bluuebunny/crossref_metadata_2025_split huggingface dataset:
Die Nutzung natürlicher Killerzellen für die Therapie des Melanoms
Authors: Hölsken Oliver , Miller Matthias , Cerwenka Adelheid 
Published: January 2015

ZusammenfassungIn den letzten Jahren hat die Immuntherapie wesentlichen Einfluss auf die klinische Therapie des malignen Melanoms gewonnen. Neben vielversprechenden T‐Lymphozyten‐basierten Ansätzen erhalten natürliche Killerzellen (NK‐Zellen) zunehmende Aufmerksamkeit als Antitumor‐Effektor‐Zellen. HLA‐Klasse‐I‐Moleküle inhibieren die Aktivierung von NK‐Zellen, so dass diese präferentiell Tumorzellen angreifen, die HLA‐Klasse‐I‐Moleküle in nur geringem Maß exprimieren. Der teilweise oder vollständige Verlust der HLA‐Klasse‐I‐Expression ist ein häufiges Ereignis bei der Melanomentstehung. Gleichzeitig werden bei der malignen Transformation NK‐Zell‐Rezeptor‐aktivierende Liganden induziert. Daher werden Melanomzellen durch NK‐Zellen zumindest in vitro erkannt und lysiert. In vivo haben Melanome jedoch umfassende Strategien entwickelt, um dem durch NK‐Zellen vermittelten Angriff zu entgehen. Eine Vielzahl neuartiger Ansätze zielt darauf ab, NK‐Zellen zu nutzen, um Melanompatienten wirksam zu therapieren und den bestehenden “Escape‐Mechanismen” der Tumorzellen entgegenzuwirken. Dieser Übersichtsartikel fasst die aktuellen Fortschritte auf diesem Gebiet zusammen.
Assessment of melanoma histotypes and associated patient related factors: Basis for a predictive statistical model
Authors: Haenssle Holger A. , Hoffmann Saskia , Buhl Timo , Emmert Steffen , Schön Michael P. , Bertsch Hans Peter , Rosenberger Albert 
Published: January 2015

SummaryBackgroundCertain melanoma histotypes carry a worse prognosis than others. We aimed to identify patient related factors associated with specific melanoma histotypes.Patients and methodsSingle center study including 347 melanoma patients, prospectively assessed for 22 variables leading to a database of more than 7 600 features.ResultsMelanomas were histologically categorized as superficial spreading (SSM, 70.6 %), nodular (NM; 12.7 %), acrolentiginous (ALM; 4.0 %), lentigo maligna (LMM; 3.8 %), or unclassified melanoma (UCM; 8.9 %). Well recognized melanoma risk indicators (i. e. many atypical nevi, freckles, previous melanoma), were significantly associated with SSM and LMM histotypes. NM and ALM patients carried significantly less common and/or atypical nevi. NM were mostly self‐detected or detected by relatives. In contrast, SSM, LMM, and ALM were most frequently detected by dermatologists. NM and UCM were preferentially located on poorly observable sites, SSM on the lower limbs, ALM on plantar sites, and LMM on the head and neck. ALM and LMM patients were significantly older than other patients. A multinomial logistic model was designed to predict a certain melanoma histotype (overall accuracy 81 %), which could be helpful to focus the attention of clinicians or may be integrated into fully automated diagnostic algorithms.ConclusionsMelanoma histotypes show significant differences regarding patients’ characteristics.
Subtypen des malignen Melanoms und assoziierte patientenbezogene Faktoren: Grundlage für ein prädiktives statistisches Modell
Authors: Haenssle Holger A. , Hoffmann Saskia , Buhl Timo , Emmert Steffen , Schön Michael P. , Bertsch Hans Peter , Rosenberger Albert 
Published: January 2015

