bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut–Liver Immune Response and Gut Microbiota Profiling Reveal the Pathogenic Mechanisms of Vibrio harveyi in Pearl Gentian Grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀)
Authors: Deng Yiqin , Zhang Yaqiu , Chen Haoxiang , Xu Liwen , Wang Qian , Feng Juan 
Published: November 2020

Vibrio harveyi causes vibriosis in nearly 70% of grouper (Epinephelus sp.), seriously limiting grouper culture. As well as directly inhibiting pathogens, the gut microbiota plays critical roles in immune homeostasis and provides essential health benefits to its host. However, there is still little information about the variations in the immune response to V. harveyi infection and the gut microbiota of grouper. To understand the virulence mechanism of V. harveyi in the pearl gentian grouper, we investigated the variations in the pathological changes, immune responses, and gut bacterial communities of pearl gentian grouper after exposure to differently virulent V. harveyi strains. Obvious histopathological changes were detected in heart, kidney, and liver. In particular, nodules appeared and huge numbers of V. harveyi cells colonized the liver at 12 h postinfection (hpi) with highly virulent V. harveyi. Although no V. harveyi was detected in the gut, the infection simultaneously induced a gut-liver immune response. In particular, the expression of 8 genes associated with cellular immune processes, including genes encoding inflammatory cytokines and receptors, and pattern recognition proteins, was markedly induced by V. harveyi infection, especially with the highly virulent V. harveyi strain. V. harveyi infection also induced significant changes in gut bacterial community, in which Vibrio and Photobacterium increased but Bradyrhizobium, Lactobacillus, Blautia, and Faecalibaculum decreased in the group infected with the highly virulent strain, with accounting for 82.01% dissimilarity. Correspondingly, four bacterial functions related to bacterial pathogenesis were increased by infection with highly virulent V. harveyi, whereas functions involving metabolism and genetic information processing were reduced. These findings indicate that V. harveyi colonizes the liver and induces a gut-liver immune response that substantially disrupts the composition of and interspecies interactions in the bacterial community in fish gut, thereby altering the gut-microbiota-mediated functions and inducing fish death.
Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum
Authors: Pizzarotti Beatrice , Palesi Fulvia , Vitali Paolo , Castellazzi Gloria , Anzalone Nicoletta , Alvisi Elena , Martinelli Daniele , Bernini Sara , Cotta Ramusino Matteo , Ceroni Mauro , Micieli Giuseppe , Sinforiani Elena , D’Angelo Egidio , Costa Alfredo , Gandini Wheeler-Kingshott Claudia A. M. 
Published: November 2020

BackgroundFrontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understand this clinical continuum.MethodsWe used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness (CT¯) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency, and semantic fluency.ResultsCommon (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS, and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g., a difference of cerebral and cerebellar involvement between FTSD and ALS). CT¯ values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and CT¯ in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions.ConclusionWe identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.
Association of the Plasma Long Non-coding RNA MEG3 With Parkinson's Disease
Authors: Quan Yi , Wang Jia , Wang Shuo , Zhao Jizong 
Published: November 2020

Objective: To investigate the expression level of the maternally expressed gene-3 (MEG3) of the free long non-coding RNA (lncRNAs) in the plasma of Parkinson's disease (PD) patients and its relationship with the disease.Methods: Thirty PD patients (PD group) who treated at Xuanwu Hospital of Capital University of Medical Sciences between January 2017 and December 2019 were selected as the research objects and 30 healthy subjects were enrolled in the study during the same period as the control group. Cognitive function was assessed according to the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function, Non-Motor Symptoms Scale (NMSS) was used to evaluate severity of non-motor symptoms. The relative expression of lncRNAs MEG3 in plasma was measured by PCR, and the levels of neuron-specific enolase (NSE), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in plasma were measured by ELISA, and the relationship with these all indexes was analyzed.Results: The NMSS score of PD group was significantly higher than that of the control group, while the MMSE and MoCA scores were significantly lower than that of the control group (P &lt; 0.05); The relative expression of lncRNAs MEG3, NGF and BDNF levels of PD group were significantly lower than that of the control group, and NSE level was significantly higher than that of the control group (P &lt; 0.05); The H&amp;Y stage and NMSS score in PD group were negatively correlated with the relative expression of lncRNAs MEG3, the levels of NGF and BDNF (P &lt; 0.05), and positively correlated with NSE (P &lt; 0.05); The MMSE and MoCA scores in PD group were positively correlated with the relative expression of lncRNAs MEG3, NGF, BDNF levels (P &lt; 0.05), and negatively correlated with NSE (P &lt; 0.05); The relative expression of lncRNAs MEG3 in PD group was positively correlated with NGF, BDNF levels (P &lt; 0.05), and negatively correlated with NSE (P &lt; 0.05).Conclusion: The expression of lncRNAs MEG3 in the plasma of PD patients was downregulated compared to that of healthy control subjects, and its expression level was closely related to the aggravation of non-motor symptoms, cognitive decline, and PD stage. These associations may reflect the synergism of the increase of NSE and decrease of NGF and BDNF levels, highlighting plasma lncRNA MEG3 as a new candidate biomarker of PD.
Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments
Authors: Merians Alma S. , Fluet Gerard G. , Qiu Qinyin , Yarossi Mathew , Patel Jigna , Mont Ashley J. , Saleh Soha , Nolan Karen J. , Barrett AM , Tunik Eugene , Adamovich Sergei V. 
Published: November 2020

