bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing the anthelmintic praziquantel to treat psoriasis
Authors: Hao Lihua , Mao Yuancheng , Park Jin , Bae Eun Ju , Park Byung‐Hyun 
Published: August 2021

Background and PurposeThe anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.Experimental ApproachPsoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period.Key ResultsMice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.Conclusion and ImplicationsThese results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
Rift interaction zones and the stages of rift linkage in active segmented continental rift systems
Authors: Kolawole Folarin , Firkins Max C. , Al Wahaibi Thuwaiba S. , Atekwana Estella A. , Soreghan Michael J. 
Published: August 2021

AbstractAlthough much is known about the interaction of faulting and sedimentation within the basins of active segmented continental rift systems, little is known about these processes within the interaction zones of varying geometries that separate the young interacting segments. We address this problem by exploring the non‐volcanic rift interaction zones (RIZ) along the humid, magma‐poor juvenile western branch of the East African Rift System (WB‐EARS). We examine the large‐scale ‘cross‐over’ relief profiles (basin‐to‐basin through‐going profiles extending across RIZs), the spatial patterns of rift‐linking faults (breaching faults), and axial stream morphology. Our results show that: (1) the RIZs are at different stages of their evolution; (2) distinct long‐wavelength 2‐D cross‐over topographic relief shapes, directionality of axial stream flow (sediment routing patterns), and breaching fault patterns characterise RIZs at the various stages of the linkage of interacting rift basins; (3) these stages include unbreached, partially‐breached, recently‐breached, and breached RIZs; (4) deforming RIZs exhibit different styles of directionality of breaching, including a unidirectional (distinct propagator and receiver segments), bi‐directional propagation (both segments act as propagators and receivers), and nucleation and outward propagation of a narrow intra‐RIZ subsidiary rift basin; (5) RIZ breaching is facilitated by overlap rift‐flank deformation, and/or rift tip propagation structures in the form of rift splaying, border fault rotation (rift‐tip rotation), and fault cluster networks and (6) the lateral propagation of breaching faults at the rift tips and flanks, facilitated by localized stress concentrations, is modulated by the extension direction and inherited basement structures. Our findings offer a broader insight into the geometries, structural, and morphological evolution of RIZs, and provide first‐order predictions of the large‐scale sedimentation patterns of humid early‐stage continental rift environments. Our models provide testable hypotheses for linking rift architecture and patterns of early stage sedimentation applicable to ancient rift basins.
The public servant’s role in democracy
Authors: Boyd Brendan , Wesley Jared J. , Rounce Andrea , Levasseur Karine , Caron Isabelle 
Published: August 2021

AbstractThis research note reports on the findings from a survey conducted in partnership with the Institute of Public Administration of Canada (IPAC). Despite robust debate among public administration experts about the role public servants should play in Canadian democracy, there has yet to be a systematic study of how public servants themselves view democracy and their role within it. We ask: What role do public servants play in democracy? The survey questions public servants about their views and contributions to democracy to gain a better understanding of what role they are playing in Canada’s system.
Evi1 upregulates Fbp1 and supports progression of acute myeloid leukemia through pentose phosphate pathway activation
Authors: Mizuno Hideaki , Koya Junji , Masamoto Yosuke , Kagoya Yuki , Kurokawa Mineo 
Published: August 2021

AbstractEvi1 is a transcription factor essential for the development as well as progression of acute myeloid leukemia (AML) and high Evi1 AML is associated with extremely poor clinical outcome. Since targeting metabolic vulnerability is the emerging therapeutic strategy of cancer, we herein investigated a novel therapeutic target of Evi1 by analyzing transcriptomic, epigenetic, and metabolomic profiling of mouse high Evi1 leukemia cells. We revealed that Evi1 overexpression and Evi1‐driven leukemic transformation upregulate transcription of gluconeogenesis enzyme Fbp1 and other pentose phosphate enzymes with interaction between Evi1 and the enhancer region of these genes. Metabolome analysis using Evi1‐overexpressing leukemia cells uncovered pentose phosphate pathway upregulation by Evi1 overexpression. Suppression of Fbp1 as well as pentose phosphate pathway enzymes by shRNA‐mediated knockdown selectively decreased Evi1‐driven leukemogenesis in vitro. Moreover, pharmacological or shRNA‐mediated Fbp1 inhibition in secondarily transplanted Evi1‐overexpressing leukemia mouse significantly decreased leukemia cell burden. Collectively, targeting FBP1 is a promising therapeutic strategy of high Evi1 AML.
The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review
Authors: Burke Joshua Richard , Helliwell Jack , Wong Jason , Quyn Aaron , Herrick Sarah , Jayne David 
Published: August 2021

