Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain Structural and Functional Alterations Specific to Low Sleep Efficiency in Major Depressive Disorder

Background Sleep disturbance is common in patients with major depressive disorder (MDD), but the exploration of its neural underpinnings is limited by subjective sleep measurement and single-modality neuroimaging analyses. Methods Ninety six patients with MDD underwent polysomnography examinations and multi-modal magnetic resonance imaging (MRI) scans. According to sleep efficiency, patients were subdivided into well-matched normal sleep efficiency (NSE, N = 42; 14 men; aged 43 ± 10 years) and low sleep efficiency (LSE, N = 54; 23 men; aged 45 ± 12 years) groups. Inter-group differences in brain structure and function were examined by applying voxel-based morphometry (VBM), regional homogeneity (ReHo) and functional connectivity strength (FCS), and tract-based spatial statistics (TBSS) approaches to structural, functional, and diffusion MRI data, respectively. Results There was no significant difference in gray matter volume (GMV) between the NSE and LSE groups. Compared with the NSE group, the LSE group showed increased axial diffusivity in the left superior and posterior corona radiata, and left posterior limb and retrolenticular part of internal capsule. In addition, the LSE group exhibited decreased ReHo in the bilateral lingual gyri and right postcentral gyrus yet increased FCS in the left angular gyrus relative to the NSE group. Moreover, validation analyses revealed that these results remained after adjusting for the medication effect. Conclusion Our data indicate that preserved gray matter morphology, impaired white matter integrity, and decreased local synchronization degree yet increased FCS are specific to low SE in MDD patients. These findings of disassociation between structural and functional alterations might provide insights into the neural mechanisms of sleep disturbance in depression.
The Role of Dynamic miRISC During Neuronal Development

Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.
Radiomics Signature as a Predictive Factor for EGFR Mutations in Advanced Lung Adenocarcinoma

Purpose: To develop and validate a radiomic signature to identify EGFR mutations in patients with advanced lung adenocarcinoma. Methods: This study involved 201 patients with advanced lung adenocarcinoma (140 in the training cohort and 61 in the validation cohort). A total of 396 features were extracted from manual segmentation based on enhanced and non-enhance CT imaging after image preprocessing. The Lasso algorithm was used for feature selection, 6 machine learning methods were used to construct radiomics models. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the performance of the radiomic signature between different data and methods. A nomogram was developed using clinical factors and the radiomics signature, then it was analyzed based on its discriminatory ability and calibration. Decision curve analysis (DCA) was implemented to evaluate the clinical utility. Results: Ten features for contrast data and eleven features for non-contrast data were selected through LASSO algorithm. The performance of the radiomics signature for contrast images was better than that for non-contrast images in all of the 6 different machine learning methods. Finally, the best radiomics signature was built with logistic regression method based on enhanced CT imaging with an area under the curve (AUC) of 0.851 (95% CI, 0.750 to 0.951) in the validation cohort. A nomogram was developed using the radiomics signature and sex with a C-index of 0.908 (95%CI, 0.862 to 0.954) in the training cohort and 0.835 (95% CI, 0.825 to 0.845) in the validation cohort. It showed good discrimination and calibration (Hosmer-Lemeshow test, P = 0.621 for the training cohort and P = 0.605 for the validation cohort). Conclusion: Radiomics signature can help to distinguish between EGFR positive and wild type advanced lung adenocarcinomas.
Nitrate Metabolism Modulates Biosynthesis of Biofilm Components in Uropathogenic Escherichia coli and Acts as a Fitness Factor During Experimental Urinary Tract Infection

To successfully colonize a variety of environments, bacteria can coordinate complex collective behaviors such as biofilm formation. To thrive in oxygen limited niches, bacteria’s versatile physiology enables the utilization of alternative electron acceptors. Nitrate, the second most favorable electron acceptor after oxygen, plays a prominent role in the physiology of uropathogenic Escherichia coli (UPEC) and is abundantly found in urine. Here we analyzed the role of extracellular nitrate in the pathogenesis of the UPEC strain CFT073 with an initial focus on biofilm formation. Colony morphotyping in combination with extensive mutational, transcriptional, and protein expression analyses of CFT073 wild-type and mutants deficient in one or several nitrate reductases revealed an association between nitrate reduction and the biosynthesis of biofilm extracellular matrix components. We identified a role for the nitrate response regulator NarL in modulating expression of the biofilm master regulator CsgD. To analyze the role of nitrate reduction during infection in vivo, we tested wild-type CFT073 and a nitrate reductase null mutant in an ascending urinary tract infection (UTI) model. Individually, each strain colonized extensively, suggesting that nitrate reduction is expendable during UTI. However, during competitive co-infection, the strain incapable of nitrate reduction was strongly outcompeted. This suggests that nitrate reduction can be considered a non-essential but advantageous fitness factor for UPEC pathogenesis. This implies that UPEC rapidly adapts their metabolic needs to the microenvironment of infected tissue. Collectively, this work demonstrates a unique association between nitrate respiration, biofilm formation, and UPEC pathogenicity, highlighting how the use of alternative electron acceptors enables bacterial pathogens to adapt to challenging infectious microenvironments.
The Generation of Dynein Networks by Multi-Layered Regulation and Their Implication in Cell Division

