bluuebunny/crossref_metadata_2025 huggingface dataset:
Young Adults’ Vaping, Readiness to Quit, and Recent Quit Attempts: The Role of Co-use With Cigarettes and Marijuana
Authors: Berg Carla J , Duan Xuejing , Romm Katelyn , Pulvers Kim , Le Daisy , Ma Yan , Krishnan Nandita , Abroms Lorien C , Getachew Betelihem , Henriksen Lisa
Published: December 2020

Introduction

E-cigarette cessation intervention research is limited. Young adult e-cigarette use and cessation is particularly nuanced, given various user profiles (ie, polytobacco use, co-use with marijuana) warranting different intervention approaches.

Methods

The current study is an analysis of baseline survey data (collected September–December 2018) among 1133 young adult (aged 18–34) e-cigarette users in a 2-year longitudinal study. We examined (1) e-cigarette user profiles (ie, e-cigarette only; e-cigarette/other tobacco; e-cigarette/marijuana; e-cigarette/other tobacco/marijuana) and (2) correlates of readiness to quit e-cigarette use in the next 6 months and past-year e-cigarette quit attempts.

Results

In this sample (Mage = 23.91, 47.3% male, 35.5% sexual minority, 75.2% White, 13.7% Hispanic), e-cigarette user profiles were as follows: 16.8% e-cigarettes-only, 23.4% e-cigarette/other tobacco, 18.0% e-cigarette/marijuana, and 41.8% e-cigarette/other tobacco/marijuana. Multinomial logistic regression (referent: e-cigarette-only use) indicated that all polyuse groups were more likely to use high-nicotine e-liquids (containing ≥9 mg of nicotine). Other predictors included e-cigarettes/other tobacco users being older and male; e-cigarettes/marijuana users using closed systems; and e-cigarettes/other tobacco/marijuana users being sexual minority (p’s < .01). Readiness to quit e-cigarettes and past-year quit attempts were reported by 20.8% and 32.3%, respectively. Per multilevel regression, readiness to quit and quit attempts correlated with using fewer days, high-nicotine e-liquids, and closed systems, but not marijuana, as well as being heterosexual and Black (vs White); readiness to quit also correlated with being single; past-year quit attempts correlated with other tobacco use and being Hispanic.

Conclusions

Young adult e-cigarette users demonstrate distinct user profiles and cessation-related experiences that should be considered in developing cessation interventions.

Implications

The vast majority of young adult e-cigarette users use other tobacco products and marijuana. Unfortunately, few reported readiness to quit or attempting quit. Moreover, certain subgroups (eg, sexual/racial/ethnic minorities) are more likely to be ready or attempt to quit, but may not be successful. Vaping cessation interventions must attend to these nuances.
Microsurgical and Tractographic Anatomical Study of Transtemporal-Transchoroidal Fissure Approaches to the Ambient Cistern
Authors: Egemen Emrah , Celtikci Pinar , Dogruel Yücel , Yakar Fatih , Sahinoglu Defne , Farouk Mohamed , Adiguzel Esat , Ugur Hasan Caglar , Coskun Erdal , Güngör Abuzer
Published: December 2020

BACKGROUND

Approaching ambient cistern lesions is still a challenge because of deep location and related white matter tracts (WMTs) and neural structures.

OBJECTIVE

To investigate the white matter anatomy in the course of 3 types of transtemporal-transchoroidal fissure approaches (TTcFA) to ambient cistern by using fiber dissection technique with translumination and magnetic resonance imaging fiber tractography.

METHODS

Eight formalin-fixed cerebral hemispheres were dissected on surgical corridor from the temporal cortex to the ambient cistern by using Klingler's method. The trans-middle temporal gyrus, trans-inferior temporal sulcus (TITS), and trans-inferior temporal gyrus (TITG) approaches were evaluated. WMTs that were identified during dissection were then reconstructed on the Human Connectome Project 1021 individual template for validation.

