bluuebunny/crossref_metadata_2025_split huggingface dataset:
DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage
Authors: Xu Yang , Nowrangi Derek , Liang Hui , Wang Tian , Yu Lingyan , Lu Tai , Lu Zhengyang , Zhang John H. , Luo Benyan , Tang Jiping 
Published: April 2020

Abstract
Background
Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinflammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that Dickkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH.

Methods
Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1β in the brain.

Results
The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated, at least partly, by the Kremen-1 and DVL-1 pathways.

Conclusions
DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1-mediated inflammation, thereby ameliorating the short- and long-term sequelae after ICH.
Inhibition of formyl peptide receptors improves the outcome in a mouse model of Alzheimer disease
Authors: Schröder Nicole , Schaffrath Anja , Welter Josua A. , Putzka Tim , Griep Angelika , Ziegler Patrick , Brandt Elisa , Samer Sebastian , Heneka Michael T. , Kaddatz Hannes , Zhan Jiangshan , Kipp Eugenia , Pufe Thomas , Tauber Simone C. , Kipp Markus , Brandenburg Lars-Ove 
Published: April 2020

Abstract
Background
An important hallmark of Alzheimer’s disease (AD) is the increase of Aβ1-42 burden and its accumulation to senile plaques, leading the reactive gliosis and neurodegeneration. The modulation of glia cell function represents an attractive therapeutic strategy, but is currently limited by an incomplete understanding of its relevance for AD. The chemotactic G-protein coupled formyl peptide receptor (FPR), which is known to modulate Aβ1-42 uptake and signal transduction, might be one candidate molecule regulating glia function in AD. Here, we investigate whether the modulation of FPR exerts beneficial effects in an AD preclinical model.

Methods
To address this question, APP/PS1 double-transgenic AD mice were treated for 20 weeks with either the pro-inflammatory FPR agonist fMLF, the FPR1/2 antagonist Boc2 or the anti-inflammatory FPR2 agonist Ac2-26. Spatial learning and memory were evaluated using a Morris water maze test. Immunohistological staining, gene expression studies, and flow cytometry analyses were performed to study neuronal loss, gliosis, and Aß-load in the hippocampus and cortex, respectively.

Results
FPR antagonism by Boc2-treatment significantly improved spatial memory performance, reduced neuronal pathology, induced the expression of homeostatic growth factors, and ameliorated microglia, but not astrocyte, reactivity. Furthermore, the elevated levels of amyloid plaques in the hippocampus were reduced by Boc2-treatment, presumably by an induction of amyloid degradation.

Conclusions
We suggest that the modulation of FPR signaling cascades might be considered as a promising therapeutic approach for alleviating the cognitive deficits associated with early AD. Additional studies are now needed to address the downstream effectors as well as the safety profile of Boc2.
Remotely monitoring ecosystem respiration from various grasslands along a large-scale east–west transect across northern China
Authors: Tang Xuguang , Zhou Yanlian , Li Hengpeng , Yao Li , Ding Zhi , Ma Mingguo , Yu Pujia 
Published: April 2020

Abstract
Background
Grassland ecosystems play an important role in the terrestrial carbon cycles through carbon emission by ecosystem respiration (Re) and carbon uptake by plant photosynthesis (GPP). Surprisingly, given Re occupies a large component of annual carbon balance, rather less attention has been paid to developing the estimates of Re compared to GPP.

Results
Based on 11 flux sites over the diverse grassland ecosystems in northern China, this study examined the amounts of carbon released by Re as well as the dominant environmental controls across temperate meadow steppe, typical steppe, desert steppe and alpine meadow, respectively. Multi-year mean Re revealed relatively less CO2 emitted by the desert steppe in comparison with other grassland ecosystems. Meanwhile, C emissions of all grasslands were mainly controlled by the growing period. Correlation analysis revealed that apart from air and soil temperature, soil water content exerted a strong effect on the variability in Re, which implied the great potential to derive Re using relevant remote sensing data. Then, these field-measured Re data were up-scaled to large areas using time-series MODIS information and remote sensing-based piecewise regression models. These semi-empirical models appeared to work well with a small margin of error (R2 and RMSE ranged from 0.45 to 0.88 and from 0.21 to 0.69 g C m−2 d−1, respectively).