Cytoplasmic dynein-1 (hereafter referred to as dynein) is a major microtubule-based motor critical for cell division. Dynein is essential for the formation and positioning of the mitotic spindle as well as the transport of various cargos in the cell. A striking feature of dynein is that, despite having a wide variety of functions, the catalytic subunit is coded in a single gene. To perform various cellular activities, there seem to be different types of dynein that share a common catalytic subunit. In this review, we will refer to the different kinds of dynein as “dyneins. ” This review attempts to classify the mechanisms underlying the emergence of multiple dyneins into four layers. Inside a cell, multiple dyneins generated through the multi-layered regulations interact with each other to form a network of dyneins. These dynein networks may be responsible for the accurate regulation of cellular activities, including cell division. How these networks function inside a cell, with a focus on the early embryogenesis of Caenorhabditis elegans embryos, is discussed, as well as future directions for the integration of our understanding of molecular layering to understand the totality of dynein’s function in living cells.
Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

The differential diagnosis between mild Traumatic Brain Injury (mTBI) sequelae and Post-Traumatic Stress Disorder (PTSD) is challenging due to their symptomatic overlap and co-morbidity. As such, there is a need to develop biomarkers which can help with differential diagnosis of these two conditions. Studies from our group and others suggest that blood and brain lipids are chronically altered in both mTBI and PTSD. Therefore, examining blood lipids presents a minimally invasive and cost-effective approach to identify promising biomarkers of these conditions. Using liquid chromatography-mass spectrometry (LC-MS) we examined hundreds of lipid species in the blood of healthy active duty soldiers (n = 52) and soldiers with mTBI (n = 21), PTSD (n = 34) as well as co-morbid mTBI and PTSD (n = 13) to test whether lipid levels were differentially altered with each. We also examined if the apolipoprotein E (APOE) ε4 allele can affect the association between diagnosis and peripheral lipid levels in this cohort. We show that several lipid classes are altered with diagnosis and that there is an interaction between diagnosis and the ε4 carrier status on these lipids. Indeed, total lipid levels as well as both the degree of unsaturation and chain lengths are differentially altered with diagnosis and ε4 status, specifically long chain unsaturated triglycerides (TG) and both saturated and mono-unsaturated diglycerides (DG). Additionally, an examination of lipid species reveals distinct profiles in each diagnostic group stratified by ε4 status, mainly in TG, saturated DG species and polyunsaturated phosphatidylserines. In summary, we show that peripheral lipids are promising biomarker candidates to assist with the differential diagnosis of mTBI and PTSD. Further, ε4 carrier status alone and in interaction with diagnosis has a strong influence on peripheral lipid levels. Therefore, examining ε4 status along with peripheral lipid levels could help with differential diagnosis of mTBI and PTSD.
Influence of Gonadotropin Hormone Releasing Hormone Agonists on Interhemispheric Functional Connectivity in Girls With Idiopathic Central Precocious Puberty

Purpose: The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa treatment influences the brain function of treated children. The present study investigated the differences in the homotopic resting-state functional connectivity patterns in girls with idiopathic central precocious puberty (ICPP) with and without GnRHa treatment using voxel-mirrored homotopic connectivity (VMHC). Methods: Eighteen girls with ICPP who underwent 12 months of GnRHa treatment, 40 treatment-naïve girls with ICPP, and 19 age-matched girls with premature thelarche underwent resting-state functional magnetic resonance imaging using a 3T MRI. VMHC method was performed to explore the differences in the resting-state interhemispheric functional connectivity. The levels of serum pubertal hormones, including luteinizing hormone (LH), follicular-stimulating hormone, and estradiol, were assessed. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales, and VMHC values of different brain regions were performed with the data of the GnRHa treated group. Results: Significant decreases in VMHC of the lingual, calcarine, superior temporal, and middle frontal gyri were identified in the untreated group, compared with the control group. Medicated patients showed decreased VMHC in the superior temporal gyrus, when compared with the controls. Compared to the unmedicated group, the medicated group showed a significant increase in VMHC in the calcarine and middle occipital gyrus. Moreover, a positive correlation was observed between basal LH levels and VMHC of the middle occipital gyrus in medicated patients. Conclusions: These findings indicate that long-term treatment with GnRHa was associated with increased interhemispheric functional connectivity within several areas responsible for memory and visual process in patients with ICPP. Higher interhemispheric functional connectivity in the middle occipital gyrus was related to higher basal LH production in the girls who underwent treatment. The present study adds to the growing body of research associated with the effects of GnRHa on brain function.
Simulation-Based Summative Assessment of Neonatal Resuscitation Providers Using the RETAIN Serious Board Game—A Pilot Study

