bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive injury and absence of monocytes promote astrocyte self‐renewal and neurological recovery
Authors: Lange Canhos Luisa , Chen Muxin , Falk Sven , Popper Bastian , Straub Tobias , Götz Magdalena , Sirko Swetlana 
Published: August 2020

AbstractUnlike microglia and NG2 glia, astrocytes are incapable of migrating to sites of injury in the posttraumatic cerebral cortex, instead relying on proliferation to replenish their numbers and distribution in the affected region. However, neither the spectrum of their proliferative repertoire nor their postinjury distribution has been examined in vivo. Using a combination of different thymidine analogs and clonal analysis in a model of repetitive traumatic brain injury, we show for the first time that astrocytes that are quiescent following an initial injury can be coerced to proliferate after a repeated insult in the cerebral cortex grey matter. Interestingly, this process is promoted by invasion of monocytes to the injury site, as their genetic ablation (using CCR2−/− mice) increased the number of repetitively dividing astrocytes at the expense of newly proliferating astrocytes in repeatedly injured parenchyma. These differences profoundly affected both the distribution of astrocytes and recovery period for posttraumatic behavior deficits suggesting key roles of astrocyte self‐renewal in brain repair after injury.
A Fibrosis‐Independent Hepatic Transcriptomic Signature Identifies Drivers of Disease Progression in Primary Sclerosing Cholangitis
Authors: Gindin Yevgeniy , Chung Chuhan , Jiang Zhaoshi , Zhou Jing Zhu , Xu Jun , Billin Andrew N. , Myers Robert P. , Goodman Zachary , Landi Abdolamir , Houghton Michael , Green Richard M. , Levy Cynthia , Kowdley Kris V. , Bowlus Christopher L. , Muir Andrew J. , Trauner Michael 
Published: August 2020

Background and Aims
Primary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n = 74) enrolled in a 96‐week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events.

Approach and Results
The effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis‐adjusted gene expression patterns were associated with time to first PSC‐related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48 years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA‐sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ = −0.80; P < 0.001). After removing the effect of fibrosis‐related genes, the first principle component was not associated with fibrosis (ρ = −0.19; P = 0.11), and a semisupervised clustering approach identified two distinct patient clusters with differential risk of time to first PSC‐related event (P < 0.0001). The two groups had similar fibrosis stage, hepatic collagen content, and α‐smooth muscle actin expression by morphometry, Enhanced Liver Fibrosis score, and serum liver biochemistry, bile acids, and IL‐8 (all P > 0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down‐regulated in the high‐risk group by log‐fold changes of −0.18 [P = 0.02] and −0.16 [P = 0.02], respectively). Clinical events were enriched in the high‐risk versus low‐risk group (38% [12/32] vs. 2.4% [1/42], P < 0.0001).

Conclusions
Removing the contribution of fibrosis‐related pathways uncovered alterations in the unfolded protein response, which were associated with liver‐related complications in PSC.
Understanding the needs of local youth to inform drug and alcohol prevention and harm reduction services: A qualitative study
Authors: Deans Emily , Ravulo Jioji , Blignault Ilse , Conroy Elizabeth 
Published: August 2020

AbstractIssue addressedReducing drug and alcohol harm is a public health priority and the Australian government has adopted a harm minimisation approach to policy. Understanding the needs of local youth is necessary for the design of relevant prevention and harm reduction services.MethodsUsing 5 unstructured focus groups and 10 interviews involving 30 participants recruited from different settings, this study explored youth perspectives around alcohol and other drugs and the psychosocial factors that influence their substance use.ResultsThree main themes were identified. First, young people perceived that drugs fell into a hierarchy related to the harm they cause and the stigma associated with use. Second, the importance of validating a young person's experience with using drugs (regardless of where they were placed on their substance‐use trajectory) as a measure to increase the credibility of drug education programs. Third, the significant influence of peers on young people's drug attitudes and behaviours.ConclusionsDrug and alcohol education strategies must be more explicit regarding harm across all drug types, regardless of legal status or perceived social acceptability. Prevention services would benefit from including lived realities from young people's varied and changing experiences with using substances. Peer involvement in the design of preventive strategies (and involvement in participatory research to identify felt needs) is paramount to ensure teachings are grounded in a young person's social context and lived realities.So what?This study provides information to guide the development of appropriate and authentic drug and alcohol prevention and harm reduction services for young people.
Fostering the healthcare workforce during the COVID‐19 pandemic: Shared leadership, social capital, and contagion among health professionals
Authors: Salas‐Vallina Andrés , Ferrer‐Franco Anna , Herrera Justo 
Published: August 2020

