bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connexin43 Expression and Associated Chronic Inflammation Presages the Development of Cerebral Radiation Necrosis
Authors: Feldman Lisa A , Haldankar Shewta , O’Carroll Simon J , Liu Karen , Fackelmeier Barbara , Broaddus William C , Anene-Maidoh Tony , Green Colin R , Garbow Joel R , Guan Jian 
Published: May 2020

Abstract
Cerebral radiation necrosis (CRN) is a delayed complication of radiosurgery that can result in severe neurological deficits. The biological changes leading to necrotic damage may identify therapeutic targets for this complication. Connexin43 expression associated with chronic inflammation may presage the development of CRN. A mouse model of delayed CRN was used. The left hemispheres of adult female mice were irradiated with single-fraction, high-dose radiation using a Leksell Gamma Knife. The brains were collected 1 and 4 days, and 1–3 weeks after the radiation. The expression of connexin43, interleukin-1β (IL-1β), GFAP, isolectin B-4, and fibrinogen was evaluated using immunohistochemical staining and image analysis. Compared with the baseline, the area of connexin43 and IL-1β staining was increased in ipsilateral hemispheres 4 days after radiation. Over the following 3 weeks, the density of connexin43 gradually increased in parallel with progressive increases in GFAP, isolectin B-4, and fibrinogen labeling. The overexpression of connexin43 in parallel with IL-1β spread into the affected brain regions first. Further intensified upregulation of connexin43 was associated with escalated astrocytosis, microgliosis, and blood-brain barrier breach. Connexin43-mediated inflammation may underlie radiation necrosis and further investigation of connexin43 hemichannel blockage is merited for the treatment of CRN.
Prognostic Value of Histopathological Features and Loss of H3K27me3 Immunolabeling in Anaplastic Meningioma: A Multicenter Retrospective Study
Authors: Gauchotte Guillaume , Peyre Matthieu , Pouget Celso , Cazals-Hatem Dominique , Polivka Marc , Rech Fabien , Varlet Pascale , Loiseau Hugues , Lacomme Stéphanie , Mokhtari Karima , Kalamarides Michel , Bielle Franck 
Published: May 2020

Abstract
The diagnosis of anaplastic meningioma (AM) (WHO grade III) is based on the presence of a high mitotic index (MI) and/or overt anaplasia. Only few data exist about the reproducibility and prognostic value of overt anaplasia. Additionally, the prognostic value of H3K27me3 loss in AM has not yet been demonstrated. Our objectives were to evaluate the reproducibility and prognostic value of WHO criteria and H3K27me3 loss in a multicenter series of 66 AM. Interobserver reproducibility was good for the determination of WHO grade (Kappa = 0.671) and MI (intraclass correlation coefficient [ICC] = 0.649), and fair for assessment of overt anaplasia (Kappa = 0.366). Patients with meningiomas showing high MI had significantly shorter overall survival (OS) than patients with meningiomas showing overt anaplasia without high MI (p = 0.009). OS was significantly lower in case of overt anaplasia with low MI (&lt;20/1.6 mm2) than in atypical meningiomas (p = 0.008). H3K27me3 loss was present in 10/47 (21%) of AM and independently associated with shorter OS (p = 0.036; Cox multivariate analysis), with a good reproducibility (Kappa = 0.643). In conclusion, the presence of overt anaplasia could give additional prognostic information in tumors lacking high MI. Finally, loss of H3K27me3 is an easy-to-use and reproducible marker of poorer prognosis.
Phase I dose-escalation trial of S-1 combined with carbon-ion radiotherapy for sinonasal squamous cell carcinoma
Authors: Takahashi Daiki , Demizu Yusuke , Park Sung Chul , Matsuo Yoshiro , Sulaiman Nor Shazrina , Terashima Kazuki , Tokumaru Sunao , Akashi Masaya , Okimoto Tomoaki 
Published: May 2020

