bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
Authors: Curci Debora , Lucafò Marianna , Cifù Adriana , Fabris Martina , Bramuzzo Matteo , Martelossi Stefano , Franca Raffaella , Decorti Giuliana , Stocco Gabriele 
Published: June 2021

AbstractInfliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.
The Dyskinetic Cerebral Palsy Functional Impact Scale: development and validation of a new tool
Authors: Stewart Kirsty , Lewis Jennifer , Wallen Margaret , Bear Natasha , Harvey Adrienne 
Published: June 2021

AimTo outline the development and examine the content and construct validity of a new tool, the Dyskinetic Cerebral Palsy Functional Impact Scale (D‐FIS), which measures the impact of dyskinesia on everyday activities in children with cerebral palsy (CP).MethodD‐FIS content was informed by a systematic review of dyskinesia outcome measures, in collaboration with children with dyskinetic CP, parents, caregivers, and expert clinicians. The D‐FIS uses parent proxy to rate impact of dyskinesia on everyday activities. Construct validity was determined by examining internal consistency; known groups validity with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS); and convergent validity with the Barry‐Albright Dystonia Scale (BADS).ResultsFifty‐seven parents of children (29 males, 28 females, mean [SD] age 11y 8mo [4y 4mo], range 2y 6mo–18y) completed the D‐FIS. Correlation between D‐FIS and GMFCS was r=0.86 (95% confidence interval [CI]: 0.77–0.91, p<0.001); MACS r=0.84 (95% CI: 0.73–0.90, p<0.001); CFCS r=0.80 (95% CI: 0.67–0.88, p<0.001); and EDACS r=0.78 (95% CI: 0.66–0.87). Correlation between D‐FIS and BADS was r=0.77 (95% CI: 0.64–0.86, p<0.001). Cronbach’s alpha was 0.96.InterpretationThe D‐FIS demonstrates good construct validity and high internal consistency. The D‐FIS will be useful for identifying priorities for intervention. It adds to the measurement tool kit for children with dyskinetic CP by addressing functional impact of dyskinetic movements and postures.
What this paper adds

The Dyskinetic Cerebral Palsy Functional Impact Scale (D‐FIS) assesses the perceived impact of dyskinesia on daily activities in children with cerebral palsy (CP).

The D‐FIS demonstrates good construct validity and high internal consistency.

The D‐FIS is a clinically feasible, family‐centred tool that fills a current gap in the dyskinetic CP assessment toolkit.
Building a competitive infrastructure to support clinical research in healthcare institution
Authors: Cimino Jonathan , Braun Claude 
Published: June 2021

AbstractBackgroundClinical research is becoming increasingly popular in Europe at a growth rate much higher than expected, especially in Benelux. Although traditionally thought to be the purview of academic health centres, clinical research to evaluate new drugs, devices and medical practices is being done more and more in healthcare organizations with little or no academic affiliation.MethodsBy managing a new infrastructure and centralizing resources and demands, clinical research unit (CRU) has become an effective mechanism for hospital research. The ‘infrastructure’ or CRU refers to the necessary resources and how the CRU is organized and communicates operationally to conduct clinical research within the institution. The creation of a new CRU within the Robert Schuman Hospital in Luxembourg is described in this article.ResultsThis article discusses the concrete steps and basic elements such as patient‐centric and hospital approaches needed to create and structure a CRU to provide academic or industry‐sponsored research support in clinical research.ConclusionsSome infrastructure challenges (insufficient engagement, regulatory and administrative barriers) and possible courses of action (standardized procedures, training and centralization) will be discussed.
Exploring spatial ability in healthcare students and the relationship to training with virtual and actual objects
Authors: Sezer Baris , Sezer Tufan Asli , Elcin Melih 
Published: June 2021

AbstractIntroductionThe relationship between the spatial ability levels of students and anatomy education is not well established in the literature, but it was stated that students should take short‐term training during the first years of their education. There is limited number of studies on this topic. In that respect, the aim of this study was to determine the spatial ability levels of medical, dental and nursing students and to evaluate whether this ability level showed difference with respect to faculty, anatomy courses attended or short‐term training, or not.Materials and MethodsStudy sample was composed of 1071 students. Data were collected by Personal Information Form, Visualization of Views Test (VoVT) and Cross Section Test (CST). Data analyses were done by SPSS 21 package software.ResultsStudents were determined to have medium level spatial ability. Medical and dental students were found to have higher spatial ability levels than nursing students. Medical and nursing students’ CST scores showed significant difference after taking anatomy course. After short‐term training, both CST and VoVT scores of students differed significantly.ConclusionSupporting anatomy courses with education materials appropriate for the spatial ability level of students and introducing spatial ability development trainings in small groups would aid in increasing spatial ability levels of students.
EBI2 is expressed in glial cells in multiple sclerosis lesions, and its knock‐out modulates remyelination in the cuprizone model
Authors: Klejbor Ilona , Shimshek Derya R. , Klimaszewska‐Łata Joanna , Velasco‐Estevez Maria , Moryś Janusz , Karaszewski Bartosz , Szutowicz Andrzej , Rutkowska Aleksandra 
Published: June 2021