AbstractAimAnastomotic leak is the most feared complication of gastrointestinal surgery. Mesenchymal stem cell technology is used clinically to promote wound healing; however, the safety and efficacy of this technology on anastomotic healing has yet to be defined. The aim of this study was to investigate whether mesenchymal stem cells confer any benefit when applied to animal models for gastrointestinal anastomotic leak, identify the methodology and how efficacy is assessed.MethodsThe MEDLINE, EMBASE, WebofScience and Cochrane Library databases were interrogated between 1 January1947 to 1 May 2020. All studies where mesenchymal stem cells were applied to laboratory animal leak models to demonstrate a healing effect were considered. All experimental and histological outcomes were examined. Compliance to ARRIVE and current International Consensus was assessed.ResultsA total of 1205 studies were screened. Twelve studies reported on 438 gastrointestinal anastomoses in four species using 11 models; seven in the colon. No studies utilised a model with a known leak rate. Significant variance was observed in histological outcomes with efficacy demonstrated in five out of 12 studies. One study demonstrated a benefit in leak rate. Colorectal studies had a greater median ARRIVE compliance, 60.8% (IQR 63.2–64.5) compared to noncolorectal 45.4% (IQR 43.8–49.0).ConclusionsMesenchymal stem cell delivery to an animal anastomosis is safe and feasible. Use may confer benefit but findings are currently limited to surrogate histological outcomes. There is consistency in outcome measures reported but variance in how this is assessed. Poor compliance to ARRIVE but good compliance to current international consensus in leak models of the colon was observed.
Normothermic with or without hypothermic oxygenated perfusion for DCD before liver transplantation: European multicentric experience
Authors: Maroni Lorenzo , Musa Nicola , Ravaioli Matteo , Dondossola Daniele Eliseo , Germinario Giuliana , Sulpice Laurent , Cescon Matteo , Rossi Giorgio Ettore , Boudjema Karim 
Published: August 2021

AbstractGrafts from donors with cardiac death (DCD) are subject to warm ischemia time (WIT) due to the no‐touch‐period (20 min in Italy and 5 min in France). These livers (LT) have higher rates of early allograft dysfunction (EAD), primary non‐function (PNF), and ischemic cholangiopathy (IC) compared to LT from brain dead donors (DBD). Normothermic regional perfusion (NRP) is a beneficial strategy to mitigate organ damage; a further approach is the application of ex vivo hypothermic oxygenated perfusion (HOPE) after cold storage (CS). We retrospectively analyzed LTs performed from 2016 to 2019 at three transplant centers using NRP‐DCD grafts: Bologna and Milan treated with HOPE (group A), Rennes preserved using CS (group B). No‐flow period, total and functional WIT were significantly higher in group A than in group B (30.5±7.7 vs. 20.5±4.1; 56.5±20.4 vs. 39.1±21.6; 41.9±12.5 vs. 25.5±3.7; respectively, P < .05), without differences in the postoperative course. In particular, the two groups had similar rates of EAD (21.1% vs. 25.0%), PNF (5.3% vs. 6.3%), IC (0% vs. 12.5%, P = .112), and non‐IC biliary complications (0% vs. 6.3%, P = .457), re‐LT (10.5% vs.12.5%). This occurred despite a high rate of UK DCD risk score > 10 (63.2% A vs. 17.6% B, P = .000), which theoretically would make a large number of these transplants “futile.” In conclusion, Italian and French groups had similar post‐LT outcomes, probably related to the use of HOPE after CS in the case of long WIT.
How can we better inform our patients about post‐heart transplantation survival? A conditional survival analysis
Authors: Clerkin Kevin J. , Griffin Jan M. , Fried Justin A. , Raikhelkar Jayant , Jain Rashmi , Topkara Veli K , Habal Marlena V. , Latif Farhana , Restaino Susan , Colombo Paolo C. , Takeda Koji , Naka Yoshifumi , Farr Maryjane A. , Sayer Gabriel , Uriel Nir 
Published: August 2021

