bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional observation after morphine withdrawal: effects of SJP-005
Authors: Verster Joris C. , Scholey Andrew , Dahl Thomas A. , Iversen Jacqueline M. 
Published: February 2021

Abstract
Rationale and objective
SJP-005 (ketotifen and ibuprofen) is being developed as a potential new treatment for opioid withdrawal. Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2–12) effects of SJP-005 on discontinuation-induced morphine withdrawal.

Methods
Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice daily, oral dosages of placebo or SJP-005 (1 mg/kg ketotifen and 15 mg/kg ibuprofen) were administered starting 4 days before (study 1), 2 days before (study 2), or immediately after (study 3) morphine cessation. Functional observations were made up to 12 h after treatment cessation on day 19 (early phase), and immediately after treatment on days 20–30 (late phase). Treatment effects (mean overall score, and individual symptoms) were compared with placebo using ANOVA, and Tukey’s tests in case of multiple comparisons.

Results
Across the studies, the number of withdrawal signs on day 19 (early phase) and days 20–30 (late phase) was lower with SJP-005 compared with placebo. The effects of SJP-005 when treatment was initiated 2 days before morphine cessation by discontinuation were most pronounced and statistically significant in the late phase (F(1,18) = 14.10, p = 0.001). In particular, a significant reduction was observed in hypersensitivity to touch (F(1,18) = 13.65, p = 0.002). A 50% reduction in withdrawal symptoms was observed 9.0 days after placebo versus 4.5 days after SJP-005. After 9.0 days, all withdrawal symptoms were absent in the SJP-005 group, while symptoms in the placebo group were still evident on day 18.

Conclusion
Compared to placebo, SJP-005 significantly reduced the incidence and duration of discontinuation-induced morphine withdrawal symptoms when treatment was initiated 2 days before morphine cessation.
Balance, gait, and navigation performance are related to physical exercise in blind and visually impaired children and adolescents
Authors: Rogge Ann-Kathrin , Hamacher Daniel , Cappagli Giulia , Kuhne Laura , Hötting Kirsten , Zech Astrid , Gori Monica , Röder Brigitte 
Published: February 2021

AbstractSelf-motion perception used for locomotion and navigation requires the integration of visual, vestibular, and proprioceptive input. In the absence of vision, postural stability and locomotor tasks become more difficult. Previous research has suggested that in visually deprived children, postural stability and levels of physical activity are overall lower than in sighted controls. Here we hypothesized that visually impaired and blind children and adolescents differ from sighted controls in postural stability and gait parameters, and that physically active individuals outperform sedentary peers in postural stability and gait parameters as well as in navigation performance. Fourteen blind and visually impaired children and adolescents (8–18 years of age) and 14 matched sighted individuals took part. Assessments included postural sway, single-leg stance time, parameters of gait variability and stability, self-reported physical activity, and navigation performance. Postural sway was larger and single-leg stance time was lower in blind and visually impaired participants than in blindfolded sighted individuals. Physical activity was higher in the sighted group. No differences between the group of blind and visually impaired and blindfolded sighted participants were observed for gait parameters and navigation performance. Higher levels of physical activity were related to lower postural sway, longer single-leg stance time, higher gait stability, and superior navigation performance in blind and visually impaired participants. The present data suggest that physical activity may enhance postural stability and gait parameters, and thereby promote navigation performance in blind and visually impaired children and adolescents.
How does curvature affect the free-energy barrier of stalk formation? Small vesicles vs apposing, planar membranes
Authors: Smirnova Y. G. , Müller M. 
Published: February 2021

AbstractUsing molecular simulations of POPC lipids in conjunction with the calculation of the Minimum Free-Energy Path (MFEP), we study the effect of strong membrane curvature on the formation of the first fusion intermediate—the stalk between a vesicle and its periodic image. We find that the thermodynamic stability of this hourglass-shaped, hydrophobic connection between two vesicles is largely increased by the strong curvature of small vesicles, whereas the intrinsic barrier to form a stalk, i.e., associated with dimple formation and lipid tails protrusions, is similar to the case of two, apposing, planar membranes. A significant reduction of the barrier of stalk formation, however, stems from the lower dehydration free energy that is required to bring highly curved vesicle into a distance, at which stalk formation may occur, compared to the case of apposing, planar membranes.
Artgames vs. Game Art – Diskurse und Strategien der Computerspielkunst zwischen spielbarer Rhetorik und unspielbarer Ästhetik
Authors: Möring Sebastian 
Published: February 2021