Introduction:Innovative motor therapies have attempted to reduce upper extremity impairment after stroke but have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits affecting their self-care and participation in daily activities. Intervention studies have focused on the role of increased dosing, however recent studies have indicated that timing of rehabilitation interventions may be as important as dosing and importantly, that dosing and timing interact in mediating effectiveness. This study is designed to empirically test dosing and timing.Methods and Analysis:In this single-blinded, interventional study, subjects will be stratified on two dimensions, impairment level (Fugl-Meyer Upper Extremity Assessment (FM) and presence or absence of Motor Evoked Potentials (MEPs) as follows; (1) Severe, FM score 10–19, MEP+, (2) Severe, FM score 10–19, MEP–, (3) Moderate, FM score 20–49, MEP+, (4) Moderate, FM score 20–49, MEP–. Subjects not eligible for TMS will be assigned to either group 2 (if severe) or group 3 (if moderate). Stratified block randomization will then be used to achieve a balanced assignment. Early Robotic/VR Therapy (EVR) experimental group will receive in-patient usual care therapy plus an extra 10 h of intensive upper extremity therapy focusing on the hand using robotically facilitated rehabilitation interventions presented in virtual environments and initiated 5–30 days post-stroke. Delayed Robotic/VR Therapy (DVR) experimental group will receive the same intervention but initiated 30–60 days post-stroke. Dose-matched usual care group (DMUC) will receive an extra 10 h of usual care initiated 5–30 days post-stroke. Usual Care Group (UC) will receive the usual amount of physical/occupational therapy.Outcomes:There are clinical, neurophysiological, and kinematic/kinetic measures, plus measures of daily arm use and quality of life. Primary outcome is the Action Research Arm Test (ARAT) measured at 4 months post-stroke.Discussion:Outcome measures will be assessed to determine whether there is an early time period in which rehabilitation will be most effective, and whether there is a difference in the recapture of premorbid patterns of movement vs. the development of an efficient, but compensatory movement strategy.Ethical Considerations:The IRBs of New Jersey Institute of Technology, Rutgers University, Northeastern University, and Kessler Foundation reviewed and approved all study protocols. Study was registered inhttps://ClinicalTrials.gov(NCT03569059) prior to recruitment. Dissemination will include submission to peer-reviewed journals and professional presentations.
Impact of Lower Limb Active Movement Training in Individuals With Spastic Type Cerebral Palsy on Neuromuscular Control Outcomes: A Systematic Review
Authors: O'Brien Shari M. , Lichtwark Glen A. , Carroll Timothy J. , Barber Lee A. 
Published: November 2020

Background: Cerebral Palsy (CP) is a non-progressive neurological condition that results in motor impairment which increases proximally to distally along the lower extremity (i.e., greatest impairment at the ankle). Consequently, motor impairment and reduced voluntary muscle activation results in reduced neuromuscular control of the lower limb in this population. CP rehabilitation traditionally aims to improve movement proficiency for functional activities, such as walking, by using a range of active movement modalities that require volitional effort; however, the underlying neural mechanisms of improved control and function remain unknown. The primary purpose of this study was to systematically determine the efficacy of lower limb active movement interventions to improve neuromuscular control in individuals with CP.Methodology: A search for studies involving an active lower limb intervention and neurophysiological outcome measures in individuals with CP was performed in five electronic databases. Studies were assessed for methodological quality using the Downs and Black assessment tool.Results: Nine of 6,263 articles met the inclusion criteria. Methodological quality of all studies was poor, ranging from 2 to 27 out of a possible score of 32 points on the Downs and Black assessment tool. The study interventions varied extensively in modality and prescription as well as in the outcome measures used.Conclusions: Whether active movement improves neuromuscular control of the lower limb in CP is unclear due to high variability in intervention protocols and selected outcomes measures. Future active intervention studies must carefully consider the selection of neurophysiological outcome measures.
An in vitro Model of Human Retinal Detachment Reveals Successive Death Pathway Activations
Authors: Potic Jelena , Mbefo Martial , Berger Adeline , Nicolas Michael , Wanner Dana , Kostic Corinne , Matet Alexandre , Behar-Cohen Francine , Moulin Alexandre , Arsenijevic Yvan 
Published: November 2020

