bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotoxic side effects in children with refractory or relapsed T‐cell malignancies treated with nelarabine based therapy
Authors: Kuhlen Michaela , Bleckmann Kirsten , Möricke Anja , Schrappe Martin , Vieth Simon , Escherich Gabriele , Bronsema Annika , Vonalt Annika , Queudeville Manon , Zwaan C. Michel , Ebinger Martin , Debatin Klaus‐Michael , Klingebiel Thomas , Koscielniak Ewa , Rossig Claudia , Burkhardt Birgit , Kolb Reinhard , Eckert Cornelia , Borkhardt Arndt , von Stackelberg Arend , Chen‐Santel Christiane 
Published: August 2017

SummaryThe prognosis in children with refractory or relapsed (r/r) T‐cell acute lymphoblastic leukaemia (T‐ALL) or lymphoblastic lymphoma (T‐LBL) is poor. Nelarabine (Ara‐G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T‐ALL/T‐LBL aged ≤19 years who were treated with Ara‐G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1–2 cycles of Ara‐G. Seventeen patients (32·7%) had refractory disease, 28 (53·8%) were in first relapse and 7 (13·5%) were in second relapse. A response to Ara‐G was achieved in 20 patients and 15 (28·8%) were in remission at last follow‐up. Twelve patients (23·1%) had neurotoxic adverse effects (neuro‐AE) of any grade, of whom 7 (13·5%) developed neurotoxicity ≥ grade III. The most frequent neuro‐AEs were peripheral motor neuropathy (19·2%), peripheral sensory neuropathy (11·5%) and seizures (9·6%). Three patients died of central neuro‐AE after 1–2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15·17 years) than those without (10·34 years, P = 0·017). No differences were observed between mono‐ and combination therapy concerning outcome and neuro‐AE. The incidence of neuro‐AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.
Transformed Waldenström macroglobulinaemia: clinical presentation and outcome. A multi‐institutional retrospective study of 77 cases from the French Innovative Leukemia Organization (FILO)
Authors: Durot Eric , Tomowiak Cécile , Michallet Anne‐Sophie , Dupuis Jehan , Hivert Bénédicte , Leprêtre Stéphane , Toussaint Elise , Godet Sophie , Merabet Fatiha , Van Den Neste Eric , Ivanoff Sarah , Roussel Xavier , Zini Jean‐Marc , Regny Caroline , Lemal Richard , Sutton Laurent , Perrot Aurore , Le Dû Katell , Kanagaratnam Lukshe , Morel Pierre , Leblond Véronique , Delmer Alain 
Published: August 2017

SummaryHistological transformation (HT) to diffuse large B‐cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy‐proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose‐positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans’ algorithm harboured a non‐germinal centre B‐cell phenotype. First‐line treatment for transformation consisted of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)‐like regimen in 85% of patients. The overall response rate after first‐line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.
Long non‐coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma
Authors: Handa Hiroshi , Kuroda Yuko , Kimura Kei , Masuda Yuta , Hattori Hikaru , Alkebsi Lobna , Matsumoto Morio , Kasamatsu Tetsuhiro , Kobayashi Nobuhiko , Tahara Ken‐ichi , Takizawa Makiko , Koiso Hiromi , Ishizaki Takuma , Shimizu Hiroaki , Yokohama Akihiko , Tsukamoto Norifumi , Saito Takayuki , Murakami Hirokazu 
Published: August 2017

SummaryExtramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo‐resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non‐coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression‐free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non‐coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.
Comparison of lesions detected and undetected by template‐guided transperineal saturation prostate biopsy
Authors: Mai Zhipeng , Xiao Yu , Yan Weigang , Zhou Yi , Zhou Zhien , Liang Zhiyong , Ji Zhigang , Li Hanzhong 
Published: August 2017