ZusammenfassungComputerspiele sind vielfältig. Freizeitvergnügen, professioneller Sport, kulturbildend und kulturkritisch. Sie inspirieren die Kunst und mit ihnen wird Kunst gemacht. Dieser Beitrag betrachtet die Diskurse und Strategien der Computerspielkunst. Im Rückgriff auf die Game Studies und die medienwissenschaftliche Computerspielforschung beleuchtet er die Unterscheidung zwischen Artgames und Game Art (insbesondere Modifikationen) und versucht zu zeigen, dass beide Genres unterschiedlichen Diskursen entstammen, die mit verschiedenen Begriffen und künstlerischen Strategien operieren: Artgames setzen auf Spielbarkeit und Rhetorik und Game Art setzt auf Unspielbarkeit und Ästhetik. Sie grenzen sich so auf unterschiedliche Weise von den Sorgestrukturen kommerzieller Computerspiele ab.
Optimally growing initial errors of El Niño events in the CESM
Authors: Xu Hui , Chen Lei , Duan Wansuo 
Published: February 2021

AbstractThe optimally growing initial errors (OGEs) of El Niño events are found in the Community Earth System Model (CESM) by the conditional nonlinear optimal perturbation (CNOP) method. Based on the characteristics of low-dimensional attractors for ENSO (El Niño Southern Oscillation) systems, we apply singular vector decomposition (SVD) to reduce the dimensions of optimization problems and calculate the CNOP in a truncated phase space by the differential evolution (DE) algorithm. In the CESM, we obtain three types of OGEs of El Niño events with different intensities and diversities and call them type-1, type-2 and type-3 initial errors. Among them, the type-1 initial error is characterized by negative SSTA errors in the equatorial Pacific accompanied by a negative west–east slope of subsurface temperature from the subsurface to the surface in the equatorial central-eastern Pacific. The type-2 initial error is similar to the type-1 initial error but with the opposite sign. The type-3 initial error behaves as a basin-wide dipolar pattern of tropical sea temperature errors from the sea surface to the subsurface, with positive errors in the upper layers of the equatorial eastern Pacific and negative errors in the lower layers of the equatorial western Pacific. For the type-1 (type-2) initial error, the negative (positive) temperature errors in the eastern equatorial Pacific develop locally into a mature La Niña (El Niño)-like mode. For the type-3 initial error, the negative errors in the lower layers of the western equatorial Pacific propagate eastward with Kelvin waves and are intensified in the eastern equatorial Pacific. Although the type-1 and type-3 initial errors have different spatial patterns and dynamic growing mechanisms, both cause El Niño events to be underpredicted as neutral states or La Niña events. However, the type-2 initial error makes a moderate El Niño event to be predicted as an extremely strong event.
Imaging assay to probe the role of telomere length shortening on telomere-gene interactions in single cells
Authors: Zhang Ning , Li Yanhui , Lai Tsung-Po , Shay Jerry W. , Danuser Gaudenz 
Published: February 2021

