Miracle-dz/UniFAR-FTUs huggingface dataset:
Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway

Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR‐192‐5p and its target gene fibulin (Fbln)‐2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)–induced depression through regulation of the TGF‐β1 signal transduction pathway. Verification of the targeting relationship between miR‐192‐5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual‐luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR‐192‐5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS‐induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF‐βl signaling pathway, and decreased expression of miR‐192‐5p, synaptophysin, brain‐derived neurotrophic factor, N‐methyl‐d‐aspartate receptor subunit 2B, and calmodulin‐dependent protein kinase II were noted. Up‐regulated miR‐192‐5p targeting Fbln2 acts to alleviate CUMS‐induced depression by inhibiting the TGF‐β1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up‐regulated levels of miR‐192‐5p expression act to suppress activation of the TGF‐β1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression. —Tang, C. ‐Z. , Yang, J.‐T. , Liu, Q. ‐H. , Wang, Y. ‐R. , Wang, W. ‐S. , Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway. FASEB J. 33, 606–618 (2019). www.fasebj. org
Upregulated Expression of Long Non-Coding RNA, LINC00460, Suppresses Proliferation of Colorectal Cancer

Through bioinformatics analysis, a novel lncRNA, LINC00460, was implicated in the development of multiple cancers. However, the precise expression pattern, clinical significance and biological function of LINC00460 in colorectal cancer (CRC) remain unknown. Network databases were used to investigate the correlation between LINC00460 and CRC. In situ hybridization was performed to verify the precise expression pattern and clinical significance of LINC00460 in a CRC tissue microarray, which included 92 pairs of CRC and adjacent normal tissues. The effect of LINC00460 on proliferation was evaluated by MTT, colony formation assays and flow cytometry employing SW620 and HCT116 cell lines. Cell migration and matrigel invasion assays were performed to investigate whether LINC00460 is involved in the metastasis of CRC. The expression of LINC00460 was significantly upregulated in CRC tissues and cells, associated with early stage CRC and low disease-free survival. The downregulated of LINC00460 expression increased cell proliferation by regulating the cell cycles of SW620 and HCT116 cells. LINC00460 knockdown did not affect cell migration or invasion in vitro. These findings suggest that LINC00460 may be an interesting target for the development of CRC.
University of Birmingham Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γ secreting cells

Citation for published version (Harvard): Liaskou, E, Patel, S, Webb, G, Bagkou Dimakou, D, Akiror, S, Krishna, M, Mells, GF, Jones, D, Bowman, S, Barone, F, Fisher, B & Hirschfield, G 2018, 'Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γ secreting cells', Journal of Autoimmunity, vol. 94, pp. 143-155. https://doi.org/10.1016/j.jaut. 2018.07. 020
Clinicopathological and prognostic significance of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) in malignant tumors: A meta-analysis

Background: Accumulating studies have demonstrated that the expression of leucine-rich repeats and immunoglobulin-like domains protein1 (LRIG1) is associated with various types of tumors. However, the conclusions of previous studies are not completely consistent. Thus, we conducted this meta-analysis to further explore the authentic value of LRIG1 in cancer outcome and clinical significance. Methods: We systematically searched electronic databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database. The hazard ratios (HRs), odds ratio (OR) and 95 % confidence intervals (CI) were calculated for effect measures. Results: 16 qualified studies involving 2043 patients with cancer were enrolled. High LRIG1 expression was associated with a good prognosis in malignant tumors (HR: 0.49, 95% CI=0.39-0.59). Furthermore, positive expression rate of LRIG1 was distinctly lower in cancer tissues than that in normal tissues (OR: 0.09, 95% CI=0.05-0.17). Positive LRIG1 expression was definitely related with smaller tumor size (OR: 1.64, 95% CI=1.11-2.42), early tumor stage (OR: 3.67, 95% CI=1.87-7.21), well degree of differentiation (OR: 4.35, 95% CI=2.12-8.93) and negative recurrence (OR: 0.29, 95% CI=0.16-0.53). Conclusions: LRIG1 expression was associated with a good prognosis in terms of overall survival (OS) and might act as a predictive factor for characteristics of cancer patients.
From Ill-defined Problems to Informed Decisions