SummaryHealth professionals managing patients with COVID‐19 disease are at high risk of contagion. All medical personnel involved in caring for patients need coordination, knowledge and trust. Empirical work on human resources has tended to focus on the effects of human resource practices on performance, whereas leadership and social interactions have been overlooked. Based upon interviews with medical staff working in specialised medical units, this study uses the social capital theory to examine relationships among shared leadership, social capital, and contagion rates. First, shared leadership was found to positively affect COVID‐19 contagion among health professionals. Second, by sharing information and a common language, and showing high levels of trust, namely social capital, medical units seem to reduce contagion rates of COVID‐19. In other words, shared leadership plays a fundamental role in improving performance in healthcare by means of social capital.
A gene expression‐based single sample predictor of lung adenocarcinoma molecular subtype and prognosis
Authors: Liljedahl Helena , Karlsson Anna , Oskarsdottir Gudrun N. , Salomonsson Annette , Brunnström Hans , Erlingsdottir Gigja , Jönsson Mats , Isaksson Sofi , Arbajian Elsa , Ortiz‐Villalón Cristian , Hussein Aziz , Bergman Bengt , Vikström Anders , Monsef Nastaran , Branden Eva , Koyi Hirsh , de Petris Luigi , Patthey Annika , Behndig Annelie F. , Johansson Mikael , Planck Maria , Staaf Johan 
Published: August 2020

AbstractDisease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression‐based AC subtypes such as the Cancer Genome Atlas Network (TCGA) terminal‐respiratory unit (TRU), proximal‐inflammatory (PI) and proximal‐proliferative (PP) subtypes have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype assignment and risk stratification that could function in a clinical setting. Two‐class (TRU/nonTRU=SSP2) and three‐class (TRU/PP/PI=SSP3) SSPs using the AIMS algorithm were trained in 1655 ACs (n = 9659 genes) from public repositories vs TCGA centroid subtypes. Validation and survival analysis were performed in 977 patients using overall survival (OS) and distant metastasis‐free survival (DMFS) as endpoints. In the validation cohort, SSP2 and SSP3 showed accuracies of 0.85 and 0.81, respectively. SSPs captured relevant biology previously associated with the TCGA subtypes and were associated with prognosis. In survival analysis, OS and DMFS for cases discordantly classified between TCGA and SSP2 favored the SSP2 classification. In resected Stage I patients, SSP2 identified TRU‐cases with better OS (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.18‐0.49) and DMFS (TRU HR = 0.52; 95% CI = 0.33‐0.83) independent of age, Stage IA/IB and gender. SSP2 was transformed into a NanoString nCounter assay and tested in 44 Stage I patients using RNA from formalin‐fixed tissue, providing prognostic stratification (relapse‐free interval, HR = 3.2; 95% CI = 1.2‐8.8). In conclusion, gene expression‐based SSPs can provide molecular subtype and independent prognostic information in early‐stage lung ACs. SSPs may overcome critical limitations in the applicability of gene signatures in lung cancer.
The dilemma between fund‐style consistency and active management over the economic cycle. Evidence from pension funds
Authors: Alda Mercedes 
Published: August 2020