RESULTS

The trans-middle gyrus approach interrupted the U fibers, arcuate fasciculus (AF), the ventral segment of inferior frontoocipital fasciculus (IFOF), the temporal extensions of the anterior commissure (AC) posterior crura, the tapetum (Tp) fibers, and the anterior loop of the optic radiation (OR). The TITS approach interrupted U fibers, inferior longitudinal fasciculus (ILF), IFOF, and OR. The TITG approach interrupted the U fibers, ILF, and OR. The middle longitudinal fasciculus, ILF, and uncinate fasciculus (UF) were not interrupted in the trans-middle gyrus approach and the AF, UF, AC, and Tp fibers were not interrupted in the TITS/gyrus approaches.

CONCLUSION

Surgical planning of the ambient cistern lesions requires detailed knowledge about WMTs. Fiber dissection and tractography techniques improve the orientation during surgery and may help decrease surgical complications.
Temporary Clipping of the Intracavernous Internal Carotid Artery: A Novel Technique for Proximal Control
Authors: Basma Jaafar , Krisht Khaled M , Lee Paul , Cai Li , Krisht Ali F
Published: December 2020

BACKGROUND

Securing proximal control in complex paraclinoid aneurysm surgery through traditional techniques may be challenging and risky in certain situations. Advancements of anatomical knowledge of the cavernous sinus (CS) and hemostasis have made it more accessible as a surgical option.

OBJECTIVE

To describe the technique of temporary clipping of the horizontal segment of the intracavernous internal carotid artery (IC-ICA) in preparation for permanent clipping of complex paraclinoid aneurysms.

METHODS

Through an extradural pretemporal approach, the lateral wall of the CS is exposed. The dura between the trochlear nerve and V1 is opened, and access is made to the horizontal segment of the IC-ICA. After circumferential dissection, the temporary clip can be introduced to the artery, and the extradural clinoidectomy can be continued under secured proximal control.

RESULTS

Seven patients with complex paraclinoid aneurysms were treated between May 2013 and May 2016 by the senior author. Temporary clipping of the IC-ICA was performed in all cases. Average time to achieve proximal control was 22.6 min (22.6 ± 13.8). One patient developed transient oculomotor palsy postoperatively. There were no other complications.

CONCLUSION

When the exposed clinoidal segment of the internal carotid artery does not offer sufficient proximal space for temporary clipping, the extradural approach can be extended to the horizontal portion of the IC-ICA. In our experience, this technique is a quick, reliable, and safe alternative to the classical modalities of temporary occlusion.
Sodium Fluorescein-Guided Gross Total Resection of Pediatric Exophytic Brainstem Glioma: 2-Dimensional Operative Video
Authors: Markosian Christopher , Mazzola Catherine A , Tomycz Luke D
Published: December 2020

Brainstem gliomas comprise 10% to 20% of pediatric intracranial tumors.
1
Gross total resection is associated with the greatest long-term survival.
1
However, due to the eloquence of surrounding brain tissue, an aggressive resection is not always achievable and can be associated with significant risk.
2
Sodium fluorescein can be used to help differentiate between tumor and normal tissue.
3,4
In this operative video, we demonstrate the step-by-step technique to utilize fluorescence in surgically resecting an exophytic glioma arising from the midbrain in a 16-yr-old male. Technical nuances are highlighted in this operative video, including the use of the YELLOW 560 (Zeiss) filter to differentiate fluorescent tumor from normal tissue as well as strategic splitting of the tentorium to expose the supratentorial component of the tumor. A decrease in motor potentials of the right leg during the case did not translate into neurological worsening postoperatively; at 3-mo follow-up, the patient attests to better strength and coordination on his affected side. In summary, sodium fluorescein can be used as a critical adjunctive tool for successful surgery in the case of a brainstem tumor. Alternatives to this procedure included gross total resection with 5-aminolevulinic acid, subtotal resection with chemotherapy, and active monitoring, but were not chosen due to their limitations in this clinical case.
5-7

 Appropriate patient consent was obtained to perform this procedure and present this clinical case and surgical video for academic purposes.
Integrated Psychosocial Group Treatment: A Randomized Pilot Trial of a Harm Reduction and Preventive Approach for Patients with Chronic Pain at Risk of Opioid Misuse
Authors: Hruschak Valerie , Rosen Daniel , Tierney Megan , Eack Shaun M , Wasan Ajay D , Cochran Gerald
Published: December 2020

Objective

To examine the benefits of an integrated psychosocial group treatment (IPGT) model for patients with chronic pain at risk of opioid misuse.

Design

This study was a small-scale, single-blinded, two-group randomized controlled trial.