Decision makers such as military leaders and security analysts are increasingly being asked to make decisions on ill-defined problems. These problems may contain uncertain or incomplete data, and are often complex to piece together. Consequently, decision makers rely heavily on intuition, knowledge and experience. We argue for rich narratives that encapsulate both explicit data and implicit knowledge, supported by three levels of provenance: data, analytical and reasoning. Our hypotheses is that visual analytics tools and methods can help to provide a valuable means to make sense of these complex data, and to help make this tacit knowledge explicit, to support the construction and presentation of the decision.
Effectiveness of robot-assisted gait training on motor impairments in people with Parkinson’s disease: a systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of robot-assisted gait training (RAGT) on motor impairments in people with Parkinson’s disease (PD). A computer-based systematic literature search was performed in six databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of RAGT on motor impairments in people with PD were included. GRADE approach and PEDro scale were used to determine the studies’ quality of evidence. Meta-analyses were performed by calculating the weighted mean difference (WMD) at 95% confidence interval. Seven RCTs (PEDro: 5–8) met the inclusion criteria for systematic review and meta-analyses. The meta-analysis showed significant improvement on Unified Parkinson Disease Rating Scale Part III after intervention [WMD=3.292; 95% confidence interval (CI)=1.378–5.207; P=0.000], and after 1-month follow-up (WMD=5.512; 95% CI=2.396–8.629; P=0.001). Stride length (WMD=9.283; 95% CI=7.153–11.414; P=0.00) and gait speed (WMD=0.166; 95% CI=−0.090 to 0.243; P=0.000) showed significant improvements after RAGT. Balance as measured by Berg Balance Scale was improved significantly after intervention (WMD=3.87; 95% CI=0.374–6.735; P=0.029) and at 1-month follow-up (WMD=3.87; 95% CI=1.324–6.413; P=0.002). The pooled analysis did not detect any significant changes regarding stride time, cadence and functional balance scales. GRADE level of evidence ranged between high and low. The RAGT showed better outcomes than conventional interventions on some motor aspects in PD. However, RAGT did not seem superior to control interventions. Further RCTs that examine the effect of RAGT on more specific outcomes and at different medication statuses are required.
Warming enhances sedimentation and decomposition of organic carbon in shallow macrophyte‐dominated systems with zero net effect on carbon burial

Temperatures have been rising throughout recent decades and are predicted to rise further in the coming century. Global warming affects carbon cycling in freshwater ecosystems, which both emit and bury substantial amounts of carbon on a global scale. Currently, most studies focus on the effect of warming on overall carbon emissions from freshwater ecosystems, while net effects on carbon budgets may strongly depend on burial in sediments. Here, we tested whether year‐round warming increases the production, sedimentation, or decomposition of particulate organic carbon and eventually alters the carbon burial in a typical shallow freshwater system. We performed an indoor experiment in eight mesocosms dominated by the common submerged aquatic plant Myriophyllum spicatum testing two temperature treatments: a temperate seasonal temperature control and a warmed (+4°C) treatment (n = 4). During a full experimental year, the carbon stock in plant biomass, dissolved organic carbon in the water column, sedimented organic matter, and decomposition of plant detritus were measured. Our results showed that year‐round warming nearly doubled the final carbon stock in plant biomass from 6.9 ± 1.1 g C in the control treatment to 12.8 ± 0.6 g C (mean ± SE), mainly due to a prolonged growing season in autumn. DOC concentrations did not differ between the treatments, but organic carbon sedimentation increased by 60% from 96 ± 9.6 to 152 ± 16 g C m−2 yaer−1 (mean ± SE) from control to warm treatments. Enhanced decomposition of plant detritus in the warm treatment, however, compensated for the increased sedimentation. As a result, net carbon burial was 40 ± 5.7 g C m−2 year−1 in both temperature treatments when fluxes were combined into a carbon budget model. These results indicate that warming can increase the turnover of organic carbon in shallow macrophyte‐dominated systems, while not necessarily affecting net carbon burial on a system scale.
Parkinson’s Disease: Pathogenesis and Clinical Aspects

Parkinson’s disease is an increasingly common neurodegenerative condition, which causes not only dysfunction of movement but also a broad range of nonmotor features, including mood disturbance, sleep dysfunction, autonomic dysfunction, cognitive deficits, and dementia, and neuropsychiatric symptoms. A major conundrum in this condition is understanding its striking clinical variability, which encompasses a spectrum from a benign phenotype with levodopa-responsive symptoms and minimal progression, to a malignant phenotype with rapid progression to severe gait dysfunction, falls and dementia. This book integrates the considerable expertise of a range of authors from different disciplines, from clinicians through to basic scientists, to present a comprehensive and up-to-date overview of Parkinson’s disease. In recent years, we have made significant progress in understanding the pathological and genetic basis of Parkinson’s disease and its heterogeneous forms, and the first section of the book is dedicated to reviewing this. The variable clinical features of Parkinson’s disease and its differential diagnosis are then considered. The final section provides a detailed overview of treatment approaches, including not only pharmacological therapies but also surgical therapies including deep brain stimulation and cell transplantation strategies. The combination of basic biology, clinical knowledge and therapeutics gives this book a very broad appeal. It will be of value to clinicians and health professionals caring for patients with Parkinson’s disease, as well as providing an excellent introduction for junior researchers entering the field.
Impact of Guideline-Discordant Treatment on Cost and Health Care Utilization in Older Adults with Early-Stage Breast Cancer.

