bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline
Authors: Wallach Asya I , Waltz Michael , Casper T Charles , Aaen Gregory , Belman Anita , Benson Leslie , Chitnis Tanuja , Gorman Mark , Graves Jennifer , Harris Yolanda , Lotze Timothy E , Mar Soe , Moodley Manikum , Ness Jayne M , Rensel Mary , Rodriguez Moses , Rose John W , Schreiner Teri , Tillema Jan-Mendelt , Waubant Emmanuelle , Weinstock-Guttman Bianca , Charvet Leigh E , Krupp; Lauren B 
Published: November 2019

Background: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. Methods: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. Results: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. Conclusion: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.
Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂)
Authors: Luo Kaikun , Wang Shi , Fu Yeqing , Zhou Pei , Huang Xuexue , Gu Qianhong , Li Wuhui , Wang Yude , Hu Fangzhou , Liu Shaojun 
Published: November 2019

AbstractBackgroundDistant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.ResultIn this study, we investigated the genetic variation of 12Hoxgenes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂).Hoxgene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations inHoxgenes in the first generation of IDMC, and almost all theHoxgene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters ofHoxgenes in both improved carp lineages, and partially recombinant clusters ofHoxgenes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, someHoxgenes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.ConclusionsOur results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.
Association between elevated blood glucose level and non-valvular atrial fibrillation: a report from the Guangzhou heart study
Authors: Fu Lu , Deng Hai , Lin Wei-dong , He Shang-fei , Liu Fang-zhou , Liu Yang , Zhan Xian-zhang , Fang Xian-hong , Liao Hong-tao , Wei Wei , Liao Zi-li , Tang Li-hong , Fu Zu-yi , Zheng Mu-rui , Wu Shu-lin , Xue Yu-mei 
Published: November 2019

Abstract
Background
To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China.

Methods
The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence.

Results
The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40–2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14–2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12–2.91, P = 0.016).

Conclusions
In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.
Differential expression and predictive value of monocyte scavenger receptor CD163 in populations with different tuberculosis infection statuses
Authors: Liu Qianqian , Ou Qinfang , Chen Huaxin , Gao Yan , Liu Yuanyuan , Xu Yuzhen , Ruan Qiaoling , Zhang Wenhong , Shao Lingyun 
Published: November 2019

Abstract
Background
Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis.

Methods
We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay.

Results
Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14−CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16− (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment.

Conclusions
Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.
LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis
Authors: Hu Yi , Ma Yan , Liu Jie , Cai Yanlin , Zhang Mengmeng , Fang Xiaoling 
Published: November 2019

Abstract
Background
Cervical cancer (CC), causing significant morbidity and mortality worldwide, is one of the most common gynecological malignancies in women. SFN has been reported as a potential prognostic marker with apparent high expression in tumors. Nevertheless, the function mechanism of SFN is not clear yet in CC.

Methods
The relative expressions of RNAs were detected by real-time quantitative PCR (RT-qPCR). Colony formation assay, EdU stained assay and CCK-8 assay were to check cell proliferation ability in CC. Flow cytometry and apoptosis related proteins analysis were used to measure cells apoptosis capacity. Luciferase reporter assay and RNA pull down assay were to verify the molecular mechanism.

Results
SFN was highly expressed in CC tissues and CC cell lines compared with normal tissues and normal cell line. After interfering SFN, cell proliferation, migration and invasion ability was inhibited as well as cell apoptosis ability was promoted. In subsequence, miR-383-5p exhibited conspicuous low expression in CC tissues. And miR-383-5p was found to bind to SFN and have anti-cancerous effects in CC. Moreover, LINC01128 displayed remarkable high expression in CC tissues. Besides, LINC01128 shortage could reduce the expression of SFN at mRNA and protein levels. And the affinity between LINC01128 and miR-383-5p was verified. In the end, it was proved that LINC01128 could enhance cell proliferation, migration and invasion as well as inhibit cell apoptosis by binding with miR-383-5p and upregulating SFN.

Conclusion
LINC01128 expedited cells cellular process in CC by binding with miR-383-5p to release SFN.

Graphical Abstract
Association between high fear-avoidance beliefs about physical activity and chronic disabling low back pain in nurses in Japan
Authors: Fujii Tomoko , Oka Hiroyuki , Takano Kenichiro , Asada Fuminari , Nomura Takuo , Kawamata Kayo , Okazaki Hiroshi , Tanaka Sakae , Matsudaira Ko 
Published: November 2019

Abstract
Background
High prevalence of low back pain (LBP) in nurses has been reported globally. Ergonomic factors and work-related psychosocial factors have been focused on as risk factors. However, evidence on the role of fear-avoidance beliefs (FABs) concerning LBP in nurses is lacking. This study examined LBP prevalence and the association between FABs and chronic disabling LBP that interfered with work and lasted ≥ 3 months.

