Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy

Depot specific expansion of orbital-adipose-tissue (OAT) in Graves’ Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO). OAT-H/OAT-GO have a single lipid-vacuole and low mitochondrial number. Lower lipolytic activity and smaller adipocytes of OAT-H/OAT-GO, accompanied by similar essential linoleic fatty acid (FA) and (low) FA synthesis to WAT, revealed a hyperplastic OAT expansion through external FA-uptake via abundant SLC27A6 (FA-transporter) expression. Mitochondrial dysfunction of OAT in GO was apparent, as evidenced by the increased mRNA expression of uncoupling protein 1 (UCP1) and mitofusin-2 (MFN2) in OAT-GO compared to OAT-H. Transcriptional profiles of OAT-H revealed high expression of Iroquois homeobox-family (IRX-3&5), and low expression in HOX-family/TBX5 (essential for WAT/BAT (brown-adipose-tissue)/BRITE (BRown-in-whITE) development). We demonstrated unique features of OAT not presented in either WAT or BAT/BRITE. This study reveals that the pathologically enhanced FA-uptake driven hyperplastic expansion of OAT in GO is associated with a depot specific mechanism (the SLC27A6 FA-transporter) and mitochondrial dysfunction. We uncovered that OAT functions as a distinctive fat depot, providing novel insights into adipocyte biology and the pathological development of OAT expansion in GO.
Neuroprotective Potential of Verbascoside Isolated from Acanthus mollis L. Leaves through Its Enzymatic Inhibition and Free Radical Scavenging Ability

The phenomenon of today’s ageing population has increased interest in the search for new active substances that delay the onset and development of neurodegenerative diseases. In this respect, the search for natural compounds, mainly phenolic compounds, with neuroprotective activity has become the focus of growing interest. Verbascoside is a phenylethanoid that has already presented several pharmacological activities. The purpose of this study is to isolate and identify verbascoside from Acanthus mollis leaves. Consequently, its neuroprotective ability through enzymatic inhibition and free radical scavenging ability has been analyzed both in vitro and in cell culture assays. The antioxidant capacity of verbascoside was evaluated in vitro through total antioxidant capacity, DPPH•, •OH, and O2•—scavenging activity assays. The effect of verbascoside on intracellular reactive oxygen species (ROS) levels of HepG2 and SH-SY5Y cell lines was studied in normal culture and under induced oxidative stress. The inhibitory ability of the phenylethanoid against several enzymes implied in neurodegenerative diseases (tyrosinase, MAO-A, and AChE) was analyzed in vitro. Verbascoside neuroprotective activity is at least in part related to its free radical scavenging ability. The effect of verbascoside on ROS production suggests its potential in the prevention of harmful cell redox changes and in boosting neuroprotection.
Left Ventricular Mass Reduction by a Low-Sodium Diet in Treated Hypertensive Patients †

Objective: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction. Patients and Methods: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread. Blood pressure (BP), 24-h urinary sodium (UNaV) and LVM were recorded at baseline, after 2 months. and after 2years. Results: In 76 patients UNaV decreased in the recommended range after 2 months and remained low at 2 years. In 62 patients UNaV levels decreased after 2 months and then increased back to baseline at 2 years. Initially the two groups did not differ in terms of BP (134.3 ± 16.10/80.84 ± 12.23 vs. 134.2 ± 16.67/81.55 ± 11.18 mmHg, mean ± SD), body weight (72.64 ± 15.17 vs. 73.79 ± 12.69 kg), UNaV (161.0 ± 42.22 vs. 158.2 ± 48.66 mEq/24 h), and LVM index (LVMI; 97.09 ± 20.42 vs. 97.31 ± 18.91 g/m2). After 2years. they did not differ in terms of BP (125.3 ± 10.69/74.97 ± 7.67 vs. 124.5 ± 9.95/75.21 ± 7.64 mmHg) and body weight (71.14 ± 14.29 vs. 71.50 ± 11.87 kg). Significant differences were seen for UNaV (97.3 ± 23.01 vs. 152.6 ± 49.96 mEq/24 h) and LVMI (86.38 ± 18.17 vs. 103.1 ± 21.06 g/m2). Multiple regression analysis: UNaV directly and independently predicted LVMI variations, either as absolute values (R2 = 0.369; β = 0.611; p < 0.001), or changes from baseline to +2years. (R2 = 0.454; β = 0.677; p < 0.001). Systolic BP was a weaker predictor of LVMI (R2 = 0.369; β = 0.168; p = 0.027; R2 = 0.454; β = 0.012; p = 0.890), whereas diastolic BP was not correlated with LVMI. The prevalence of left ventricular hypertrophy decreased (29/76 to 15/76) in the first group while it increased in the less compliant patients (25/62 to 36/62; Chi2 p = 0.002). Conclusion: LVM seems linked to sodium consumption in patients already under proper BP control by medications.
Awareness and Utilization of Obstetric Epidural Analgesia in Labour Among Pregnant Women in Wesley Guild Hospital Ilesha, Nigeria