AbstractEBI2 receptor regulates the immune system, and in multiple, sclerosis is upregulated in the central nervous system infiltrating lymphocytes. In newborn EBI2‐deficient mice, myelin development is delayed, and its persistent antagonism inhibits remyelination in chemically demyelinated organotypic cerebellar slices. We used the cuprizone model of multiple sclerosis to elucidate the role of central nervous system‐expressed EBI2 in de‐ and remyelination. The wild‐type and EBI2 knock‐out mice were fed 0.2% cuprizone in chow for 5 weeks and allowed to recover on a normal diet for 2 weeks. The data showed less efficient recovery of myelin, attenuated oligodendrocyte loss, fewer astrocytes and increased total cholesterol levels in the EBI2 knock‐out mice after recovery. Moreover, the wild‐type mice upregulated EBI2 expression after recovery confirming the involvement of EBI2 signalling during recovery from demyelination in the cuprizone model. The pro‐inflammatory cytokine levels were at comparable levels in the wild‐type and EBI2 knock‐out mice, with only minor differences in TNFα and IL1β levels either at peak or during recovery. The neuroinflammatory signalling molecules, Abl1 kinase and NFКB1 (p105/p50) subunit, were significantly downregulated in the EBI2 knock‐out mice at peak of disease. Immunohistochemical investigations of EBI2 receptor distribution in the central nervous system (CNS) cells in multiple sclerosis (MS) brain revealed strong expression of EBI2 in astrocytes and microglia inside the plaques implicating glia‐expressed EBI2 in multiple sclerosis pathophysiology. Taken together, these findings demonstrate the involvement of EBI2 signalling in the recovery from demyelination rather than in demyelination and as such warrant further research into the role of EBI2 in remyelination.
No evidence for a single oscillator underlying discrete visual percepts
Authors: Morrow Audrey , Samaha Jason 
Published: June 2021

AbstractTheories of perception based on discrete sampling posit that visual consciousness is reconstructed based on snapshot‐like perceptual moments, as opposed to being updated continuously. According to a model proposed by Schneider (2018), discrete sampling can explain both the flash–lag and the Fröhlich illusion, whereby a lag in the conscious updating of a moving stimulus alters its perceived spatial location in comparison to stationary stimulus. The alpha‐band frequency, which is associated with phasic modulation of stimulus detection and the temporal resolution of perception, has been proposed to reflect the duration of perceptual moments. The goal of this study was to determine whether a single oscillator (e.g., alpha) is underlying the duration of perceptual moments, which would predict that the point of subjective equality (PSE) in the flash–lag and Fröhlich illusions are positively correlated across individuals. Although our displays induced robust flash–lag and Fröhlich effects, virtually zero correlation was seen between the PSE in the two illusions, indicating that the illusion magnitudes are unrelated across observers. These findings suggest that, if discrete sampling theory is true, these illusory percepts either rely on different oscillatory frequencies or not on oscillations at all. Alternatively, discrete sampling may not be the mechanism underlying these two motion illusions or our methods were ill‐suited to test the theory.
Neural correlates of visual stimulus encoding and verbal working memory differ between cochlear implant users and normal‐hearing controls
Authors: Prince Priyanka , Paul Brandon T. , Chen Joseph , Le Trung , Lin Vincent , Dimitrijevic Andrew 
Published: June 2021

AbstractA common concern for individuals with severe‐to‐profound hearing loss fitted with cochlear implants (CIs) is difficulty following conversations in noisy environments. Recent work has suggested that these difficulties are related to individual differences in brain function, including verbal working memory and the degree of cross‐modal reorganization of auditory areas for visual processing. However, the neural basis for these relationships is not fully understood. Here, we investigated neural correlates of visual verbal working memory and sensory plasticity in 14 CI users and age‐matched normal‐hearing (NH) controls. While we recorded the high‐density electroencephalogram (EEG), participants completed a modified Sternberg visual working memory task where sets of letters and numbers were presented visually and then recalled at a later time. Results suggested that CI users had comparable behavioural working memory performance compared with NH. However, CI users had more pronounced neural activity during visual stimulus encoding, including stronger visual‐evoked activity in auditory and visual cortices, larger modulations of neural oscillations and increased frontotemporal connectivity. In contrast, during memory retention of the characters, CI users had descriptively weaker neural oscillations and significantly lower frontotemporal connectivity. We interpret the differences in neural correlates of visual stimulus processing in CI users through the lens of cross‐modal and intramodal plasticity.
Interplay of population size and environmental fluctuations: A new explanation for fitness cost rarity in asexuals
Authors: Chavhan Yashraj , Malusare Sarthak , Dey Sutirth 
Published: June 2021