ObjectivesTo compare the characteristics of lesions detected or undetected by template‐guided transperineal saturation prostate biopsy and to evaluate the potential impact of undetected lesions.Materials and MethodsWe evaluated the characteristics of lesions in radical prostatectomy (RP) specimens, compared the differences between lesions detected and undetected by systematic transperineal ultrasonography‐guided 11‐region biopsy with regard to tumour volume, Gleason score, surgical margin, spatial location and clinical significance, and assessed the potential impact of undetected clinically significant lesions.ResultsThe median number of biopsy cores was 24. Sixty‐four percent of the clinically significant lesions (170/264) were detected. There were significant differences between the detected and undetected lesions in tumour volume, Gleason score and clinical significance. Inconsistencies found in lesion position between biopsy and RP specimens in the anterior and posterior zones and the left and right sides was 3.4% (7/203) and 5.4% (11/203), respectively. Of the 129 patients, 13 (10.1%) were found to have undetected clinically significant lesions in the biopsy lying on the same side but in a different zone from the detected clinically significant lesions, whereas 23 patients (17.8%) had undetected clinically significant lesions in the biopsy lying on the opposite side from the detected clinically significant lesions.ConclusionsTemplate‐guided transperineal saturation prostate biopsy detected approximately two‐thirds of clinically significant lesions. Most of the undetected lesions were those with small tumour volume. Approximately 20–30% of patients had clinically significant undetected lesions in a different lobe or different quadrant from the detected lesions in the biopsy.
Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats
Authors: Zubrzycki Marek , Janecka Anna , Liebold Andreas , Ziegler Mechthild , Zubrzycka Maria 
Published: August 2017

Background and PurposeEndocannabinoids and opioids play a vital role in mediating pain‐induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles.Experimental ApproachThe study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures.Key ResultsPerfusion of cerebral ventricles with anandamide (AEA), endomorphin‐2 (EM‐2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM‐2, URB597 and JZL195 was blocked by CB1receptor antagonist, AM251 and by μ receptor‐antagonist, β‐funaltrexamine. In contrast to AEA, 2‐arachidonoylglycerol alone did not decrease ETJ amplitude.Conclusions and ImplicationsWe demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM‐2‐induced antinociception was mediated by μ and CB1receptors. The action of AEA and EM‐2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.
Cognitive impairment in adolescents and adults with congenital adrenal hyperplasia
Authors: Karlsson Leif , Gezelius Anton , Nordenström Anna , Hirvikoski Tatja , Lajic Svetlana 
Published: August 2017

SummaryObjectiveImpaired cognition has been reported in patients with congenital adrenal hyperplasia (CAH), although the findings have been conflicting. It has been hypothesized that the major causes of the deficits are prenatal hormonal imbalances and/or excessive glucocorticoid treatment.DesignAn observational study investigating cognition in patients with CAH.PatientsA total of 55 patients with CAH and 58 control subjects from the general population, aged 16–33 years. Nine CAH subjects had been treated prenatally with dexamethasone.SettingSingel research institute.MeasurementsStandardized neuropsychological tests (Wechsler Scales and Stroop Interference Test) and questionnaires (Barkley Deficit in Executive Functioning Scale) were used.ResultsCompared to controls, patients with CAH had impaired performance in tests measuring verbal working memory (P = .024), visual‐spatial working memory (P = .005 and P = .003) and inhibition (P = .002). In measures of fluid intelligence/nonverbal logical reasoning, males with CAH performed poorer than control males (P = .033). Patients with salt‐wasting CAH performed equally compared to patients with simple virilizing CAH. However, patients with a null genotype performed poorer than patients with a non‐null genotype and significantly worse on fluid intelligence/nonverbal logical reasoning (P = .042). Prenatally‐treated women performed worse on most cognitive measures than women with CAH not treated prenatally.ConclusionsPatients with CAH had normal psychometric intelligence but impaired executive functions compared with population controls. A null CAH genotype was associated with poorer general cognitive capacity.
Hospitality and Immigration in a Greek Urban Neighborhood: An Ethnography of Mimesis
Authors: ANDRIKOPOULOS APOSTOLOS 
Published: August 2017

