bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of 18F-fluorodeoxyglucose positron emission tomography to monitor tocilizumab effect on vascular inflammation in giant cell arteritis
Authors: Quinn Kaitlin A. , Dashora Himanshu , Novakovich Elaine , Ahlman Mark A. , Grayson Peter C. 
Published: December 2020

Abstract

Objectives
To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA.

Methods
Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints.

Results
Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); P &lt;0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P &lt;0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse.

Conclusion
Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.
Decreased serum ACE2 levels in patients with connective tissue diseases
Authors: Tang Xiaojun , Geng Linyu , Feng Xuebing , Sun Lingyun 
Published: December 2020

Abstract

Objective
To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs).

Methods
Serum samples from healthy subjects and patients with SLE, systemic sclerosis (SSc), primary Sjögren’s syndrome (SS) and RA were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method, respectively, and analysed for associations with clinical features and concurrent medications.

Results
In total, 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed.

Conclusion
The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggest ACE2 levels are not affected by most of the treatments.
Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS
Authors: Zhao Sizheng Steven , Jones Gareth T , Macfarlane Gary J , Hughes David M , Moots Robert J , Goodson Nicola J 
Published: December 2020

Abstract

Objective
Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and: (i) change in disease indices over time; (ii) binary response definitions; and (iii) time to treatment discontinuation.

Methods
We studied participants starting their first TNFi from a national axSpA register. Comorbidity categories were created from 14 physician-diagnosed conditions and compared against: change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unit reduction) and BASDAI &lt; 4 at 6 months using logistic models; and time to treatment discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.

Results
In total, 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2 comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 [odds ratio (OR) 0.81; 95% CI: 0.45, 1.45] and BASDAI &lt; 4 (OR 0.57; 95% CI: 0.32, 1.04). Treatment discontinuation was increased in those with two comorbidities [hazard ratio (HR) 1.32; 95% CI: 0.88, 2.00] and ≥3 comorbidities (HR 2.18; 95% CI: 1.20, 3.93) compared with none.

Conclusions
Participants with multiple comorbidities had poorer treatment outcomes, particularly increased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidity burden.
Disastrous Defaults
Authors: Gouriéroux Christian , Monfort Alain , Mouabbi Sarah , Renne Jean-Paul 
Published: December 2020

AbstractWe define a disastrous default as the default of a systemic entity. Such an event is expected to have a negative effect on the economy and to be contagious. Bringing macroeconomic structure to a no-arbitrage asset-pricing framework, we exploit prices of disaster-exposed assets (credit and equity derivatives) to extract information on (i) the expected influence of a disastrous default on consumption and (ii) the probability of a financial meltdown. Using European data, we find that the returns of disaster-exposed assets are consistent with a systemic default being followed by a 2% decrease in consumption. The recessionary influence of disastrous defaults implies that financial instruments whose payoffs are exposed to such credit events carry substantial risk premiums. We also produce systemic risk indicators based on the probability of observing a certain number of systemic defaults or a sharp drop of consumption.
Post-implant care pathway: lessons learned and recommendations after 5 years of clinical implementation of hypoglossal nerve stimulation therapy
Authors: Soose Ryan J , Faber Kevin , Greenberg Harly , Boon Maurits , Woodson Tucker , Strollo Patrick 
Published: December 2020

Abstract
Hypoglossal nerve stimulation (HNS) therapy is now an established and widely-available obstructive sleep apnea (OSA) treatment alternative for continuous positive airway pressure (CPAP)-intolerant patients. Additionally, the HNS body of literature is robust with strong data on safety, efficacy, and durability—from the 5-year STAR Trial outcomes, to post-approval studies of independent institutions, to the multicenter ADHERE registry which recently reported outcomes on over 1,000 patients and is poised to enroll 5,000 HNS patients total. Nevertheless, now with thousands of implanted patients across hundreds of certified centers, and that number growing rapidly, the post-implant management of the HNS patient represents the next critical frontier. Post-implant patient management (therapy titration, troubleshooting, adjustments, and adherence monitoring) across a longitudinal care model is key to ensuring long-term therapy success and optimizing patient outcomes and health benefits. As with CPAP, patient education and close clinical monitoring are often essential to successful long-term management. Although many HNS patients are clear responders with excellent comfort and adherence as well as effective improvement in symptomatic and objective outcome measures, and even a smaller subset is clear non-responders, there is a growing body of patients somewhere in the middle: good outcomes but not great; partial but incomplete response. These are the patients in whom a standardized best-practice approach to treatment monitoring and targeted therapy modifications is likely critical to optimizing long-term outcomes.
The Breach of Trust doctrine under Liechtenstein Trust Law and its impact on the preservation and enforcement of beneficiaries’ rights
Authors: Auer Sebastian , Marxer Dominique 
Published: December 2020