AbstractThis paper examines whether equity‐allocation shifts (equity‐holding and equity‐style shifts) jeopardize retirement savings in U.K. equity pension funds. Fund‐style shifts may deviate pension funds from their original risk profile and expose participants to undesired results. Nonetheless, these shifts may be the result of an active management to adapt to market cycles. Financial literature usually points out the policy‐allocation importance versus the active management in explaining fund returns; however, we find significant relation between them. Our results show that managers vary their portfolios to add value, avoid the constraints of preserving consistent styles, and adapt to market conditions. Participants do not negatively react to style changes because top shifter funds are run by skillful managers and outperform. Nevertheless, managers must be aware of their limitations and the risk taken with this strategy. Poor skilled managers do not successfully implement style‐shift strategies, especially in crises.
The effect of tax preparers on corporate tax aggressiveness: Evidence form the UK context
Authors: Assidi Soufiene , Hussainey Khaled 
Published: August 2020

AbstractThis paper studies the role of tax preparers in tax aggressiveness. Based on a sample of 342 UK companies indexed on the Financial Times Stock Exchange (FTSE) 350 from 2006 to 2016, it finds that external tax preparers are more tax aggressive than internal ones. The result is explained by the capability of external preparers to take more aggressive tax positions than internal preparers because of their knowledge in different changes to tax law, and their higher expertise in this field. The findings has implications for managers, policymakers and researchers.
Does corporate social responsibility mediate the influence of national culture on investment inefficiency? Firm‐level evidence from Asia Pacific
Authors: Rehman Ijaz Ur , Shahzad Faisal , Latif Khawaja Fawad , Nawab Noman , Rashid Abdul , Hyder Shabir 
Published: August 2020

AbstractA systematic understanding of how national culture translates its effect on firm‐level CSR performance which resultantly increases or decreases firm‐level investment inefficiency is critical void in the extant literature which the current study aims to fill over and above what previous studies have documented on the relationship between national culture and investment inefficiency and national culture and CSR performance. Building on Hofstede's four culture dimensions, we examine the direct and indirect links between national culture and investment inefficiency by considering the mediating role of Corporate Social Responsibility performance. Our study sample comprises of firms registered and remained list on the stock exchanges of 12 different Asia Pacific countries over the period of 2006–2016. To test the pathway in which national culture act on investment efficacy, Sobel intermediary factor test method is used to analyse the intermediary effect. We provide evidence that high degree of individualism, uncertainty avoidance and masculinity significantly reduce investment inefficiency. We also show that these variables decrease firm investment inefficiencies mainly through the increased CSR performance. In contrast, our results suggest that higher power distance increases the investment inefficiency of firms through declines in CSR performance. Our findings are robust after controlling for endogeneity, self‐selection and sample selection biases.
Good variance, bad variance, and stock return predictability
Authors: Zhang Yaojie , Ma Feng , Liang Chao , Zhang Yi 
Published: August 2020

AbstractIn the stock market, past winners and losers usually have different attitudes to variance risk. In light of this, we decompose stock variance into good and bad variances, and further construct a composite signed variance. The recursively estimated coefficient of standard variance is volatile over time, but the ones of good, bad, and signed variances are fairly stable. This suggests the high efficiency of our decomposition approach. We provide convincing evidence that bad variance and composite signed variance can significantly predict future stock returns both in‐ and out‐of‐sample. Furthermore, a mean–variance investor can realize substantial economic gains by using our bad and signed variances relative to the traditional variance predictor and simple mean benchmark. Our decomposition approach can outperform other similar but complex techniques, including threshold regression and Markov regime switching. The results are consistent across multiple robustness tests.
Inside Cover
Authors: Tsai Chung‐Min , Chang Shwu‐Fen , Chang Hsi 
Published: August 2020

AbstractTranscranial photobiomodulation (tPBM) with wavelength at 808 nm was applied to a rat model of acute seizures. The tPBM successfully attenuated convulsive status epilepticus, and the tPBM was shown to reduce the apoptosis of parvalbumin‐positive interneurons (PV‐INs) and preserved the integrity of perisomatic inhibitory network of PV‐INs to principle cells in the hippocampus.Further details can be found in the article by Chung‐Min Tsai, Shwu‐Fen Chang, and Hsi Chang (e202000095).
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Inside Cover
Authors: Liberda Danuta , Hermes Michael , Koziol Paulina , Stone Nick , Wrobel Tomasz P. 
Published: August 2020

