. 1830s to 1900s
Authors: Bonea Amelia 
Published: May 2014

AbstractThis essay argues that a focus on technologies of communication such as the electric telegraph helps us to rethink the historiography of the press in colonial India by drawing attention to the ‘moments of transition’ of the 19th century and questioning dominant narratives of a media revolution spurred by telegraphy. It also enables us to overcome some of the limitations of previous nation‐centric research by recovering the networks of technology and news which integrated newspapers during this period and providing insights into the development of news reporting in 19th‐century India.
Immunohistochemistry in the diagnosis of papillary lesions of the breast
Authors: Tse Gary M , Ni Yun‐Bi , Tsang Julia Y S , Shao Mu‐Min , Huang Yu‐Hua , Luo Ming‐Hua , Lacambra Maribel D , Yamaguchi Rin , Tan Puay‐Hoon 
Published: May 2014

AimsMany immunohistochemical markers have been studied for differentiating papillary lesions. However, their differentiating power has not been evaluated comprehensively. Additionally, assessment of some markers will require the difficult task of identifying different cell types. In the current study, we aimed to devise a simple papillary panel which can aid in diagnosis irrespective of architectural pattern and cell type differentiation.Methods and resultsImmunohistochemical analysis of papillary lesions using myoepithelial markers [p63 and smooth muscle actin (SMA)], high molecular weight cytokeratins (HMWCKs: CK5, CK5/6, CK14 and 34βE12), hormone receptors (ER and PR) and neuroendocrine markers (chromogranin and synaptophysin) was performed. Among them, neuroendocrine markers showed high specificity but low sensitivity. HMWCK specificity was better than that for myoepithelial markers. Homogeneous staining pattern for hormonal receptors rather than their percentage positivity was more effective in identifying malignant lesions. Negative staining for two or more of HMWCKs, namely CK5/6, CK14 and 34βE12, achieved the best overall specificity and sensitivity of 87.8% and 94.1%, respectively, irrespective of the architecture. Their discriminatory power was validated with an independent cohort of core needle biopsies.ConclusionsA marker panel with HMWCKs could be used in differentiating papillary lesions irrespective of architectural pattern or cell type differentiation.
Epstein–Barr virus‐associated lymphoepithelioma‐like cholangiocarcinoma: a rare variant of intrahepatic cholangiocarcinoma with favourable outcome
Authors: Chan Anthony W H , Tong Joanna H M , Sung Mandy Y M , Lai Paul B S , To Ka‐Fai 
Published: May 2014

AimsLymphoepithelioma‐like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (IHCC). Only 16 cases have reported previously in the literature, and about 62.5% of these cases were associated with Epstein–Barr virus (EBV).Methods and resultsWe present the largest series (seven cases) of LELCC with descriptions of clinical and pathological characteristics, investigations of aberrant DNA methylation and mutation analyses of EGFR and KRAS. The evaluation also included 11 cases of stage‐matched conventional IHCC for comparison.ResultsAll seven patients of LELCC were female and had stage I disease. LELCC had significantly better 2‐ and 5‐year overall survival than IHCC (100% versus 52.8%, and 100% versus 13.2%, respectively, P = 0.003). All seven LELCCs were EBV‐associated and composed exclusively of adenocarcinoma with varied glandular differentiation, dense lymphoplasmacytic infiltrate, and variable expression of biliary‐type cytokeratins (CK7 and CK19) and stemness markers (CD133 and EpCAM). Gene hypermethylation was more frequent in LELCC than IHCC. CRBPI (85.7% versus 9.1%, P < 0.003) and CRBPIV (85.7% versus 0%, P < 0.001) showed statistically higher methylation frequencies in LELCC than IHCC. No LELCC harboured any EGFR or KRAS mutation.ConclusionEpstein–Barr virus‐associated LELCC is a variant of IHCC, characterized by marked female predominance, favourable overall survival and distinctively frequent DNA hypermethylation.
HIV/hepatitis C virus coinfection management: changing guidelines and changing paradigms
Authors: Cooper CL , Klein MB 
Published: May 2014

ObjectivesThe aim of the study was to consider the impact of new direct‐acting antiviral (DAA) regimens on hepatitis C virus (HCV) treatment in HIV/HCV coinfection.MethodsCurrent coinfection guidelines were reviewed and the impact of recent DAA publications evaluating HIV‐coinfected individuals was considered.ResultsCurrent coinfection guidelines recommend HIV antiretroviral therapy initiation prior to HCV antiviral therapy. New all‐oral, combination antiviral therapy composed of one or more DAAs with or without ribavirin will change this paradigm. As these regimens are better tolerated, it will be possible to offer nearly all HCV‐infected patients antiviral therapy, including those with HIV infection. All‐oral regimens may impact the incidence of HCV infection by providing a treatment option that can be safely and broadly utilized in high‐risk populations with the benefits of curing individual patients and addressing broader public health concerns related to HCV.ConclusionsHCV infection treatment should no longer be a secondary consideration restricted to the minority of HIV/HCV‐coinfected patients.
Evidence for aldosterone‐dependent growth of renal cell carcinoma
Authors: King Sharon , Bray Susan , Galbraith Sarah , Christie Lesley , Fleming Stewart 
Published: May 2014

