bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graft‐versus‐mastocytosis effect after donor lymphocyte infusion: Proof of principle
Authors: Hägglund Hans , Yavuz Akif Selim , Dreimane Arta , Malm Claes , Sundin Anders , Sander Birgitta , Nilsson Gunnar 
Published: October 2020

AbstractAdvanced systemic mastocytosis is a relatively rare entity where allogeneic stem cell transplantation can lead to the cure of the disease in selected patients. Delayed incomplete responses with graft‐versus‐mastocytosis effect were published in a few cases. In this particular patient's report, we describe the direct evidence and potency of graft‐versus‐mastocytosis effect of donor lymphocyte infusions in a patient with systemic mastocytosis with associated hematological neoplasm (SM‐AHN). In a 53‐year‐old female patient, an allogeneic stem cell transplantation after conventional induction treatment was performed for transformed acute myeloid leukemia (AML) during the course of polycythemia vera. After 6 years of remission period of AML and PV, the patient developed aleukemic mast cell leukemia and JAK2‐positive myeloproliferative neoplasm (SM‐AHN). We were able to achieve a sustained complete remission of SM‐AHN lasting for 6 years with only donor lymphocyte infusions in a status of mixed chimerism. The patient is in a good clinical condition and remission. The potent graft‐versus‐mastocytosis effect in this patient resembles the favorable effect of donor lymphocyte infusions in relapsing chronic myeloid leukemia patients after transplantation. This patient is, to our knowledge, the first case showing the proof of principle of graft‐versus‐mastocytosis effect.
Constraint‐induced movement therapy promotes motor recovery after neonatal stroke in the absence of neural precursor activation
Authors: Adams Kelsey V. , Mahmud Neemat , Green‐Holland Madeline , Vonderwalde Ilan , Umebayashi Daisuke , Sachewsky Nadia , Coles Brenda L. , van der Kooy Derek , Morshead Cindi M. 
Published: October 2020

AbstractNeonatal stroke is a leading cause of long‐term disability and currently available rehabilitation treatments are insufficient to promote recovery. Activating neural precursor cells (NPCs) in adult rodents, in combination with rehabilitation, can accelerate functional recovery following stroke. Here, we describe a novel method of constraint‐induced movement therapy (CIMT) in a rodent model of neonatal stroke that leads to improved functional outcomes, and we asked whether the recovery was correlated with expansion of NPCs. A hypoxia/ischemia (H/I) injury was induced on postnatal day 8 (PND8) via unilateral carotid artery ligation followed by systemic hypoxia. One week and two weeks post‐H/I, CIMT was administered in the form of 3 botulinum toxin (Botox) injections, which induced temporary paralysis in the unaffected limb. Functional recovery was assessed using the foot fault task. NPC proliferation was assessed using the neurosphere assay and EdU immunohistochemistry. We found that neonatal H/I injury alone expands the NPC pool by >2.5‐fold relative to controls. We determined that using Botox injections as a method to provide CIMT results in significant functional motor recovery after H/I. However, CIMT does not lead to enhanced NPC activation or migration into the injured parenchyma in vivo. At the time of functional recovery, increased numbers of proliferating inflammatory cells were found within the injured motor cortex. Together, these findings suggest that NPC activation following CIMT does not account for the observed functional improvement and suggests that CIMT‐mediated modification of the CNS inflammatory response may play a role in the motor recovery.
Transcriptional frontloading contributes to cross‐tolerance between stressors
Authors: Collins Michael , Clark Melody S. , Spicer John I. , Truebano Manuela 
Published: October 2020

