Miracle-dz/UniFAR-FTUs huggingface dataset:
Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural variants show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.
Ultrasound to Localize the Peripherally Inserted Central Catheter Tip Position in Newborn Infants

Abstract Objective This study aimed to evaluate the application of ultrasound for the localization of the tip position of peripherally inserted central catheters (PICCs) in newborn infants. Study Design This study was a retrospective analysis on ultrasonic localization for PICC placement conducted in our department over the past 2 years. Ultrasonic localization was performed immediately after PICC placement in all neonatal patients. Successful PICC placement was confirmed if the PICC tip position was located at the inferior/superior cavoatrial junction. Chest X-ray localization was performed on 32 infants immediately after ultrasound examination to compare the accuracy of ultrasound localization. Results Of the 186 patients, 174 (93.5%) had successful PICC placement on the first attempt. In 11 (5.9%) patients, the catheter tip was placed beyond the ideal location as follows: too deep (in the right atrium) in 4 patients, too shallow in 4 patients, and malpositioned in 3 patients. Both the sensitivity and the specificity of ultrasound for identifying PICC tip localization were 100%. Complications occurred in 2.7% of this group of patients. Conclusion Ultrasonic localization of the PICC tip position is a timely, accurate, and reliable method and can identify the catheter tip with high accuracy. This method could be widely applied in neonatal wards.
Nonabsorbable Suture Knot on the Tendon Affects Rotator Cuff Healing: A Comparative Study of the Knots on Tendon and Bone in a Rat Model of Rotator Cuff Tear

Background: Nonabsorbable suture knots are usually used to link the tendon and bone during rotator cuff repair surgery. There are many variations in the arthroscopic knot-tying technique; however, the location of suture knot placement for rotator cuff healing has rarely been studied. Hypothesis: The authors compared the rotator cuff healing between knots tied on tendon and bone in a rotator cuff tear rat model. It has been hypothesized that knots can cause chronic inflammation and create the weakest link between tendon and bone, thus affecting rotator cuff healing. Study Design: Controlled laboratory study. Methods: Bilateral supraspinatus tenotomy and rotator cuff repair at the greater tuberosity were performed on 24 Wistar rats. Nonabsorbable surgical suture knots were made on the right supraspinatus tendon tissue and left humerus inferior to the greater tuberosity, respectively. Twelve rats each were sacrificed at 3 and 9 weeks. Six of the 12 rats were used for biomechanical testing and the remaining 6 for histologic evaluation. Results: The surgical knots placed on the bursal side of the tendon migrated to the articular side, as noted on gross observation in 22 of 24 samples. The knots on the tendon group showed significantly inferior tendon-bone integration and significantly inferior biomechanical results in terms of maximum load to failure and stiffness. An obvious chronic foreign body inflammatory reaction was found in the knots on the tendon group at 3 and 9 weeks. Furthermore, inferior bone-tendon interface regeneration and weakest link formation were obtained in the knots on the tendon group compared with those on the bone group. Conclusion: Nonabsorbable suture knots placed on the tendon migrate to the articular side, causing chronic inflammation and weakening tendon-bone healing, which may explain some retears after rotator cuff repair. Clinical Relevance: The present animal study suggests that it is not recommended in clinical practice to make several bulky nonabsorbable suture knots on the rotator cuff tendon during rotator cuff repair surgery. It may be better to tie the knots at the bone side or do knotless repair.
Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor due to its invasive phenotype. Ras suppressor 1 (RSU-1) is a cell-extracellular matrix adhesion protein and we recently found that it promotes cell invasion in aggressive cells and inhibits it in non-invasive. Growth differentiation factor-15 (GDF15) is known to be involved in actin cytoskeleton reorganization and metastasis. In this study, we used three brain cell lines (H4, SW1088 and A172) with increasing RSU-1 expression levels and invasive capacity and decreasing GDF15 levels to investigate the interplay between RSU-1 and GDF15 with regard to cell invasion. Four experimental approaches were used: (a) GDF15 treatment, (b) Rsu-1 silencing, (c) GDF15 silencing, and (d) combined GDF15 treatment and RSU-1 silencing. We found that the differential expression of RSU-1 and GDF15 in H4 and A172 cells leading to inhibition of cell invasion in H4 cells and promotion in A172 through respective changes in PINCH1, RhoA and MMP-13 expression. Interestingly SW1088, with intermediate RSU-1 and GDF15 expression, were not affected by any treatment. We conclude that there is a strong connection between RSU-1 and GDF15 in H4, SW1088 and A172 cells and the relative expression of these two proteins is fundamental in affecting their invasive fate.
Changes in the content of thiol compounds and the activity of glutathione s-transferase in maize seedlings in response to a rose-grass aphid infestation