AbstractTelomeres are repetitive non-coding nucleotide sequences (TTAGGGn) capping the ends of chromosomes. Progressive telomere shortening with increasing age has been associated with shifts in gene expression through models such as the telomere position effect (TPE), which suggests reduced interference of the telomere with transcriptional activity of increasingly more distant genes. A modification of the TPE model, referred to as Telomere Position Effects over Long Distance (TPE-OLD), explains why some genes 1–10 MB from a telomere are still affected by TPE, but genes closer to the telomere are not. Here, we describe an imaging approach to systematically examine the occurrence of TPE-OLD at the single cell level. Compared to existing methods, the pipeline allows rapid analysis of hundreds to thousands of cells, which is necessary to establish TPE-OLD as an acceptable mechanism of gene expression regulation. We examined two human genes, ISG15 and TERT, for which TPE-OLD has been described before. For both genes, we found less interaction with the telomere on the same chromosome in old cells compared to young cells; and experimentally elongated telomeres in old cells rescued the level of telomere interaction for both genes. However, the dependency of the interactions on the age progression from young to old cells varied. One model for the differences between ISG15 and TERT may relate to the markedly distinct interstitial telomeric sequence arrangement in the two genes. Overall, this provides a strong rationale for the role of telomere length shortening in the regulation of gene expression.
Intronic variant in POU1F1 associated with canine pituitary dwarfism
Authors: Kyöstilä Kaisa , Niskanen Julia E. , Arumilli Meharji , Donner Jonas , Hytönen Marjo K. , Lohi Hannes 
Published: February 2021

AbstractThe anterior pituitary gland secretes several endocrine hormones, essential for growth, reproduction and other basic physiological functions. Abnormal development or function of the pituitary gland leads to isolated or combined pituitary hormone deficiency (CPHD). At least 30 genes have been associated with human CPHD, including many transcription factors, such as POU1F1. CPHD occurs spontaneously also in mice and dogs. Two affected breeds have been reported in dogs: German Shepherds with a splice defect in the LHX3 gene and Karelian Bear Dogs (KBD) with an unknown genetic cause. We obtained samples from five KBDs presenting dwarfism and abnormal coats. A combined analysis of genome-wide association and next-generation sequencing mapped the disease to a region in chromosome 31 and identified a homozygous intronic variant in the fourth exon of the POU1F1 gene in the affected dogs. The identified variant, c.605-3C>A, resided in the splice region and was predicted to affect splicing. The variant's screening in three new prospective cases, related breeds, and ~ 8000 dogs from 207 breeds indicated complete segregation in KBDs with a carrier frequency of 8%, and high breed-specificity as carriers were found at a low frequency only in Lapponian Herders, a related breed. Our study establishes a novel canine model for CPHD with a candidate POU1F1 defect.
Adaptive numerical integration of exponential finite elements for a phase field fracture model
Authors: Olesch Darius , Kuhn Charlotte , Schlüter Alexander , Müller Ralf 
Published: February 2021

AbstractPhase field models for fracture are energy-based and employ a continuous field variable, the phase field, to indicate cracks. The width of the transition zone of this field variable between damaged and intact regions is controlled by a regularization parameter. Narrow transition zones are required for a good approximation of the fracture energy which involves steep gradients of the phase field. This demands a high mesh density in finite element simulations if 4-node elements with standard bilinear shape functions are used. In order to improve the quality of the results with coarser meshes, exponential shape functions derived from the analytic solution of the 1D model are introduced for the discretization of the phase field variable. Compared to the bilinear shape functions these special shape functions allow for a better approximation of the fracture field. Unfortunately, lower-order Gauss-Legendre quadrature schemes, which are sufficiently accurate for the integration of bilinear shape functions, are not sufficient for an accurate integration of the exponential shape functions. Therefore in this work, the numerical accuracy of higher-order Gauss-Legendre formulas and a double exponential formula for numerical integration is analyzed.
Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water–fat MRI and relationship to patient-reported outcome measures
Authors: Fields Aaron J. , Ballatori Alexander , Han Misung , Bailey Jeannie F. , McCormick Zachary L. , O’Neill Conor W. , Demir-Deviren Sibel , Krug Roland , Lotz Jeffrey C. 
Published: February 2021

Abstract
Purpose
Vertebral endplate bone marrow lesions (“Modic changes”, MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water–fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics.

Methods
In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression.

Results
Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference −22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029–0.032) and were not associated with pain (p = 0.49–0.83).