BACKGROUND National Comprehensive Cancer Network (NCCN) guideline-based treatment is a marker of high-quality care. The impact of guideline discordance on cost and health care utilization is unclear. MATERIALS AND METHODS This retrospective cohort study of Medicare claims data from 2012 to 2015 included women age ≥65 with stage I-III breast cancer receiving care within the University of Alabama at Birmingham Cancer Community Network. Concordance with NCCN guidelines was assessed for treatment regimens. Costs to Medicare and health care utilization were identified from start of cancer treatment until death or available follow-up. Adjusted monthly cost and utilization rates were estimated using linear mixed effect and generalized linear models. RESULTS Of 1,177 patients, 16% received guideline-discordant treatment, which was associated with nonwhite race, estrogen receptor/progesterone receptor negative, human epidermal growth receptor 2 (HER2) positive, and later-stage cancer. Discordant therapy was primarily related to reduced-intensity treatments (single-agent chemotherapy, HER2-targeted therapy without chemotherapy, bevacizumab without chemotherapy, platinum combinations without anthracyclines). In adjusted models, average monthly costs for guideline-discordant patients were $936 higher compared with concordant (95% confidence limits $611, $1,260). For guideline-discordant patients, adjusted rates of emergency department visits and hospitalizations per thousand observations were 25% higher (49.9 vs. 39.9) and 19% higher (24.0 vs. 20.1) per month than concordant patients, respectively. CONCLUSION One in six patients with early-stage breast cancer received guideline-discordant care, predominantly related to undertreatment, which was associated with higher costs and rates of health care utilization. Additional randomized trials are needed to test lower-toxicity regimens and guide clinicians in treatment for older breast cancer patients. IMPLICATIONS FOR PRACTICE Previous studies lack details about types of deviations from chemotherapy guidelines that occur in older early-stage breast cancer patients. Understanding the patterns of guideline discordance and its impact on patient outcomes will be particularly important for these patients. This study found 16% received guideline-discordant care, predominantly related to reduced intensity treatment and associated with higher costs and rates of health care utilization. Increasing older adult participation in clinical trials should be a priority in order to fill the knowledge gap about how to treat older, less fit patients with breast cancer.
Social media discomfort: The clash between the old and the new at work

This research investigates a conventional professional work practice and hesitant attitudes and feelings related to an introduction of a social media tool for communication and collaboration. The study was conducted at a well- established, international product development company in the electronic industry. Semi-structured in-depth interviews were carried out with engineers from the company's R&D site. Based on the data analysis, the key findings focus upon a perception of Social Media Discomfort (SMD). Factors that constitute SMD can be divided into factors relating to arenas of social interaction (socialness) and into factors mirroring a goal-orientation in attending to work duties (usefulness). The study extends our understanding of why people might reject new social media tools. The results of this study indicate that it happens if the tools are perceived as disconnected to established structures, tools, norms and ideals shared in the workplace. The SMD occurs especially in connection with the adoption of the tool. Understanding the dual nature of uncertainty, i.e. socialness and usefulness, in relation to new social media tools is of relevance for both practitioners and scholars working with issues of the increasingly complex information environment at work.
Molecular analysis of gastric cancer identifies genomic markers of drug sensitivity in Asian gastric cancer

Background: Gastric cancer (GC) is one of the leading causes of lethal malignancies worldwide, especially in Eastern Asia. Clinical responses to antitumor therapies are often limited to a subset of patients. Methods: To uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we performed ultra-deep targeted sequencing in a cohort with 72 patients (41 with chemotherapy sensitivity and 31 with chemotherapy resistance). Results: We found that sixteen mutated cancer genes were associated with widely used agent in chemotherapy of gastric cancer. Genes identified in these study are mainly involved in activation and inactivation of cancer chemotherapeutic agents, changes of apoptosis and proliferation, drug efflux, DNA damage repair, and the tumor microenvironment. Discussion: A novel group of chemo-sensitivity related genes provided new therapeutic strategies to overcome the development and evolution of resistance to cancer chemotherapy.
Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1.

