bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B‐cell receptor signalling
Authors: Friedman Daphne R. , Guadalupe Eross , Volkheimer Alicia , Moore Joseph O. , Weinberg J. Brice 
Published: November 2018

SummaryChronic lymphocytic leukaemia (CLL) is characterized by expression of CD5 on clonal B cells, and is partly driven by activated B‐cell receptor (BCR) signalling. While CD5 is known to be a negative regulator of BCR signalling, it is unknown if variability in CD5 expression exists among patients and whether CLL cell CD5 expression affects CLL clinical outcomes. We assessed the extent to which CD5 expression is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated CD5 expression from 1275 blood samples, established prognostic markers and time to event data from 423 CLL patients followed at the Duke University and Durham VA Medical Centers. CD5 median fluorescence intensity (MFI) was largely stable over time in individual patients, but ranged between 0·5 and 760 in the entire cohort. Lower CD5 MFI was significantly associated with a shorter time to first therapy. CD5 MFI, combined with established clinical and molecular prognostic markers, significantly improved risk‐stratification. CD5 may affect disease outcomes by suppressing signalling through the BCR. Thus, a strategy to modulate CLL cell CD5 expression or function could be a therapeutic approach in CLL.
The role of transplantation in Hodgkin lymphoma
Authors: Broccoli Alessandro , Zinzani Pier Luigi 
Published: November 2018

SummaryAutologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first‐line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti‐programmed death 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post‐autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high‐risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post‐autologous salvage treatments still remain to be determined.
Cytokine release syndrome and neurotoxicity afterCD19 chimeric antigen receptor‐modified (CAR‐) T cell therapy
Authors: Hay Kevin A. 
Published: November 2018

SummaryChimeric antigen receptor‐modified (CAR)‐T cells have demonstrated impressive results in the treatment of haematological malignancies. However, cytokine release syndrome (CRS) and neurotoxicity are common toxicities which are potentially life‐threatening in severe cases. Risk factors forCRSand neurotoxicity identified so far include disease burden, lymphodepletion intensity andCAR‐T cell dose administered. Risk‐adapted dosing, with lowerCAR‐T cell doses administered to B‐cell acute lymphoblastic leukaemia patients with high marrow blast counts, has been successful at decreasing severeCRSrates in this population. Intervention with therapies, such as tocilizumab and corticosteroids, have been effective at ameliorating toxicity, enablingCAR‐T cells to be administered safely to many patients without significantly compromising efficacy. Deeper understanding of the pathophysiology of underlyingCRSand neurotoxicity will enable the development of novel approaches to reduce toxicity and improve outcomes.
Understanding how older age drives decision‐making and outcome in Immune Thrombocytopenia. A single centre study on 465 adult patients
Authors: Palandri Francesca , Catani Lucia , Auteri Giuseppe , Bartoletti Daniela , Fatica Sofia , Fusco Alessio , Bacchi Reggiani Maria L. , Cavo Michele , Vianelli Nicola 
Published: November 2018

SummaryWe analysed the impact of older age on the management of immune thrombocytopenia (ITP) in 465 adult patients diagnosed between 1995 and 2017 and followed at our institution for a minimum of 12 months. Over a follow‐up of 4248 patient‐years, front‐line corticosteroids therapy was required in 334 patients (71·8%), mainly (85·3%) within 1 year from diagnosis. Need for first‐, second‐ and third‐line therapy was comparable in younger and older (age ≥65 years, n = 154) patients. Older patients presented more frequently with severe haemorrhages, started therapy with a higher platelet count and received lower dose front‐line corticosteroids; thereafter, they were preferentially treated with mild immunosuppressive therapies/thrombopoietin‐receptor agonists. Conversely, younger patients were more frequently treated with rituximab and splenectomy, achieving higher rates of complete responses. Incidence rates of ≥grade 2 complications were: 2·87 (haemorrhages), 1·55 (infections) and 0·66 (thromboses) per 100 patient‐years. Older age (P = 0·01) and active haemorrhages at diagnosis (P = 0·01) significantly predicted grade ≥2 haemorrhages during follow‐up. Older age (P = 0·01), male gender (P = 0·01), and thrombopoietin receptor agonist use (P = 0·02) were significantly associated with a higher probability of thrombosis over time. Older age is a significant driver of diagnostic/therapeutic strategy in ITP resulting in different responses and complications rates.
The Basophil Activation Test reduces the need for a food challenge test in children suspected of IgE‐mediated cow's milk allergy
Authors: Ruinemans‐Koerts Janneke , Schmidt‐Hieltjes Yvonne , Jansen Ad , Savelkoul Huub F.J. , Plaisier Annejet , van Setten Petra 
Published: November 2018