AbstractBackgroundConditional survival (CS) is a dynamic method of survival analysis that provides an estimate of how an individual's future survival probability changes based on time post‐transplant, individual characteristics, and post‐transplant events. This study sought to provide post‐transplant CS probabilities for heart transplant recipients based on different prognostic variables and provide a discussion tool for the providers and the patients.MethodsAdult heart transplant recipients from January 1, 2004, through October 18, 2018, were identified in the UNOS registry. CS probabilities were calculated using data from Kaplan‐Meier survival estimates.ResultsCS probability exceeded actuarial survival probability at all times post‐transplant. Women had similar short‐term, but greater long‐term CS than men at all times post‐transplant (10‐year CS 1.8‐11.5% greater [95% CI 1.2–12.9]). Patients with ECMO or a surgical BiVAD had decreased survival at the time of transplant, but their CS was indistinguishable from all others by 1‐year post‐transplant. Rejection and infection requiring hospitalization during the first year were associated with a persistently decreased CS probability.ConclusionsIn this study, we report differential conditional survival outcomes based on time, patient characteristics, and clinical events post‐transplant, providing a dynamic assessment of survival. The survival probabilities will better inform patients and clinicians of future outcomes.
Individual‐resource network between Xylocopa bees and plant resources: generalist species, specialist individuals?
Authors: Araújo Thayane Nogueira , Pires Luís Paulo , Meireles Desirée Ayume Lopes , Augusto Solange Cristina 
Published: August 2021

1. The resource partitioning hypothesis states that sympatric, morphologically, and functionally similar species can coexist by temporal separation or low food overlap. Also, the interindividual variations about the use of resources, i.e. individual specialisation, can promote the resilience and stability of their populations when an environmental disturbance affects food availability.2. Two sympatric and polylectic species of carpenter bees to test both the hypotheses of food niche partitioning and the occurrence of individual specialisation were used.3. The study was conducted in two Brazilian Savanna areas and the trophic niches of Xylocopa grisescens and X. frontalis were determined by the diversity of pollen types obtained from larval food samples. Individual‐resource networks were constructed to elucidate the patterns of resource use by the individuals of each species.4. The populations of the two bee species moderately overlapped their trophic niche. Xylocopa grisescens mainly used the pollen of non‐poricidal plants, whereas X. frontalis used pollen from plants with poricidal anthers. Individual‐resource networks of both species are weakly connected, highly specialised, and modular.5. In conclusion, the results suggest that the coexistence between Xylocopa grisescens and X. frontalis probably occurs due to food resource partitioning. Furthermore, the results about individual‐resource networks of both species seem to reveal the occurrence of interindividual variations regarding food resource foraging.
A single prenatal lipopolysaccharide injection has acute, but not long‐lasting, effects on cerebral kynurenine pathway metabolism in mice
Authors: Notarangelo Francesca M. , Schwarcz Robert 
Published: August 2021