Purposewas to create an in vitro model of human retinal detachment (RD) to study the mechanisms of photoreceptor death.MethodsHuman retinas were obtained through eye globe donations for research purposes and cultivated as explants. Cell death was investigated in retinas with (control) and without retinal pigment epithelium (RPE) cells to mimic RD. Tissues were studied at different time points and immunohistological analyses for TUNEL, Cleaved caspase3, AIF, CDK4 and the epigenetic mark H3K27me3 were performed. Human and monkey eye globes with retinal detachment served as controls.ResultsThe number of TUNEL-positive cells, compared between 1 and 7 days, increased with time in both retinas with RPE (from 1.2 ± 0.46 to 8 ± 0.89, n = 4) and without RPE (from 2.6 ± 0.73 to 16.3 ± 1.27, p &lt; 0.014). In the group without RPE, cell death peaked at day 3 (p = 0.014) and was high until day 7. Almost no Cleaved-Caspase3 signal was observed, whereas a transient augmentation at day 3 of AIF-positive cells was observed to be about 10-fold in comparison to the control group (n = 2). Few CDK4-positive cells were found in both groups, but significantly more in the RD group at day 7 (1.8 ± 0.24 vs. 4.7 ± 0.58, p = 0.014). The H3K27me3 mark increased by 7-fold after 5 days in the RD group (p = 0.014) and slightly decreased at day 7 and was also observed to be markedly increased in human and monkey detached retina samples.ConclusionAIF expression coincides with the first peak of cell death, whereas the H3K27me3 mark increases during the cell death plateau, suggesting that photoreceptor death is induced by different successive pathways after RD. This in vitro model should permit the identification of neuroprotective drugs with clinical relevance.
Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis
Authors: Meng Fanqiao , Chen Xiuqiong , Yu Shunjie , Ren Xiaotong , Liu Zhaoyun , Fu Rong , Li Lijuan 
Published: November 2020

Background and AimMany studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.MethodsA full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.ResultsThis meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47–0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36–0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41–0.83, P = 0.003) and 0.6 (95% CI: 0.37–0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45–0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.ConclusionsThrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.
A Novel Tool to Predict Early Death in Uterine Sarcoma Patients: A Surveillance, Epidemiology, and End Results-Based Study
Authors: Song Zixuan , Wang Yizi , Zhang Dandan , Zhou Yangzi 
Published: November 2020

BackgroundUterine sarcoma is a rare gynecologic tumor with a high degree of malignancy. There is a lack of effective prognostic tools to predict early death of uterine sarcoma.MethodsData on patients with uterine sarcoma registered between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) data. Important independent prognostic factors were identified by univariate and multivariate logistic regression analyses to construct a nomogram for total early deaths and cancer-specific early deaths.ResultsA total of 5,274 patients with uterine sarcoma were included in this study. Of which, 397 patients experienced early death (≤3 months), and 356 of whom died from cancer-specific causes. A nomogram for total early deaths and cancer-specific early deaths was created using data on age, race, tumor size, the International Federation of Gynecology and Obstetrics (FIGO) staging, histological classification, histological staging, treatment (surgery, radiotherapy, chemotherapy), and brain metastases. On comparing the C-index, area under the curve, and decision curve analysis, the created nomogram showed better predictive power and clinical practicality than one made exclusively with FIGO staging. Calibration of the nomogram by internal validation showed good consistency between the predicted and actual early death.ConclusionsNomograms that include clinical characteristics can provide a better prediction of the risk of early death for uterine sarcoma patients than nomograms only comprising the FIGO stage system. In doing so, this tool can help in identifying patients at high risk for early death because of uterine sarcoma.
Evaluating Price and Availability of Essential Medicines in China: A Mixed Cross-Sectional and Longitudinal Study
Authors: Yang Caijun , Hu Shuchen , Ye Dan , Jiang Minghuan , Babar Zaheer-Ud-Din , Fang Yu 
Published: November 2020