ZusammenfassungHintergrundBestimmte Subtypen des Melanoms haben eine schlechtere Prognose als andere. Unser Ziel war es, patientenbezogene Faktoren zu identifizieren, die mit spezifischen Subtypen des Melanoms vergesellschaftet sind.Patienten und MethodenMonozentrische Studie an 347 Melanompatienten, bei denen prospektiv 22 patientenbezogene Variablen erhoben wurden, woraus eine Datenbank mit mehr als 7600 Merkmalen erstellt wurde.ErgebnisseMelanome wurden histologisch als superfiziell‐spreitend (SSM, 70,6 %), nodulär (NM; 12,7 %), akrolentiginös (ALM; 4,0 %), Lentigo maligna (LMM; 3,8 %) oder nicht klassifiziertes Melanom (UCM; 8,9 %) klassifiziert. Bekannte Risikofaktoren (i. e. zahlreiche atypische Nävi, Sommersprossen, Z. n., Melanom) waren signifikant mit den Subtypen SSM und LMM assoziiert. NM und ALM‐Patienten wiesen signifikant weniger gewöhnliche oder atypische Nävi auf. NM waren zumeist vom Patienten selbst oder einem Verwandten entdeckt worden, wohingegen SSM, LMM und ALM zumeist vom Dermatologen entdeckt wurden. NM und UCM waren präferentiell an schlecht beobachtbaren Körperstellen lokalisiert, SSM an der unteren Extremität, ALM im Plantarbereich und LMM an Kopf und Hals. ALM und LMM‐Patienten waren signifikant älter als die anderen Patienten. Wir entwickelten ein multinomiales logistisches Modell zur Vorhersage eines Melanomsubtyps (Gesamtgenauigkeit 81 %), welches geeignet sein könnte, um die Aufmerksamkeit klinisch tätiger Ärzte entsprechend zu fokussieren oder in vollautomatisierte Diagnosealgorithmen eingeschlossen zu werden.SchlussfolgerungenMelanomsubtypen zeigen signifikante Unterschiede hinsichtlich patientenbezogener Faktoren.
Pathogenicity of ophiostomatoid fungi on Picea abies in Slovenia
Authors: Repe A. , Bojović S. , Jurc M. 
Published: January 2015

SummaryPathogenic fungi can survive and develop in living plants, often causing diseases in the host. Some theories speculate that pathogenic ophiostomatoid fungi provide benefits to its vectors – bark beetles – by overcoming the tree's defence mechanisms. This study reports the results of an experiment in south‐eastern Europe in which mature and seedling Norway spruce trees were artificially inoculated with various ophiostomatoid fungi. The aim of the experiment was to determine the relative virulence of ophiostomatoid fungi by assessing the ability of the fungi to stimulate host tree defence mechanisms through inoculation experiments. Experiments were performed by inoculation of Picea abies in seedling and mature trees. The following fungi were used in low‐density and seedling inoculations: Ophiostoma ainoae, O. brunneo‐ciliatum, Grosmannia cucullata and an unidentified Leptographium sp., O. bicolor, O. fuscum, O. piceae, G. penicillata and G. piceiperda. Endoconidiophora polonica was used in mass and seedling inoculations. Various characteristics such as host vitality, blue stain, lesion and resin outflow were measured before and after the trees were felled. E. polonica caused blue stain, induced large lesions and killed some of the mature trees and seedlings, confirming earlier reports that it is a strong wound pathogen. Only E. polonica, Leptographium sp. and O. ainoae caused blue stains in the sapwood of inoculated seedlings. In low‐density inoculations, G. piceiperda induced intense necrosis and had higher values for all the characteristics monitored. Some of the other ophiostomatoid fungi showed a moderate level of pathogenicity. Fungi with the capacity to stimulate a host defence mechanism could play a role in the establishment of bark beetle populations.
Quality of supervision: postgraduate dental research trainees’ perspectives
Authors: Beaudin A. , Emami E. , Palumbo M. , Tran S. D. 
Published: January 2015

AbstractIntroductionSupervision is a pillar in enhancing the student's learning environment throughout her/his higher education. Multiple studies qualify graduate supervision among the most important contributors to the successful completion of a higher education degree and to graduate students' positive academic experience. The aim of this study was to assess the views of graduate students enrolled in the Dental Sciences and Craniofacial Research Graduate Programs at McGill University (n = 64) regarding the quality of supervision they are receiving.Methods and materialsAn online questionnaire composed of 22 open and closed‐ended format items was used and covered five domains: student profile, supervisory relationship, conflict resolution, student progress/thesis writing and career development. Descriptive statistics, chi‐square tests and interpretative qualitative analysis were used to evaluate students' perspectives.ResultsFifty‐nine students completed the survey (92.2%). The distribution of sample in regard to the graduate student level was almost identical (M.Sc. level n = 28, Ph.D. n = 31). Overall, most graduate students appeared satisfied with the supervision they received and had similar perspectives about the surveyed domains. There was one statistically significant difference (P < 0.05) between MSc and PhD students when asked if their supervisors aided them in career development outside the supervisory relationship, where 77.4% (n = 24) of doctoral students agreed as opposed to 21.4% (n = 12) of Masters’ students.ConclusionsOur results showed that McGill graduate students appeared to be overall satisfied with the supervision they received. The main elements contributing to a positive supervision experience were support, guidance, availability and good communication between supervisees and supervisors.
Non‐genetic risk factors and their influence on the management of patients in the clinic
Authors: Álvarez Teresa , Soto Immaculada , Astermark Jan 
Published: January 2015