AbstractIn rodents, a single injection of lipopolysaccharide (LPS) during gestation causes chemical and functional abnormalities in the offspring. These effects may involve changes in the kynurenine pathway (KP) of tryptophan degradation and may provide insights into the pathophysiology of psychiatric diseases. Using CD1 mice, we examined acute and long‐term effects of prenatal LPS treatment on the levels of kynurenine and its neuroactive downstream products kynurenic acid (KYNA), 3‐hydroxykynurenine (3‐HK) and quinolinic acid. To this end, LPS (100 μg/kg, i.p.) was administered on gestational day 15, and KP metabolites were measured 4 and 24 h later or in adulthood. After 4 h, kynurenine, KYNA and 3‐HK levels were elevated in the fetal brain, 3‐HK and KYNA levels were increased in the maternal plasma, and kynurenine was increased in the maternal brain, whereas no changes were seen in the placenta. These effects were less prominent after 24 h, and prenatal LPS did not affect the basal levels of KP metabolites in the forebrain of adult animals. In addition, a second LPS injection (1 mg/kg) in adulthood in the offspring of prenatally saline‐ and LPS‐treated mice caused a similar elevation in 3‐HK levels in both groups after 24 h, but the effect was significantly more pronounced in male mice. Thus, acute immune activation during pregnancy has only short‐lasting effects on KP metabolism and does not cause cerebral KP metabolites to be disproportionally affected by a second immune challenge in adulthood. However, prenatal KYNA elevations still contribute to functional abnormalities in the offspring.
Calibrating rhythmic stimulation parameters to individual electroencephalography markers: The consistency of individual alpha frequency in practical lab settings
Authors: Janssens Shanice E. W. , Sack Alexander T. , Ten Oever Sanne , de Graaf Tom A. 
Published: August 2021

AbstractRhythmic stimulation can be applied to modulate neuronal oscillations. Such ‘entrainment’ is optimized when stimulation frequency is individually calibrated based on magneto/encephalography markers. It remains unknown how consistent such individual markers are across days/sessions, within a session, or across cognitive states, hemispheres and estimation methods, especially in a realistic, practical, lab setting. We here estimated individual alpha frequency (IAF) repeatedly from short electroencephalography (EEG) measurements at rest or during an attention task (cognitive state), using single parieto‐occipital electrodes in 24 participants on 4 days (between‐sessions), with multiple measurements over an hour on 1 day (within‐session). First, we introduce an algorithm to automatically reject power spectra without a sufficiently clear peak to ensure unbiased IAF estimations. Then we estimated IAF via the traditional ‘maximum’ method and a ‘Gaussian fit’ method. IAF was reliable within‐ and between‐sessions for both cognitive states and hemispheres, though task‐IAF estimates tended to be more variable. Overall, the ‘Gaussian fit’ method was more reliable than the ‘maximum’ method. Furthermore, we evaluated how far from an approximated ‘true’ task‐related IAF the selected ‘stimulation frequency’ was, when calibrating this frequency based on a short rest‐EEG, a short task‐EEG, or simply selecting 10 Hz for all participants. For the ‘maximum’ method, rest‐EEG calibration was best, followed by task‐EEG, and then 10 Hz. For the ‘Gaussian fit’ method, rest‐EEG and task‐EEG‐based calibration were similarly accurate, and better than 10 Hz. These results lead to concrete recommendations about valid, and automated, estimation of individual oscillation markers in experimental and clinical settings.
The prevalence of anxiety in adult‐onset isolated dystonia: A systematic review and meta‐analysis
Authors: Medina Escobar Alex , Martino Davide , Goodarzi Zahra 
Published: August 2021

