Miracle-dz/UniFAR-FTUs huggingface dataset:
Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

Alzheimer’s disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ are generated from the full-length amyloid beta precursor protein (APP) via dysregulated proteolytic processing; however, in the case of sporadic AD, the mechanism of Aβ biogenesis remains elusive. circRNAs are a class of transcripts preferentially expressed in brain. We identified a circRNA harboring the Aβ-coding region of the APP gene termed circAβ-a. This circular RNA was detected in the brains of AD patients and non-dementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-containing Aβ175 polypeptide (19.2 KDa) in both cultured cells and human brain. Furthermore, Aβ175 was shown to be processed into Aβ peptides—a hallmark of AD. In summary, our analysis revealed an alternative pathway of Aβ biogenesis. Consequently, circAβ-a and its corresponding translation product could potentially represent novel therapeutic targets for AD treatment. Importantly, our data point to yet another evolutionary route for potentially increasing proteome complexity by generating additional polypeptide variants using back-splicing of primary transcripts that yield circular RNA templates.
Clinical application and efficacy of negative pressure wound therapy with instillation and dwell time (NPWTi‐d): A systematic review and meta‐analysis

This study evaluates the current clinical evidence of Negative Pressure Wound Therapy with Instillation and dwell time (NPWTi‐d) to establish its clinical application and efficacy. MEDLINE, EMBASE, and CENTRAL databases were searched from 1946 to July 2019 for studies reporting clinical outcomes on wounds treated with NPWTi‐d. The primary outcome was proportion of wounds with complete healing. The secondary outcomes were mean time for healing, NPWTi‐d settings, cost, length of stay, and adverse events. Thirteen articles were included with a total of 624 wounds in 542 patients involving wounds of various aetiology. The pooled proportion of wound that achieved complete healing was 93.65% (95%CI: 84.02‐99.04). Normal saline was the most commonly used instillation solution with the mean dwell time of 14.23 minutes (95%CI: 10.88‐17.59) and instillation cycle every 4.17 ± 2.32 hourly. The mean therapy duration was 10.69 days (95%CI: 10.46‐10.91) with daily cost of $194.80. The mean hospital stay was 18.1 days (95%CI: 17.20‐19.00). There were no severe adverse effects reported. NPWTi‐d is an adjuntive therapy to aid complete healing of the vast majority of wounds. However, the current data are limited by the lack of level 1 evidence.
A Pharmacokinetic and Pharmacodynamic Study of Oral Dexmedetomidine

Background: Dexmedetomidine is only approved for use in humans as an intravenous medication. An oral formulation may broaden the use and benefits of dexmedetomidine to numerous care settings. The authors hypothesized that oral dexmedetomidine (300 mcg to 700 mcg) would result in plasma concentrations consistent with sedation while maintaining hemodynamic stability. Methods: The authors performed a single-site, open-label, phase I dose-escalation study of a solid oral dosage formulation of dexmedetomidine in healthy volunteers (n = 5, 300 mcg; followed by n = 5, 500 mcg; followed by n = 5, 700 mcg). The primary study outcome was hemodynamic stability defined as lack of hypertension, hypotension, or bradycardia. The authors assessed this outcome by analyzing raw hemodynamic data. Plasma dexmedetomidine concentrations were determined by liquid chromatograph–tandem mass spectrometry. Nonlinear mixed effect models were used for pharmacokinetic and pharmacodynamic analyses. Results: Oral dexmedetomidine was associated with plasma concentration–dependent decreases in heart rate and mean arterial pressure. All but one subject in the 500-mcg group met our criteria for hemodynamic stability. The plasma concentration profile was adequately described by a 2-compartment, weight allometric, first-order absorption, first-order elimination pharmacokinetic model. The standardized estimated parameters for an individual of 70 kg was V1 = 35.6 [95% CI, 23.8 to 52.8] l; V2 = 54.7 [34.2 to 81.7] l; CL = 0.56 [0.49 to 0.64] l/min; and F = 7.2 [4.7 to 14.4]%. Linear models with effect sites adequately described the decreases in mean arterial pressure and heart rate associated with oral dexmedetomidine administration. However, only the 700-mcg group reached plasma concentrations that have previously been associated with sedation (>0.2 ng/ml). Conclusions: Oral administration of dexmedetomidine in doses between 300 and 700 mcg was associated with decreases in heart rate and mean arterial pressure. Despite low oral absorption, the 700-mcg dose scheme reached clinically relevant concentrations for possible use as a sleep-enhancing medication. The hypotheses that oral dexmedetomidine would be associated with hemodynamic stability and plasma concentrations consistent with rousable sedation were tested in a phase I dose-escalation study in 15 normal volunteers. Oral dexmedetomidine bioavailability was low (7.2% [95% CI, 4.7 to 14%]). Oral dexmedetomidine (300 µg, 500 µg, and 700 µg) was associated with plasma concentration–dependent decreases in mean arterial pressure and heart rate. Only the 700-µg oral dose produced plasma concentrations associated with sedation. Supplemental Digital Content is available in the text.
Numerical Simulation of the Rheological Behavior of Nanoparticulate Suspensions