AbstractEsophagus tissue classification models based on FT‐IR imaging data were successfully created (AUC>0.95). The conditions for translating a histopathological FT‐IR based model to a fast Quantum Cascade Laser (QCL) system microscope were investigated.Further details can be found in the article by Danuta Liberda, Michael Hermes, Paulina Koziol, Nick Stone and Tomasz P. Wrobel (e202000122).
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Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer
Authors: Sadeghi Hossein , Nazemalhosseini‐Mojarad Ehsan , Sahebi Unes , Fazeli Elnaz , Azizi‐Tabesh Ghasem , Yassaee Vahid R. , Savabkar Sanaz , Asadzadeh Aghdaei Hamid , Zali Mohammad R. , Mirfakhraie Reza 
Published: August 2020

AbstractLong noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism pathway. In the present research, we surveyed the expression levels and clinical significance of novel lncRNAs related to CYP24A1 and PFDN4 genes in colorectal cancer (CRC) using real‐time polymerase chain reaction. Furthermore, we assessed the expression of these genes after vitamin D treatment in HCT‐116 and HT‐29 colon cancer cell lines. Our results indicated that the transcription of CYP24A1, PFDN4, and nearby lncRNAs was affected by vitamin D treatment in HCT‐116 and HT‐29 cell lines. Moreover, CYP24A1, PFDN4, lnc‐CYP24A1‐3:1, and lnc‐TSHZ2‐19:1 were upregulated and had the potential to distinguish colorectal cancer tissues from the adjacent tissues by the large area under the receiver operating characteristic curve (0.94, 0.66, 0.70, and 0.60, respectively). lnc‐TSHZ2‐19:1 expression level significantly correlated with gender (p = .03). In conclusion, CYP24A1, PFDN4, lnc‐CYP24A1‐3:1, and lnc‐TSHZ2‐19:1 can be used as potential diagnostic biomarkers in the specific and sensitive assessment of CRC. Besides this, vitamin D treatment may modulate the expression of these genes in a cell‐specific manner.
Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis
Authors: Mou Junjie , Xu Jinhui , Wang Zhe , Wang Chuanli , Yang Xueqi , Wang Xingchen , Xue Huiliang , Wu Ming , Xu Laixiang 
Published: August 2020

AbstractPhotoperiod regulates the seasonal reproductive rhythms of mammals by influencing the development and function of sexual organs; however, the underlying mechanism remains unclear. We examined the morphology and functioning of the main sex organs of striped dwarf hamsters (Cricetulus barabensis) under different photoperiods (short daylight [SD], moderate daylight [MD], and long daylight [LD]) and further investigated the underlying molecular mechanisms. There was an inverse correlation between blood melatonin levels and photoperiod in the order SD > MD > LD. Decreases in body and tissue weights were observed under SD, whereas testis and epididymis weights between MD and LD were comparable. The diameters of the spermatogenic tubules, thickness of the spermatogenic epithelium, and the number of spermatogonia and Sertoli cells decreased under SD, whereas the serum‐luteinizing hormone, follicle‐stimulating hormone, and fecal testosterone concentrations decreased under LD. In SD, bax/bcl2 protein expression increased in the testes and decreased in the epididymides, whereas LC3II/LC3I remained unchanged in the testes and increased in the epididymides compared with the MD group. In LD, bax/bcl2 and LC3II/LC3I protein expression levels were unchanged in the testes but were decreased in the epididymides. In SD and LD, adenosine triphosphate synthase and citrate synthase protein expression levels were unchanged in the testes but were decreased in the epididymides. Drp1 and Mff protein expression increased in the testes and decreased in the epididymides. Overall, different regulatory mechanisms in the testis and epididymis led to degeneration under SD and maintenance under LD, preferentially protecting mitochondrial function in the testis by regulating mitochondrial fission.
An expedient multi‐component synthesis of pyridinyl‐spirooxindoles and their effect on proliferation of lung cancer A549 cells
Authors: Yan Liang , Wu Xu , Zhang Yizongheng , Sankaran Mathan , Xu Lei , Ling Liefeng , Wang Yi , Jiang Yuxin , Ma Jinzhu , Kong Lingyu 
Published: August 2020