The rose-grass aphid (Methopolophium dirhodum Walk.) is a major pest of maize (Zea mays L.), but little is known about the biochemical interactions between M. dirhodum and its host plant. Thiol compounds and glutathione S-transferase (GST) play a crucial role in the defense responses of maize to biotic stress factors, including aphids. The purpose of this research was to evaluate the impact of M. dirhodum herbivory on the total thiol (TT), protein bound thiol (PT), reduced glutathione (GSH) and oxidized glutathione (GSSG) contents as well as the activity of GST in three varieties of Z. mays (Złota Karłowa, Ambrozja and Płomyk), that were classified as aphid-susceptible, aphid-relatively resistant and aphid-resistant, respectively. The earliest and strongest aphid-triggered alterations in the levels of TT, PT and GSH, and the greatest induction of GST activity, were recorded in the resistant Płomyk seedlings in relation to the relatively resistant Ambrozja and the susceptible Złota Karłowa.
Performance of an artificial intelligence algorithm for reporting urine cytopathology

Unlike Papanicolaou tests, there are no commercially available computer‐assisted automated screening systems for urine specimens. Despite The Paris System for Reporting Urinary Cytology, there still is poor interobserver agreement with urine cytology and many cases in which a definitive diagnosis cannot be made. In the current study, the authors have reported on the development of an image algorithm that applies computational methods to digitized liquid‐based urine cytology slides.
Female family physicians and the first 5 years: In pursuit of gender equity, work-life integration, and wellness.

> We have still not shattered that highest and hardest glass ceiling. > > Hillary Rodham Clinton The feminization of family medicine in Canada has seen the representation of women tripling to 45% in the past 4 decades. [1][1] With this shift, we see numerous benefits to our health care system,
Exosomes secreted from osteocalcin-overexpressed endothelial progenitor cells promoted endothelial cell angiogenesis.

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs has been found to be increased in cardiovascular disease patients and considered to be involved in the process of coronary atherosclerosis. Since OCN has been proved to prevent endothelial dysfunction, this study aims to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor, G-protein coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay and the migration of endothelial cells were detected by wound healing assay. Tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here we presented that OCN was packed into Exos and able to be transferred to the RAOECs via exosomes incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efﬁciencies on promoting RAOEC proliferation, migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPC have beneficial regulating effect on endothelial cells, which involved the enhanced OCN-GPRC6A signaling.
The IT artifact and its spirit: a nexus of human values, affordances, symbolic expressions, and IT features

Abstract This article theorises the IT artifact using a new conceptualisation of IT Spirit that highlights the interrelationships between IT Features, Affordances, and Symbolic Expressions. Although these concepts have been discussed in the IS literature, researchers have mostly examined them independently. Drawing on the philosophical theories of Aristotle and Heidegger, this article discusses the “essence of technology” by conceptualising the IT artifact in terms of the intertwining relationships that exist between IT Features, their Symbolic Expressions, the Affordances connected to them at different levels of abstraction, and the Values that emerge from the enactment of their action possibilities within a user group. It is argued that these essential components of the IT artifact operate at variant levels of abstraction, instigate user sense-making, and subsequently form the overarching IT Spirit. The latter is presented as the incorporeal essence of a technology that shapes – and is itself shaped by – user sense-making and appropriation. With the emphasis that it gives to human values, the concept of IT Spirit offers researchers a high-level unit of analysis to tackle the IT artifact and a systematic framework that facilitates the identification of its prominent action possibilities.
Persistent Isolated Elevation of Aspartate Aminotransferase in an Asymptomatic Female Patient: a Case Report and Review of Current Literature.