Background: Each year, 13–26 million newborn babies require help to breathe at birth. Healthcare professionals (HCPs) who provide neonatal resuscitative care must be frequently evaluated to maintain and improve the quality of healthcare delivered. While simulation-based competence assessment is preferred, resource constraints hinder uptake. We aimed to examine if the RETAIN simulation-based boardgame can be used to assess HCPs' neonatal resuscitation knowledge. Method: Twenty neonatal HCPs (19 females) from the Royal Alexandra Hospital (Edmonton, Canada) were recruited. First, they completed an open-answer written test of one neonatal resuscitation scenario. Then, they completed one neonatal resuscitation scenario of difficulty comparable to that of the open-answer written test, but this time using the RETAIN board game. In the RETAIN board game (https://playretain.com, RETAIN Labs Medical Inc, Edmonton, Canada), players perform simulated neonatal resuscitation scenarios based on real-life cases, using action cards, and equipment pieces. Sessions were video-recorded and scored using Neonatal Resuscitation Program 2015 guidelines. Data are reported as mean (standard deviation) for normally distributed continuous variables, and as median (interquartile range) for non-normal continuous variables. Results: Participants consisted of the following HCPs: 8 nurses, 4 respiratory therapists, 4 nurse practitioners, and 4 neonatal fellows with median (IQR) 10.5(3–17) years of clinical experience. Overall mean (SD) Open-answer test and Game Performance was 8.6(2.1) out of 16 possible points (53%) and 29(3.2) out of 40 possible points (74%), respectively. Out of the 10 actions shared between the open-answer test and game scenario, performance on the open-answer test was mean (SD) 7.2(1.3) (72%) and game performance was mean (SD) 8.8(1.4) (88%) (V = 17, p < 0.01). Conclusion: RETAIN may provide an enjoyable and standardized alternative toward summative assessment of neonatal resuscitation providers. RETAIN may be used to improve more frequent and ubiquitous uptake of simulation-based competence assessment in healthcare settings.
VP1-binding protein glucose-regulated protein 78 as an important mediator for enterovirus 71 infecting human brain microvascular endothelial cells

Purpose: Enterovirus 71 (EV71) is one of the main pathogens causing hand, foot and mouth disease, which could even induce severe brain damage in some patients. As the underlying mechanism of the invasion and replication process still remains largely unknown, we investigated the role of candidate proteins expressed during EV71 invasion in human brain microvascular endothelial cells (HBMECs) to delineate the pathophysiological mechanism of EV-71 infection. Materials and Methods: Ninety-one candidate EV71-associated proteins which could bind the major capsid protein (viral protein 1 [VP1]) of EV71 on the HBMEC were identified by applying an analysis of glutathione-S-transferase pull-down coupling with liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). Seventy-eight kDa glucose-regulated protein 78 (GRP78) binding to the VP1 protein was further validated by co-immunoprecipitation, immunofluorescence and western blot analysis. To explore the role of GRP78 in EV71 infection, GRP78 was knocked down and overexpressed in HBMEC and was verified by TCID50 assay. Results: LC-ESI-MS/MS-identified 91 proteins were subjected to gene ontology analysis, and on molecular and biological function analysis revealed GRP78 act as an important binding protein in mediating EV71 infection. In addition, immunofluorescence demonstrated the co-localisation of GRP78 and VP1 in cytoplasm of the infected HBMEC. The TCID50 assay showed that knockdown of GRP78 could attenuate the replication capacity of EV71 in HBMEC, and the overexpression could increase the virus titre in HBEMC at 24 h post-infection suggesting that GRP78 was associated with the replication capacity of EV71 in HBMEC. Conclusion: These findings provided evidence that GRP78 plays an important role during the progression of EV71 infection as a mediator in HBMEC.
Evaluation of serum albumin concentration in generalized chronic periodontitis patients after surgical periodontal therapy