Conclusions
Generally, the piecewise models from the growth period and dormant season performed better than model developed directly from the entire year. Moreover, the biases between annual mean Re observations and the remotely-derived products were usually within 20%. Finally, the regional Re emissions across northern China’s grasslands was approximately 100.66 Tg C in 2010, about 1/3 of carbon fixed from the MODIS GPP product. Specially, the desert steppe exhibited the highest ratio, followed by the temperate meadow steppe, typical steppe and alpine meadow. Therefore, this work provides a novel framework to accurately predict the spatio-temporal patterns of Re over large areas, which can greatly reduce the uncertainties in global carbon estimates and climate projections.
Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice
Authors: Jiang Rong , Wu Xue-Fei , Wang Bin , Guan Rong-Xiao , Lv Lang-Man , Li Ai-Ping , Lei Lei , Ma Ye , Li Na , Li Qi-Fa , Ma Quan-Hong , Zhao Jie , Li Shao 
Published: April 2020

Abstract
Background
Amyloid beta (Aβ) which is recognized as a main feature of Alzheimer’s disease (AD) has been proposed to “spread” through anatomically and functionally connected brain regions. The entorhinal cortex and perforant path are the earliest affected brain regions in AD. The perforant path is the most vulnerable circuit in the cortex with respect to both aging and AD. Previous data show that the origins and terminations of the perforant path are susceptible to amyloid deposition at the younger age in AD. Nogo receptor (NgR) plays an essential role in limiting injury-induced axonal growth and experience-dependent plasticity in the adult brain. It has been suggested that NgR is involved in AD pathological features, but the results have been conflicting and the detailed mechanism needs further investigation. In this study, the effect of NgR in the perforant path on the pathological and functional phenotype of APP/PS1 transgenic mice was studied.

Methods
To genetically manipulate NgR expression, adeno-associated virus (AAV) with short hairpin (shRNA) against NgR was injected into the perforant path of APP/PS1 transgenic mice, followed by an assessment of behavioral, synaptic plasticity and neuropathological phenotypes. NgR was overexpressed or knockdown in neuroblastoma N2a cells and APPswe/HEK293 cells to investigate the interaction between NgR and amyloid precursor protein (APP).

Results
It is shown that reduction of NgR in the perforant path rescued cognitive and synaptic deficits in APP/PS1 transgenic mice. Concurrently, Aβ production in the perforant path and levels of soluble Aβ and amyloid plaques in the hippocampus were significantly decreased. There was a positive correlation between the total APP protein level and NgR expression both in transgenic mice and in cultured cells, where the α-secretase and β-secretase cleavage products both changed with APP level in parallel. Finally, NgR might inhibit APP degradation through lysosome by Rho/Rho-associated protein kinases (ROCK) signaling pathway.

Conclusions
Our findings demonstrate that perforant path NgR plays an important role in regulating APP/Aβ level and cognitive functions in AD transgenic mice, which might be related to the suppression of APP degradation by NgR. Our study suggests that NgR in the perforant path could be a potential target for modulating AD progression.
A systematic review and taxonomy of tools for evaluating evidence-based medicine teaching in medical education
Authors: Kumaravel Bharathy , Hearn Jasmine Heath , Jahangiri Leila , Pollard Rachel , Stocker Claire J. , Nunan David 
Published: April 2020

Abstract
Background
The importance of teaching the skills and practice of evidence-based medicine (EBM) for medical professionals has steadily grown in recent years. Alongside this growth is a need to evaluate the effectiveness of EBM curriculum as assessed by competency in the five ‘A’s’: asking, acquiring, appraising, applying and assessing (impact and performance). EBM educators in medical education will benefit from a compendium of existing assessment tools for assessing EBM competencies in their settings. The purpose of this review is to provide a systematic review and taxonomy of validated tools that evaluate EBM teaching in medical education.