Nanoparticles significantly alter the rheological properties of a polymer or monomeric resin with major effect on the further processing of the materials. In this matter, especially the influence of particle material and disperse properties on the viscosity is not yet understood fully, but can only be modelled to some extent empirically after extensive experimental effort. In this paper, a numerical study on an uncured monomeric epoxy resin, which is filled with boehmite nanoparticles, is presented to elucidate the working principles, which govern the rheological behavior of nanoparticulate suspensions and to simulate the suspension viscosity based on assessable material and system properties. To account for the effect of particle surface forces and hydrodynamic interactions on the rheological behavior, a resolved CFD is coupled with DEM. It can be shown that the particle interactions caused by surface forces induce velocity differences between the particles and their surrounding fluid, which result in increased drag forces and cause the additional energy dissipation during shearing. The paper points out the limits of the used simulation method and presents a correction technique with respect to the Péclet number, which broadens the range of applicability. Valuable information is gained for a future mechanistic modelling of nanoparticulate suspension viscosity by elucidating the interdependency between surface forces, shear rate and resulting drag forces on the particles.
The levels of oxidative and nitrosative stress in patients who had 99mTc-MIBI myocardial perfusion scintigraphy and 99mTc-DMSA, 99mTc-MAG-3 renal scintigraphy.

BACKGROUND Ionizing radiation is a strong stimulator of reactive oxygen specises (ROS) and reactive nitrogen species (RNS). These reactive species may cause oxidative and nitrosative stress. In this study, we aimed to evaluate possible effects of 99mTechnetium (99mTc)-methoxyisobuthylisonitrite (MIBI), 99mTc-dimercaptosuccinic acid (DMSA), 99mTc-mercaptoacetyltriglycine (MAG-3) on oxidative and nitrosative stress biomarkers in patients who were performed myocardial perfusion scintigraphy (MPS) and renal scintigraphy. MATERIAL AND METHODS Patients (n = 29) who were referred to nuclear medicine department were chosen as the patient group. They were divided into three subgroups according to the type of disease and 99mTc labelled agent. The first patient group had MPS (n = 9). The second patient group had 99mTc-DMSA renal scintigraphy (n = 12). The third patient group had 99mTc-MAG-3 renal scintigraphy (n = 8). The blood samples were taken from first, second and third patient groups 1 h, 3 h, 45 min after injection of the agent, respectively. The samples were taken from healthy volunteers (n = 25) as a control group. Alterations in catalase (CAT),superoxide dismutase (SOD), malondialdehyde (MDA) levels as oxidative stress biomarkers and nitric oxide (NO) and 3-Nitrotyrosine (3-NTx) levels as nitrosative stress biomarkers in all blood samples were evaluated. RESULTS Results of MPS and renal scintigraphy performed patients were compared with control group separately. CAT, SOD, MDA and 3-NTx levels were higher in the first group than the control group (p < 0.05). Although NO levels were higher in the first group than the control group, it was not statistically significant (p > 0.05). CAT and SOD levels were lower in second and third groups than the control group (p < 0.0 5). However, MDA, NO, 3-NTx levels were higher in second and third groups than the control group (p < 0.05). CONCLUSIONS These results show that oxidative and nitrosative balance is impaired due to ionization radiation. These reactive species might stimulate an adaptive and protective cellular defense mechanism in irradiated cells soon after exposure to radiation. Thereby, this mechanism protect organism from the effects of low dose ionizing radiation.
An In Vitro Study on the Antimicrobial Properties of Essential Oil Modified Resin Composite against Oral Pathogens