SummaryThe aim if this study was to investigate the hypothesis that K‐RAS 4A is upregulated in a mineralocorticoid‐dependent manner in renal cell carcinoma and that this supports the proliferation and survival of some renal cancers. Expression of the K‐RAS in renal tumour tissues and cell lines was examined by real‐time PCR and Western blot and mineralocorticoid receptor, and its gatekeeper enzyme 11β‐hydroxysteroid dehydrogenase‐2 was examined by immunocytochemistry on a tissue microarray of 27 cases of renal cell carcinoma. Renal cancer cells lines 04A018 (RCC4 plus VHL) and 04A019 (RCC4 plus vector alone) were examined for the expression of K‐RAS4A and for the effect on K‐RAS expression of spironolactone blockade of the mineralocorticoid receptor. K‐RAS4A was suppressed by siRNA, and the effect on cell survival, proliferation and activation of the Akt and Raf signalling pathways was investigated in vitro. K‐RAS4A was expressed in RCC tissue and in the renal cancer cell lines but K‐RAS was downregulated by spironolactone and upregulated by aldosterone. Spironolactone treatment and K‐RAS suppression both led to a reduction in cell number in vitro. Both Akt and Raf pathways showed activation which was dependent on K‐RAS expression. K‐RAS expression in renal cell carcinoma is at least partially induced by aldosterone. Aldosterone supports the survival and proliferation of RCC cells by upregulation of K‐RAS acting through the Akt and Raf pathways.
Living in supportive housing for people with serious mental illness: A paradoxical everyday life
Authors: Bengtsson‐Tops Anita , Ericsson Ulf , Ehliasson Kent 
Published: May 2014

AbstractSince the closure of large psychiatric institutions, various types of community‐based supportive housing for people with serious mental illness (SMI) have been developed. There is currently limited knowledge about users' experiences of living in supportive housing. The aim of the present study was to describe user experiences of living in supportive housing for people withSMI. Twenty‐nine people living in such facilities participated in open, qualitative interviews. Data were subjected to latent content analysis. Three main themes emerged from this analysis: (i) having a nest, which included the subthemes of a place to rest and having someone to attach to; (ii) being part of a group, with the subthemes of being brought together and a community spirit; and (iii) leading an oppressive life, including the subthemes of questioning one's identity, sense of inequality, and a life of gloom. It could be concluded that user experiences of living in supportive housing are complex and paradoxical. In order to provide supportive housing, staff need to recognize and work within social group processes, and perform continual and structural evaluations of users' social and emotional needs.
Clinical severity of rhinovirus/enterovirus compared to other respiratory viruses in children
Authors: Asner Sandra A. , Petrich Astrid , Hamid Jemila S. , Mertz Dominik , Richardson Susan E. , Smieja Marek 
Published: May 2014

BackgroundHuman rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remain limited.ObjectivesWe compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU), and other common respiratory viruses in children.Patients/MethodsRetrospective study of children with ARIs and confirmed single positive viral infections on mid‐turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite endpoint consisting of intensive care admission, hospitalization >5 days, oxygen requirements or death.ResultsA total of 116 HRV/ENT, 102 RSV, 99 FLU, and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37·9% versus 13·6%; P < 0·001), FLU (37·9% versus 22%; P = 0·018) or any other single viral infection (37·9% versus 22·5%; P = 0·024). In multivariable analysis adjusted for underlying conditions and age, children with HRV/ENT infections had increased odds of hospitalization compared to children with RSV infections (OR 2·6; 95% CI 1·4, 4·8; P < 0·003) or FLU infections (OR 3·0; 95% CI 1·6, 5·8; <0·001) and increased odds of severe clinical disease among inpatients (OR 3·0; 95% CI 1·6,5·6; P = 0·001) when compared to those with FLU infections.ConclusionsChildren with HRV/ENT had a more severe clinical course than those with RSV and FLUA/B infections and often had significant comorbidities. These findings emphasize the importance of considering HRV/ENT infection in children presenting with severe acute respiratory tract infections.
Cardiorespiratory Changes and Pain Response of Lift Laparoscopy Compared to Capnoperitoneum Laparoscopy in Dogs
Authors: Fransson Boel A. , Grubb Tamara L. , Perez Tania E. , Flores Krystina , Gay John M. 
Published: May 2014