AbstractA series of new functionalized pyridinyl‐spirooxindoles have been synthesized through three‐component cyclization reactions. The selected compounds were screened for their in vitro antiproliferative activity against human lung cancer cell line A549. Among the candidate structures, compound 1o demonstrated maximum inhibitory activity against A549 cells with IC50 values of 28.38 μM. EdU (5‐Ethynyl‐2′‐ deoxyuridine, EdU) assay and cell colony formation test showed that cell proliferation of A549 cells was inhibited. In addition, Western blot analysis revealed that the phosphorylation levels of Akt, mTOR, 70S6, and S6 were down‐regulated. Thus, these results indicated that 1o may inhibit the proliferation of A549 cells through inhibiting the phosphorylation levels of Akt, mTOR, 70S6, and S6. 1o may be developed as a potential antitumor agent for lung cancer treatment.
The relationship between trauma symptoms and immediate and delayed suggestibility in children who have been sexually abused
Authors: Gudjonsson Gisli , Vagni Monia , Maiorano Tiziana , Pajardi Daniela 
Published: August 2020

AbstractThere is general absence of research about the relationship between trauma symptoms and immediate and delayed suggestibility in children who have been sexually abused. The participants were 134 children aged between 7 and 17 years with a history of reported sexual abuse. All children completed the Gudjonsson Suggestibility Scale (2), a non‐verbal IQ test, and The University of California at Los Angeles Child/Adolescent Reaction Index for post‐traumatic stress (UCLA‐PTSD‐RI‐5). Delayed suggestibility was measured after a 1 week delay. A Hierarchical Regression showed that trauma symptoms accounted overall for 43.4% of the variance in delayed suggestibility after controlling for age, sex, IQ, and immediate recall (a large effect size). There was a small shared variance between trauma and immediate suggestibility (low effect size). The findings strongly suggest that the severity of trauma symptoms impact more on delayed than immediate suggestibility. The theoretical and forensic implications are discussed.
MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression
Authors: Luiz João Paulo M , Toller-Kawahisa Juliana E , Viacava Paula R , Nascimento Daniele C , Pereira Priscilla T , Saraiva André L , Prado Douglas S , Le Bert Marc , Giurisato Emanuele , Tournier Cathy , Cunha Thiago M , Cunha Fernando Q , Quesniaux Valerie , Ryffel Bernhard , Alves-Filho José C 
Published: August 2020

Abstract
Macrophages are highly plastic cells, responding to diverse environmental stimuli to acquire different functional phenotypes. Signaling through MAPKs has been reported to regulate the differentiation of macrophages, but the role of ERK5 in IL-4-mediated M2 macrophage differentiation is still unclear. Here, we showed that the ERK5 signaling pathway plays a critical role in IL-4-induced M2 macrophage differentiation. Pharmacologic inhibition of MEK5, an upstream activator of ERK5, markedly reduced the expression of classical M2 markers, such as Arg-1, Ym-1, and Fizz-1, as well as the production of M2-related chemokines and cytokines, CCL22, CCL17, and IGF-1 in IL-4-stimulated macrophages. Moreover, pharmacologic inhibition of ERK5 also decreased the expression of several M2 markers induced by IL-4. In accordance, myeloid cell-specific Erk5 depletion (Erk5∆mye), using LysMcre/Erk5f/f mice, confirmed the involvement of ERK5 in IL-4-induced M2 polarization. Mechanistically, the inhibition of ERK5 did not affect STAT3 or STAT6 phosphorylation, suggesting that ERK5 signaling regulates M2 differentiation in a STAT3 and STAT6-independent manner. However, genetic deficiency or pharmacologic inhibition of the MEK5/ERK5 pathway reduced the expression of c-Myc in IL-4-activated macrophages, which is a critical transcription factor involved in M2 differentiation. Our study thus suggests that the MEK5/ERK5 signaling pathway is crucial in IL-4-induced M2 macrophage differentiation through the induction of c-Myc expression.