AbstractBackground and purposeClinically relevant anxiety and anxiety disorders are commonly associated with adult‐onset isolated dystonia, contributing substantially to quality‐of‐life impairment in patients with this movement disorder. However, the prevalence of anxiety symptoms and disorders in adult‐onset isolated dystonia remains unclear. We aimed to conduct a systematic review and meta‐analysis of the prevalence of anxiety symptoms/disorders in adult‐onset isolated dystonia.MethodsStudies reporting the prevalence of anxiety disorders determined through diagnostic interviews or from clinically relevant anxiety symptoms detected with rating scales were identified in three databases (MEDLINE, EMBASE and PsycINFO). The gray literature was also examined to detect studies not captured through the search strategy.ResultsThe search strategy yielded 6535 citations; 34 studies met the inclusion criteria. The overall prevalence of clinically relevant anxiety symptoms and anxiety disorders for cervical dystonia was 40% (95% confidence interval [CI] 20% to 60%); for studies examining cranial dystonia it was 25% (95% CI 21% to 30%); for studies exploring mixed populations of adult‐onset isolated dystonia it was 33.3% (95% CI 22% to 43%), 26% (95% CI 12% to 40%) for laryngeal dystonia, and 32% (95% CI 21% to 43%) for upper limb dystonia. Social phobia was the most prevalent anxiety disorder across the different forms of adult‐onset isolated dystonia. Between‐study statistical heterogeneity was high for most prevalence estimates.ConclusionsClinically relevant anxiety and anxiety disorders are common across all forms of adult‐onset isolated dystonia. New research avenues should explore and plan the development of pathways of care targeting these important non‐motor features.
Development and initial validation of a patient‐centered stroke outcome measure in young stroke survivors
Authors: Kodumuri Nishanth , Edmunds Amy , Seidel Amy , Fleming Phil , Vezzetti Alexandra , Mascari Rachel , Kothari Ravish , Lowe Justin , Sen Souvik 
Published: August 2021

AbstractBackground and purposeThis study was undertaken to develop a patient‐centered stroke outcome measure and initial validation of the proposed Young Stroke Questionnaire (YSQ).MethodsThis study assessed the reliability and discriminant validity of the YSQ. The initial questionnaire evolved from a focus group comprised of six young stroke survivors and six stroke neurologists centralized around four patient‐centered domains. To determine the reliability and discriminant validity of the YSQ, 100 young stroke survivors were recruited and provided consent. Standardized clinical assessments completed included the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, and Stroke Impact Scale. Additionally, all patients were asked to complete the patient‐centered YSQ.ResultsOf the 100 enrolled patients in the study (mean age ± standard deviation = 49 ± 11.3, 58% females, 53% African American, 44% White), Cronbach alpha for all domains was >0.7. Moreover, Cronbach alpha for entire questionnaire was >0.9, indicating that the scale, with four subdomains, is internally consistent and reproducible. Discriminant validity of the scale was assessed by comparing the means of each subdomain of the YSQ among healthy subjects to the groups of stroke patients as defined by the mRS. The YSQ was able to differentiate subjects with good outcome (mRS = 0–1) from subjects with varying degree of disability as defined by the mRS (p = 0.026).ConclusionsStandardized clinical assessments are not sensitive to disabilities in young stroke survivors. When compared to standardized clinical assessments, the YSQ is significantly capable of differentiating the young survivor perspective of the impact of stroke in all four subdomains.
Enhancement of ecosystem carbon uptake in a dry shrubland under moderate warming: The role of nitrogen‐driven changes in plant morphology
Authors: Liberati Dario , Guidolotti Gabriele , de Dato Giovanbattista , De Angelis Paolo 
Published: August 2021

AbstractNet ecosystem CO2 exchange is the result of net carbon uptake by plant photosynthesis and carbon loss by soil and plant respiration. Temperature increases due to climate change can modify the equilibrium between these fluxes and trigger ecosystem‐climate feedbacks that can accelerate climate warming. As these dynamics have not been well studied in dry shrublands, we subjected a Mediterranean shrubland to a 10‐year night‐time temperature manipulation experiment that analyzed ecosystem carbon fluxes associated with dominant shrub species, together with several plant parameters related to leaf photosynthesis, leaf morphology, and canopy structure. Under moderate night‐time warming (+0.9°C minimum daily temperature, no significant reduction in soil moisture), Cistus monspeliensis formed shoots with more leaves that were relatively larger and denser canopies that supported higher plant‐level photosynthesis rates. Given that ecosystem respiration was not affected, this change in canopy morphology led to a significant enhancement in net ecosystem exchange (+47% at midday). The observed changes in shoot and canopy morphology were attributed to the improved nutritional state of the warmed plants, primarily due to changes in nitrogen cycling and higher nitrogen resorption efficiency in senescent leaves. Our results show that modifications in plant morphology triggered by moderate warming affected ecosystem CO2 fluxes, providing the first evidence for enhanced daytime carbon uptake in a dry shrubland ecosystem under experimental warming.