Methods
We searched MEDLINE, EMBASE, Cochrane library, Educational Resources Information Centre (ERIC), Best Evidence Medical Education (BEME) databases and references of retrieved articles published between January 2005 and March 2019. We have presented the identified tools along with their psychometric properties including validity, reliability and relevance to the five domains of EBM practice and dimensions of EBM learning. We also assessed the quality of the tools to identify high quality tools as those supported by established interrater reliability (if applicable), objective (non-self-reported) outcome measures and achieved ≥ 3 types of established validity evidence. We have reported our study in accordance with the PRISMA guidelines.

Results
We identified 1719 potentially relevant articles of which 63 full text articles were assessed for eligibility against inclusion and exclusion criteria. Twelve articles each with a unique and newly identified tool were included in the final analysis. Of the twelve tools, all of them assessed the third step of EBM practice (appraise) and four assessed just that one step. None of the twelve tools assessed the last step of EBM practice (assess). Of the seven domains of EBM learning, ten tools assessed knowledge gain, nine assessed skills and-one assessed attitude. None addressed reaction to EBM teaching, self-efficacy, behaviours or patient benefit. Of the twelve tools identified, six were high quality. We have also provided a taxonomy of tools using the CREATE framework, for EBM teachers in medical education.

Conclusions
Six tools of reasonable validity are available for evaluating most steps of EBM and some domains of EBM learning. Further development and validation of tools that evaluate all the steps in EBM and all educational outcome domains are needed.

Systematic review registration
PROSPERO CRD42018116203.
The Samuelson macroeconomic model as a singular linear matrix difference equation
Authors: Ortega Fernando , Barros Maria Filomena 
Published: April 2020

AbstractIn this paper, we revisit the famous classical Samuelson’s multiplier–accelerator model for national economy. We reform this model into a singular discrete time system and study its solutions. The advantage of this study gives a better understanding of the structure of the model and more deep and elegant results.
Behavioral rhythms of an opportunistic predator living in anthropogenic landscapes
Authors: Parra-Torres Yaiza , Ramírez Francisco , Afán Isabel , Aguzzi Jacopo , Bouten Willem , Forero Manuela G. , Navarro Joan 
Published: April 2020

Abstract
Background
Human activities have profoundly altered the spatio-temporal availability of food resources. Yet, there is a clear lack of knowledge on how opportunistic species adapt to these new circumstances by scheduling their daily rhythms and adjust their foraging decisions to predicable patterns of anthropic food subsidies. Here, we used nearly continuous GPS tracking data to investigate the adaptability of daily foraging activity in an opportunistic predator, the yellow-legged gull (Larus michahellis), in response to human schedules.

Methods
By using waveform analysis, we compared timing and magnitude of peaks in daily activity of different GPS-tracked individuals in eleven different habitat types, in relation to type of day (i.e., weekday vs. weekend).

Results
Daily activity rhythms varied greatly depending on whether it was a weekday or weekend, thus suggesting that gulls’ activity peaks matched the routines of human activity in each habitat type. We observed for the first time two types of activity as modelled by waveforms analysis: marine habitats showed unimodal patterns with prolonged activity and terrestrial habitats showed bimodal patterns with two shorter and variable activity peaks.

Conclusions
Our results suggest that gulls are able to fine-tune their daily activity rhythms to habitat-specific human schedules, since these likely provide feeding opportunities. Behavioral plasticity may thus be an important driver of expansive population dynamics. Information on predictable relationships between daily activity patterns of gulls and human activities is therefore relevant to their population management.
Predicting Cancer Cell Line Dependencies From the Protein Expression Data of Reverse-Phase Protein Arrays
Authors: Chen Mei-Ju May , Li Jun , Mills Gordon B. , Liang Han 
Published: April 2020