Abstract
In a recent decision, the Liechtenstein Supreme Court has clarified which remedies the discretionary beneficiaries of a Liechtenstein trust have or don't have, if a trustee violates his duties under the law or the trust deed. While the Supreme Court has restricted the rights of discretionary beneficiaries in that regard, it has at the same time pointed to alternative means for them to hold the trustee accountable. One of these means is the possibility to claim damages from the trustee for breach of trust. This article analyses the doctrine of a breach of trust under Liechtenstein Trust Law and examines the conditions for and modalities of such claim by which a discretionary beneficiary can hold a trustee personally liable if he is acting in breach of his duties.
Investigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury
Authors: Cao Yanshan , Bairam Ahsan , Jee Alison , Liu Ming , Uetrecht Jack 
Published: December 2020

Abstract
Trimethoprim (TMP)-induced skin rash and liver injury are likely to involve the formation of reactive metabolites. Analogous to nevirapine-induced skin rash, 1 possible reactive metabolite is the sulfate conjugate of α-hydroxyTMP, a metabolite of TMP. We synthesized this sulfate and found that it reacts with proteins in vitro. We produced a TMP-antiserum and found covalent binding of TMP in the liver of TMP-treated rats. However, we found that α-hydroxyTMP is not a substrate for human sulfotransferases, and we did not detect covalent binding in the skin of TMP-treated rats. Although less reactive than the sulfate, α-hydroxyTMP was found to covalently bind to liver and skin proteins in vitro. Even though there was covalent binding to liver proteins, TMP did not cause liver injury in rats or in our impaired immune tolerance mouse model that has been able to unmask the ability of other drugs to cause immune-mediated liver injury. This is likely because there was much less covalent binding of TMP in the livers of TMP-treated mice than TMP-treated rats. It is possible that some patients have a sulfotransferase that can produce the reactive benzylic sulfate; however, α-hydroxyTMP, itself, has sufficient reactivity to covalently bind to proteins in the skin and may be responsible for TMP-induced skin rash. Interspecies and interindividual differences in TMP metabolism may be 1 factor that determines the risk of TMP-induced skin rash. This study provides important data required to understand the mechanism of TMP-induced skin rash and drug-induced skin rash in general.
Regional radiomics similarity networks (R2SN) in the human brain: reproducibility, small-world and biological basis
Authors: Zhao Kun , Zheng Qiang , Che Tongtong , Martin Dyrba , Li Qiongling , Ding Yanhui , Zheng Yuanjie , Liu Yong , Li Shuyu 
Published: December 2020

AbstractBackgroundStructural covariance network (SCN) has been applied successfully to structural magnetic resonance imaging (MRI) study. However, most SCNs were constructed by the unitary marker, which was insensitive for the different disease phases. The aim of this study is to devise a novel regional radiomics similarity network (R2SN) that could provide more comprehensive information in morphological network analysis.MethodsRegional radiomics similarity network (R2SN) was constructed by computing the Pearson correlations between the radiomics features extracted from any pair of regions for each subject. We further assessed the small-world property of R2SN using the graph theory method, as well as the reproducibility in the different datasets and the reliability with test-retest analysis. The relationship between the R2SN and inter-regional co-expression of gene enriched was also explored, as well as the relationship with general intelligence.ResultsThe R2SN can be replicated in different datasets, also regardless of using different feature subsets. The R2SN showed high reliability with the test-retest analysis (ICC>0.7). Besides, the small-word property (σ>2) and the high correlation with the gene expression (R=0.24, P<0.001) and the general intelligence was found by R2SN.ConclusionR2SN provides a novel, reliable, and biologically plausible method to understand human morphological covariance based on structural MRI.Impact StatementImaging biomarkers are the cornerstone of modern radiology, and the development of valid biomarkers is crucial for optimizing individualized prediction in neurological disorders like AD. Thus, the development of the data mining method from neuroimaging is crucial for adding the biomarkers of disease. This study confirmed that R2SN provides a novel, robust and biologically plausible model and a new perspective for understanding the human brain, therefore. Thus, the R2SN has great promise in further study.
VIRUSBreakend: Viral Integration Recognition Using Single Breakends
Authors: Cameron Daniel L. , Papenfuss Anthony T. 
Published: December 2020