AbstractBackgroundThe gold standard for the diagnosis of cow's milk allergy is the Double‐Blind Placebo‐Controlled Food Challenge (DBPCFC) test. However, disadvantages of the DBPCFC are the potential risk of anaphylactic reactions, the time‐consuming procedure and high costs.ObjectiveThe aim of this study was to determine the reliability of the Basophil Activation Test (BAT) both for the initial diagnosis of cow's milk allergy in children and for the determination of tolerance in children with cow's milk allergy.MethodsNinety‐seven BATs and cow's milk‐specific IgE (sIgE) tests were performed in 86 infants/young children, suspected of (persistent) cow's milk allergy, who were qualified for an in‐hospital DBPCFC. The BAT was performed with cow's milk extract and the purified major allergens casein, α‐lactalbumin, β‐lactoglubulin. Basophil activation was determined by CD63 upregulation measured by flow cytometry. The BAT results were compared to the DBPCFC outcomes.ResultsBased on unequivocal DBPCFC and BAT result combinations (80%), the BAT had a sensitivity and specificity of 100% (CI: 86%‐100% and 68%‐100%, respectively) in IgE‐sensitized children (41% of the tested children). All non‐IgE‐sensitized children (59%) had a negative DBPCFC and BAT, except for five patients. These latter showed delayed and relatively mild symptoms in the DBPCFC with a negative BAT, supporting a non‐IgE‐mediated allergy in these children.Conclusions and Clinical RelevanceThe BAT seems reliable and cost‐effective to diagnose patients with an IgE‐mediated cow's milk allergy. In IgE‐sensitized patients, a BAT might replace a DBPCFC. For non‐IgE‐sensitized patients presenting with mild symptoms, we propose to consider a (double‐blind) extended (time) challenge test at home.
HowMoroccan‐Dutch parents learn in communities of practice:Evaluating a bottom‐up parenting programme
Authors: van Beurden Spark L. , de Haan Mariette , Jongmans Marian J. 
Published: November 2018

AbstractResearch shows that top‐down‐designed parenting programmes do not always meet the needs of postmigration parents. Bottom‐up programmes by migrant organizations hold a promise to fill this gap; however, research about these programmes and appropriate evaluation methodologies is scarce. Drawing upon Wenger's () “communities of practice,” this paper explores an alternative perspective on parenting programme evaluation. Findings are presented from a study looking into social learning processes of postmigration parents who participated in a bottom‐up programme about raising teenagers in urban areas. Using an ethnographically inspired method combined with a preprogramme and postprogramme design, 115 Moroccan‐Dutch mothers and fathers from 15 programme groups participated. Results show that the programme provided a social learning space in which parents used themselves as resources to learn collectively about parenting. Moreover, parents consciously engaged in learning interactions across learning spaces stretched into their social networks. These analyses showed how parents' development of “learning citizenship” (Wenger,) provides us with insight in collective learning dimensions present in a bottom‐up parenting programme, which is often not included in evaluation studies. Implications for practitioners as facilitators of parents' collective learning are presented.
Receiver operating characteristic analysis to determine optimal fluid management during open colorectal surgery
Authors: Pache B. , Hübner M. , Solà J. , Hahnloser D. , Demartines N. , Grass F. 
Published: November 2018

AbstractAimThe present study aimed to analyse fluid management and to define optimal fluid‐related thresholds for elective open colorectal surgery.MethodA retrospective analysis was made of all consecutive elective open colorectal resections performed in our tertiary centre between May 2011 and May 2017. The main outcomes were postoperative complications [overall (I–V) and severe (IIIB–V) according to the Clavien classification], respiratory complications and postoperative ileus (POI). Critical thresholds regarding perioperative fluid management and postoperative weight gain were identified by using receiver operator characteristic (ROC) analysis. Independent risk factors for overall complications were identified by multivariable logistic regression analysis.ResultsOf 121 patients who had open operations, 84 (69%) had some complication and 26 (21%) had severe complications. Respiratory complications and POI occurred in 15 (12%) and 46 patients (38%), respectively. The thresholds for intravenous fluids were 3.5 l at postoperative day (POD) 0 [area under ROC curve (AUROC) 0.7 for any 0.69 for respiratory complications] and 3.5 kg weight gain at POD 2 (AUROC 0.82 for respiratory complications). Multivariable analysis revealed weight gain of > 3.5 kg at POD 2 (OR 5.9; 95% CI 1.3–16.6) as a significant risk factor for overall complications. Acute kidney injury was observed in five patients (4%), three (5%) in the group with > 3.5 l at POD 0 and two (3%) in the group with < 3.5 l at POD 0 (P = 0.64). Creatinine increase was transitory and all patients regained baseline levels before discharge.ConclusionA weight gain of > 3.5 kg at POD 2 has been identified as the critical threshold for overall and respiratory complications and prolonged length of stay after open elective colorectal surgery.
Fungal colorants in applications – focus on Cortinarius species
Authors: Räisänen Riikka 
Published: November 2018