Abstract
This study aimed to determine the maximum tolerance dose (MTD) and to estimate the recommended dose (RD) of concomitant S-1 with carbon-ion radiotherapy (RT) for sinonasal squamous cell carcinoma (SCC). Nine patients with sinonasal SCC received carbon-ion RT with escalating doses of S-1 according to phase I methods. Doses of 40, 60 and 80 mg/m2/day were administered twice daily in dose levels 1, 2 and 3, respectively, from days 1 to 14 and 22 to 35. Carbon-ion RT was administered at a dose of 70.4 Gy (relative biological effectiveness) in 32 fractions, 5 days a week. Two patients developed grade 3 acute dermatitis. However, none developed dose-limiting toxicities. Therefore, the MTD of S-1 could not be determined; the RD was estimated to be 80 mg/m2/day with concurrent carbon-ion RT. Partial response and stable disease were noted in 5 and 4 patients, respectively. The 2-year overall survival and local control rates were 56 and 74%, respectively. Overall, 2 patients developed ≥grade 3 late toxicities; among them, 1 patient developed grade 3 cataract and the other developed grade 4 cataract, optic nerve disorder and hearing impairment. To the best of our knowledge, this phase I study is the first clinical trial to evaluate concomitant S-1 with carbon-ion RT for sinonasal SCC. The MTD of S-1 could not be determined, and the RD was estimated to be 80 mg/m2/day. This study demonstrated a manageable safety profile for this combination. The observed outcomes may facilitate further evaluation of this novel therapy.
Frontal sinus inverted papilloma managed with Draf III
Authors: Al Mahdi Mohammed Jihad , Asiri Mohammed , Pharaon Majed , Mubark Ali 
Published: May 2020

Abstract
Inverted papilloma (IP) is a rare benign tumor that originates from nasal and paranasal sinus mucosa. Although it is considered a benign lesion, it is locally aggressive and has risk between 7 and 15% for malignant transformation. The management of frontal sinus (FS) IP is still challenging due to its rarity and local invasiveness. We report a rare case of IP originating from FS, and to review the literature to delineate the possible surgical strategy. A 52-year-old male presented with long-standing history of bilateral nasal obstruction and left eye proptosis. Sinus navigation computed tomography showed soft tissue density occupying frontal, ethmoid, right sphenoid sinuses with extension to nasal cavities, postnasal space and left orbital space plus erosive bony changes. Transnasal endoscopic biopsy suggested IP the lesion was completely resected by Draf III procedure. After 1 month of the surgery, the patient is doing well with no complaints.
On the different types of collective attacks in abstract argumentation: equivalence results for SETAFs
Authors: Dvořák Wolfgang , Rapberger Anna , Woltran Stefan 
Published: May 2020

Abstract
Argumentation frameworks with collective attacks are a prominent extension of Dung’s abstract argumentation frameworks, where an attack can be drawn from a set of arguments to another argument. These frameworks are often abbreviated as SETAFs. Although SETAFs have received increasing interest recently, a thorough study on the actual behaviour of collective attacks has not been carried out yet. In particular, the richer attack structure SETAFs provide can lead to different forms of redundant attacks, i.e. attacks that are subsumed by attacks involving less arguments. Also the notion of strong equivalence, which is fundamental in nonmonotonic formalisms to characterize equivalent replacements, has not been investigated for SETAFs so far. In this paper, we first provide a classification of different types of collective attacks and analyse for which semantics they can be proven redundant. We do so for eleven well-established abstract argumentation semantics. We then study how strong equivalence between SETAFs can be decided with respect to the considered semantics and also consider variants of strong equivalence. Our results show that removing redundant attacks in a suitable way provides direct means to characterize strong equivalence by syntactical equivalence of so-called kernels, thus generalizing well-known results on strong equivalence between Dung AFs.
The role of 3′UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization
Authors: Ribeiro Diogo M , Prod’homme Alexis , Teixeira Adrien , Zanzoni Andreas , Brun Christine 
Published: May 2020