Conclusion
BMF is significantly altered in MC. Water–fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.
Acute bilateral foot drop with or without cauda equina syndrome—a case series
Authors: Demetriades Andreas K. , Mancuso-Marcello Marco , Baig Mirza Asfand , Frantzias Joseph , Bell David A. , Selway Richard , Gullan Richard 
Published: February 2021

Abstract

Introduction

Isolated acute bilateral foot drop due to degenerative spine disease is an extremely rare neurosurgical presentation, whilst the literature is rich with accounts of chronic bilateral foot drop occurring as a sequela of systemic illnesses. We present, to our knowledge, the largest case series of acute bilateral foot drop, with trauma and relevant systemic illness excluded.

Methods

Data from three different centres had been collected at the time of historic treatment, and records were subsequently reviewed retrospectively, documenting the clinical presentation, radiological level of compression, timing of surgery, and degree of neurological recovery.

Results

Seven patients are presented. The mean age at presentation was 52.1 years (range 41–66). All patients but one were male. All had a painful radiculopathic presentation. Relevant discopathy was observed from L2/3 to L5/S1, the commonest level being L3/4. Five were treated within 24 h of presentation, and two within 48 h. Three had concomitant cauda equina syndrome; of these, the first two made a full motor recovery, one by 6 weeks follow-up and the second on the same-day post-op evaluation. Overall, five out of seven cases had full resolution of their ankle dorsiflexion pareses. One patient with 1/5 power has not improved. Another with 1/5 weakness improved to normal on the one side and to 3/5 on the other.

Conclusion

When bilateral foot drop occurs acutely, we encourage the consideration of degenerative spinal disease. Relevant discopathy was observed from L2/3 to L5/S1; aberrant innervation may be at play. Cauda equina syndrome is not necessarily associated with acute bilateral foot drop. The prognosis seems to be pretty good with respect to recovery of the foot drop, especially if partial at presentation and if treated within 48 h.
Development of internalizing symptoms during adolescence in three countries: the role of temperament and parenting behaviors
Authors: Lunetti Carolina , Iselin Anne-Marie R. , Di Giunta Laura , Lansford Jennifer E. , Eisenberg Nancy , Pastorelli Concetta , Bacchini Dario , Uribe Tirado Liliana Maria , Thartori Eriona , Basili Emanuele , Fiasconaro Irene , Favini Ainzara , Gerbino Maria , Cirimele Flavia , Remondi Chiara , Skinner Ann T. , Rothenberg W. Andrew 
Published: February 2021

AbstractThis longitudinal study examined the unique and joint effects of early adolescent temperament and parenting in predicting the development of adolescent internalizing symptoms in a cross-cultural sample. Participants were 544 early adolescents (T1: Mage = 12.58; 49.5% female) and their mothers (n = 530) from Medellín, Colombia (n = 88), Naples, Italy (n = 90), Rome, Italy (n = 100) and Durham, North Carolina, United States (African Americans n = 92, European Americans n = 97, and Latinx n = 77). Early adolescent negative emotionality (i.e., anger and sadness experience), self-regulation (i.e., effortful control), and parent monitoring and psychological control were measured at T1. Adolescent internalizing symptoms were measured at three time points. Latent Growth Curve Modeling (LGCM) without covariates or predictors indicated a slight linear increase in internalizing symptoms from ages 13–16 years across nearly all cultural groups. Multi-group LGCMs demonstrated several paths were consistently invariant across groups when examining how well temperament and parenting predicted intercept and slope factors. Higher initial levels of internalizing symptoms were significantly predicted by higher adolescent negative emotionality and parental psychological control as well as lower adolescent effortful control and parental monitoring measured one year earlier. Overall, adolescent effortful control appeared to protect against the emergence of internalizing symptoms in all cultures, but this effect faded over time. This study advances knowledge of the normative development of internalizing symptoms during adolescence across cultures while highlighting the predictive value of early adolescent temperament and parenting.
Unsupervised Deep Anomaly Detection in Chest Radiographs
Authors: Nakao Takahiro , Hanaoka Shouhei , Nomura Yukihiro , Murata Masaki , Takenaga Tomomi , Miki Soichiro , Watadani Takeyuki , Yoshikawa Takeharu , Hayashi Naoto , Abe Osamu 
Published: February 2021