Modifying the composition of dental restorative materials with antimicrobial agents might induce their antibacterial potential against cariogenic bacteria, e.g., S. mutans and L. acidophilus, as well as antifungal effect on C. albicans that are major oral pathogens. Essential oils (EOs) are widely known for antimicrobial activity and are successfully used in dental industry. The study aimed at evaluating antibacterial and antifungal activity of EOs and composite resin material (CR) modified with EO against oral pathogens. Ten EOs (i.e., anise, cinnamon, citronella, clove, geranium, lavender, limette, mint, rosemary thyme) were tested using agar diffusion method. Cinnamon and thyme EOs showed significantly highest antibacterial activity against S. mutans and L. acidophilus among all tested EOs. Anise and limette EOs showed no antibacterial activity against S. mutans. All tested EOs exhibited antifungal activity against C. albicans, whereas cinnamon EO showed significantly highest and limette EO significantly lowest activity. Next, 1, 2 or 5 µL of cinnamon EO was introduced into 2 g of CR and microbiologically tested. The modified CR showed higher antimicrobial activity in comparison to unmodified one. CR containing 2 µL of EO showed the best antimicrobial properties against S. mutans and C. albicans, while CR modified with 1 µL of EO showed the best antimicrobial properties against L. acidophilus.
Oxidative Stress and Microglial Response in Retinitis Pigmentosa

An imbalance between the production of reactive oxygen species (ROS) and anti-oxidant capacity results in oxidative injury to cellular components and molecules, which in turn disturbs the homeostasis of cells and organs. Although retinitis pigmentosa (RP) is a hereditary disease, non-genetic biological factors including oxidative stress also modulate or contribute to the disease progression. In animal models of RP, the degenerating retina exhibits marked oxidative damage in the nucleic acids, proteins, and lipids, and anti-oxidant treatments substantially suppress photoreceptor cell death and microgliosis. Although the mechanisms by which oxidative stress mediates retinal degeneration have not been fully elucidated, our group has shown that oxidative DNA damage and its defense system are key regulators of microglial activation and photoreceptor degeneration in RP. In this review, we summarize the current evidence regarding oxidative stress in animal models and patients with RP. The clinical efficacy of anti-oxidant treatments for RP has not been fully established. Nevertheless, elucidating key biological processes that underlie oxidative damage in RP will be pivotal to understanding the pathology and developing a potent anti-oxidant strategy that targets specific cell types or molecules under oxidative stress.
Preparing participants for the use of the tongue visual sensory substitution device