AbstractThe adaptive value of phenotypic plasticity for performance under single stressors is well documented. However, plasticity may only truly be adaptive in the natural multifactorial environment if it confers resilience to stressors of a different nature, a phenomenon known as cross‐tolerance. An understanding of the mechanistic basis of cross‐tolerance is essential to aid prediction of species resilience to future environmental change. Here, we identified mechanisms underpinning cross‐tolerance between two stressors predicted to increasingly challenge aquatic ecosystems under climate change, chronic warming and hypoxia, in an ecologically‐important aquatic invertebrate. Warm acclimation improved hypoxic performance through an adaptive hypometabolic strategy and changes in the expression of hundreds of genes that are important in the response to hypoxia. These ‘frontloaded’ genes showed a reduced reaction to hypoxia in the warm acclimated compared to the cold acclimated group. Frontloaded genes included stress indicators, immune response and protein synthesis genes that are protective at the cellular level. We conclude that increased constitutive gene expression as a result of warm acclimation reduced the requirement for inducible stress responses to hypoxia. We propose that transcriptional frontloading contributes to cross‐tolerance between stressors and may promote fitness of organisms in environments increasingly challenged by multiple anthropogenic threats.
New frontiers in translational research: Touchscreens, open science, and the mouse translational research accelerator platform
Authors: Sullivan Jacqueline A. , Dumont Julie R. , Memar Sara , Skirzewski Miguel , Wan Jinxia , Mofrad Maryam H. , Ansari Hassam Zafar , Li Yulong , Muller Lyle , Prado Vania F. , Prado Marco A. M. , Saksida Lisa M. , Bussey Timothy J. 
Published: October 2020

AbstractMany neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high‐level cognitive functions including memory, attention, motivation, and decision‐making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state‐of‐the‐art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is centered on the touchscreen cognitive testing system for rodents. It integrates touchscreen‐based tests of high‐level cognitive assessment with state‐of‐the art neurotechnology to record and manipulate molecular and circuit level activity in vivo in animal models during human‐relevant cognitive performance. The platform also is integrated with two Open Science platforms designed to facilitate knowledge and data‐sharing practices within the rodent touchscreen community, touchscreencognition.org and mousebytes.ca. Touchscreencognition.org includes the Wall, showcasing touchscreen news and publications, the Forum, for community discussion, and Training, which includes courses, videos, SOPs, and symposia. To get started, interested researchers simply create user accounts. We describe the origins of the touchscreen testing system, the novel lines of research it has facilitated, and its increasingly widespread use in translational research, which is attributable in part to knowledge‐sharing efforts over the past decade. We then identify the unique features of MouseTRAP that stand to potentially revolutionize translational research, and describe new initiatives to partner with similar platforms such as McGill's M3 platform (m3platform.org).
Ethnic identity and local government responsiveness in Taiwan
Authors: Newland Sara A. , Liu John Chung‐En 
Published: October 2020

AbstractCountless studies have shown that local officials are less responsive to ethnic minority citizens. Surprisingly, we find no similar pattern of discrimination by Taiwanese local officials. In an online contacting experiment, we send citizen service requests to the websites of 358 township and district chiefs, randomly varying the name of the putative citizen to reflect an indigenous or an ethnically Chinese identity and collecting data on officials' responses. We find that officials are equally responsive to both identities. Drawing on in‐depth interviews and nonparticipant observation in government service centers, we attribute this surprising finding to institutional elements of Taiwan's local bureaucracy that limit the impact of individual‐level bias. However, our research provides preliminary evidence that local governments are generally less responsive in indigenous areas. While clearly defined procedures may prevent discrimination against indigenous individuals, interregional differences in local state capacity can nonetheless produce unequal experiences with local governance.
3D gait analysis, haemophilia joint health score, leg muscle laterality and biomarkers of joint damage: A cross‐sectional comparative assessment of haemophilic arthropathy
Authors: Putz Peter , Durstberger Sebastian , Kaufmann Christina , Klinger Meike , Plessl Kerstin , Rejtö Judit , Widhalm Klaus , Male Christoph , Pabinger Ingrid 
Published: October 2020