PURPOSEPredicting cancer dependencies from molecular data can help stratify patients and identify novel therapeutic targets. Recently available data on large-scale cancer cell line dependency allow a systematic assessment of the predictive power of diverse molecular features; however, the protein expression data have not been rigorously evaluated. By using the protein expression data generated by reverse-phase protein arrays, we aimed to assess their predictive power in identifying cancer dependencies and to develop a related analytic tool for community use.MATERIALS AND METHODSBy using a machine learning schema, we conducted an analysis of feature importance based on cancer dependency and multiomic data from the DepMap and Cancer Cell Line Encyclopedia projects. We assessed the consistency of cancer dependency data between CRISPR/Cas9 and short hairpin RNA–mediated perturbation platforms. For a fair comparison, we focused on a set of genes with robust dependency data and four available expression-related features (copy number alteration, DNA methylation, messenger RNA expression, and protein expression) and performed the same-gene predictions of the cancer dependency using different molecular features.RESULTSFor the genes surveyed, we observed that the protein expression data contained substantial predictive power for cancer dependencies, and they were the best predictive feature for the CRISPR/Cas9-based dependency data. We also developed a user-friendly protein-dependency analytic module and integrated it with The Cancer Proteome Atlas; this module allows researchers to explore and analyze our results intuitively.CONCLUSIONThis study provides a systematic assessment for predicting cancer dependencies of cell lines from different expression-related features of a gene. Our results suggest that protein expression data are a highly valuable information resource for understanding tumor vulnerabilities and identifying therapeutic opportunities.
Consistent Physical Activity and Future Neurocognitive Problems in Adult Survivors of Childhood Cancers: A Report From the Childhood Cancer Survivor Study
Authors: Barlow-Krelina Emily , Chen Yan , Yasui Yutaka , Till Christine , Gibson Todd M. , Ness Kirsten K. , Leisenring Wendy M. , Howell Rebecca M. , Nathan Paul C. , Oeffinger Kevin C. , Robison Leslie L. , Armstrong Gregory T. , Krull Kevin R. , Edelstein Kim 
Published: April 2020

PURPOSE To investigate longitudinal associations between physical activity (PA) and neurocognitive problems in adult survivors of childhood cancer. METHODS A total of 12,123 5-year survivors diagnosed between 1970 and 1999 (median [range] age at diagnosis, 7 [0-21] years, time since diagnosis at baseline, 16 [6-30] years) and 720 siblings self-reported PA and neurocognitive problems. PA was collected at baseline, and PA and neurocognitive data were obtained 7 (1-12) years and 12 (9-14) years later. PA consistency was defined as any combination of ≥ 75 minutes of vigorous or 150 minutes of moderate activity per week on all surveys. Multiple linear regressions, conducted separately for CNS and non-CNS survivors, identified associations between PA consistency and neurocognitive outcomes (expected mean, 50; standard deviation [SD], 10). Mediating effects of body mass index (BMI) and chronic health conditions (CHCs) were evaluated. RESULTS Survivors were less likely than siblings to report consistent PA (28.1% v 33.6%) and more likely to report problems in Task Efficiency (T-scores mean ± SD: siblings, 50.0 ± 0.4; CNS, 61.4 ± 0.4; non-CNS, 53.3 ± 0.3), Emotion Regulation (siblings, 51.4 ± 0.4; CNS, 54.5 ± 0.3; non-CNS 53.4 ± 0.2), and Memory (siblings, 50.8 ± 0.4; CNS, 58.9 ± 0.4; non-CNS, 53.5 ± 0.2; all P < .001). Survivors of CNS cancers (52.8 ± 0.3) also reported poorer Organization than siblings (49.9 ± 0.4; P < .001). After adjusting for age at diagnosis, age at questionnaire, emotional distress, and cancer treatment exposures, consistent PA was associated with fewer neurocognitive problems compared with consistent inactivity for both CNS and non-CNS groups (T-score differences ranging from −7.9 to −2.2) and larger neurocognitive improvements over time (−6.0 to −2.5), all P ≤ .01. BMI and severe CHCs partially mediated the PA-neurocognitive associations, but the mediation effects were small (change in β ≤ 0.4). CONCLUSION Adult survivors of childhood cancer who report more consistent PA have fewer neurocognitive problems and larger improvements in these concerns many years after treatment.
Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis
Authors: Volkmar Norbert , Christianson John C. 
Published: April 2020