Setting

Outpatient.

Subjects

Adults with chronic pain of >3 months’ duration who were currently prescribed opioid medication and were at risk of opioid misuse.

Methods

Patients with chronic pain who were at risk of opioid misuse (n = 30) were randomly assigned to IPGT or treatment as usual. IPGT consists of six group sessions of psychoeducation, motivational interviewing, cognitive behavioral therapy, mindfulness, and peer support. Participants were assessed at baseline, first follow-up at 6 weeks, and a posttreatment follow-up at 9 weeks. Outcomes included feasibility, acceptability, and preliminary efficacy. Data were analyzed with descriptive and multivariate analyses.

Results

All intervention components were delivered to 87% of the participants, and IPGT recipients reported a high level of satisfaction. Results of the multivariate analyses demonstrated nonsignificant improvements in pain severity (β = 0.22, 95% CI: –0.24 to 0.66, P = 0.35). However, we observed significant treatment × time interactions on pain interference (β = 3.32, 95% confidence interval [CI]: 0.01 to 6.65, P = 0.05) and pain catastrophizing (β = 2.74, 95% CI: 0.49 to 4.99, P = 0.02). Lastly, we detected no significant differences in opioid misuse (adjusted odds ratio = 0.69, 95% CI: –0.26 to 1.64, P = 0.16).

Conclusion

This study provides support for the IPGT intervention being acceptable and feasible for delivery in patients with chronic pain at risk of opioid misuse. Efficacy was achieved in pain interference and pain catastrophizing.
Can the ARAT Be Used to Measure Arm Function in People With Cerebellar Ataxia?
Authors: Reoli Rachel , Cherry-Allen Kendra , Therrien Amanda , Keller Jennifer , Leech Kristan , Whitt Abigail Leddy , Bastian Amy
Published: December 2020

Objective

For people with ataxia, there are validated outcome measures to address body function and structure (BFS) impairments and participation; however, no outcome measure exists for upper extremity (UE) activity level in this population. The purpose of this study was to determine whether the action research arm test (ARAT), a measure of UE activity validated for other neurological conditions, might be a useful outcome measure for capturing UE activity limitations in ataxia.

Methods

A total of 22 participants with ataxia were evaluated to assess construct validity of the ARAT; 19 of the participants were included in the interrater reliability assessment. Participants received a neurologic examination and completed a battery of outcome measures, including the ARAT. ARAT performance was video recorded and scored by 4 additional raters.

Results

For construct validity, Spearman rho showed a significant moderate relationship between the ARAT and BSF outcome measures. A small, nonsignificant relationship was noted for the ARAT and the participation measure. For interrater reliability, Spearman rho showed a large, significant relationship among all raters for the ARAT (range = .87–.94). High reliability was demonstrated using the intraclass correlation coefficient ([2,1] = .97).

Conclusion

The ARAT is moderately correlated with ataxia BFS outcome measures, but not with participation scores. The ARAT is a measure of UE activity, which is different from BFS and participation outcome measures. The ARAT was identified to have strong interrater reliability among raters with varying amounts of experience administering the ARAT. Thus, for the ataxic population, the ARAT may be useful for assessing UE activity limitations.

Impact

Ataxia can negatively affect reaching tasks; therefore, it is important to assess UE activity level in people with ataxia. Until this study, no outcome measure had been identified for this purpose.

Lay Summary

People with ataxia may have difficulty with daily tasks that require reaching. The ARAT is an outcome measure that clinicians can use to assess UE activity limitations to help design a treatment program.
Managing Expectations: Instruments Versus Targets
Authors: Angeletos George-Marios , Sastry Karthik A
Published: December 2020

Should policy communications aim at anchoring expectations of the policy instrument (“keep interest rates at zero until date τ”) or of the targeted outcome (“do whatever it takes to bring unemployment down to $y\%$”)? We study how the optimal approach depends on a departure from rational expectations. People have limited depth of knowledge and rationality, or form otherwise distorted beliefs about the behavior of others and the general equilibrium (GE) effects of policy. The bite of this distortion on implementability and welfare is minimized by target-based guidance if and only if GE feedback is strong enough. This offers a rationale for why central banks should shine the spotlight on unemployment when faced with a prolonged liquidity trap, a steep Keynesian cross, or a large financial accelerator.
Who Gets a Second Chance? Effectiveness and Equity in Supervision of Criminal Offenders
Authors: Rose Evan K
Published: December 2020