Mohd W. Nasser, Jharna Datta, Gerard Nuovo, Huban Kutay, Tasneem Motiwala, Sarmila Majumder, Bo Wang, Saul Suster, Samson T. Jacob, and Kalpana Ghoshal This article has been withdrawn by the authors. The Journal questioned Figs. 8A and S1. The authors stand by the reproducibility of the experimental data and the conclusions of the paper. The paper, with confirmatory data supporting the results, can be obtained by contacting the authors. WITHDRAWALS/RETRACTIONS
Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency mediated chronically increased cardiac Ca2+ cycling in vivo.

Cardiomyopathy is a significant contributor to morbidity and mortality in Duchenne muscular dystrophy (DMD). Membrane instability, leading to intracellular Ca2+ mishandling and overload, causes myocyte death and subsequent fibrosis in DMD cardiomyopathy. On a cellular level, cardiac myocytes from mdx mice have dysregulated Ca2+ handling, including increased resting Ca2+ and slow Ca2+ decay, especially evident under stress conditions. Sarco(endo)plasmic reticulum Ca2+ ATPase and its regulatory protein phospholamban (PLN) are potential therapeutic targets for DMD cardiomyopathy owing to their key role in regulating intracellular Ca2+ cycling. We tested the hypothesis that enhanced cardiac Ca2+ cycling would remediate cardiomyopathy caused by dystrophin deficiency. We used a genetic complementation model approach by crossing dystrophin-deficient mdx mice with PLN knockout (PLNKO) mice [termed double-knockout (DKO) mice]. As expected, adult cardiac myocytes isolated from DKO mice exhibited increased contractility and faster relaxation associated with increased Ca2+ transient peak height and faster Ca2+ decay rate compared with control mice. However, compared with wild-type, mdx, and PLNKO mice, DKO mice unexpectedly had reduced in vivo systolic and diastolic function as measured by echocardiography. Furthermore, Evans blue dye uptake was increased in DKO hearts compared with control, mdx, and PLNKO hearts, demonstrating increased membrane damage, which subsequently led to increased fibrosis in the DKO myocardium in vivo. In conclusion, despite enhanced intracellular Ca2+ handling at the myocyte level, DMD cardiomyopathy was exacerbated owing to unregulated chronic increases in Ca2+ cycling in DKO mice in vivo. These findings have potentially important implications for ongoing therapeutic strategies for the dystrophic heart. NEW & NOTEWORTHY This study examined the effects of phospholamban ablation on the pathophysiology of cardiomyopathy in dystrophin-deficient mice. In this setting, contractility and Ca2+ cycling were enhanced in isolated myocytes; however, in vivo heart function was diminished. Additionally, sarcolemmal integrity was compromised and fibrosis was increased. This is the first study, to our knowledge, examining unregulated Ca2+ cycling in the dystrophin-deficient heart. Results from this study have implications for potential therapies targeting Ca2+ handling in dystrophic cardiomyopathy. Listen to this article's corresponding podcast at https://ajpheart.podbean. com/e/unregulated-ca2-cycling-exacerbates-dmd-cardiomyopathy/ .
Classifying values in informal communication: Adapting the meta-inventory of human values for tweets

This study builds upon and expands the Meta-Inventory of Human Values (MIHV) proposed by Cheng and Fleischmann (2010) for application in informal communication settings such as Twitter. A corpus of 5,313 tweets from 32 individuals during a three-week period in March/April 2011 was analyzed using thematic analysis. In addition to the 16 value categories in the MIHV, two new categories emerged within the informal communication context – connectedness and comfort.
Vulnerability of diatom communities in the Peace–Athabasca Delta to environmental change

Habitat degradation associated with resource development is a major ecological concern, particularly in Canada’s boreal zone where limited information on biodiversity is available. Habitat degradation can lead to reductions in biodiversity and ecosystem function, especially when drivers of variability and diversity patterns have not been identified for a region of interest. In this study, the distribution of diatom genera in the Peace–Athabasca Delta in northeastern Alberta was examined in relation to seasonal, geographic, and alkalinity gradients. Grab samples of six abiotic variables (total dissolved nitrogen, total dissolved phosphorus, dissolved iron, turbidity, pH, and specific conductance (SPC)) were taken from 12 remote wetlands over three sampling periods, and regressed against an ordination of diatom community composition to identify key environmental drivers of diatom community variation. Indirect gradient analysis identified two major gradients among sites. First, separation of sites among sampling periods showed successional seasonal changes in diatom community composition. Second, separation of sites from the Peace sub-delta and Birch sub-delta showed a gradient of geographic separation. Direct gradient analysis failed to explain the underlying drivers of these two gradients, but did show that alkalinity is a key driver of diatom community composition in the Embarras sub-delta, and that these sites could be particularly vulnerable to community changes associated with acidification.