AbstractIntegration of viruses into infected host cell DNA can causes DNA damage and can disrupt genes. Recent cost reductions and growth of whole genome sequencing has produced a wealth of data in which viral presence and integration detection is possible. While key research and clinically relevant insights can be uncovered, existing software has not achieved widespread adoption, limited in part due to high computational costs, the inability to detect a wide range of viruses, as well as precision and sensitivity. Here, we describe VIRUSBreakend, a high-speed tool that identifies viral DNA presence and genomic integration recognition tool using single breakend variant calling. Single breakends are breakpoints in which only one side has been unambiguously placed. We show that by using a novel virus-centric single breakend variant calling and assembly approach, viral integrations can be identified with high sensitivity and a near-zero false discovery rate, even when integrated in regions of the host genome with low mappability, such as centromeres and telomeres that cannot be reliably called by existing tools. Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including HPV, HBV, MCPyV, EBV, and HHV-8.
Testing impacts of goal-oriented outreach with the Girl Scouts: Can a single activity change attitudes towards insects?
Authors: Mongue Andrew J. , Colyott Kaila L. 
Published: December 2020

AbstractMost people meet insects with fear and disgust but this reputation is largely unfounded, as few insects pose health risks. In fact, many are beneficial and their absence would adversely affect human life; thus insect conservation is important but unpopular. We have begun addressing these concerns as part of a broader effort to establish an ongoing outreach partnership between graduate students at the University of Kansas and the Girl Scouts of Northeast Kansas/Northwest Missouri. To explore ways to advocate for insect conservation, we held an insect collecting activity at a Girl Scout summer camp and surveyed changes in attitudes towards insects afterwards. This activity positively changed reactions to insect encounters and increased confidence in identifying harmful insects but did not strongly reduce fears or increase curiosity towards insects. Beyond these proximate results, this project highlights the potential of Girl Scout troops as targets for informal science education that can benefit both academics and the broader community.
Serum response factor is essential for synaptic maturation in the hippocampus
Authors: Krysiak Anna , Roszkowska Matylda , Majchrowicz Lena , Beroun Anna , Michaluk Piotr , Nader Karolina , Pekala Martyna , Jaworski Jacek , Kondrakiewicz Ludwika , Puścian Alicja , Knapska Ewelina , Kaczmarek Leszek , Kalita Katarzyna 
Published: December 2020

AbstractDisturbances of gene expression patterns that occur during brain development can severely affect signal transmission, connectivity, and plasticity—key features that underlie memory formation and storage in neurons. Abnormalities at the molecular level can manifest as changes in the structural and functional plasticity of dendritic spines that harbor excitatory synapses. This can lead to such developmental neuropsychiatric conditions as Autism spectrum disorders, intellectual disabilities, and schizophrenia. The present study investigated the role of the major transcriptional regulator serum response factor (SRF) in synapse maturation and its impact on behavioral phenotypes. Usingin vitroandin vivomodels of early postnatal SRF deletion, we studied its influence on key morphological and physiological hallmarks of spine development. The elimination of SRF in developing neurons resulted in a phenotype of immature dendritic spines and impairments in excitatory transmission. Moreover, using a combination of molecular and imaging techniques, we showed that SRF-depleted neurons exhibited a lower level of specific glutamate receptor mRNAs and a decrease in their surface expression. Additionally, the early postnatal elimination of SRF in hippocampal CA1 excitatory neurons caused spine immaturity and a specific social deficit that is frequently observed in autism patients. Altogether, our data suggest that the regulation of structural and functional dendritic spine maturation begins at the stage of gene transcription, which underpins the crucial role of such transcription factors as SRF. Moreover, disturbances of the postnatal expression of SRF translate to behavioral changes in adult animals.
Cognitive and GABAergic protection by hAPPSw,Indand hTauVLWcoexpression: a model of Non-Demented with Alzheimer’s disease Neuropathology
Authors: Dávila-Bouziguet Eva , Casòliba-Melich Arnau , Targa-Fabra Georgina , Galera-López Lorena , Ozaita Andrés , Maldonado Rafael , Delgado-García José M. , Gruart Agnès , Ávila Jesús , Soriano Eduardo , Pascual Marta 
Published: December 2020