AbstractThis article uses the concept of hospitality to examine the relations between native‐born Greeks and recently arrived immigrants in a Greek urban neighborhood. Beyond romanticized notions of hospitality as a moral obligation or national virtue, this article considers hospitality as a power relation and a control mechanism of social behavior and cultural production. Although relations between hosts and guests are interpersonal, their (perceived) statuses are often enmeshed in macro hierarchical structures. The concept of hospitality helps us to shift scales and examine host‐guest relations at the micro‐level of a neighborhood in relation to wider political and economic constellations. However, the scalar dimensions of hospitality have limitations. This ethnographic study shows that ethnic Greek ‘repatriates’ from the former Soviet Union, despite their ideological incorporation in the home of the Greek nation, are treated by native‐born Greeks, at the neighborhood level, as guests who must comply with the rules of hospitality. At the same time, regardless of their legal exclusion and stigmatization in official discourses, Albanian immigrants, who have accepted the role of guests and imitate the socio‐cultural patterns of their native‐Greek neighbors, are received better than Greek ‘repatriates’.
German “National Cancer Aid Monitoring” 2015–2019 – study protocol and initial results
Authors: Schneider Sven , Görig Tatiana , Schilling Laura , Breitbart Eckhard W. , Greinert Rüdiger , Diehl Katharina 
Published: August 2017

SummaryBackground and objectivesThe National Cancer Aid Monitoring of Tanning Bed Use (NCAM) project is a major German study that aims to observe the most significant risk factors for skin cancer: natural sunlight and artificial UV radiation.Participants and methodsNCAM is a nationwide cross‐sectional survey that will initially involve four rounds of data collection (so‐called waves) between 2015 and 2018. Every year, a representative nationwide sample consisting of 3,000 individuals aged between 14 and 45 years will be surveyed. The cross‐sectional survey will be complemented by a panel of n = 450 current tanning bed users.ResultsThe initial wave in 2015 shows an overall prevalence of tanning bed use of 29.5 %. Eleven percent of all participants had used a tanning bed within the past twelve months. Determinants of current tanning bed use included younger age, female gender, and full‐time/part‐time employment. The main motivations for tanning bed use reported were relaxation and increased attractiveness.ConclusionsNCAM is the first study worldwide to monitor skin cancer risk factors at one‐year intervals using a large, nationally representative sample. Initial results indicate that, despite WHO warnings, millions of Germans use tanning beds, and that many of these users are adolescents despite legal restrictions aimed at preventing minors from using tanning beds.
Season length, body size, and social polymorphism: size clines but not saw tooth clines in sweat bees
Authors: DAVISON PAUL J. , FIELD JEREMY 
Published: August 2017

1. Annual insects are predicted to grow larger where the growing season is longer. However, transitions from one to two generations per year can occur when the season becomes sufficiently long, and are predicted to result in a sharp decrease in body size because available development time is halved. The potential for resulting saw‐tooth clines has been investigated only in solitary taxa with free‐living larvae.2. Size clines were investigated in two socially polymorphic sweat bees (Halictidae): transitions between solitary and social nesting occur along gradients of increasing season length, characterised by the absence or presence of workers and offspring that are individually mass provisioned by adults. How the body size changes with season length was examined, and whether transitions in social phenotype generate saw‐tooth size clines. We measured Lasioglossum calceatum and Halictus rubicundus nest foundresses originating from more than 1000 km of latitude, encompassing the transition between social and solitary nesting.3. Using satellite‐collected temperature data to estimate season length, it was shown that both species were largest where the season was longest. Body size increased linearly with season length in L. calceatum and non‐linearly in H. rubicundus but the existence of saw‐tooth clines was not supported.4. The present results suggest that because the amount of food consumed by offspring during development is determined by adults, environmental and social influences on the provisioning strategies of adult bees may be more important factors than available feeding time in determining offspring body size in socially polymorphic sweat bees.
Plant and insect genetic variation mediate the impact of arbuscular mycorrhizal fungi on a natural plant–herbivore interaction
Authors: RASMUSSEN PIL U. , AMIN TARIQUE , BENNETT ALISON E. , KARLSSON GREEN KRISTINA , TIMONEN SARI , VAN NOUHUYS SASKYA , TACK AYCO J. M. 
Published: August 2017