Epidural analgesia is widely used as an effective method of pain relief in labor. This study was therefore designed to investigate the awareness and level of utilization of obstetric analgesia in labour among pregnant women in Wesley Guild Hospital Ilesha, Nigeria. The descriptive study involving 110 pregnant women revealed that about half (41.8%) of the respondents had poor knowledge score, 37.3% had fair knowledge, while 20.9% had good knowledge score on obstetric epidural analgesia. Only 10.9% of the respondents had used epidural analgesia and 83.3% were satisfied with the use. There was a significant relationship between knowledge of respondents and the use of obstetric epidural analgesia. Moderate awareness, poor knowledge and low level of utilization of obstetric epidural analgesia were documented. There is a need for adequate awareness programs to enhance the knowledge of epidural analgesia and its utilization among pregnant women in order to reduce the excruciating labour pain.
BAD inactivation exacerbates rheumatoid arthritis pathology by promoting survival of sublining macrophages

The resistance of synovial sublining macrophages to apoptosis has a crucial role in joint inflammation and destruction in rheumatoid arthritis (RA). However, the underlying mechanism is incompletely understood. Here we report that inactivation of the pro-apoptotic BCL-2 family protein BAD is essential for survival of synovial sublining macrophage in RA. Genetic disruption of Bad leads to more severe joint inflammation and cartilage and bone damage with reduced apoptosis of synovial sublining macrophages in collagen-induced arthritis (CIA) and TNFα transgenic (TNF-Tg) mouse models. Conversely, Bad3SA/3SA mice, in which BAD can no longer be inactivated by phosphorylation, are protected from collagen-induced arthritis. Mechanistically, phosphorylation-mediated inactivation of BAD specifically protects synovial sublining macrophages from apoptosis in highly inflammatory environment of arthritic joints in CIA and TNF-Tg mice, and in patients with RA, thereby contributing to RA pathology. Our findings put forward a model in which inactivation of BAD confers the apoptosis resistance on synovial sublining macrophages, thereby contributing to the development of arthritis, suggesting that BAD may be a potential therapeutic target for RA.
Creation of Gold Nanoparticles in ZnO by Ion Implantation–DFT and Experimental Studies

Three different crystallographic orientations of the wurtzite ZnO structure (labeled as c-plane, a-plane and m-plane) were implanted with Au+ ions using various energies and fluences to form gold nanoparticles (GNPs). The ion implantation process was followed by annealing at 600 °C in an oxygen atmosphere to decrease the number of unwanted defects and improve luminescence properties. With regard to our previous publications, the paper provides a summary of theoretical and experimental results, i.e., both DFT and FLUX simulations, as well as experimental results from TEM, HRTEM, RBS, RBS/C, Raman spectroscopy and photoluminescence. From the results, it follows that in the ZnO structure, implanted gold atoms are located in random interstitial positions —experimentally, the amount of interstitial gold atoms increased with increasing ion implantation fluence. During ion implantation and subsequent annealing, the metal clusters and nanoparticles with sizes from 2 to 20 nm were formed. The crystal structure of the resulting gold was not cubic (confirmed by diffraction patterns), but it had a hexagonal close-packed (hcp) arrangement. The ion implantation of gold leads to the creation of Zn and O interstitial defects and extended defects with distinct character in various crystallographic cuts of ZnO, where significant O-sublattice disordering occurred in m-plane ZnO.
Resurrecting the ancient glow of the fireflies

Resurrection of extinct firefly luciferases sheds light on the evolutionary history of ancient glow of the beetles. The color of firefly bioluminescence is determined by the structure of luciferase. Firefly luciferase genes have been isolated from more than 30 species, producing light ranging in color from green to orange-yellow. Here, we reconstructed seven ancestral firefly luciferase genes, characterized the enzymatic properties of the recombinant proteins, and determined the crystal structures of the gene from ancestral Lampyridae. Results showed that the synthetic luciferase for the last common firefly ancestor exhibited green light caused by a spatial constraint on the luciferin molecule in enzyme, while fatty acyl-CoA synthetic activity, an original function of firefly luciferase, was diminished in exchange. All known firefly species are bioluminescent in the larvae, with a common ancestor arising approximately 100 million years ago. Combined, our findings propose that, within the mid-Cretaceous forest, the common ancestor of fireflies evolved green light luciferase via trade-off of the original function, which was likely aposematic warning display against nocturnal predation.
Study of haemolysis interference limit on serum potassium assay on Roche® Cobas 8000 and evaluation of corrected potassium