ABSTRACTAlzheimer’s disease comprises amyloid-β (Aβ) and hyperphosphorylated Tau (P-Tau) accumulation, imbalanced neuronal activity, aberrant oscillatory rhythms, and cognitive deficits. Non-Demented with Alzheimer’s disease Neuropathology (NDAN) defines a novel clinical entity with Aβ and Tau pathologies, but preserved cognition. The mechanisms underlying such neuroprotection remain undetermined and animal models are currently unavailable for NDAN. We show that J20/VLW mice, accumulating Aβ and P-Tau, exhibit preserved hippocampal rhythmic activity and cognition, altered in J20 and VLW animals. Furthermore, we show that coexistence with Aβ renders a particular P-Tau signature in hippocampal interneurons. The GABAergic septohippocampal pathway, responsible for hippocampal rhythmic activity, is preserved in J20/VLW mice, in contrast to single mutants. Our data highlight J20/VLW mice as a suitable animal model to understand the mechanisms driving cognitive preservation in NDAN and suggest that a differential P-Tau pattern in hippocampal interneurons prevents GABAergic septohippocampal innervation loss and alterations in local field potentials, avoiding cognitive deficits.
Effects of Malaysian strains ofToxoplasma gondiion behaviours and their possible risk in schizophrenia-like rat model
Authors: Wana Mohammed Nasiru , Watanabe Malaika , Chiroma Samaila Musa , Unyah Ngah Zasmy , Abdullahi Sharif Alhassan , Mahdi Onesimus , Alapid Ashraf Ahmad Isa , Nordin Shariza , Basir Rusliza , Moklas Mohamad Aris Mohd , Majid Roslaini Abd. 
Published: December 2020

ABSTRACTToxoplasma gondii(T. gondii) is a protozoan parasite that reside majorly in the brain of its intermediate host.T. gondiiinfected rodent’s shows some degree of behaviour deficits, whileT. gondiiinfection in humans is associated with psychiatric problems such as schizophrenia. The present study aimed to evaluate the effects of Malaysian strains ofT. gondiion rats. Forty five, four weeks old, male Wistar rats were used. The rats were assigned into five groups: two control groups (CG1 and CG2) and three experimental groups (EG1, EG2, EG3). CG1 rats received phosphate buffered saline (PBS), CG2 received MK-801 (as a model for schizophrenia), EG1, EG2, EG3 received orally 5 × 103singleT. gondiioocysts strain of type I, type II and type III respectively. After infection, all the five groups of rats were tested forT. gondiiantibodies at two weeks post-infection (PI). Behavioural tests of exploratory activity (open field) and spatial learning and memory retention (Morris water maze) were performed on the ninth and tenth weeks PI followed by histological staining of rat brain.T. gondiiIgM antibodies were detected in EG1, EG2 and EG3, but not in CG1 and CG2. The behaviour results demonstrated that rats from CG2, EG1, EG2 and EG3 had increased in their locomotor activities and memory deficits compared to control, while learning remain intact. Moreover, tissue cysts were found widely distributed exclusively in the whole brain of EG1, EG2 and EG3 without tropism. These findings taken together, implies that Malaysian strains ofT. gondiiare implicated in some causes of behaviour changes that are responsible for schizophrenia-like conditions if humans were infected.
Convergent evolution of distinct immune sensor systems for fungal polygalacturonases inBrassicaceae
Authors: Zhang Lisha , Hua Chenlei , Pruitt Rory N. , Qin Si , Wang Lei , Albert Isabell , Albert Markus , van Kan Jan A. L. , Nürnberger Thorsten 
Published: December 2020

AbstractPlant pattern recognition receptors (PRRs) facilitate recognition of microbial surface patterns and mediate activation of plant immunity.Arabidopsis thalianaRLP42, a leucine-rich repeat (LRR) receptor protein (LRR-RP), senses fungal endopolygalacturonases (PGs) through a ternary complex comprising RLP42, the adapter kinase SOBIR1, and SERK proteins. Several fungal PGs harbor a conserved 9-amino acid fragment pg9(At), which is sufficient to activate RLP42-dependent plant immunity. Domain swap experiments using RLP42 and paralogous RLP40 sequences revealed a dominant role of the island domain (ID) for ligand binding and PRR complex assembly. Involvement of the ID in plant receptor function is reminiscent of plant phytosulfokine (PSK) perception through the receptor, PSKR, a LRR receptor kinase. Sensitivity to pg9(At), which is restricted toA. thaliana, exhibits notable accession specificity as active RLP42 alleles were found in only 16 of 52 accessions tested.Arabidopsis arenosaandBrassica rapa, twoBrassicaceaespecies closely related toA. thaliana, perceive plant immunogenic PG fragments pg20(Aa) or pg36(Bra), which are distinct from pg9(At). Our study unveils unprecedented complexity and dynamics of PG pattern recognition receptor evolution within a single plant family. PG perception systems may have evolved rather independently as a result of convergent evolution even among closely related species.