bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia
Authors: Rivera-Escalera Fátima , Pinney Jonathan J. , Owlett Laura , Ahmed Hoda , Thakar Juilee , Olschowka John A. , Elliott Michael R. , O’Banion M. Kerry 
Published: December 2019

AbstractBackgroundNeuroinflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of IL-1β in the hippocampus of APP/PS1 mice decreases amyloid plaque burden independent of recruited CCR2+myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1β-induced plaque clearance. To date, however, the mechanisms of IL-1β-induced plaque clearance remain poorly understood.MethodsTo determine whether microglia are involved in IL-1β-induced plaque clearance, APP/PS1 mice induced to express mature human IL-1β in the hippocampus via adenoviral transduction were treated with the Aβ fluorescent probe methoxy-X04 (MX04) and microglial internalization of fibrillar Aβ (fAβ) was analyzed by flow cytometry and immunohistochemistry. To assess microglial proliferation, APP/PS1 mice transduced with IL-1β or control were injected intraperitoneally with BrdU and hippocampal tissue was analyzed by flow cytometry. RNAseq analysis was conducted on microglia FACS sorted from the hippocampus of control or IL-1β-treated APP/PS1 mice. These microglia were also sorted based on MX04 labeling (MX04+and MX04−microglia).ResultsResident microglia (CD45loCD11b+) constituted > 70% of the MX04+cells in both Phe- and IL-1β-treated conditions, and < 15% of MX04+cells were recruited myeloid cells (CD45hiCD11b+). However, IL-1β treatment did not augment the percentage of MX04+microglia nor the quantity of fAβ internalized by individual microglia. Instead, IL-1β increased the total number of MX04+microglia in the hippocampus due to IL-1β-induced proliferation. In addition, transcriptomic analyses revealed that IL-1β treatment was associated with large-scale changes in the expression of genes related to immune responses, proliferation, and cytokine signaling.ConclusionsThese studies show that IL-1β overexpression early in amyloid pathogenesis induces a change in the microglial gene expression profile and an expansion of microglial cells that facilitates Aβ plaque clearance.
A high-performance 8 nV/√Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals
Authors: Petkos Konstantinos , Koutsoftidis Simos , Guiho Thomas , Degenaar Patrick , Jackson Andrew , Greenwald Stephen E. , Brown Peter , Denison Timothy , Drakakis Emmanuel M. 
Published: December 2019

Abstract
Background
It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals.

Methods
To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments.

Results
To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented.

Conclusions
The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5–500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments.
The prevalence of burnout syndrome among resident physicians in Syria
Authors: Alhaffar Bahaa Aldin , Abbas Ghadir , Alhaffar Alaa Aldin 
Published: December 2019

Abstract
Introduction
Burnout syndrome is a work-related chronic stress that is described as emotional exhaustion, a decreased sense of personal accomplishment, and depersonalization. it has been considered an important problem especially among workers in the health sector.

Objectives
The aim of this research was to study the prevalence of burnout among Syrian residents during the Syrian crisis, which started 9 years ago, and to assess the factors related to burnout syndrome.

Methods
A cross-sectional study was conducted to assess the levels of burnout syndrome; data were collected from residents doing their residency in 12 different hospitals spread over 8 governorates in Syria. A web-based Arabic version of Maslach Burnout Inventory questionnaire was used. The final sample size was 3350 residents from different specialties. SPSS V.22 was used to analyses the data using descriptive and inferential statistics.

Results
(93.75%) had a high level in at least one of the three domains of the burnout index, and (19.3%) of the residents had a high level of burnout in all three domains. Significant relation was found between gender, age group and affiliated authority variables and the levels of burnout. However no significant relation was found between burnout and the specialties or geographic variables. Males, residents in Ministry of Defense, and emergency medicine residents had the highest levels of burnout.