Objectives: To evaluate the price and availability of medicines in China.Methods: A standard methodology developed by WHO and Health Action International was used to collect medicine price and availability data. We obtained cross-sectional data for 48 medicines from 519 facilities (280 public hospitals and 239 private retail pharmacies) in five provinces in China in 2018. We also collected longitudinal data for 31 medicines in Shaanxi Province in 2010, 2012, 2014, and 2018. Medicine price was compared with the international reference price to obtain a median price ratio (MPR). The availability and price in five provinces were compared in matched sets. We used general estimating equations to calculate differences in availability and median prices from 2010 to 2018.Findings: Mean availability of surveyed medicines in five provinces was low in both public (4.29–32.87%) and private sectors (13.50–43.75%). The MPR for lowest priced generics (LPGs) was acceptable (1.80–3.02) and for originator brands (OBs) was much higher (9.14–12.65). The variation was significant for both availability and price of medicines across provinces. In Shaanxi Province, the availability of medicines decreased between 2010 and 2018, but this was not significant in the public or private sector. Compared with 2010, the median adjusted patient price was significantly lower in 2018 for nine OBs (difference −22.4%; p = 0.005) and 20 LPGs (−20.5%; p = 0.046) in the public sector and 10 OBs (−10.2%; p = 0.047) in the private sector.Conclusion: Access to medicines was found to be poor and unequal across China in 2018. Future interventions are needed, and possible strategies include effective and efficient procurement, promoting the development of retail pharmacies and increasing medicine price transparency.
A Meta-Analysis on the Association Between TNFSF4 Polymorphisms (rs3861950 T > C and rs1234313 A > G) and Susceptibility to Coronary Artery Disease
Authors: Liu Shuyan , Wang Xiju , Yu Shoujun , Yan Miao , Peng Yue , Zhang Guilong , Xu Zhaowei 
Published: November 2020

Background: Coronary artery disease (CAD) remains the leading cause of mortality worldwide, and its susceptibility is closely associated with genetic modifications. The association between inflammation and CAD has been investigated in detail. This meta-analysis was conducted based on the PRISMA guidelines to evaluate the association between the tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms (rs3861950 T &gt; C and rs1234313 A &gt; G) and the risk of CAD.Methods: The selected criteria included 11 eligible articles containing 18 studies (nine studies included 7,395 cases and 5,296 controls for rs3861950 and nine studies with 6,951 cases and 4,959 controls for rs1234313). Correlations between the two polymorphisms and CAD were estimated by pooling the odds ratios (ORs) with 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous, and homozygous models.Results: The pooled analyses demonstrated that the rs3861950 T &gt; C polymorphism was significantly associated with an increased risk of CAD in the Asian population in the allelic model, dominant model, and homozygous model. Furthermore, subgroup analysis based on disease type showed that TNFSF4 rs3861950 T &gt; C had a robust correlation with increased risk of cerebral infarction (CI) in the allelic model, dominant model, heterozygous model, and homozygous model. However, the rs1234313 A &gt; G polymorphism mostly tended to decrease the risk of CAD in the Asian and Caucasian populations in the allelic and dominant model. This single nucleotide polymorphism (SNP) had a close relation to myocardial infarction (MI) susceptibility in the allelic model, dominant model, and heterozygous model.Conclusion: This meta-analysis identified two novel SNPs in TNFSF4 significantly associated with CAD susceptibility.
The Bright Side of Abstraction: Abstractness Promoted More Empathic Concern, a More Positive Emotional Climate, and More Humanity-Esteem After the Paris Terrorist Attacks in 2015
Authors: Fernández Itziar , Caballero Amparo , Sevillano Verónica , Muñoz Dolores , Oceja Luis , Carrera Pilar 
Published: November 2020

AntecedentsPrevious research on citizens’ reactions after terrorist events has shown that positive reactions can also emerge alongside pain and horror. Positive emotions have been widely associated with an abstract style of thinking. In the context of the Paris terrorist attacks in 2015, we explored Spanish citizens’ positive reactions – empathic concern, positive emotional climate, and esteem for humanity – and examined the relationships of these responses with an abstract (vs. concrete) style of thinking.MethodA longitudinal study was designed involving an online questionnaire that was administered 10 days, 3 weeks, and 2 months after the attacks (N = 253).ResultsEmpathic concern and personal distress toward Parisians decreased from the weeks following the attacks to 2 months later, with empathic concern always being more intense than personal distress. Emotional climate was perceived as more hostile than positive, although positive feelings persisted. People reported moderately positive esteem for humanity. Individuals with a more abstract style of thinking reported greater empathic concern, a more positive emotional climate, and more esteem for humanity.ConclusionsOur results support and extend previous research showing that abstraction enhances people’s resilience, even under traumatic circumstances such as those surrounding a terrorist attack.