Abstract
Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3′UTRs were found to regulate the cellular localization of newly synthesized proteins through the formation of 3′UTR-protein complexes. Here, we investigate the formation of 3′UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3′UTR-protein complexes involving 54% of those proteins and evaluated their role in regulating protein cellular localization and multifunctionality. We find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3′UTR-protein complexes, and that the formation of these complexes could provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Our findings are reinforced by archetypal moonlighting proteins predicted to form 3′UTR-protein complexes. Finally, the formation of 3′UTR-protein complexes that involves up to 17% of the proteins in the human protein-protein interaction network, may be a common and yet underestimated protein trafficking mechanism, particularly suited to regulate the localization of multifunctional proteins.
Residential Stability Versus Residents’ Interactions: The Determinants of Voluntary Participation in Police Block Activity
Authors: Coats Jonathan E 
Published: May 2020

Abstract
This research examines the influence of residential stability and resident’s interactions on participation in police block activity. Community engagement is one approach used by the police to increase the co-production of crime prevention by providing opportunities and engaging the community in group-level informal and voluntary activities. These optional activities are designed to promote a working relationship between the residents and the police. Multilevel ordinal logistic regression was run to estimate participation in police block activity, using the Seattle Neighborhood and Crime Survey data. The results demonstrate two things. First, this study extends the standard variables, used in examining voluntary involvement, to the frequency of participation in police block activity. Secondly, using interaction terms between residential stability and between residents’ interactions, the results suggest that between residents’ interaction may be a better predictor of frequent participation in police block activity than homeownership or length of residency. Finally, policy implications and future research avenues are discussed.
Elevated circulating pro-inflammatory low-density granulocytes in adult-onset Still’s disease
Authors: Liu Yudong , Xia Changsheng , Chen Jiali , Fan Chunhong , He Jing 
Published: May 2020

Abstract

Objectives
Neutrophilia is a hallmark of adult-onset Still’s disease (AOSD). This study aimed to investigate the role of a distinct subset of granulocytes, the low-density granulocytes (LDGs) in the pathogenesis of AOSD.

Methods
A total of 56 patients with AOSD were included in the study. LDGs were quantified by flow cytometry. Correlations between LDGs with disease activity and laboratory parameters were determined by Spearman’s nonparametric test. The cellular sources of the pro-inflammatory cytokines in AOSD were determined by intracellular staining.

Results
Active AOSD patients displayed significantly higher levels of LDGs compared with inactive AOSD patients and healthy controls (HCs) (P&lt;0.001). Circulating LDGs were significantly correlated with CRP, ESR and the modified Pouchot score in patients with AOSD (P&lt;0.01). The levels of LDGs were significantly decreased after the active AOSD patients achieved disease remission (P=0.0391). CD14+ monocytes constituted over 90% IL-1β+ peripheral blood mononuclear cells (PBMCs) and over 80% TNF-α+ PBMCs in both active AOSD patients and HCs, respectively. In active AOSD, CD14+ monocytes accounted for 24.6% to 75.0% of IL-6+ PBMCs, while LDGs comprised 22.8% to 72.2% of IL-6+ PBMCs. In contrast, over 90% IL-6+ PBMCs were CD14+ monocytes in HCs. A significant correlation was identified between the levels of LDGs and serum IL-6 levels in AOSD (P&lt;0.0001).

Conclusion
Active AOSD is associated with elevated levels of a pro-inflammatory subset of neutrophils, the LDGs that produce IL-6. Our data highlight an unappreciated role of LDGs in the aberrant innate immune responses in AOSD.
0152 Insomnia Severity and Daytime Complaints: What is to be Learned When These Domains are Discordant?
Authors: Perlis M L , Boyle J T , Vargas I , Giller J , Seewald M , D’Antonio B , Muench A , Williams N J , Rosenfield B , Klingman K 
Published: May 2020

Abstract

Introduction
If illness severity and daytime dysfunction are construed as categorical entities, it is possible to conceptualize the relationship between these variables in terms of a 2x2 matrix where the resultant cells represent a concordant dimension (quadrants 2 & 4 [high-high and low-low]) and a discordant dimension (quadrants 1 & 3 [high-low and low-high]). The question for the present analysis was, what percentage of subjects populate each quadrant and is it the case that the discordant dimension contains only a small percentage of subjects?