Conclusion
High levels of burnout was found among residents during the Syrian crisis in comparison with other studies, which highlights the role of the current situation in raising workload on the Syrian residents.
Finite element analysis of two cephalomedullary nails in treatment of elderly reverse obliquity intertrochanteric fractures: zimmer natural nail and proximal femoral nail antirotation-ΙΙ
Authors: Chen Jian , Ma Jian-xiong , Wang Ying , Bai Hao-hao , Sun Lei , Wang Yan , Lu Bin , Dong Ben-chao , Tian Ai-xian , Ma Xin-long 
Published: December 2019

Abstract
Background
More elderly patients are suffering from intertrochanteric fractures. However, the choice of internal fixation is still controversial, especially in the treatment of unstable intertrochanteric fracture; thus, previous implants continue to be improved, and new ones are being developed. The purpose of our study was to compare the biomechanical advantages between the zimmer natural nail (ZNN) and proximal femoral nail antirotation-II (PFNA-II) in the treatment of elderly reverse obliquity intertrochanteric fractures.

Methods
A three-dimensional finite element was applied for reverse obliquity intertrochanteric fracture models (AO31-A3.1) fixed with the ZNN or PFNA-II. The distribution, peak value and position of the von Mises stress and the displacement were the criteria for comparison between the two groups.

Results
The stresses of the internal fixation and femur in the ZNN model were smaller than those in the PFNA-II model, and the peak values of the two groups were 364.8 MPa and 171.8 MPa (ZNN) and 832.3 MPa and 1795.0 MPa (PFNA-II). The maximum amount of displacement of the two groups was similar, and their locations were the same, i.e., in the femoral head vertex (3.768 mm in the ZNN model and 3.713 mm in the PFNA-II model).

Conclusions
The displacement in the two models was similar, but the stresses in the implant and bone were reduced with the ZNN. Therefore, the ZNN implant may provide biomechanical advantages over PFNA-II in reverse obliquity intertrochanteric fractures, as shown through the finite element analysis. These findings from our study may provide a reference for the perioperative selection of internal fixations.
Magnetic resonance imaging and computed tomography of equine cheek teeth and adjacent structures: comparative study of image quality in horses in vivo, post-mortem and frozen-thawed
Authors: Röttiger Christin , Hellige Maren , Ohnesorge Bernhard , Bienert-Zeit Astrid 
Published: December 2019

Abstract
Background
The use of cadavers for radiology research methodologies involving subjective image quality evaluation of anatomical criteria is well-documented. The purpose of this method comparison study was to evaluate the image quality of dental and adjacent structures in computed tomography (CT) and high-field (3 T) magnetic resonance (MR) images in cadaveric heads, based on an objective four-point rating scale. Whilst CT is a well-established technique, MR imaging (MRI) is rarely used for equine dental diagnostics. The use of a grading system in this study allowed an objective assessment of CT and MRI advantages in portraying equine cheek teeth. As imaging is commonly performed with cadaveric or frozen and thawed heads for dental research investigations, the second objective was to quantify the impact of the specimens’ conditions (in vivo, post-mortem, frozen-thawed) on the image quality in CT and MRI.

Results
The CT and MR images of nine horses, focused on the maxillary premolar 08s and molar 09s, were acquired post-mortem (Group A). Three observers scored the dental and adjacent tissues. Results showed that MR sequences gave an excellent depiction of endo- and periodontal structures, whereas CT produced high-quality images of the hard tooth and bony tissues. Additional CT and MRI was performed in vivo (Group B) and frozen-thawed (Group C) in three of these nine horses to specify the condition of the best specimens for further research. Assessing the impact of the specimens’ conditions on image quality, specific soft tissues of the maxillary 08s and 09s including adjacent structures (pulps, mucosa of the maxillary sinuses, periodontal ligament, soft tissue inside the infraorbital canal) were graded in group B and C and analysed for significant differences within CT and MR modalities in comparison to group A. Results showed that MRI scores in vivo were superior to the post-mortem and frozen-thawed condition.