Abstract Roche Diagnostics® decided a more restrictive haemolysis index (≤20 HI) for approval the release of serum potassium results. This study examined the risk of overestimating serum potassium results related to the HI according to the Ricos total error (±5.6%) and evaluated the approach of Martinez-Morillo and Alvarez to determine a corrected potassium. According to Ricos’ criteria, our study showed compliant potassium results with HI less than or equal to 75. Between 90 and 100 HI, the results did not show a significant overestimation. The equation to obtain Kcorrected was: Kmeasured – (0.004 × HI). The use of corrective formulas for adjusting results of potassium could help the laboratory to identify patients at increased risk and to repeat the test as soon as possible.
Translation elongation rate varies among organs and decreases with age

Abstract There has been a surge of interest towards targeting protein synthesis to treat diseases and extend lifespan. Despite the progress, few options are available to assess translation in live animals, as their complexity limits the repertoire of experimental tools to monitor and manipulate processes within organs and individual cells. It this study, we developed a labeling-free method for measuring organ- and cell-type-specific translation elongation rates in vivo. It is based on time-resolved delivery of translation initiation and elongation inhibitors in live animals followed by ribosome profiling. It also reports translation initiation sites in an organ-specific manner. Using this method, we found that the elongation rates differ more than 50% among mouse organs and determined them to be 6.8, 5.0 and 4.3 amino acids per second for liver, kidney, and skeletal muscle, respectively. We further found that the elongation rate is reduced by 20% between young adulthood and mid-life. Thus, translation, a major metabolic process in cells, is tightly regulated at the level of elongation of nascent polypeptide chains.
Modulation of the functional connectome in major depressive disorder by ketamine therapy

Abstract Background Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized. Methods Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status. Results Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern. Conclusion Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
STI/HIV testing among Medicaid/CHIP-insured enrollees aged 15-60 years who were diagnosed with high risk sexual behaviors with their opposite-sex or same-sex partners.

BACKGROUND There is a lack of information about high risk sexual behaviors (HRSB) related to gender of sex partner and associated STI/HIV testing among Medicaid enrollees. METHODS We used the 2016 CMS Medicaid claims data to identify enrollees aged 15-60 years with HRSB by ICD-10 codes (Z72.51, Z72.52, and Z72.53). Enrollees diagnosed with HRSB were classified into two groups:1) with same-sex partners and 2) with opposite-sex partners. The date when the initial diagnosis for HRSB was documented was used to define as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing on the index date, in the 6-month period before and after the index date (excluded the index date). HIV testing was limited to enrollees without documented HIV infection. RESULTS Of 50 million Medicaid enrollees aged 15-60 years, 1.2% were identified as enrollees with HRSB in 2016. Of those enrollees with HRSB, 2.7% were enrollees with same-sex partners and 0.71% had documented HIV infection. Chlamydia, gonorrhea, syphilis, and HIV testing rates were 82.4%, 81.9%, 33.2%, and 44.3%, respectively, at the index date. The chlamydia testing rate was ≥ 90% among enrollees who resided in the West, compared to 53% to 61% across other regions. HIV testing was more likely among males and among those with same-sex partners. STI/HIV testing was <30% in the 6-month periods before and after the index date. CONCLUSIONS Among Medicaid enrollees with HRSB, STI/HIV testing varied regionally. Many enrollees were not tested for STI/HIV at the index visit in which they were identified as HRSB.
Reply to Kidd et al., “New Names for Fungi of Medical Importance: Can We Have Our Cake and Eat It Too?”

We are grateful to Dr Kidd and her colleagues for the sensible and supportive stance adopted in their letter (1) in reply to our recent manuscript summarising proposed name changes for fungi of medical importance (2), and for offering voices of reason in the heated Twitter exchanges that ensued following the publication of said taxonomy update. ….
Functional Comparison of Blood-Derived Human Neural Progenitor Cells

Induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) are promising tools to model complex neurological or psychiatric diseases, including schizophrenia. Multiple studies have compared patient-derived and healthy control NPCs derived from iPSCs in order to investigate cellular phenotypes of this disease, although the establishment, stabilization, and directed differentiation of iPSC lines are rather expensive and time-demanding. However, interrupted reprogramming by omitting the stabilization of iPSCs may allow for the generation of a plastic stage of the cells and thus provide a shortcut to derive NPSCs directly from tissue samples. Here, we demonstrate a method to generate shortcut NPCs (sNPCs) from blood mononuclear cells and present a detailed comparison of these sNPCs with NPCs obtained from the same blood samples through stable iPSC clones and a subsequent neural differentiation (classical NPCs—cNPCs). Peripheral blood cells were obtained from a schizophrenia patient and his two healthy parents (a case–parent trio), while a further umbilical cord blood sample was obtained from the cord of a healthy new-born. The expression of stage-specific markers in sNPCs and cNPCs were compared both at the protein and RNA levels. We also performed functional tests to investigate Wnt and glutamate signaling and the oxidative stress, as these pathways have been suggested to play important roles in the pathophysiology of schizophrenia. We found similar responses in the two types of NPCs, suggesting that the shortcut procedure provides sNPCs, allowing an efficient screening of disease-related phenotypes.
A ppm Ethanol Sensor Based on Fabry–Perot Interferometric Surface Stress Transducer at Room Temperature

Disease screening by exhaled breath diagnosis is less burdensome for patients, and various devices have been developed as promising diagnostic methods. We developed a microelectromechanical system (MEMS) optical interferometric surface stress sensor to detect volatile ethanol gas at room temperature (26~27 °C) with high sensitivity. A sub-micron air gap in the optical interferometric sensor reduces interference orders, leading to increased spectral response associated with nanomechanical deflection caused by ethanol adsorption. The sub-micron cavity was embedded in a substrate using a transfer technique of parylene-C nanosheet. The sensor with a 0.4 µm gap shows a linear stable reaction, with small standard deviations, even at low ethanol gas concentrations of 5–110 ppm and a reversible reaction to the gas concentration change. Furthermore, the possibility of detecting sub-ppm ethanol concentration by optimizing the diameter and thickness of the deformable membrane is suggested. Compared with conventional MEMS surface stress gas sensors, the proposed optical interferometric sensor demonstrated high-sensitivity gas detection with exceeding the detection limit by two orders of magnitude while reducing the sensing area.
Arsenic adsorption onto silicon stepped surfaces: a study at semiempirical level

As adsorption onto Si surfaces vicinal to (100) has been studied using the Hartree–Fock method at a semiempirical level and a cluster model of the surface steps. The simulation conditions apply to the dilute limit of the adsorbate concentration. Accordingly, one As atom is placed on the step in a substitutional or interstitial location, either above or below the surface. The optimal configuration of the system is evaluated from a steepest-descent energy minimization. The central finding is that As is preferably adsorbed in the interstitial location and the physical explanation is that this location allows both a stronger electrostatic coupling with the surface and a lower stress than in the case of the substitutional impurity. This result represents a significant divergence with respect to the known properties of the bulk impurity. It can, however, consistently account for known features of heteroepitaxial growth of As on Si(100).
The Impact of Pretrained Language Models on Negation and Speculation Detection in Cross-Lingual Medical Text: Comparative Study

Background Negation and speculation are critical elements in natural language processing (NLP)-related tasks, such as information extraction, as these phenomena change the truth value of a proposition. In the clinical narrative that is informal, these linguistic facts are used extensively with the objective of indicating hypotheses, impressions, or negative findings. Previous state-of-the-art approaches addressed negation and speculation detection tasks using rule-based methods, but in the last few years, models based on machine learning and deep learning exploiting morphological, syntactic, and semantic features represented as spare and dense vectors have emerged. However, although such methods of named entity recognition (NER) employ a broad set of features, they are limited to existing pretrained models for a specific domain or language. Objective As a fundamental subsystem of any information extraction pipeline, a system for cross-lingual and domain-independent negation and speculation detection was introduced with special focus on the biomedical scientific literature and clinical narrative. In this work, detection of negation and speculation was considered as a sequence-labeling task where cues and the scopes of both phenomena are recognized as a sequence of nested labels recognized in a single step. Methods We proposed the following two approaches for negation and speculation detection: (1) bidirectional long short-term memory (Bi-LSTM) and conditional random field using character, word, and sense embeddings to deal with the extraction of semantic, syntactic, and contextual patterns and (2) bidirectional encoder representations for transformers (BERT) with fine tuning for NER. Results The approach was evaluated for English and Spanish languages on biomedical and review text, particularly with the BioScope corpus, IULA corpus, and SFU Spanish Review corpus, with F-measures of 86.6%, 85.0%, and 88.1%, respectively, for NeuroNER and 86.4%, 80.8%, and 91.7%, respectively, for BERT. Conclusions These results show that these architectures perform considerably better than the previous rule-based and conventional machine learning–based systems. Moreover, our analysis results show that pretrained word embedding and particularly contextualized embedding for biomedical corpora help to understand complexities inherent to biomedical text.