Abstract Purpose Visual sensory substitution devices (SSDs) convey visual information to a blind person through another sensory modality. Using a visual SSD in various daily activities requires training prior to use the device independently. Yet, there is limited literature about procedures and outcomes of the training conducted for preparing users for practical use of SSDs in daily activities. Methods We trained 29 blind adults (9 with congenital and 20 with acquired blindness) in the use of a commercially available electro-tactile SSD, BrainPort. We describe a structured training protocol adapted from the previous studies, responses of participants, and we present retrospective qualitative data on the progress of participants during the training. Results The length of the training was not a critical factor in reaching an advanced stage. Though performance in the first two sessions seems to be a good indicator of participants' ability to progress in the training protocol, there are large individual differences in how far and how fast each participant can progress in the training protocol. There are differences between congenital blind users and those blinded later in life. Conclusions The information on the training progression would be of interest to researchers preparing studies, and to eye care professionals, who may advise patients to use SSDs. IMPLICATIONS FOR REHABILITATION There are large individual differences in how far and how fast each participant can learn to use a visual-to-tactile sensory substitution device for a variety of tasks. Recognition is mainly achieved through top-down processing with prior knowledge about the possible responses. Therefore, the generalizability is still questionable. Users develop different strategies in order to succeed in training tasks.
Uterine Dysfunction in Diabetic Mice: The Role of Hydrogen Sulfide

It is well-known that the physiological uterine peristalsis, related to several phases of reproductive functions, plays a pivotal role in fertility and female reproductive health. Here, we have addressed the role of hydrogen sulfide (H2S) signaling in changes of uterine contractions driven by diabetes in non-obese diabetic (NOD) mice, a murine model of type-1 diabetes mellitus. The isolated uterus of NOD mice showed a significant reduction in spontaneous motility coupled to a generalized hypo-contractility to uterotonic agents. The levels of cyclic nucleotides, cAMP and cGMP, notoriously involved in the regulation of uterus homeostasis, were significantly elevated in NOD mouse uteri. This increase was well-correlated with the higher levels of H2S, a non-specific endogenous inhibitor of phosphodiesterases. The exposure of isolated uterus to L-cysteine (L-Cys), but not to sodium hydrogen sulfide, the exogenous source of H2S, showed a weak tocolytic effect in the uterus of NOD mice. Western blot analysis revealed a reorganization of the enzymatic expression with an upregulation of 3-mercaptopyruvate-sulfurtransferase (3-MST) coupled to a reduction in both cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) expression. In conclusion, the increased levels of cyclic nucleotides dysregulate the uterus peristalsis and contractility in diabetic mice through an increase in basal H2S synthesis suggesting a role of 3-MST.
The transcription factor C/EBPβ orchestrates dendritic cell maturation and functionality under homeostatic and malignant conditions

Significance Complex transcription factor networks regulate the development, maturation, and lineage commitment of dendritic cell (DC) subsets. Here, we demonstrate a previously unexpected role of the transcription factor C/EBPβ in murine DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Regulated expression of functional C/EBPβ isoforms enables a controlled maturation of DCs. In contrast, the presence of lymphoma cells leads to an up-regulation of C/EBPβ in DCs which transforms them into an immature and protumorigenic subtype. This study also shows that inhibition of the C/EBPβ/mTOR signaling axis abrogates the protumorigenic function of human DCs, suggesting that inhibitors regulating C/EBPβ activity can be used for blocking tumor-promoting functions of DCs in the treatment of hematological neoplasms. Dendritic cell (DC) maturation is a prerequisite for the induction of adaptive immune responses against pathogens and cancer. Transcription factor (TF) networks control differential aspects of early DC progenitor versus late-stage DC cell fate decisions. Here, we identified the TF C/EBPβ as a key regulator for DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Upon cell-specific deletion of C/EBPβ in CD11c+MHCIIhi DCs, gene expression profiles of splenic C/EBPβ−/− DCs showed a down-regulation of E2F cell cycle target genes and associated proliferation signaling pathways, whereas maturation signatures were enriched. Total splenic DC cell numbers were modestly increased but differentiation into cDC1 and cDC2 subsets were unaltered. The splenic CD11c+MHCIIhiCD64+ DC compartment was also increased, suggesting that C/EBPβ deficiency favors the expansion of monocytic-derived DCs. Expression of C/EBPβ could be mimicked in LAP/LAP* isoform knockin DCs, whereas the short isoform LIP supported a differentiation program similar to deletion of the full-length TF. In accordance with E2F1 being a negative regulator of DC maturation, C/EBPβ−/− bone marrow-derived DCs matured much faster enabling them to activate and polarize T cells stronger. In contrast to a homeostatic condition, lymphoma-exposed DCs exhibited an up-regulation of the E2F transcriptional pathways and an impaired maturation. Pharmacological blockade of C/EBPβ/mTOR signaling in human DCs abrogated their protumorigenic function in primary B cell lymphoma cocultures. Thus, C/EBPβ plays a unique role in DC maturation and immunostimulatory functionality and emerges as a key factor of the tumor microenvironment that promotes lymphomagenesis.
Evaluation of Dried Amniotic Membrane on Wound Healing at Split-Thickness Skin Graft Donor Sites: A Randomized, Placebo-Controlled, Double-blind Trial