Secondary metabolites in fungi offer an interesting source of bio‐based compounds that could be used as colorants in many applications. From a historical point of view, fungal natural dyes have been used more rarely than plant‐based dyes. This paper investigates the potential of fungal colorants, using Cortinarius species as examples. In our research, fruiting bodies of the fungi Cortinarius sanguineus and Cortinarius semisanguineus were used as sources of anthraquinone dyestuffs. From 10 kg of fresh fruiting bodies, 60 g of anthraquinone powder was obtained, 6% of the dry weight content. The most abundant compounds were emodin, dermocybin and their glucosides, which formed over 90% of the total dyestuff amount. Pure emodin and dermocybin, as well as the crude water extract, were used for the dyeing and printing of natural and synthetic fibres. Conventional mordant techniques and high‐temperature (HT) disperse dye techniques were applied, and light and washing fastness were tested according to International Organization for Standardization standards. Our experiments show that the yields of dye powders extracted from fungi are reasonable compared with the yields of, for example, madder (Rubia tinctorum). Natural anthraquinones produce strong and bright colours on several types of fibres. In particular, for HT disperse dyed polyester, the light and washing fastness properties were excellent. Anthraquinones are common in nature and there are many fungal species which produce them, so there are a variety of possibilities for growing fungi. The use of large‐scale cultures is an interesting perspective for future biocolorant production.
Extraction of polyphenolic substances from bark as natural colorants for wool dyeing
Authors: Fitz‐Binder Christa , Bechtold Thomas 
Published: November 2018

In Europe, considerable amounts of bark are available from wood‐processing industries such as forestry and timber production. Polyphenolic components can be collected by hot water extraction. The extracted compounds can then be applied as colorants in textile dyeing operations. In this study, a comparative assessment of four different tree species with regard to their colouristic potential for wool dyeing was performed. Aqueous extracts from alder, ash tree, spruce and oak bark were prepared and analysed for their total phenolic content and ultraviolet (UV) absorption at 360–370 nm. The extracts were used for meta‐mordant dyeing by adding iron sulphate mordant (FeSO4 × 7H2O). For comparison, iron salt‐based dye lakes were prepared and used in dyeing experiments. For each tree species, a specific correlation between the total phenolic content of the dyebath and the colour depth in terms of K/S and CIELab coordinates was observed, both for the aqueous extracts and the dye lakes. Based on this relationship, standardisation and quality control of raw materials and dye lakes can be installed as important stages in the industrialisation of natural colorants from bark. The preparation of concentrated dye lakes permits formation of a concentrated colorant as dye product, which then can be standardised and delivered to textile dyehouses, similar to synthetic dyes. The preparation of dye lakes offers a relevant route towards achieving the commercialisation of bark extracts as natural colorants.
LncRNA NEAT1 promotes the tumorigenesis of colorectal cancer by sponging miR‐193a‐3p
Authors: Yu Hong‐Mei , Wang Chen , Yuan Zhen , Chen Guang‐Liang , Ye Tao , Yang Bi‐Wei 
Published: November 2018