AbstractThe development of inhibitors is the most serious iatrogenic complication affecting patients with haemophilia. This complication is associated with impaired vital or functional prognosis, reduced quality of life and increased cost of treatment. The reasons why some patients develop antibodies to factor replacement and others do not remain unclear. It is however clear that inhibitor development results from a complex multifactorial interaction between genetic and non‐genetic risk factors. Environmental influences implicated in increasing the risk of inhibitor formation can be viewed as modifiable risk factors. Therefore, identification of the non‐genetic risk factors may offer the possibility of personalising haemophilia therapy by modifying treatment strategies in high‐risk patients in the critical early phase of factor VIII exposure. In this article, we review the non‐genetic factors reported as well as the potential impact of danger signals and the different scores for inhibitor development risk stratification.
Genetic risk factors for inhibitors in haemophilia A
Authors: Bardi Edit , Astermark Jan 
Published: January 2015

AbstractThe current most serious side effect of haemophilia treatment is inhibitor development. Significant progress has been made over the last decades to understand why this complication occurs in some patients and it seems clear that both genetic and non‐genetic factors are involved. Several issues however remain to be settled. A review was undertaken to summarise some key findings regarding the current view and available data on genetic markers of potential importance within this area. The causative F8 mutation, together with the HLA class II alleles, plays a pivotal pathophysiological role in inhibitor development. The types of mutation most frequently associated with inhibitors are large deletions, nonsense mutations, inversions, small deletions/insertions without A‐runs, splice‐site mutations at conserved nucleotides and certain missense mutations. Regarding HLA class II allele, it has been hard to consistently identify risk alleles. Ethnicity has consistently been associated with inhibitor risk, but the causality of this has so far not been resolved. Among immune regulatory molecules, several polymorphic molecules have been suggested to be of importance. Most of these need additional studies and immune system challenges have to be fully evaluated. Inhibitor risk should be further defined, as patients in the future may be offered non‐immunogenic treatments.
Various regimens for prophylactic treatment of patients with haemophilia
Authors: Schwarz Rudolf , Ljung Rolf , Tedgård Ulf 
Published: January 2015

AbstractHaemophilia prophylaxis is superior to on‐demand treatment to prevent joint damage. ‘High‐dose prophylaxis’ as used in Sweden is more effective in preventing arthropathy than an ‘intermediate‐dose regimen’ (the Netherlands) and the Canadian tailored primary prophylaxis. Prophylaxis may reduce the risk of developing inhibitors. There is no difference in inhibitor risk between plasma derived and recombinant factor VIII (rFVIII) products but the Rodin study showed increased risk with second‐generation rFVIII products. MRI is a new and very sensitive tool to detect the symptoms of early arthropathy but some results (soft tissue changes in ‘bleed‐free joints’) still need to be investigated. Ultrasound is a very helpful method to aid diagnosis especially during the acute phase of a bleed. The risk of infection with central venous access remains a matter of debate. A fully implanted central venous access device (CVAD) has a significant lower risk of infection compared to external CVADs. Patient's age under 6 yr and inhibitor presence are additional risk factors for infections. The role of arteriovenous fistulae needs to be investigated because significant complications have been reported. Disease‐specific quality of life instruments are complementary to generic instruments evaluating QoL in patients with haemophilia and have become important health outcome measures.
The ageing patient with haemophilia
Authors: Canaro Mariana , Goranova‐Marinova Veselina , Berntorp Erik 
Published: January 2015

AbstractOlder patients with haemophilia (PWH) face many challenges related not only to haemophilia but also to general comorbidities associated with ageing. This article discusses the clinical experience published about the high prevalence of diseases in older PWH. These conditions are managed in the general population by healthcare workers with little training in haemophilia. Haemophilic arthropathy is common in elderly PWH. Prophylaxis starting at an early age in sufficient dose regimens to prevent arthropathy did not occur in patients who are now older than around 40 yr. Many PWH above this age thus have limitations in their activities of daily life. Cardiovascular diseases have become increasingly common in the growing, ageing cohort of PWH. Lifestyle issues such as sexual dysfunction may be exacerbated by the medical issues and psychological problems associated with haemophilia. Hepatitis C virus is a leading problem in PWH. Coinfection with HIV accelerates the progression to end‐stage liver disease. Acute and chronic renal failure is more common in adult PWH than in general population. Other comorbidities are reviewed. The evidence is scarce, so it is imperative to report any experience regarding the diagnosis and treatment of these entities, to improve the quality of life of older PWH.
One‐stage vs. chromogenic assays in haemophilia A
Authors: Potgieter Joachim J. , Damgaard Michael , Hillarp Andreas 
Published: January 2015