ABSTRACT OBJECTIVE To evaluate the effect of amniotic membrane (AM) at split-thickness skin graft (STSG) donor sites. METHODS This double-blind randomized controlled trial was conducted on 35 eligible participants referred to the burn unit of Vasei Hospital of Sabzevar, Iran, during 2017 and 2018. Each STSG donor site was divided into two sides, and the respective halves were covered with either a dried AM or petrolatum gauze (control). Outcomes were evaluated on postprocedure days 10, 20, and 30 using the Vancouver Scar Scale. RESULTS The mean age of the patients was 39.4 ± 13.97 years, and 62.8% (n = 22) were male. There was no statistically significant difference in wound healing rate on day 10 (P = .261), 20 (P = .214), or 30 (P = .187) between groups. The intervention group had significantly better epithelialization than the control group on day 10 (investigator 1, 1.62 ± 0.59 vs 1.40 ± 0.88 [P = .009); investigator 2, 1.22 ± 0.84 vs 0.91 ± 0.85 [P = . 003]), as well as pain reduction (P < .001 during the follow-up period). However, there was no statistically significant difference between groups in terms of pigmentation or vascularization (P > .05). CONCLUSIONS Findings suggest that the use of AM is not superior to petrolatum gauze in terms of STSG healing rate; however, AM achieved better pain reduction and epithelialization on day 10.
Sex-speci c prevalence of coronary heart disease among Tehranian adult population across different glycemic status: Tehran Lipid and Glucose Study, 2008-2011

Seyyed Saeed Moazzeni Tehran University of Medical Sciences Hamidreza Ghafelehbashi Shahid Beheshti University of Medical Sciences Mitra Hasheminia Shahid Beheshti University of Medical Sciences Donna Parizadeh Shahid Beheshti University of Medical Sciences Arash Ghanbarian Shahid Beheshti University of Medical Sciences Freidoun Azizi Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases Farzad Hadaegh (  fzhadaegh@endocrine.ac.ir ) prevention of metabolic disorders research center,Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences https://orcid.org/0000-0002-8935-2744
IVIG ameliorate inflammation in collagen‐induced arthritis: projection for IVIG therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous immunoglobulins (IVIG), a pooled polyspecific immunoglobulin (Ig)G extracted from 5000 to 20 000 healthy subjects, showed beneficial therapeutic effect in patients with immune deficiency, sepsis and autoimmune diseases. The current study aimed to investigate the beneficial effect of treatment with IVIG in established collagen‐induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. Treatment with IVIG began when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma and the paws were hematoxylin and eosin (H&E)‐stained. Cytokine profile in the plasma was analyzed by Luminex technology and titers of circulating anti‐collagen antibodies in the plasma was tested by enzyme‐linked immunosorbent assay. Our results show that treatment with IVIG in murine significantly reduced the clinical arthritis score (P < 0·001). Moreover, mode of action showed that IVIG significantly reduced circulating levels of inflammatory cytokines [interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐17, IL‐6, tumor necrosis factor (TNF)‐α, P < 0·001], inhibiting anti‐collagen antibodies (P < 0·001) in the plasma of collagen‐induced arthritis mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti‐inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with rheumatologically related diseases.