1. While both arbuscular mycorrhizal (AM) fungi and plant and insect genotype are well known to influence plant and herbivore growth and performance, information is lacking on how these factors jointly influence the relationship between plants and their natural herbivores.2. The aim of the present study was to investigate how a natural community of arbuscular mycorrhizal fungi affects the growth of the perennial herbPlantago lanceolataL. (Plantaginaceae), as well as its interaction with theGlanville fritillary butterfly [Melitaea cinxiaL. (Nymphalidae)]. For this, a multifactorial experiment was conducted using plant lines originating from multiple plant populations in theÅlandIslands,Finland, grown either with or without mycorrhizal fungi. For a subset of plant lines, the impact of mycorrhizal inoculation, plant line, and larval family on the performance ofM. cinxialarvae were tested.3. Arbuscular mycorrhizal inoculation did not have a consistently positive or negative impact on plant growth or herbivore performance. Instead, plant genetic variation mediated the impact of arbuscular mycorrhizal fungi on plant growth, and both plant genetic variation and herbivore genetic variation mediated the response of the herbivore. For both the plant and insect, the impact of the arbuscular mycorrhizal community ranged from mutualistic to antagonistic. Overall, the present findings illustrate that genetic variation in response to mycorrhizal fungi may play a key role in the ecology and evolution of plant–insect interactions.
Justice without Solidarity? Collective Identity and the Fate of the ‘Ethical’ in Habermas' Recent Political Theory
Authors: Pierce Andrew J. 
Published: August 2017

AbstractIn past work, Habermas has claimed that justice and solidarity stand in a complementary relationship—that ‘ethical’ relations of solidarity are the ‘reverse side’ of justice. Yet in a recent address to the World Congress of Philosophy, he rejects this idea. This paper argues against this rejection. After explaining the idea, arguing for its centrality to Habermas' thought, and evaluating Habermas' scant reflections on this major transformation, I argue that his rejection of the idea is a result of a newfound skepticism about the power of secular reason, and should thus be understood in terms of his corresponding turn to religious traditions as alternative sources of solidarity. I argue against this ‘religious turn’ by developing an alternative advocated by Habermas himself in earlier reflections—attention to real sociopolitical movements. In particular, I analyze feminist and black liberation movements to demonstrate that Habermas' pessimism about secular sources of justice‐producing solidarity is unwarranted, and that, while ‘postsecular’ sources may provide one avenue for actionable solidarity, they are not the only one. I conclude by identifying a conceptual commonality in these two alternatives: an inclusive conception of what it means to be human.
Clinical and mutational spectrum of Charcot–Marie–Tooth disease type 2Z caused by MORC2 variants in Japan
Authors: Ando M. , Okamoto Y. , Yoshimura A. , Yuan J.‐H. , Hiramatsu Y. , Higuchi Y. , Hashiguchi A. , Mitsui J. , Ishiura H. , Fukumura S. , Matsushima M. , Ochi N. , Tsugawa J. , Morishita S. , Tsuji S. , Takashima H. 
Published: August 2017

Background and purposeThe microrchidia family CW‐type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot–Marie–Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan.MethodsWe analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next‐generation sequencing, and samples from 434 mutation‐negative patients were subjected to whole‐exome sequencing. We extracted MORC2 variants from these whole‐exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines.ResultsWe identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length‐dependent polyneuropathy, and electrophysiological studies revealed sensory‐dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys.ConclusionsOur study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.
Glucocorticoids: The mode of action in bullous pemphigoid
Authors: Kubin Minna E. , Hellberg Lars , Palatsi Riitta 
Published: August 2017

AbstractBullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first‐line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non‐genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of GC: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell type. In addition, GR exerts rapid, non‐genomic effects possibly mediated by membrane‐localized receptors or by translocation to mitochondria. GCs can also interact directly with several enzymes and cytokines. As a target treatment for BP, the production of autoantibodies should be discontinued. GCs, in spite of their wide immunosuppressive actions, are weak to stop immunoglobulin G (IgG) autoantibody formation. However, both systemic and topical GCs are able to reduce the clinical symptoms of BP. GCs are used to inhibit the secondary inflammation and symptoms, such as blistering and pruritus, and it is shown that GC treatment will gradually decrease also the autoantibody formation. Our review article analyses the mode of action of GC treatment in BP, as far it is possible due to paucity of modern immunological studies.