AbstractHaemophilia A severity is closely correlated to the factor VIII (FVIII) activity, which can be measured in different ways. The original one‐stage clotting assay is still the most widely used. The two‐stage coagulation assay eliminated many of the drawbacks of the one‐stage assay and was further developed into the chromogenic assay, a two‐staged test with purified coagulation factors in the first stage, and a FXa‐specific chromogenic substrate in the second stage. In many patients with mild or moderate haemophilia A, there is a discrepancy between the one‐stage and the two‐stage assays. If only the one‐stage assay is used, some patients will have normal FVIII levels and not be diagnosed as having haemophilia or be considered to have a milder bleeding risk than is the case. Other patients who have normal FVIII activity will be diagnosed as haemophilia A. All haemophilia treatment centre laboratories should have access to both one‐stage and chromogenic FVIII:C assays. Appropriate standards should be employed to enable accurate FVIII:C measurement. Different assays to measure inhibitor activity to infused FVIII have been developed since 1959. Inhibitor results based on the one‐stage or chromogenic FVIII:C assays are well correlated, but the one‐stage assay may be influenced by nonspecific inhibition.
Strategies for reducing inhibitor formation in severe haemophilia
Authors: Tunstall Oliver , Astermark Jan 
Published: January 2015

AbstractThe greatest barrier to successful haemophilia A care in resource‐rich countries is the development of inhibitors to therapeutic factor VIII. Children with inhibitors suffer through increased bleeding and joint damage as well as frequent venepuncture. Costs associated with inhibitors are beyond many healthcare systems. Over the last two decades, there has been no improvement in our ability to reduce inhibitor development. Current strategies based on early prophylaxis and avoidance of immunological danger signals have given rise to conflicting results. Registry data suggest an increasing problem. Our understanding of the immunological systems involved in inhibitor formation should inform efforts to prevent inhibitors. Great efforts with mouse models are being undertaken in this field. However, there is no guarantee of the availability of any new agents arising from experimental work in the near future. Global immunomodulatory agents may be one solution. Compounds with a long history of use in inflammatory conditions have demonstrated efficacy in preventing antibodies to protein therapeutics both in animal models and in humans. As these compounds have a long history of use in humans, including babies, it may be that these agents offer an option for reducing inhibitor formation in previously untreated patients.
BH3‐only proteins: a 20‐year stock‐take
Authors: Doerflinger Marcel , Glab Jason A. , Puthalakath Hamsa 
Published: January 2015

BH3‐only proteins are the sentinels of cellular stress, and their activation commits cells to apoptosis. Since the discovery of the first BH3‐only protein BAD almost 20 years ago, at least seven more BH3‐only proteins have been identified in mammals. They are regulated by a variety of environmental stimuli or by developmental cues, and play a crucial role in cellular homeostasis. Some are considered to be tumor suppressors, and also play a significant role in other pathologies. Their non‐apoptotic functions are controversial, but there is broad consensus emerging regarding their role in apoptosis, which may help in designing better therapeutic agents for treating a variety of human diseases.
Treatment of symptomatic coronary artery disease in patients with end‐stage renal disease on hemodialysis with paclitaxel‐eluting TAXUS stent
Authors: Wiernek Szymon L. , Kiesz R. Stefan , Wiernek Barbara K. , Buszman Piotr P. , Janas Adam , Martin Jack L. , Trela Blazej , Szewc Robert G. , Buszman Pawel E. 
Published: January 2015