AbstractObjectivesLncRNA nuclear‐enriched abundant transcript 1 (NEAT1) participates in the development and progression of multiple malignancies. However, the molecular mechanism by which NEAT1 contributes to colorectal cancer (CRC) remains unclear.MethodsThe association between lncRNA NEAT1 expression and clinicopathological characteristics and prognosis in patients with CRC was analysed by TCGA RNA‐sequencing data. MTT, colony formation, flow cytometry, transwell assays and a xenograft tumour model were used to assess the functions of NEAT1. Bioinformatics and spearman correlation analysis were used to identify the NEAT1‐specific binding with miRNAs, and luciferase gene report and RIP assays were performed to confirm the interaction between miR‐193a‐3p (miR‐193a) and NEAT1 in CRC cells.ResultsUpregulation of NEAT1 expression was significantly correlated with TNM stage, poor survival and tumour recurrence in patients with CRC, and acted as an independent prognostic factor for tumour recurrence. Knockdown of NEAT1 suppressed cell proliferation, colony formation abilities and invasive potential and induced cell apoptosis, but overexpression of NEAT1 reversed these effects. Furthermore, NEAT1 was confirmed to act as a sponge of miR‐193a, and knockdown of NEAT1 attenuated miR‐193a inhibitor‐induced tumour promoting effects and L17RD expression in CRC cells. miR‐193a harboured negative correlation with NEAT1 and IL17RD expression in CRC specimens. In vivo experiment further validated the inhibitory effects of NEAT1 knockdown on xenograft tumour growth.ConclusionOur findings demonstrate that lncRNA NEAT1 acts as an oncogenic role in CRC cells by sponging miR‐193a and may represent a potential marker for CRC patients.
Deterministic fate assignment of Müller glia cells in the zebrafish retina suggests a clonal backbone during development
Authors: Rulands Steffen , Iglesias‐Gonzalez Ana Belen , Boije Henrik 
Published: November 2018

AbstractThe optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post‐fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis.
Behavioral, neuroendocrine and physiological indicators of the circadian biology of male and female rabbits
Authors: Aguilar‐Roblero Raúl , González‐Mariscal Gabriela 
Published: November 2018

AbstractAdult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a light‐entrained circadian clock and a food‐entrained oscillator. Nursing periodicity, however, relies on a suckling stimulation threshold. Brain structures regulating this activity include the paraventricular nucleus and preoptic area, as determined by lesions and quantification of cFOS‐ and PER1 clock gene‐immunoreactive proteins. Melatonin synthesis in the rabbit pineal gland shows a diurnal rhythm, with highest values at night and lowest ones during the day. In kits the main zeitgeber is milk intake, which synchronizes locomotor activity, body temperature, and corticosterone secretion. Brain regions involved in these effects include the median preoptic nucleus and several olfactory structures. As models for particular human illnesses rabbits have been valuable for studying glaucoma and cardiovascular disease. Circadian variations in intraocular pressure (main risk factor for glaucoma) have been found, with highest values at night, which depend on sympathetic innervation. Rabbits fed a high fat diet develop cholesterol plaques and high blood pressure, as do humans, and such increased fat intake directly modulates cardiovascular homeostasis and circadian patterns, independently of white adipose tissue accumulation. Rabbits have also been useful to investigate the characteristics of sleep across the day and its modulation by infections, cytokines and other endogenous humoral factors. Rabbit circadian biology warrants deeper investigation of the role of the suprachiasmatic nucleus in regulating most behavioral and physiological rhythms described above.
Pushing attention to one side: Force field adaptation alters neural correlates of orienting and disengagement of spatial attention
Authors: Reuter Eva‐Maria , Mattingley Jason B. , Cunnington Ross , Riek Stephan , Carroll Timothy J. 
Published: November 2018

AbstractSensorimotor adaptation to wedge prisms can alter the balance of attention between left and right space in healthy adults, and improve symptoms of spatial neglect after stroke. Here we asked whether the orienting of spatial attention to visual stimuli is affected by a different form of sensorimotor adaptation that involves physical perturbations of arm movement, rather than distortion of visual feedback. Healthy participants performed a cued discrimination task before and after they made reaching movements to a central target. A velocity‐dependent force field pushed the hand aside during each reach, and required participants to apply compensatory forces toward the opposite side. We used event‐related potentials (ERPs) to determine whether electroencephalography (EEG) responses reflecting orienting (cue‐locked N1) and disengagement (target‐locked P1) of spatial attention are affected by adaptation to force fields. After adaptation, the cue‐locked N1 was relatively larger for stimuli presented in the hemispace corresponding to the direction of compensatory hand force. P1 amplitudes evoked by invalidly cued targets presented on the opposite side were reduced. This suggests that force field adaptation boosted attentional orienting responses toward the side of hand forces, and impeded attentional disengagement from that side, mimicking previously reported effects of prism adaptation. Thus, remapping between motor commands and intended movement direction is sufficient to bias ERPs, reflecting changes in the orienting of spatial attention in the absence of visuo‐spatial distortion or visuo‐proprioceptive mismatch. Findings are relevant to theories of how sensorimotor adaptation can modulate attention, and may open new avenues for treatment of spatial neglect.