Methods
Female nurses (N = 3066; mean age = 35.8 ± 10.6 years) from 12 hospitals in Japan participated. A self-reported questionnaire was used to collect information on sociodemographics, LBP, work-related factors, and psychological distress. FABs about physical activity were assessed using a subscale from the FAB Questionnaire (score range = 0–24). The participants were asked to choose one of four statements regarding their LBP in the past 4 weeks: 1) I did not have LBP, 2) I had LBP without work difficulty, 3) I had LBP with work difficulty but without requiring absence from work, and 4) I had LBP requiring absence from work. If the participant had LBP in the past 4 weeks, it was also inquired if the LBP had lasted for ≥ 3 months. Chronic disabling LBP was defined as experiencing LBP with work difficulty in the past 4 weeks which had lasted for ≥ 3 months. In the nurses who had experienced any LBP in the past 4 weeks, we examined the association between FABs and experiencing chronic disabling LBP using multiple logistic regression models adjusting for pain intensity, age, body mass index, smoking status, psychological distress, hospital department, weekly work hours, night shift work, and the12 hospitals where the participants worked.

Results
Four-week and one-year LBP prevalence were 58.7 and 75.9%, respectively. High FABs (≥ 15) were associated with chronic disabling LBP (adjusted odds ratio = 1.76, 95% confidence interval [1.21–2.57], p = 0.003).

Conclusions
LBP is common among nurses in Japan. FABs about physical activity might be a potential target for LBP management in nurses.

Trial registration
UMIN-CTR UMIN000018087. Registered: June 25, 2015.
What motivates informal caregivers of people with dementia (PWD): a qualitative study
Authors: Zahed Shakiba , Emami Maryam , Bazargan-Hejazi Shahrzad , Eslami Ahmad Ali , Barekatain Majid , Zamani-Alavijeh Fereshteh 
Published: November 2019

Abstract
Background
The burden of caring for People with Dementia (PWD) is heavy; identifying incentives that motivate them in providing care is essential in facilitating and optimizing care. This study aims to explore and describe these motivating factors.

Methods
We conducted this qualitative study between January 2016 and January 2017 in Isfahan, Iran. Data were extracted through in-depth, semi-structured interviews with 19 caregivers of PWD. These data were then examined through thematic content analysis.

Results
We identified four categories of psychological motives based on the caregivers’ feedback and experience. These include 1) Moral-based motives, 2) Religious, and spiritual motives; 3) Financial motives, and 4) Wicked motives.

Conclusions
Our results revealed several aspects of caregivers’ motives. They include moral, religious, and spiritual aspects; sharing housing accommodations, and the likelihood of inheriting a portion of the patient’s assets based on unspoken rules and informal arrangements in the family, and wicked and immoral aspects. These findings can inform future efforts in enhancing the experiences of caregivers of PWD, and subsequently, the quality of care these patients receive. It further suggests that family members, members of a religious and spiritual organization, as well as social media, could play important roles in setting the stage.
The role of SCF ubiquitin-ligase complex at the beginning of life
Authors: Xie Jiayan , Jin Yimei , Wang Guang 
Published: November 2019

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.
Analyzing the impact of trade and investment agreements on pharmaceutical policy: provisions, pathways and potential impacts
Authors: Gleeson Deborah , Lexchin Joel , Labonté Ronald , Townsend Belinda , Gagnon Marc-André , Kohler Jillian , Forman Lisa , Shadlen Kenneth C. 
Published: November 2019

Abstract
Background
Trade and investment agreements negotiated after the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have included increasingly elevated protection of intellectual property rights along with an expanding array of rules impacting many aspects of pharmaceutical policy. Despite the large body of literature on intellectual property and access to affordable medicines, the ways in which other provisions in trade agreements can affect pharmaceutical policy and, in turn, access to medicines have been little studied. There is a need for an analytical framework covering the full range of provisions, pathways, and potential impacts, on which to base future health and human rights impact assessment and research. A framework exploring the ways in which trade and investment agreements may affect pharmaceutical policy was developed, based on an analysis of four recently negotiated regional trade agreements. First a set of core pharmaceutical policy objectives based on international consensus was identified. A systematic comparative analysis of the publicly available legal texts of the four agreements was undertaken, and the potential impacts of the provisions in these agreements on the core pharmaceutical policy objectives were traced through an analysis of possible pathways.

Results
An analytical framework is presented, linking ten types of provisions in the four trade agreements to potential impacts on four core pharmaceutical policy objectives (access and affordability; safety, efficacy, and quality; rational use of medicines; and local production capacity and health security) via various pathways.