AbstractTheoretical models of ecological specialisation commonly assume that adaptation to one environment leads to fitness reductions (costs) in others. However, experiments often fail to detect such costs. We addressed this conundrum using experimental evolution with Escherichia coli in several constant and fluctuating environments at multiple population sizes. We found that in fluctuating environments, smaller populations paid significant costs, but larger ones avoided them altogether. Contrastingly, in constant environments, larger populations paid more costs than the smaller ones. Overall, large population sizes and fluctuating environments led to cost avoidance only when present together. Mutational frequency distributions obtained from whole‐genome whole‐population sequencing revealed that the primary mechanism of cost avoidance was the enrichment of multiple beneficial mutations within the same lineage. Since the conditions revealed by our study for avoiding costs are widespread, it provides a novel explanation of the conundrum of why the costs expected in theory are rarely detected in experiments.
Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency
Authors: Khawajazada Tahmina , Kass Konni , Rudolf Karen , de Stricker Borch Josefine , Sheikh Aisha Munawar , Witting Nanna , Vissing John 
Published: June 2021

AbstractObjectiveUsing magnetic resonance imaging (MRI) and stationary dynamometry, the aim was to investigate the muscle affection in paraspinal muscles and lower extremities and compare the muscle affection in men and women with anoctamin 5 (ANO5) deficiency.MethodsSeventeen patients (seven women) with pathogenic ANO5‐mutations were included. Quantitative muscle fat fraction of back and leg muscles were assessed by Dixon MRI. Muscle strength was assessed by stationary dynamometer. Results were compared with 11 matched, healthy controls.ResultsMuscle involvement pattern in men with ANO5‐deficiency is characterized by a severe fat replacement of hamstrings, adductor and gastrocnemius muscles, while paraspinal muscles are only mildly affected, while preserved gracilis and sartorius muscles were hypertrophied. Women with ANO5‐myopathy, of the same age as male patients, were very mildly affected, showing muscle affection and strength resembling that found in healthy persons, with the exception of the gluteus minimus and medius and gastrocnemii muscles that were significantly replaced by fat. Although individual muscles showed clear asymmetric involvement in a few muscle groups, the overall muscle involvement was symmetric.ConclusionsPatients with ANO5‐deficiency have relatively preserved paraspinal muscles on imaging and only mild reduction of trunk extension strength in men only. Our study quantifies the large difference in muscle affection in lower extremity between women and men with ANO5‐deficiency. The clinical notion is that affection may be very asymmetric in ANO5‐deficiency, but the present study shows that while this may be true for a few muscles, the general impression is that muscle affection is very symmetric.
Drop‐in ready jet biofuel from carinata: A real options analysis of processing plant investments
Authors: Zhao Chong , Colson Greg , Karali Berna , Philippidis George P. 
Published: June 2021

AbstractA promising feedstock for large‐scale production of sustainable jet biofuel is the inedible oilseed Brassica carinata (referred to simply as “carinata”), but transitioning to large‐scale fuel production entails significant economic uncertainty and requires substantial up‐front capital requirements for biorefinery construction. Furthermore, for carinata and other feedstocks attempting to compete within the established fossil jet fuel market, historically volatile aviation fuel prices affect the economic feasibility and return of biorefinery investments. In this study, we assess the impact of jet fuel price volatility on the return on investment in a carinata biorefinery employing a real options analysis (ROA). The key advantage of ROA over traditional net present value (NPV) analysis is that it simultaneously assesses the optimal timing for investments and the impact of jet fuel price dynamics on the likelihood of positive economic returns from investments in processing plants. Given the nonstationary nature of jet fuel prices and the presence of structural breaks, the price series are modeled as a geometric Brownian motion. Taking into account the volatility of jet fuel price, the ROA price threshold for a profitable investment is 45% greater than the NPV threshold. The ROA model identifies the necessary market conditions for a profitable investment and highlights the importance of considering market price dynamics before making substantial capital investments in a carinata biorefinery.
Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study
Authors: Versloot Olav , van Balen Erna C. , Hassan Shermarke , Schols Saskia E.M. , Leebeek Frank W.G. , Eikenboom Jeroen , Coppens Michiel , van Vulpen Lize F.D. , Smit Cees , Driessens Mariëtte H.E. , van der Net Janjaap , Gouw Samantha C. , Fischer Kathelijn ,   the Haemophilia in the Netherlands 6 steering committee
Published: June 2021