ABSTRACT
Integral membrane proteins play key functional roles at organelles and the plasma membrane, necessitating their efficient and accurate biogenesis to ensure appropriate targeting and activity. The endoplasmic reticulum membrane protein complex (EMC) has recently emerged as an important eukaryotic complex for biogenesis of integral membrane proteins by promoting insertion and stability of atypical and sub-optimal transmembrane domains (TMDs). Although confirmed as a bona fide complex almost a decade ago, light is just now being shed on the mechanism and selectivity underlying the cellular responsibilities of the EMC. In this Review, we revisit the myriad of functions attributed the EMC through the lens of these new mechanistic insights, to address questions of the cellular and organismal roles the EMC has evolved to undertake.
Nasal fractures: a dedicated clinic providing reduction under local anaesthesia improves time to manipulation
Authors: Pinto R , Wright R , Ghosh S 
Published: April 2020

Introduction Guidelines for nasal injury state that assessment should be at 7–10 days post-injury and manipulation within 14 days. We performed a plan, do, study, act improvement cycle to assess whether a dedicated nasal fracture service led to better outcomes. Materials and methods A retrospective study was carried out of all patients undergoing manipulation under anaesthesia for nasal trauma between February 2013 and December 2016 in a district general hospital. A dedicated nasal fracture clinic providing manipulation under local anaesthesia was implemented followed by a prospective study of all patients presenting to the clinic between February and November 2017. Main outcome measures included time from injury to otolaryngology assessment, time from injury to manipulation and incidence of secondary septorhinoplasty. Results The retrospective series involved 525 patients including 381 males (72.6%) and 144 females (27.4%). Mean time from injury to assessment was 10 days. Mean time from injury to surgery was 14.5 days. Mean time from assessment to surgery was five days. The incidence of septorhinoplasty was 2.3%. The prospective series involved 119 patients including 78 males (65.5%) and 41 females (34.5%). Following implementation of a nasal fracture clinic, mean time from injury to assessment and manipulation was 6.1 days and 5.4% of patients underwent septorhinoplasty for secondary deformity. Discussion Implementation of a nasal fracture clinic providing reduction under local anaesthesia reduced the time to assessment and manipulation. The incidence of septorhinoplasty is low following reduction under general or local anaesthesia. Assessment earlier than seven days is feasible and advice for referral can be changed accordingly.
Stable high-energy, high-repetition-rate, frequency doubling in a large aperture temperature-controlled LBO at 515  nm
Authors: Phillips Jonathan P. , Banerjee Saumyabrata , Ertel Klaus , Mason Paul , Smith Jodie , Butcher Thomas , De Vido Mariastefania , Edwards Chris , Hernandez-Gomez Cristina , Collier John 
Published: April 2020

We report on frequency doubling of high-energy, high-repetition-rate ns pulses from a cryogenically gas cooled, multi-slab Yb:YAG laser system, using a type-I phase–matched lithium triborate (LBO) crystal. Pulse energy of 4.3 J was extracted at 515 nm for a fundamental input of 5.4 J at 10 Hz (54 W), corresponding to a conversion efficiency of 77%. However, during long-term operation, a significant reduction of efficiency (more than 25%) was observed owing to the phase mismatch arising due to the temperature-dependent refractive index change in the crystal. This forced frequent angle tuning of the crystal to recover the second-harmonic generation (SHG) energy. More than a five-fold improvement in energy stability of SHG was observed when the LBO crystal was mounted in an oven, and its temperature was controlled at 27°C. Stable frequency doubling with 0.8% rms energy variation was achieved at a higher input power of 74 W when the LBO temperature was controlled at 50°C.