AbstractThe purposes of this study are to propose an unsupervised anomaly detection method based on a deep neural network (DNN) model, which requires only normal images for training, and to evaluate its performance with a large chest radiograph dataset. We used the auto-encoding generative adversarial network (α-GAN) framework, which is a combination of a GAN and a variational autoencoder, as a DNN model. A total of 29,684 frontal chest radiographs from the Radiological Society of North America Pneumonia Detection Challenge dataset were used for this study (16,880 male and 12,804 female patients; average age, 47.0 years). All these images were labeled as “Normal,” “No Opacity/Not Normal,” or “Opacity” by board-certified radiologists. About 70% (6,853/9,790) of the Normal images were randomly sampled as the training dataset, and the rest were randomly split into the validation and test datasets in a ratio of 1:2 (7,610 and 15,221). Our anomaly detection system could correctly visualize various lesions including a lung mass, cardiomegaly, pleural effusion, bilateral hilar lymphadenopathy, and even dextrocardia. Our system detected the abnormal images with an area under the receiver operating characteristic curve (AUROC) of 0.752. The AUROCs for the abnormal labels Opacity and No Opacity/Not Normal were 0.838 and 0.704, respectively. Our DNN-based unsupervised anomaly detection method could successfully detect various diseases or anomalies in chest radiographs by training with only the normal images.
Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization
Authors: Baganha Fabiana , de Jong Rob C. M. , Peters Erna A. , Voorham Wietske , Jukema J. Wouter , Delibegovic Mirela , de Vries Margreet R. , Quax Paul H. A. 
Published: February 2021

Abstract
Objective
Statins pleiotropically provide additional benefits in reducing atherosclerosis, but their effects on intraplaque angiogenesis (IPA) and hemorrhage (IPH) remain unclear. Therefore, we discriminated statin’s lipid-lowering dependent and independent effects on IPA and IPH.

Approach and results
ApoE3*Leiden mice are statin-responsive due to ApoE and LDLR presence, but also allow to titrate plasma cholesterol levels by diet. Therefore, ApoE3*Leiden mice were fed a high-cholesterol-inducing-diet (HCD) with or without atorvastatin (A) or a moderate-cholesterol-inducing-diet (MCD). Mice underwent vein graft surgery to induce lesions with IPA and IPH. Cholesterol levels were significantly reduced in MCD (56%) and HCD + A (39%) compared to HCD with no significant differences between MCD and HCD + A. Both MCD and HCD + A have a similar reduction in vessel remodeling and inflammation comparing to HCD. IPA was significantly decreased by 30% in HCD + A compared to HCD or MCD. Atorvastatin treatment reduced the presence of immature vessels by 34% vs. HCD and by 25% vs. MCD, resulting in a significant reduction of IPH. Atorvastatin’s anti-angiogenic capacity was further illustrated by a dose-dependent reduction of ECs proliferation and migration. Cultured mouse aortic-segments lost sprouting capacity upon atorvastatin treatment and became 30% richer in VE-Cadherin expression and pericyte coverage. Moreover, Atorvastatin inhibited ANGPT2 release and decreased VE-Cadherin(Y685)-phosphorylation in ECs.

Conclusions
Atorvastatin has beneficial effects on vessel remodeling due to its lipid-lowering capacity. Atorvastatin has strong pleiotropic effects on IPA by decreasing the number of neovessels and on IPH by increasing vessel maturation. Atorvastatin improves vessel maturation by inhibiting ANGPT2 release and phospho(Y658)-mediated VE-Cadherin internalization.
Maurer–Cartan Moduli and Theorems of Riemann–Hilbert Type
Authors: Chuang Joseph , Holstein Julian , Lazarev Andrey 
Published: February 2021

AbstractWe study Maurer–Cartan moduli spaces of dg algebras and associated dg categories and show that, while not quasi-isomorphism invariants, they are invariants of strong homotopy type, a natural notion that has not been studied before. We prove, in several different contexts, Schlessinger–Stasheff type theorems comparing the notions of homotopy and gauge equivalence for Maurer–Cartan elements as well as their categorified versions. As an application, we re-prove and generalize Block–Smith’s higher Riemann–Hilbert correspondence, and develop its analogue for simplicial complexes and topological spaces.