AbstractIntroductionAlthough sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking.Aimto assess sports participation in Dutch PWH (6‐65 years) compared to the Dutch general population (GP).MethodsData from a nationwide, cross‐sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high‐risk sports. Groups were compared using Chi‐square testing.ResultsA total of 524 Adult PWH (median age: 45 (IQR: 30–55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8–14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High‐risk sports participation decreased with age in PWH: from 65% (6‐12 years) to 17% (50‐65 years), which was also observed in the GP. Sports participation in children was independent of severity (non‐severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non‐severe: 75%, severe: 62%; P < 0.01). Non‐severe PWH played more high‐risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07).DiscussionThese results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high‐risk sports than adults. More studies on sports‐related injury‐risk are needed for adequate counselling.
VALUE PRESERVING WELFARE WEIGHTS FOR SOCIAL OPTIMIZATION PROBLEMS
Authors: Anagnostopoulos Alexis , Carceles‐Poveda Eva , Tauman Yair 
Published: June 2021

AbstractWe propose endogenous, value preserving (VP) welfare weights as an alternative to equal weights utilitarianism. VP weights require that the contribution of an agent's endowments to social welfare is proportional to the contribution of the final allocation to his welfare. Under three axioms, the per unit contribution of a good to welfare is shown to equal the gradient of the welfare function. VP weights coincide with Negishi weights in frictionless environments but prescribe redistribution toward a good's owner when the good's social value exceeds its market value. When ability is treated as an endowment, VP weights reward ability and effort.
Polymer (PCL) fibers with Zn‐doped mesoporous bioactive glass nanoparticles for tissue regeneration
Authors: Neščáková Zuzana , Kaňková Hana , Galusková Dagmar , Galusek Dušan , Boccaccini Aldo R. , Liverani Liliana 
Published: June 2021

AbstractComposite fibrous membranes based on poly(ɛ‐caprolactone) (PCL) and mesoporous bioactive glass nanoparticles (MBGNs) were fabricated by electrospinning. MBGNs and Zn‐doped MBGNs prepared by microemulsion sol–gel method were successfully incorporated inside the polymeric fibers of 240 and 385 nm in diameter for undoped and Zn‐doped PCL_MBGNs fibers, respectively. Thermal analysis showed that the concentration of MBGNs reached a maximum of around 21 wt% for Zn‐doped MBGNs. Both PCL_MBGNs and PCL_MBGNs_Zn composite membrane exhibited bioactivity after immersion in simulated body fluid (SBF). X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed the evolution of composite membranes, confirming the formation of hydroxyapatite (HAp). However, the degradation products of membranes did not affect the viability and proliferation of murine stromal cells (ST‐2) and thus the new fiber structures represent a suitable environment for cell adhesion. Therefore, the incorporation of mesoporous glass nanoparticles doped with therapeutically active Zn2+ ions inside the PCL fibers offers the possibility to create a multifunctional biomaterial suitable for drug delivery and tissue engineering.
Clinical characteristics and prognosis of acral lentiginous melanoma: a single‐center series of 211 cases in China
Authors: Wang Lei , Wu Junshen , Dai Zhibing , Ji Suzhi , Jiang Renbing 
Published: June 2021

AbstractBackgroundAcral lentiginous melanoma (ALM) is common in China with poor prognosis. However, there are only a few studies of ALM in the Asian population. We aimed to summarize and analyze the clinical characteristics, treatment strategy, treatment effect, and prognostic factors of ALM in a Chinese population.MethodsWe included a total of 249 ALM patients (211 with follow‐up data) from a single institution. Demographic, laboratory data, treatment strategy, and prognosis were analyzed.ResultsThe ratio of male and female was 1.3 ∶ 1.0. The median age was 58 years old. The majority of patients (70.3%) had lesions on the sole. Trauma history and irritation were associated with lesion size increase in some patients. The prognosis of patients in stage II–III undergoing standard operation was significantly better compared with those without surgical treatment. Patients who did not receive postoperative adjuvant treatment had shorter time to distant metastasis. In multivariable analysis, distant metastasis, duration of disease, LDH level, and Ki67 index were independently associated with survival.ConclusionsPrognosis for ALM patients was poor in our study. Distant metastasis, duration of disease, LDH level, and Ki67 index were independently associated with prognosis.