Conclusions
On comparing the imaging performance of CT and MRI, both techniques show a huge potential for application in equine dentistry. Further studies are needed to assess the clinical suitability of MRI. For further research investigations it must be considered, that the best MR image quality is provided in live horses.
Peripheral blood metabolome predicts mood change-related activity in mouse model of bipolar disorder
Authors: Hagihara Hideo , Horikawa Tomoyasu , Irino Yasuhiro , Nakamura Hironori K. , Umemori Juzoh , Shoji Hirotaka , Yoshida Masaru , Kamitani Yukiyasu , Miyakawa Tsuyoshi 
Published: December 2019

AbstractBipolar disorder is a major mental illness characterized by severe swings in mood and activity levels which occur with variable amplitude and frequency. Attempts have been made to identify mood states and biological features associated with mood changes to compensate for current clinical diagnosis, which is mainly based on patients’ subjective reports. Here, we used infradian (a cycle > 24 h) cyclic locomotor activity in a mouse model useful for the study of bipolar disorder as a proxy for mood changes. We show that metabolome patterns in peripheral blood could retrospectively predict the locomotor activity levels. We longitudinally monitored locomotor activity in the home cage, and subsequently collected peripheral blood and performed metabolomic analyses. We then constructed cross-validated linear regression models based on blood metabolome patterns to predict locomotor activity levels of individual mice. Our analysis revealed a significant correlation between actual and predicted activity levels, indicative of successful predictions. Pathway analysis of metabolites used for successful predictions showed enrichment in mitochondria metabolism-related terms, such as “Warburg effect” and “citric acid cycle.” In addition, we found that peripheral blood metabolome patterns predicted expression levels of genes implicated in bipolar disorder in the hippocampus, a brain region responsible for mood regulation, suggesting that the brain–periphery axis is related to mood-change-associated behaviors. Our results may serve as a basis for predicting individual mood states through blood metabolomics in bipolar disorder and other mood disorders and may provide potential insight into systemic metabolic activity in relation to mood changes.
The atypical cadherin flamingo determines the competence of neurons for activity-dependent fine-scale topography
Authors: Li Ruonan , Liang Yuhua , Zheng Siyang , He Qun , Yang Limin 
Published: December 2019

AbstractThe topographic projection of afferent terminals into two-dimensional maps is essential for sensory systems to encode the locations of sensory stimuli. In vertebrates, guidance cues are critical for establishing a coarse topographic map, while neuronal activity directs fine-scale topography between adjacent afferent terminals. However, the molecular mechanism underlying activity-dependent fine-scale topography is not well known. Studies in the Drosophila visual system have demonstrated that cell-adhesion molecules direct fine-scale topography, but whether or not these molecules are involved in activity-dependent fine-scale topography remains to be determined. We previously reported that the nociceptors in Drosophila larvae form an activity-dependent fine-scale topographic system. The establishment of this system is instructed by the level of neuronal activity in individual nociceptors. Here, we show that the atypical cadherin Flamingo (Fmi) is required for establishing the nociceptor topographic map. We found that the topographic defect caused by loss of fmi was epistatic to the inhibition of neuronal activity and the overexpression of the activity-regulated gene Trim9. These results suggest that Fmi and neuronal activity interact to regulate fine-scale topography. This study provides a link between neuronal activity and the cell-adhesion molecule in the establishment of fine-scale topography.
OPG/RANK/RANKL signaling axis in patients with type I diabetes: Associations with parathormone and vitamin D
Authors: Karalazou Paraskevi , Ntelios Dimitrios , Chatzopoulou Fani , Fragou Aikaterini , Taousani Maria , Mouzaki Konstantina , Galli-Tsinopoulou Assimina , Kouidou Sofia , Tzimagiorgis Georgios 
Published: December 2019

AbstractBackgroundType 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence theOPG/RANK/RANKLsignaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age.MethodsSerum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender.ResultsPlasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls.ConclusionsOur results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.
The Pseudomonas aeruginosa accessory genome elements influence virulence towards Caenorhabditis elegans
Authors: Vasquez-Rifo Alejandro , Veksler-Lublinsky Isana , Cheng Zhenyu , Ausubel Frederick M. , Ambros Victor 
Published: December 2019

AbstractBackgroundMulticellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship betweenPseudomonas aeruginosaand the nematodeCaenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability inP. aeruginosavirulence towardsC. elegansto provide evolutionary insights into host-pathogen relationships.ResultsNatural isolates ofP. aeruginosathat exhibit diverse genomes display a broad range of virulence towardsC. elegans. Using gene association and genetic analysis, we identify accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we find a viral-like mobile element, thetegblock, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence while the presence of CRISPR-Cas associates with higher virulence.ConclusionsOur analysis demonstrates substantial strain variation inP. aeruginosavirulence, mediated by specific accessory genome elements that promote increased or decreased virulence. We exemplify that viral-like accessory genome elements that decrease virulence can be restricted by bacterial CRISPR-Cas immune defense systems, and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in virulence maintenance.
Accuracy, robustness and scalability of dimensionality reduction methods for single-cell RNA-seq analysis
Authors: Sun Shiquan , Zhu Jiaqiang , Ma Ying , Zhou Xiang 
Published: December 2019

Abstract
Background
Dimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of dimensionality reduction in scRNA-seq analysis and the vast number of dimensionality reduction methods developed for scRNA-seq studies, few comprehensive comparison studies have been performed to evaluate the effectiveness of different dimensionality reduction methods in scRNA-seq.

Results
We aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used dimensionality reduction methods for scRNA-seq studies. Specifically, we compare 18 different dimensionality reduction methods on 30 publicly available scRNA-seq datasets that cover a range of sequencing techniques and sample sizes. We evaluate the performance of different dimensionality reduction methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluate the computational scalability of different dimensionality reduction methods by recording their computational cost.

Conclusions
Based on the comprehensive evaluation results, we provide important guidelines for choosing dimensionality reduction methods for scRNA-seq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html.
Measurement training and feedback system for implementation of evidence-based treatment for adolescent externalizing problems: protocol for a randomized trial of pragmatic clinician training
Authors: Hogue Aaron , Bobek Molly , MacLean Alexandra , Porter Nicole , Jensen-Doss Amanda , Henderson Craig E. 
Published: December 2019

Abstract
Background
Innovations in clinical training and support that enhance fidelity to evidence-based treatment (EBT) for adolescent behavior problems are sorely needed. This study will develop an online training system to address this gap: Measurement Training and Feedback System for Implementation (MTFS-I). Using procedures intended to be practical and sustainable, MTFS-I is designed to increase two aspects of therapist behavior that are fundamental to boosting EBT fidelity: therapist self-monitoring of EBT delivery, and therapist utilization of core techniques of EBTs in treatment sessions. This version of MTFS-I focuses on two empirically supported treatment approaches for adolescent conduct and substance use problems: family therapy and cognitive behavioral therapy (CBT).

Methods/design
MTFS-I expands on conventional measurement feedback systems for client outcomes by adding training in observational coding to promote EBT self-monitoring and focusing on implementation of EBT treatment techniques. It has two primary components. (1) The training component, delivered weekly in two connected parts, involves self-monitored learning modules containing brief clinical descriptions of core EBT techniques and mock session coding exercises based on 5–8 min video segments that illustrate delivery of core techniques. (2) The feedback component summarizes aggregated therapist-reported data on EBT techniques used with their active caseloads. MTFS-I is hosted online and requires approximately 20 min per week to complete for each treatment approach. This randomized trial will first collect data on existing delivery of family therapy and CBT techniques for youth in outpatient behavioral health sites (Baseline phase). It will then randomize site clinicians to two study conditions (Implementation phase): Training Only versus Training + Feedback + Consultation. Therapists will choose whether to train in family therapy, CBT, or both. Study aims will compare clinician performance across study phase and between study conditions on MTFS-I uptake, reliability and accuracy in EBT self-monitoring, and utilization of EBT techniques in treatment sessions (based on observer coding of audiotapes).

Discussion
Study contributions to implementation science and considerations of MTFS-I sustainability are discussed.

Trial registration
ClinicalTrials.gov, NCT03722654. Registered on 29 October 2018.
Correction to: A downstream box fusion allows stable accumulation of a bacterial cellulase in Chlamydomonas reinhardtii chloroplasts
Authors: Richter Lubna V. , Yang Huijun , Yazdani Mohammad , Hanson Maureen R. , Ahner Beth A. 
Published: December 2019

In the original version of the article [1], a calculation error resulted in a 3-order of magnitude mistake for the y-axis of the data reported in Fig. 5c and d.