AbstractPercutaneous coronary intervention (PCI) utilizing drug‐eluting stents is becoming a very common revascularization technique in the dialysis cohort; therefore, we sought to identify the impact of dialysis on outcomes in this group of patients. This is a multicenter registry comparing results of 290 patients (186 with normal kidney function, 104 on dialysis) who underwent PCI with exclusive use of paclitaxel‐eluting TAXUS stent. The primary endpoint was an assessment of major adverse cardiac events (MACE) at 1‐ and 2‐year observation. Mean follow‐up was 23.3 ± 6.1 months. Results at 12 months showed: MACE 11.8% vs. 7.7% (P = not significant [ns]), composite major adverse cardiac and cerebrovascular events (MACCE) 12.4% vs. 11.5% (P = ns), all‐cause death 2.7% vs. 8.6% (P < 0.05), cardiac death 2.7% vs. 1.9% (P = ns), target vessel revascularization (TVR) 9.1% vs. 6.7% (P = ns), acute myocardial infarction (AMI) 3.8% vs. 2.9% (P = ns), cerebrovascular events (CVA) 0.5% vs. 1.0% (P = ns); and results at 24 months showed: MACE 17.7% vs. 18.3% (P = ns), MACCE 21.5% vs. 26.0% (P = ns), all‐cause death 4.3% vs. 14.4% (P < 0.01), cardiac death 3.2% vs. 1.9% (P = ns), TVR 14.0% vs. 16.3% (P = ns), AMI 5.4% vs. 5.8% (P = ns), CVA 3.2% vs. 2.9% (P = ns) for non–end‐stage renal disease (ESRD) and dialysis group, respectively. Prior coronary artery bypass graft (CABG) was found to be single risk factor for MACE, TVR, and MACCE in patients with ESRD, while dialysis and prior CABG were found to be single risk factors for death in the entire population. PCI with TAXUS is a feasible procedure and presents promising results in dialysis‐dependent patients.
Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging as a useful detection method for advanced primary biliary cirrhosis
Authors: Takeyama Yasuaki , Tsuchiya Naoaki , Kunimoto Hideo , Fukunaga Atsushi , Sakurai Kunitoshi , Hirano Genryu , Yokoyama Keiji , Morihara Daisuke , Anan Akira , Irie Makoto , Shakado Satoshi , Sohda Tetsuro , Sakisaka Shotaro 
Published: January 2015

AimIn primary biliary cirrhosis (PBC), damaged hepatocytes resulting from chronic cholestasis follow a compensatory mechanism that alters hepatobiliary transporter expression to reduce the accumulation of potentially toxic compounds such as bile acid. Organic anion transporter peptide 1B3 (OATP1B3), which transports agents such as gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA), has reduced expression in the late stages of PBC. Therefore, we investigated the use of Gd‐EOB‐DTPA‐enhanced magnetic resonance imaging (MRI) as a useful detection method for the advanced staging of PBC.MethodsStage I−III PBC (non‐liver cirrhosis [LC]‐PBC, n = 12), stage IV (LC‐PBC, n = 6), and non−PBC patients (control group, n = 4) were included in this study. We obtained liver tissue samples by percutaneous liver biopsy. Hepatic OATP1B3 expression was determined immunohistochemically, and OATP1B3 mRNA levels were assessed using real‐time reverse transcription polymerase chain reaction. The relative enhancement (RE) in the hepatobiliary phase was calculated using the signal intensity of Gd‐EOB‐DTPA‐enhanced MRI.ResultsImmunohistochemistry revealed markedly reduced expression of OATP1B3 in hepatocytes around the central vein in LC‐PBC patients. Hepatic OATP1B3 mRNA expression in LC‐PBC patients was significantly lower than that in non‐LC‐PBC patients (P < 0.05). The RE on MRI was significantly decreased in the LC‐PBC group (0.33 ± 0.14) compared with the non‐LC‐PBC (0.91 ± 0.15, P < 0.01) and control (0.92 ± 0.20, P < 0.01) groups.ConclusionGd‐EOB‐DTPA‐enhanced MRI may provide a useful detection method for liver disease in patients with LC‐PBC.
Disentangling the influence of plants and herbivores on the local diversity of parasitoids in the Brazilian Cerrado
Authors: Nascimento André R. , Almeida‐Neto Mário , Almeida Adriana M. , Fonseca Carlos R. , Lewinsohn Thomas M. , Penteado‐Dias Angélica 
Published: January 2015

Abstract

This study investigated the extent to which host plants and their associated herbivores determine the local diversity of parasitoids, which depend, directly or indirectly, on these two groups as food resource or shelter for their development.

The tritrophic system studied here is composed of Asteraceae, endophagous herbivores associated with their flower heads and parasitoid wasps. Samplings were undertaken in 18 remnants of the Brazilian Cerrado.

Path analysis was used to unveil the direct and indirect effects of species richness, average taxonomic distinctness (AvTD), and sampling effort of plants and herbivores on parasitoid richness and AvTD.

Plant species richness had only an indirect effect – mediated by herbivores – on parasitoid species richness. On the other hand, there were both direct and indirect effects of plant species richness on the AvTD of parasitoids.

An implication of our findings is that the local extinction of plant species promotes not only the local loss of their herbivores but also the loss of parasitoid species and a decrease in the phylogenetic diversity of parasitoids, which can jeopardise their future evolutionary history.