Methods
Illness severity and daytime dysfunction data was collected from individuals with sleep continuity complaints in archival/community-based sample (N = 4680; 60% female; Ages 18–89) (www.sleeplessinphilly.com). Illness severity was operationalized as Total Wake Time (TWT; [SL+WASO+EMA=TWT]) and daytime dysfunction was operationalized as the composite score of six daytime symptoms items. Median splits were calculated for each variable and subjects were typed accordingly (HH, LL, HL, & LH).

Results
Surprisingly, the sample was relatively equally distributed into the two dimensions; 38% and 23% for the concordant dimension and 13% and 26% for discordant dimension.

Conclusion
The 39% of subjects in the discordant groups might be thought of as complaining good sleepers (LH) and noncomplaining poor sleepers (HL). Other investigators have identified the LH subjects as individuals with “insomnia identity”. Alternatively, it is possible to characterize the whole dimension as being related to a mismatch between the individual’s sleep need and sleep ability. Those who need a lot, may suffer a lot, in the face of only a little (LH) whereas those who need a little, may suffer only a little, in the face of a lot (HL).

Support
0174 Examining Circadian Disadvantages in the National Basketball Association’s Playoffs
Authors: Pradhan S , Gregory K , Alton D , Chachad R , Flynn-Evans E E 
Published: May 2020

Abstract

Introduction
Prior research on travel in the National Basketball Association’s (NBA) regular season has shown that teams journeying west relative to their home base face circadian disadvantages for evening games, while those traveling east have advantages. The current study extends previous research by examining these effects within the NBA playoffs. We hypothesized that teams would have a greater circadian advantage during eastward compared to westward travel.

Methods
In 2013, the NBA implemented a 7-game series playoff structure, in which teams play an alternating home/away 2-2-1-1-1 format. Data for all 499 postseason games played during the 2013–14 to 2018–2019 seasons were collected from Basketball-Reference and FiveThirtyEight. We investigated the impact of direction of travel based on home base city (same time zone, westward, eastward) and time zones traveled on game outcomes, Elo rating differences (i.e., a team quality metric based on wins and losses), win probability, and team scoring.

Results
Teams had lower win probabilities following 3-hour westward than same time zone and all eastward travel, while 3-hour eastward travel related to higher probabilities of winning compared to same time and all westward travel (p &lt; .001, d &gt; .95). Teams travelling westward with 2-hour time changes lost significantly more games than those experiencing 1-hour westward (p = .04, OR = 2.45), 1-hour eastward (p = .05, OR = 2.34), and 3-hour eastward changes (p = .02, OR = 4.68). Scoring was significantly higher following eastward travel compared to both westward (p = .001, d = 0.60) and same time zone travel (p = .003, d = 0.44). There were no differences in team quality based on direction of travel or number of time zones traveled, and game outcomes based on overall direction of travel (p &gt; .05).

Conclusion
Direction and magnitude of travel were related to win probability, team scoring, and game outcomes, whereby teams travelling eastward and within the same time zone gained an advantage over those travelling westward. Adjustment to travel and time changes appear to influence in-game performances and outcomes in the NBA playoffs.

Support
None
0393 The Effect of Trazadone Use on Non-REM Sleep Instability in Community-Dwelling Older Men
Authors: Hartmann S , Baumert M 
Published: May 2020

Abstract

Introduction
With steadily growing numbers of patients with a depressive disorder, the effect of antidepressants on sleep architecture is of increasing concern. One major oral antidepressant medication is trazadone, which has also been prescribed in low doses for sleep insomnia treatment. Here, we investigate the effect of trazadone on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men.

Methods
CAP was scored in overnight EEG recordings from 41 older men on trazadone (TRZ) and 50 age-matched men who did not use trazadone (NTRZ), participating in the Osteoporotic Fractures in Men Sleep Study. A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The effect of TRZ on CAP parameters was determined using the Mann-Whitney U test.