AbstractIntroduction3D gait analysis has been proposed as a reproducible and valid method to assess abnormal gait patterns and to monitor disease progression in patients with haemophilia (PWH).AimThis study aimed at comparing Gait Deviation Index (GDI) between adult PWH and healthy controls, and at assessing the agreement between outcome measures of haemophilic arthropathy.MethodsMale PWH aged 18‐49 years (prespecified subgroups: 18‐25 vs 26‐49 years) on prophylactic replacement therapy, and male healthy age‐matched controls passed through a cross‐sectional assessment panel. Besides the 3D gait analysis derived GDI, secondary outcomes included kinematic, kinetic and spatio‐temporal gait parameters, the Haemophilia Joint Health Score (HJHS), electric impedance derived leg muscle laterality and inflammatory biomarkers.ResultsPatients with haemophilia (n = 18) walked slower, in shorter steps and accordingly with less functional range of motion in the hips and ankles, as compared to healthy controls (n = 24). Overall, PWH did not differ significantly in GDI and specific gait parameters. PWH had a higher mean HJHS (18.8 vs 2.6, P = .000) and leg muscle laterality (4.3% vs 1.5%, P = .004). A subgroup analysis revealed progressed gait pathology in PWH aged 26‐49 years (not statistically significant). Leg muscle laterality was strongly correlated with HJHS (r = .76, P = .000), whereas GDI just moderately (r = −.39, P = .110). PWH had higher levels of the inflammatory markers CRP and IL‐6.ConclusionProgressed gait pathology was found in PWH, mainly those aged 26‐49 years. Leg muscle laterality correlated strongly with HJHS and was identified as a promising tool for detecting progression and physiological consequences of haemophilic joint arthropathy.
No “Wearing‐Off Effect” Seen in Quarterly or Monthly Dosing of Fremanezumab: Subanalysis of a Randomized Long‐Term Study
Authors: Blumenfeld Andrew M. , Stevanovic Darko M. , Ortega Mario , Cohen Joshua M. , Seminerio Michael J. , Yang Ronghua , Jiang Bo , Tepper Stewart J. 
Published: October 2020

ObjectiveTo evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy toward the end of the dosing interval (wearing‐off effect).BackgroundThe main goals of migraine preventive treatment are to reduce the frequency, severity, and duration of migraine attacks, and migraine‐associated disability. Wearing‐off refers to the phenomenon whereby clinical symptoms return or worsen before the next dose of a drug is due and has been reported previously with migraine preventive medications.Design and MethodsThis was a long‐term, 12‐month, multicenter, randomized, double‐blind, parallel‐group phase 3 study (NCT02638103) that included chronic (CM) and episodic migraine (EM) patients who rolled over from the 12‐week phase 3 HALO CM (NCT02621931) and EM trials (NCT02629861), as well as an additional subset of 312 new patients. Patients with CM or EM received fremanezumab either monthly or quarterly. In this post hoc analysis, for selected months, the difference in the average number of migraine days between weeks 1‐2 and weeks 3‐4, between weeks 1‐3 and week 4, and between weeks 1‐2 and weeks 11‐12 were calculated.ResultsA total of 1890 patients (CM, 1110; EM, 780) were enrolled. At months 3, 6, 9, and 15, there were no substantial differences in mean weekly migraine days between weeks 1‐2 and weeks 3‐4 or between weeks 1‐3 and week 4 with quarterly or monthly fremanezumab in the CM or EM subgroups. There were no substantial increases in mean weekly migraine days between weeks 1‐2 and weeks 11‐12 during the first quarter of treatment (months 1‐3) or the second quarter of treatment (months 4‐6) with quarterly or monthly fremanezumab in the CM or EM subgroups. Across both dosing subgroups in CM and EM patients, the mean weekly number of migraine days decreased substantially (30%‐42%) during the first 2 weeks; decreases in weekly migraine days remained steady during the last 2 weeks of the first quarter, with a similar maintenance of response during the second quarter.ConclusionsThis analysis of data from a long‐term, phase 3 study showed that patients receiving quarterly fremanezumab or monthly fremanezumab did not experience a wearing‐off effect toward the end of the dosing interval.
Phenotypic divergence in two sibling species of shorebird: Common Snipe and Wilson’s Snipe (Charadriiformes: Scolopacidae)
Authors: Rodrigues Tiago M. , Miller Edward H. , Drovetski Sergei V. , Zink Robert M. , Fjeldså Jon , Gonçalves David 
Published: October 2020