Conclusions
The analytical framework highlights provisions in trade and investment agreements that need to be examined, pathways that should be explored, and potential impacts that should be taken into consideration with respect to pharmaceutical policy. This may serve as a useful checklist or template for health and human rights impact assessments and research on the implications of trade agreements for pharmaceuticals.
Omalizumab and mepolizumab in the landscape of biological therapy for severe asthma in children: how to choose?
Authors: Giovannini Mattia , Mori Francesca , Barni Simona , de Martino Maurizio , Novembre Elio 
Published: November 2019

AbstractSevere asthma has a substantial epidemiological impact on children and biological treatments can be an option to take into account, as they target specific molecules and pathways involved in its pathogenesis. Modern medicine is continuously and progressively oriented towards tailored treatments designed specifically for the pathology patterns observed in individual patients and identified as endotypes with associated biomarkers. In this regard, biologic treatments in asthma are one of the best examples. Among the biological drugs currently available, omalizumab is the one with the greatest amount of data on efficacy and safety, and the one we have more real-life clinical experience with. However, mepolizumab will likely be accessible soon globally for clinical use. Moreover, research on biological drugs for the treatment of severe asthma is expanding rapidly, with some molecules currently used in adult patients that could be registered also for pediatric use and new molecules that could be available in the future. On the other hand, due to this potential abundance of therapeutic options, new criteria could become necessary to guide clinicians through an evidence-based choice between omalizumab and these new drugs. For the same reason, more data collected specifically from pediatric clinical trials are necessary. In this review we aim to analyze the factors that could help clinicians make their choice and to highlight the unmet need for a more evidence-based choice.
Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids
Authors: Seymour Christopher W. , Kerti Samantha J. , Lewis Anthony J. , Kennedy Jason , Brant Emily , Griepentrog John E. , Zhang Xianghong , Angus Derek C. , Chang Chung-Chou H. , Rosengart Matthew R. 
Published: November 2019

Abstract
Background
Clinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids.

Methods
We performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials. In cohort 1, mice (n = 118) underwent biotelemetry-enhanced CLP, and we applied latent class mixed models to determine optimal number of phenotypes using clinical data collected between injury and physiologic deterioration. In cohort 2 (N = 73 mice), inflammatory cytokines measured at 24 h after deterioration were explored by phenotype. In a subset of 46 mice enrolled in two trials from cohort 1, we tested the association of phenotypes with the response to immediate (0 h) vs. delayed (2 to 4 h) antibiotics or fluids initiated after physiologic deterioration.

Results
Latent class mixture modeling derived a two-class model in cohort 1. Class 2 (N = 97) demonstrated a shorter time to deterioration (mean SD 7.3 (0.9) vs. 9.7 (3.2) h, p < 0.001) and lower heart rate at 7 h after injury (mean (SD) 564 (55) vs. 626 (35) beats per minute, p < 0.001). Overall mortality was similar between phenotypes (p = 0.75). In cohort 2 used for biomarker measurement, class 2 mice had greater plasma concentrations of IL6 and IL10 at 24 h after CLP (p = 0.05). In pilot randomized trials, the effects of sepsis treatment (immediate vs. delayed antibiotics) differed by phenotype (p = 0.03), with immediate treatment associated with greater survival in class 2 mice only. Similar differential treatment effect by class was observed in the trial of immediate vs. delayed fluids (p = 0.02).

Conclusions
We identified two sepsis phenotypes in a murine cecal ligation and puncture model, one of which is characterized by faster deterioration and more severe inflammation. Response to treatment in a randomized trial of immediate versus delayed antibiotics and fluids differed on the basis of phenotype.
547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates
Authors: Li Ming-Li , Wu Shi-Hao , Zhang Jin-Jin , Tian Hang-Yu , Shao Yong , Wang Zheng-Bo , Irwin David M. , Li Jia-Li , Hu Xin-Tian , Wu Dong-Dong 
Published: November 2019

Abstract
Background
Brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates.

Results
Here, we explore non-human primate brain aging using 547 transcriptomes originating from 44 brain areas in rhesus macaques (Macaca mulatta). We show that expression connectivity between pairs of cerebral cortex areas as well as expression symmetry between the left and right hemispheres both decrease after aging. Although the aging mechanisms across different brain areas are largely convergent, changes in gene expression and alternative splicing vary at diverse genes, reinforcing the complex multifactorial basis of aging. Through gene co-expression network analysis, we identify nine modules that exhibit gain of connectivity in the aged brain and uncovered a hub gene, PGLS, underlying brain aging. We further confirm the functional significance of PGLS in mice at the gene transcription, molecular, and behavioral levels.

Conclusions
Taken together, our study provides comprehensive transcriptomes on multiple brain regions in non-human primates and provides novel insights into the molecular mechanism of healthy brain aging.