Introduction: Chronic periodontitis is one of the most prevalent diseases which affect patient's mastication and nutrition. Chronic inflammation of the gingiva also causes loss of serum albumin. Serum albumin is considered as a marker for general health as it has many functions in human body. Protein deficiency also accentuates the destructive effects of local irritants and occlusal trauma. Aims: The aim is to study the effect of surgical periodontal therapy (flap surgery) on serum albumin in chronic periodontitis patients. Subjects and Methods: Fifty participants of generalized chronic periodontitis were selected from the outpatient department. Clinical parameters were recorded at baseline, after 1 month, and 3 months. Venous blood was collected at baseline and 3 months after surgery from the participants to measure serum albumin by the bromocresol green albumin method. Statistical Analysis Used: Effect of surgical periodontal therapy on clinical parameters analyzed using one-way ANOVA (repeated-measures one-way ANOVA) followed by Tukey's multiple comparison tests for intragroup and intergroup comparison. A paired t-test was applied for serum albumin analysis. Results: Serum albumin level increased from baseline to follow-up period after surgical periodontal treatment, i.e., 3 months. This effect was found to be statistically significant (<0.001) in both groups as per the paired t-test. Conclusion: Surgical periodontal treatment (open flap debridement) has a positive effect on serum albumin level.
Effect of preemptive pregabalin for postoperative pain relief in myringoplasty

Context: Myringoplasty is a common surgical procedure done by ENT surgeons. Postoperative period requires use of analgesics which are being given on a regular basis. Aims: The aim of this study was to investigate the effect of preemptive pregabalin on postoperative pain reduction after endoscopic myringoplasty. Settings and Design: This was a prospective, experimental study conducted in the department of ENT and Head and Neck surgery in Dhulikhel Hospital, Kathmandu University Hospital, Kavre from September 2015 to December 2017. Subjects and Methods: Patient were randomly assigned to one of the two groups with 30 participants each by lottery method. Pregabalin group received capsule pregabalin 150 mg and placebo group were given Vitamin B capsule 1 h before surgery. Statistical Analysis Used: Normally distributed variables were analyzed with the Student's t-test and nonnormally distributed variables with the Mann–Whitney test. SPSS v. 21.0 for Windows (SPSS Inc., Chicago, USA) was used for the statistical data analysis. Results: Pain scores were significantly lower in pregabalin group as compared to placebo group at 6 h (U = 123, P < 0.01), 12 h (U = 107.5, P < 0.01), 24 h (U = 160.5, P < 0.01), and 48 h (U = 121.5, P < 0.01). Number of patients who required rescue analgesics and dosage was lower in pregabalin group than placebo group (P < 0.01). Conclusions: The preemptive administration of single dose of pregabalin 150 mg is an effective way to reduce postoperative pain and analgesic consumption in patients undergoing endoscopic myringoplasty.
In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line

Background & objectives: Statins are one of the most widely used drugs and have antilipidemic effects as well as antioxidant, anti-inflammatory, anti-angiogenic and anti-tumorigenic effects. It has been shown that the synergistic combinations of statins which can provide better clinical benefit in the treatment of cancer and if administered with other anticancer agents, may be an alternative treatment modality. The aim of this study was to assess the efficacy of administrating statin in multiple myeloma (MM) cell line on cell proliferation. Methods: U266 myeloma cells were cultured in 25 or 75 cm[2] flasks by using cell culture medium mixtures obtained with the supplementation of 10 per cent foetal bovine serum and one per cent of penicillin-streptomycin into RPMI 1640 medium. When the cells reached confluence (reached to the density of 70%), they were reproduced by passaging. Cytotoxicity was evaluated by using the XTT test. Results: Statins (atorvastatin and simvastatin), were administered to the U266 myeloma cell line at 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations. Inhibitor concentration 50 (IC50) values calculated for atorvastatin and simvastatin were determined as 94 and 38 μM, respectively. While 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations were used for bortezomib, the IC50value calculated for this agent was 18.2 nM. When six concentrations of bortezomib used in the study were combined with 12.5 μM inactive concentrations of statins that did not cause inhibition in cell proliferation, both atorvastatin and simvastatin increased the effect of bortezomib at all the concentrations used, and simvastatin showed a stronger efficacy than atorvastatin. Interpretation & conclusions: Our in vitro results indicated that atorvastatin and simvastatin when used along with the conventional treatment in myeloma patients, may improve the effectiveness of the standard therapy and prevent the bortezomib-induced cytotoxic and neurotoxic side effects when used at a low dose. Further studies need to be done in MM patints to confirm these findings.
A Review of Theory, Evidence, and Issues

The main objective of this paper is to understand the causes and symptoms of currency crises by reviewing its seminal literature, establishing its determinants, and outlining some of the relevant issues. The paper highlights the need to comprehend the process, which may lead to the inconsistency of the policies and render the situation favourable for a speculative attack. This involves, broadening the determinants of exchange rate crises beyond pure economic fundamentals through incorporating non-economic factors, such as political incentives on macroeconomic policy making. In effect, the review accentuates upon the need to develop a model that bridges the gap between the conventional and non-conventional determinants of a currency crisis. Visiting Research Fellow at the German Institute for Economic Research (DIW Berlin). University of Joensuu, Department of Business and Economic Studies, FIN-80101 Joensuu, Finland.