ObjectiveTo compare intraoperative physiologic variables and post‐operative pain associated with lift laparoscopy and conventional capnoperitoneum laparoscopy.Study DesignProspective randomized case controlled study.AnimalsHealthy dogs (n = 30).MethodsDogs having laparoscopic ovariohysterectomy were randomly assigned to lift laparoscopy (n = 14) or capnoperitoneum (16) laparoscopy. Physiologic variables measured intraoperatively were documented. Postoperatively, pain response was assessed in a blinded fashion using the short Glasgow pain scale and von Frey filament aesthesiometry.ResultsLift laparoscopy was associated with less frequency of hypercapnia, required less anesthetic gas, and was not more time‐consuming or painful than capnoperitoneum laparoscopy.ConclusionsLift laparoscopy is a feasible alternative to capnoperitoneum laparoscopy, especially in dogs where pressurized capnoperitoneum is not desired.
Altered gene expression signature of early stages of the germ line supports the pre‐meiotic origin of human spermatogenic failure
Authors: Bonache S. , Algaba F. , Franco E. , Bassas L. , Larriba S. 
Published: May 2014

SummaryThe molecular basis of spermatogenic failure (SpF) is still largely unknown. Accumulating evidence suggests that a series of specific events such as meiosis, are determined at the early stage of spermatogenesis. This study aims to assess the expression profile of pre‐meiotic genes of infertile testicular biopsies that might help to define the molecular phenotype associated with human deficiency of sperm production. An accurate quantification of testicular mRNA levels of genes expressed in spermatogonia was carried out by RT‐qPCR in individuals showing SpF owing to germ cell maturation defects, Sertoli cell‐only syndrome or conserved spermatogenesis. In addition, the gene expression profile of SpF was compared with that of testicular tumour, which is considered to be a severe developmental disease of germ cell differentiation. Protein expression from selected genes was evaluated by immunohistochemistry. Our results indicate that SpF is accompanied by differences in expression of certain genes associated with spermatogonia in the absence of any apparent morphological and/or numerical change in this specific cell type. In SpF testicular samples, we observed down‐regulation of genes involved in cell cycle (CCNE1 and POLD1), transcription and post‐transcription regulation (DAZL, RBM15 and DICER1), protein degradation (FBXO32 and TM9SF2) and homologous recombination in meiosis (MRE11A and RAD50) which suggests that the expression of these genes is critical for a proper germ cell development. Interestingly, a decrease in the CCNE1, DAZL, RBM15 and STRA8 cellular transcript levels was also observed, suggesting that the gene expression capacity of spermatogonia is altered in SpF contributing to an unsuccessful sperm production. Altogether, these data point to the spermatogenic derangement being already determined at, or arising in, the initial stages of the germ line.
Why Should We Save Nature's Hidden Gems?
Authors: Parsons Glenn 
Published: May 2014

AbstractAesthetic preservation is the idea of sparing natural areas from development because of their aesthetic value. In this article I discuss a problem for aesthetic preservation that I call the ‘hidden gems problem’: in certain cases, the natural area under consideration is so remote and/or fragile that few people can actually experience it. In these cases, it becomes unclear how nature's aesthetic value can justify its preservation when development promises practical human benefits. After rejecting some potential responses to the hidden gems problem, I offer a different solution. I argue that we have an aesthetic reason to preserve nature's hidden gems because they are required to produce ‘true judges’ of aesthetic value, who are capable of improving the general quality of taste for landscape. I develop this argument using the example of recent preservationist efforts to save the isolated landscape of Sable Island, Nova Scotia.
Successful human long‐term application of in situ bone tissue engineering
Authors: Horch Raymund E. , Beier Justus P. , Kneser Ulrich , Arkudas Andreas 
Published: May 2014

AbstractTissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor‐site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β‐tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto‐transplanted bone marrow aspirate from the iliac crest. The following post‐operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio‐venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain‐free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor‐site defect utilizing TE and RM techniques in human patients with long‐term stability.
Effect of rhBMP‐2 dose on bone formation/maturation in a rat critical‐size calvarial defect model
Authors: Pelaez Manuel , Susin Cristiano , Lee Jaebum , Fiorini Tiago , Bisch Frederick C. , Dixon Douglas R. , McPherson James C. , Buxton Amanda N. , Wikesjö Ulf M.E. 
Published: May 2014

AbstractBackgroundApplication of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP‐2 dose, frequency/severity of adverse events increasing with rising dose.ObjectiveThe objective of this study was to determine the most effective dose for rhBMP‐2 soak‐loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model.MethodsOne hundred sixty‐eight outbred male Sprague‐Dawley rats, age 11–13 weeks, weight 325–375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP‐2/ACS into critical‐size, ø8‐mm, through‐through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 μg rhBMP‐2/defect, or serve as ACS or sham‐surgery controls.ResultsrhBMP‐2 dosages ≥2.5 μg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8‐week healing interval.ConclusionsrhBMP‐2/ACS accelerates local bone formation in the rat critical‐size through‐through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25‐/2.5‐μg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP‐2 above the 2.5‐μg dose. The 1.25–20.0 μg dose range did not invoke appreciable aberrant healing events.