Results
CAP rate was significantly decreased in men using trazadone (NTRZ: 58.2±19.7%, TRZ: 47.9±15.9%) as compared to non-trazadone user (p &lt; 0.01). Subtype indices did not show any significant difference between both groups but to some extent less frequent A2-A3 phases for TRZ user (A1-phases: NTRZ 13.0±18.7 no./h vs. TRZ 10.8±20.4 no./h, p = 0.35; A2+A3-phases: NTRZ 51.5±33.7 no./h vs. TRZ 44.7±23.3 no./h, p = 0.068).

Conclusion
CAP rate was significantly decreased in older men on trazadone as compared to older men who did not use trazadone, suggesting that trazadone usage has a stabilising effect on sleep micro-structure.

Support
The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.
0834 Different Neural Circuits Were Associated With Different Parts of Relationships Among Sleep, Pain and Anxiety in Women with Primary Dysmenorrhoea
Authors: Chein K , Wei S , Hung C , Tu C , Hsieh J 
Published: May 2020

Abstract

Introduction
Although the relationships amongst sleep, pain and anxiety have been evidenced, the underlying neurological mechanisms remain elusive. Primary dysmenorrhea is a good model of spontaneous pain with clear painful (menstruation, state) and pain free (e.g., peri-ovulatory phase, trait) conditions. We sought to investigate the state- and trait-related neural signatures that link sleep and anxiety in primary dysmenorrhea.

Methods
Thirty female subjects with primary dysmenorrhea and 30 healthy female controls completed resting-state functional magnetic resonance imaging, the State-Trait Anxiety Inventory and sleep quality assessments during menstruation and peri-ovulatory phases. As we have reported that there was altered default mode network in the primary dysmenorrhea, posterior parietal cortex (PPC) was therefore chosen as the seed to elucidate the functional connectivity that may correlate with sleep and anxiety.

Results
The primary dysmenorrheic subjects exhibited sleep disturbances throughout the menstrual cycle with increased state anxiety. The primary dysmenorrheic subjects demonstrated significantly higher correlations between the sleep quality and the PPC-insula and -putamen functional connectivity during the peri-ovulatory phase. During menstruation, the primary dysmenorrheic subjects demonstrated significantly lower correlations between their state-anxiety scores and the PPC-occipital cortex functional connectivity.

Conclusion
After regressing out the effects of trait anxiety, the correlation between sleep quality and the PPC-putamen functional connectivity was not significant, indicating anxiety-mediated sleep-pain relationship. The PPC-insula functional connectivity, by contrast, was remained significant. Furthermore, state anxiety was associated with the PPC-occipital cortex functional connectivity that was significantly impaired in primary dysmenorrheic subjects. These findings hinted pain and anxiety mediating sleep quality in different neurological circuits.

Support
Taipei City Goverment(10401-62-046 and 10501-62-046)
Predicting left ventricular contractile function via Gaussian process emulation in aortic-banded rats
Authors: Longobardi S. , Lewalle A. , Coveney S. , Sjaastad I. , Espe E. K. S. , Louch W. E. , Musante C. J. , Sher A. , Niederer S. A. 
Published: May 2020

Cardiac contraction is the result of integrated cellular, tissue and organ function. Biophysical
in silico
cardiac models offer a systematic approach for studying these multi-scale interactions. The computational cost of such models is high, due to their multi-parametric and nonlinear nature. This has so far made it difficult to perform model fitting and prevented global sensitivity analysis (GSA) studies. We propose a machine learning approach based on Gaussian process emulation of model simulations using probabilistic surrogate models, which enables model parameter inference via a Bayesian history matching (HM) technique and GSA on whole-organ mechanics. This framework is applied to model healthy and aortic-banded hypertensive rats, a commonly used animal model of heart failure disease. The obtained probabilistic surrogate models accurately predicted the left ventricular pump function (
R
2
= 0.92 for ejection fraction). The HM technique allowed us to fit both the control and diseased virtual bi-ventricular rat heart models to magnetic resonance imaging and literature data, with model outputs from the constrained parameter space falling within 2 SD of the respective experimental values. The GSA identified Troponin C and cross-bridge kinetics as key parameters in determining both systolic and diastolic ventricular function.

This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.