BACKGROUND Persistent isolated elevation of aspartate aminotransferase (AST) is a rare observation and might lead to unnecessary laboratory testing and invasive procedures, if the possibility of macro-AST is not considered. METHODS We report the case of a healthy 28-year-old female patient with persistent isolated elevation of AST. In order to confirm the suspected diagnosis of macro-AST, polyethylene glycol (PEG) precipitation and repeated measurements of enzyme activity after refrigeration at 2 - 8°C were performed. RESULTS PEG precipitation confirmed the presence of macro-AST, while repeated measurements after refrigeration did not show any relevant decrease in enzyme activity. CONCLUSIONS Especially in clinically asymptomatic patients, macro-AST must be considered as a cause of persistent isolated elevations in AST activity to avoid costly and potentially harmful medical tests or procedures. PEG precipitation is a feasible and cost-effective way to establish the diagnosis, while repeated measurement of enzyme activity after refrigeration potentially leads to wrong conclusions.
Repression of ferritin light chain translation by human eIF3

A central problem in human biology remains the discovery of causal molecular links between mutations identified in genome-wide association studies (GWAS) and their corresponding disease traits. This challenge is magnified for variants residing in non-coding regions of the genome. Single-nucleotide polymorphisms (SNPs) in the 5ʹ untranslated region (5ʹ-UTR) of the ferritin light chain (FTL) gene that cause hyperferritinemia are reported to disrupt translation repression by altering iron regulatory protein (IRP) interactions with the FTL mRNA 5ʹ-UTR. Here, we show that human eukaryotic translation initiation factor 3 (eIF3) acts as a distinct repressor of FTL mRNA translation, and eIF3-mediated FTL repression is disrupted by a subset of SNPs in FTL that cause hyperferritinemia. These results identify a direct role for eIF3-mediated translational control in a specific human disease.
The Autophagy Signaling Pathway: A Potential Multifunctional Therapeutic Target of Curcumin in Neurological and Neuromuscular Diseases

Autophagy is the major intracellular machinery for degrading proteins, lipids, polysaccharides, and organelles. This cellular process is essential for the maintenance of the correct cellular balance in both physiological and stress conditions. Because of its role in maintaining cellular homeostasis, dysregulation of autophagy leads to various disease manifestations, such as inflammation, metabolic alterations, aging, and neurodegeneration. A common feature of many neurologic and neuromuscular diseases is the alteration of the autophagy-lysosomal pathways. For this reason, autophagy is considered a target for the prevention and/or cure of these diseases. Dietary intake of polyphenols has been demonstrated to prevent/ameliorate several of these diseases. Thus, natural products that can modulate the autophagy machinery are considered a promising therapeutic strategy. In particular, curcumin, a phenolic compound widely used as a dietary supplement, exerts an important effect in modulating autophagy. Herein, we report on the current knowledge concerning the role of curcumin in modulating the autophagy machinery in various neurological and neuromuscular diseases as well as its role in restoring the autophagy molecular mechanism in several cell types that have different effects on the progression of neurological and neuromuscular disorders.
Hydrolysed Collagen from Sheepskins as a Source of Functional Peptides with Antioxidant Activity

The extraction and enzymatic hydrolysis of collagen from sheepskins at different times of hydrolysis (0, 10, 15, 20, 30 min, 1, 2, 3 and 4 h) were investigated in terms of amino acid content (hydroxyproline), isoelectric point, molecular weight (Mw) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, viscosity, Fourier-transform infrared (FTIR) spectroscopy, antioxidant capacity by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, thermal properties (Differential Scanning Calorimetry) and morphology by scanning electron microscopy (SEM) technique. The kinetics of hydrolysis showed an increase in the protein and hydroxyproline concentration as the hydrolysis time increased to 4 h. FTIR spectra allowed us to identify the functional groups of hydrolysed collagen (HC) in the amide I region for collagen. The isoelectric point shifted to lower values compared to the native collagen precursor. The change in molecular weight and viscosity from time 0 min to 4 h promoted important antioxidant activity in the resulting HC. The lower the Mw, the greater the ability to donate an electron or hydrogen to stabilize radicals. From the SEM images it was evident that HC after 2 h had a porous and spongy structure. These results suggest that HC could be a good alternative to replace HC from typical sources like pigs, cows and fish.
Comparison of Optical Coherence Tomography Angiography Findings in Patients with Behçet’s Disease and Healthy Controls