Most convicted offenders serve their sentences under “community supervision” at home instead of in prison. Under supervision, however, a technical rule violation, such as not paying fees, can result in incarceration. Rule violations account for 25% of prison admissions nationally and are significantly more common among black offenders. I test whether technical rules are effective tools for identifying likely reoffenders and deterring crime and examine their disparate racial impacts using administrative data from North Carolina. Analysis of a 2011 reform reducing prison punishments for technical violations on probation reveals that 40% of rule breakers would go on to commit crimes if spared harsh punishment. The same reform also closed a 33% black-white gap in incarceration rates without substantially increasing the black-white reoffending gap. These effects combined imply that technical rules target riskier probationers overall but disproportionately affect low-risk black offenders. To justify black probationers’ higher violation rate on efficiency grounds, their crimes must be roughly twice as socially costly as that of white probationers. Exploiting the repeat spell nature of the North Carolina data, I estimate a semiparametric competing risks model that allows me to distinguish the effects of particular types of technical rules from unobserved probationer heterogeneity. Rules related to the payment of fees and fines, which are common in many states, are ineffective in tagging likely reoffenders and drive differential effects by race. These findings illustrate the potentially large influence of ostensibly race-neutral policies on racial disparities in the justice system.
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

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 <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P <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

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

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 < 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 < 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

We 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

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

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

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.
Human-Robot Interaction with Robust Prediction of Movement Intention Surpasses Manual Control
Authors: Veselic Sebastijan , Zito Claudio , Farina Dario
Published: December 2020

Designing robotic assistance devices for manipulation tasks is challenging. This work aims at improving accuracy and usability of physical human-robot interaction (pHRI) where a user interacts with a physical robotic device (e.g., a human operated manipulator or exoskeleton) by transmitting signals which need to be interpreted by the machine. Typically these signals are used as an open-loop control, but this approach has several limitations such as low take-up and high cognitive burden for the user. In contrast, a control framework is proposed that can respond robustly and efficiently to intentions of a user by reacting proactively to their commands. The key insight is to include context- and user-awareness in the controller, improving decision making on how to assist the user. Context-awareness is achieved by creating a set of candidate grasp targets and reach-to grasp trajectories in a cluttered scene. User-awareness is implemented as a linear time-variant feedback controller (TV-LQR) over the generated trajectories to facilitate the motion towards the most likely intention of a user. The system also dynamically recovers from incorrect predictions. Experimental results in a virtual environment of two degrees of freedom control show the capability of this approach to outperform manual control. By robustly predicting the user’s intention, the proposed controller allows the subject to achieve superhuman performance in terms of accuracy and thereby usability.
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

Background

Structural 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.

Methods

Regional 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.

Results

The 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.

Conclusion

R2SN provides a novel, reliable, and biologically plausible method to understand human morphological covariance based on structural MRI.

Impact Statement

Imaging 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

Integration 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

Most 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

Disturbances 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

Alzheimer’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

Toxoplasma 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

Plant 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.
Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery
Authors: Karlsson Henry K. , Tuominen Lauri , Helin Semi , Salminen Paulina , Nuutila Pirjo , Nummenmaa Lauri
Published: December 2020

Background

Obesity is a growing burden to health and economy worldwide. Obesity is associated with central μ-opioid receptor (MOR) downregulation, and the interaction between MOR and dopamine D2receptor (D2R) system in the ventral striatum is disrupted among obese subjects. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying subjects undergoing surgical weight loss (bariatric surgery) procedure.

Methods

We recruited 20 healthy non-obese (mean BMI 22) and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability was measured using positron emission tomography (PET) with [11C]carfentanil and [11C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed to obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery.

Results

In the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r= .62) and dorsal caudate (r= .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r= .12) but unaltered association in dorsal caudate (r= .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r= .62) among obese subjects following the surgery-induced weight loss (mean total weight loss 22 %).

Conclusions

Bariatric surgery and concomitant weight loss recovers the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioural interventions for treating obesity.