Natural and social selection are among the main shapers of biological diversity but their relative importance in divergence remains understudied. Additionally, although neutral evolutionary processes may promote phenotypic divergence, their potential contribution in speciation is often overlooked in studies of comparative morphology. In this study, we investigated phenotypic differentiation in two allopatric shorebirds: the Palaearctic Common Snipe Gallinago gallinago and the Nearctic Wilson's Snipe Gallinago delicata. Specimens of Common Snipe (n = 355 skins, n = 163 skeletons) and Wilson's Snipe (n = 403 skins, n = 141 skeletons) in natural history collections were examined to quantify differences in skeletal and external measurements, and measures of wing and tail plumage variables. The species do not differ in skeletal variables except for the relatively larger sternum of the Common Snipe. The two species do not differ in multivariate wing size or shape (pointedness). Previously known plumage differences between these species were confirmed: the Common Snipe has fewer rectrices, longer and wider outermost rectrices, more extensive white on tips of the secondary feathers, and more white in the axillaries. Between‐species variance in skeleton, primary length and plumage variables was greater than expected if drift was mainly responsible for phenotypic divergence, suggesting a role of selective processes. However, drift could not be rejected after adjusting for multiple comparisons. Differences in plumage traits were greater than in skeletal or external measurements. Because snipe use plumage traits in signalling, the results suggest a more rapid divergence in socially selected traits between these species than in traits related to resource use.
Cytomegalovirus in inflammatory bowel disease: a clinical approach
Authors: Gilmore Robert B. , Taylor Kirstin M. , Morrissey C. Orla , Gardiner Bradley J. 
Published: October 2020

AbstractCytomegalovirus (CMV) infection can be a challenging clinical problem in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis. Clinical presentation is difficult to distinguish from an underlying disease flare. Several diagnostic modalities are now available and when combined can aid clinicians in the identification of patients who are most likely to benefit from antiviral therapy. The aim of this article is to review the available literature and outline a practical approach to the diagnosis and management of CMV in patients with IBD.
Inpatient usage of faecal calprotectin in a tertiary hospital
Authors: Barnes Alex , Spizzo Paul , Mountifield Réme 
Published: October 2020

AbstractBackgroundFaecal calprotectin (FCP) is a highly sensitive non‐invasive marker of intestinal inflammation that has evidence‐based roles in outpatient diagnosis and management of inflammatory bowel disease.AimsTo examine indications for FCP in a tertiary inpatient population and its role in inpatient management and subsequent investigations.MethodsAn electronic database was used to identify all patients over the age of 18 years who had FCP performed during a hospital admission over a 3‐year period from March 2016 to the end of March 2019. Electronic records and case notes were reviewed with follow up to March 2020, seeking indication for testing, healthcare units requesting, and subsequent investigations and treatment resulting from FCP.ResultsOver a 3‐year period, 111 FCP inpatient results were identified. There were three changes in management based on the FCP result that led to further investigations that did not lead to any clinically significant pathology. There was no observable difference in the number of colonoscopies performed based on FCP level. The numerical FCP value was associated with clinically significant findings on colonoscopy. Negative predictive value of FCP level (≤50 μg/g) for clinically significant finding on colonoscopy was 64%.ConclusionNon‐guideline‐based hospital inpatient usage of FCP rarely changes inpatient management and had no observable difference in the usage of subsequent diagnostic colonoscopy. Regardless, the FCP level remained a strong predictor of clinically significant pathology on colonoscopy.
Improved prediction of HLA antigen presentation hotspots: Applications for immunogenicity risk assessment of therapeutic proteins
Authors: Attermann Anders Steenholdt , Barra Carolina , Reynisson Birkir , Schultz Heidi Schiøler , Leurs Ulrike , Lamberth Kasper , Nielsen Morten 
Published: October 2020