ABSTRACT Purpose To investigate optical coherence tomography angiography (OCTA) findings in patients with Behçet’s disease (BD). Methods Ninety-four eyes of 49 patients with BD and 53 eyes of 53 healthy subjects were included. Vascular density (VD), foveal avascular zone (FAZ) area, perifoveal capillary hypoperfusion, perifoveal capillary network disorganization, and FAZ irregularity were analyzed. Results OCTA revealed retinal VD reduction and higher perifoveal capillary hypoperfusion, perifoveal capillary network disorganization and FAZ irregularity in ocular Behçet’s compared to nonocular Behçet’s (p = .000). However, compared to normal eyes, there was no difference between any OCTA measurements in nonocular BD patients. The mean area of FAZ was not different in any group (p = .266). In ocular Behçet, visual acuity was inversely correlated with FAZ area and FAZ irregularity. Conclusion Retinal VD decreases and perifoveal microvascular network changes in ocular Behçet’s. FAZ irregularity may be a more valuable marker than FAZ area for indicating ocular involvement.
Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models

Introduction: MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed. Materials and methods: The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR (“lung diseases”[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English. Results and Conclusions: A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.
Identification and characterization of telocytes in rat testis

In this study, we investigated the localization, morphological features and cellular interactions of telocytes in the rat testicular interstitium. Transmission electron microscopy (TEM) and immunohistochemical and immunofluorescence analyses of the rat testicular interstitium showed a distinct layer of telocytes surround the seminiferous tubules along with inner layer of peritubular myoid cells. The majority of the telocytes were made up of a small cell body and moniliform prolongations that contained mitochondria and secretory vesicles. Some other telocytes were observed possessing large cell bodies. Within the testicular interstitium, the telocytes formed a network connecting peritubular myoid cells, Leydig cells as well as blood vessels. Immunohistochemical and double immunofluorescence analyses showed that rat testicular telocytes express CD34 and PDGFRα, but are negative for vimentin and α-SMA. Our findings demonstrate the presence of telocytes in the rat testicular interstitium. These cells interact with peritubular myoid cells, seminiferous tubules, Leydig cells and blood vessels via long telopode extensions, which suggests their vital role in the intercellular communication between different cell types within the rat testis.
Interleukin‐1 blockade treatment decreasing cardiovascular risk

Abstract Background Interleukin‐1 (IL‐1) played a role in the occurrence and development of atherosclerosis and cardiovascular events. However, the association between IL‐1 blockage treatment and reducing of cardiovascular risk remains poorly defined. Hypothesis IL‐1 blockage treatment reduce the risk and incidence rate of overall major adverse cardiovascular events (MACE), all‐cause death, acute myocardial infarction(MI), unstable angina and heart failure. Methods We performed a search of published reports by using MEDLINE database (January 1, 2005 to April 1, 2018). The randomized controlled trials (RCTs) that reported sample size and occurrence numbers in test group and placebo group for the associations of interest were included. Results Eight RCT studies involving 15 647 participants were identified. Compared with those who took no IL‐1 blockage, patients taking IL‐1 blockage experienced a decreased risk of overall MACE (RR 0.88, 95% CI 0.82‐0.94), unstable angina (RR 0.80, 95% CI 0.66‐0.98), and breakthrough or recurrence of heart failure (RR 0.44, 95% CI 0.22‐0.87). No association was found between IL‐1 blockage treatment and death from all cause (RR 0.91, 95% CI 0.83‐1.00) as well as acute MI (RR 0.85, 95% CI 0.71‐1.01). The RRs associated with overall MACE, death from all cause, acute MI, and unstable angina for anakinra were 1.05, 1.16, 2.97, and 0.56, respectively, and for canakinumab were 1.05, 0.91, 0.80, and 0.80, respectively. Conclusions Administration of IL‐1 blockage was associated with decrease risks of overall MACE, unstable angina, and breakthrough or recurrence of heart failure, but not with death from all cause as well as acute MI.