Clinical Trials Registration

SleevePET2,NCT01373892,http://www.clinicaltrials.gov
APOE4 affects basal and NMDAR mediated protein synthesis in neurons by perturbing calcium homeostasis
Authors: Ramakrishna Sarayu , Jhaveri Vishwaja , Konings Sabine C , Chakraborty Sumita , Holst Bjørn , Schmid Benjamin , Gouras Gunnar K , Freude Kristine K , Muddashetty Ravi S
Published: December 2020

Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans – APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the pre-disposition for Alzheimer’s disease. The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4 induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons to APOE4 leads to a significant decrease in global protein synthesis. APOE4 treatment also abrogates the NMDA mediated translation response indicating an impairment of synaptic signaling. Importantly, we demonstrate that both APOE3 and APOE4 generate a distinct translation response which is closely linked to their respective calcium signature. Acute exposure to APOE3 causes a short burst of calcium through NMDARs in neurons leading to an initial decrease in protein synthesis which quickly recovers. Contrarily, APOE4 leads to a sustained increase in calcium levels by activating both NMDARs and L-VGCCs, thereby causing sustained translation inhibition through eEF2 phosphorylation, which in turn disrupts NMDAR response. Thus, we show that APOE4 affects basal and activity mediated protein synthesis response in neurons by affecting calcium homeostasis. We propose this as a possible mechanism to explain the synaptic dysfunction caused by APOE4.

Highlights / Summary

APOE3 treatment causes a short burst of calcium through NMDARs, leading to an acute increase in eEF2 phosphorylation which eventually recovers to basal levels.

Global translation follows a similar temporal profile of initial inhibition followed by recovery in APOE3 treated neurons, thus unaffecting the NMDA mediated translation response.

APOE4 treatment activates both NMDARs and L-VGCCs leading to a marked elevation in calcium levels, thus causing sustained increase in eEF2 phosphorylation as well as global translation inhibition.

Hence, the NMDA mediated response is perturbed, potentially causing a stress-related phenotype in APOE4 treated neurons.

Thus, different calcium signatures and sources lead to distinct temporal profiles of translation.
Identification of eight SARS-CoV-2 ORF7a deletion variants in 2,726 clinical specimens
Authors: Rosenthal Sun Hee , Kagan Ron M. , Gerasimova Anna , Anderson Ben , Grover David , Hua Michael , Liu Yan , Owen Renius , Lacbawan Felicitas
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF7a, the ortholog of SARS-CoV ORF7a, is a type I transmembrane protein and plays an important role in virus-host interactions. Deletion variants in ORF7a may influence virulence, but only a few such isolates have been reported. Here, we report 8 unique ORF7a deletion variants of 6 to 96 nucleotides in length identified from 2,726 clinical specimens collected in March of 2020.
Macrocybin, a mushroom natural triglyceride, reduces tumor growthin vitroandin vivothrough caveolin-mediated interference with the actin cytoskeleton
Authors: Vilariño Marcos , García-Sanmartín Josune , Ochoa-Callejero Laura , López-Rodríguez Alberto , Blanco-Urgoiti Jaime , Martínez Alfredo
Published: December 2020

Mushrooms have been used for millennia as cancer remedies. Our goal was to screen several species from the rain forest of Costa Rica looking for new antitumor molecules. Mushroom extracts were screened using two human cell lines: A549 (lung adenocarcinoma) and NL20 (immortalized normal lung epithelium). Extracts able to kill tumor cells while preserving nontumor cells were considered “anticancer”. The mushroom with better properties wasMacrocybe titans. Positive extracts were fractionated further and tested for biological activity on the cell lines. The chemical structure of the active compound was partially elucidated through nuclear magnetic resonance, mass spectrometry, and other ancillary techniques. Chemical analysis showed that the active molecule was a triglyceride containing oleic acid, palmitic acid, and a more complex fatty acid with 2 double bonds. Synthesis of all possible triglycerides and biological testing identified the natural compound, which was named Macrocybin. A xenograft study showed that Macrocybin significantly reduces A549 tumor growth. In addition, Macrocybin treatment resulted in the upregulation of Caveolin-1 expression and the disassembly of the actin cytoskeleton in tumor cells (but not in normal cells). In conclusion, we have shown that Macrocybin constitutes a new biologically active compound that may be taken into consideration for cancer treatment.