SummaryImmunogenicity risk assessment is a critical element in protein drug development. Currently, the risk assessment is most often performed using MHC‐associated peptide proteomics (MAPPs) and/or T‐cell activation assays. However, this is a highly costly procedure that encompasses limited sensitivity imposed by sample sizes, the MHC repertoire of the tested donor cohort and the experimental procedures applied. Recent work has suggested that these techniques could be complemented by accurate, high‐throughput and cost‐effective prediction of in silico models. However, this work covered a very limited set of therapeutic proteins and eluted ligand (EL) data. Here, we resolved these limitations by showcasing, in a broader setting, the versatility of in silico models for assessment of protein drug immunogenicity. A method for prediction of MHC class II antigen presentation was developed on the hereto largest available mass spectrometry (MS) HLA‐DR EL data set. Using independent test sets, the performance of the method for prediction of HLA‐DR antigen presentation hotspots was benchmarked. In particular, the method was showcased on a set of protein sequences including four therapeutic proteins and demonstrated to accurately predict the experimental MS hotspot regions at a significantly lower false‐positive rate compared with other methods. This gain in performance was particularly pronounced when compared to the NetMHCIIpan‐3.2 method trained on binding affinity data. These results suggest that in silico methods trained on MS HLA EL data can effectively and accurately be used to complement MAPPs assays for the risk assessment of protein drugs.
Coupling distinct MOLP interactive approaches with a novel DEA hybrid model
Authors: Henriques Carla , Luque Mariano , Marcenaro‐Gutierrez Oscar 
Published: October 2020

AbstractWe propose a modelling framework which allows considering different priorities and individual expansion and contraction scales for distinct types of inputs and outputs, through the Weighted Russell Directional Distance Model (WRDDM). An equivalence model between the WRDDM and the super‐ideal point model has also been established, which is then incorporated into several interactive Multiobjective Linear Programming (MOLP) approaches. The use of these diverse interactive methodologies allows obtaining the benchmark Decision Making Units (DMUs) which best suit the decision maker's (DM) preferences. This feature can be useful since traditional Data Envelopment Analysis (DEA) models tend to completely neglect the DM's preferences and value judgements in the computation of the DMUs used as a reference of best practices. Therefore, with this tool the DMs have the possibility of translating into the decision‐making process management constraints (namely, budgetary) and aspiration levels regarding the inputs and outputs, providing much more realistic support for actual decision‐making.
The association between mindfulness and health promotion in undergraduate nursing students: A serial multiple mediator analysis
Authors: Rababah Jehad A. , Al‐Hammouri Mohammed M. , Drew Barbara L. 
Published: October 2020

AbstractAimThis study was conducted to examine the association between mindfulness and health promotion among undergraduate nursing students and explore the mediation effect of certain factors (perceived stress, depressive symptoms, self‐care agency, and impulsivity) on this relationship.DesignCross‐sectional quantitative design.MethodsA total of 195 undergraduate nursing students from a public university in Jordan participated in this study. A demographic questionnaire was used in addition to using well‐established, validated tools to measure health promotion, mindfulness, perceived stress, depressive symptoms, impulsivity, and self‐care agency. Data were collected between March and November 2018. Data were analysed using PROCESS macros.ResultsThe direct association between mindfulness and health promotion was positive but not statistically significant. Simple mediation analysis showed that perceived stress is the only statistically significant mediator (effect = 0.03; 95% CI: LL = 0.008, UL = 0.057). The serial multiple mediator analyses revealed that three combinations of the mediators made the mindfulness effect on health promotion statistically significant; perceived stress and self‐care agency (effect = −0.01, 95% CI: LL = −0.022, UL = −0.01); depressive symptoms and self‐care agency (effect = 0.016, 95% CI: LL = 0.006, UL = 0.03); and perceived stress with depressive symptoms and self‐care agency (effect = 0.006, 95% CI: LL = 0.002, UL = 0.013).ConclusionsThe results of this study add to the literature evidence concerning the mediation role of perceived stress, depressive symptoms, and self‐care agency on the relationship between mindfulness and health promotion among nursing students.ImpactThis study examined the complex relationship between mindfulness and health promotion. There is a mediation effect of nursing students’ perceived stress, depressive symptoms, and self‐care agency on the relationship between mindfulness and health promotion. Researchers interested in designing mindfulness‐based interventions to optimize health promotion of nursing students could benefit from the findings of this study.