Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of the vinculin tail domain and a model for activation

Title: Crystal structure of the vinculin tail domain and a model for activation. Author: Constantina Bakolitsa Cell adhesion is a fundamental requirement in multicellular organisms for a variety of biological processes, such as tissue integrity, cell growth and differentiation, and wound healing. At sites of cell-matrix adhesion, termed focal adhesions, protein networks converge in a variety of multimolecular complexes composed of transmembrane adhesion receptors, anchoring intracellular cytoskeletal structural proteins and signal transduction molecules. Basic physical mechanisms underlying the regulation of focal adhesion formation and function include aggregation, phosphorylation and conformational changes of the molecules involved. Vinculin is a protein located at sites of cell-cell and cell-matrix adhesion where it plays a dynamic role in the assembly of the actin cytoskeleton. A strong interaction between its head and tail domains that regulates binding to other cytoskeletal components is disrupted by acidic phospholipids. The crystal structure of the vinculin tail, residues 879-1066, was determined by the method of single isomorphous replacement with anomalous scattering. Five amphipathic helices form an antiparallel bundle that resembles exchangeable apolipoproteins. A C-terminal arm wraps across the base of the bundle and emerges as a hydrophobic hairpin surrounded by a collar of basic residues, adjacent to the N-terminus. A series of structure-designed solution studies were carried out on the vinculin tail and a C-terminal deletion mutant. Co-sedimentation assays showed that the C-terminal arm is required for binding to acidic phospholipids but not to F-actin, while limited proteolysis and stopped-flow measurements indicated that binding to either ligand induces conformational changes in the Nand C-terminal regions of the molecule. These changes may represent the first step in a model for the activation of the intact vinculin, where PIP2-triggered unfurling of the tail domain would lead to subsequent sequestration of the head and neck regions allowing binding to F-actin. Crystals of the intact vinculin diffracting synchrotron radiation to medium resolution have also been obtained.
The untold perspective: Parents’ experiences of the autism spectrum disorder assessment process when the child did not receive a diagnosis

This research explored parents’ lived experience of the autism spectrum disorder assessment process when a diagnosis was not received. Six mothers and one stepfather were interviewed and transcripts were analysed using interpretative phenomenological analysis. The identified themes: ‘My child is different’, The emotional and psychological journey and Understanding the outcome, illustrated issues encountered by parents during the assessment process and parenting a child with autistic-like characteristics but without a valid label. As a previously understudied area, clinical implications at the professional, service and policy level are discussed. Lay abstract Autism is diagnosed by a process of child assessment and parental interview. It has been well-documented by parents of children who received a diagnosis of autism, that the process can be lengthy and cause distress for families. Nevertheless, the outcome often compensated for the difficult assessment journey as it enables families to gain access to further information, support and intervention. However, less is known about the assessment process from parents who undertake the same process but at the end are told their child does not meet the diagnostic criteria, meaning no diagnosis is given. We interviewed six parents in North Wales, whose child did not receive a diagnostic of autism following an assessment. During the interview, parents were asked about their experience of the autism assessment process. We found that parents reflected on their experience according to three themes: (1) parents tried to navigate how they could make sense of their child being different despite not receiving a diagnosis; (2) parents referred to the assessment process as a journey, which encompassed many emotional and psychological components and (3) parents discussed what it was like to hear a non-diagnosis outcome, in terms of feeling relieved, confused and raising questions for the child’s future. These findings are important for professionals working in autism assessment services to help improve the assessment process for families, particularly when the assessment does not result in a diagnosis.
Preparation and Spectroscopic, Microscopic, Thermogravimetric, and Electrochemical Characterization of Silver-Doped Cerium(IV) Oxide Nanoparticles

ABSTRACT Silver ion-doped cerium oxide nanoparticles were prepared by polyol-based coprecipitation. Here, the impact of silver doping is evaluated on the crystallographic, optoelectronic, thermogravimetric, and redox behavior of cerium oxide nanoparticles. Spectroscopic techniques were used to characterize the phase purity, crystallinity, morphological structure, and optical and redox properties of nanoproducts. X-ray diffraction confirmed the formation of well-crystallized cerium oxide tetragonal fluorite. The optical absorption spectra and band gap energy were significantly affected following doping that was influenced by the crystalline size. Temperature production reduction investigated the influence of silver concentration on the redox properties of cerium oxide nanoparticles. These catalysts were reversible in cyclic redox reaction to 500°C, nonpyrophoric, and therefore demonstrated potential for applications for hydrogen generation for fuel cells and electrochemical biosensors.
Cerebral Hemodynamics and Executive Function in Sickle Cell Anemia

Supplemental Digital Content is available in the text. Background and Purpose: Individuals with sickle cell anemia experience cognitive deficits, even in the absence of cerebral infarcts or strokes. This study tested the hypothesis that elevated cerebral blood flow and oxygen extraction fraction are associated with lower executive function in individuals with sickle cell anemia. Methods: Three-Tesla brain magnetic resonance imaging was performed, including anatomic, gray matter cerebral blood flow, and global oxygen extraction fraction imaging. Executive function was measured using the working memory index from an age-appropriate Wechsler battery and tasks from the National Institutes of Health Toolbox Cognition Battery. Bivariate and multivariate models were examined (significance: P<0.05). Results: Fifty-four participants (age range=6–31 years) with sickle cell anemia were enrolled. Hematocrit was positively related to fluid cognition, cerebral blood flow was inversely related to working memory and inhibitory control, and oxygen extraction fraction was inversely related to processing speed. Associations remained significant in multivariate analyses controlling for age, income, and infarcts. Conclusions: Elevated cerebral blood flow and oxygen extraction fraction, markers of hemodynamic impairment, are associated with deficits in executive function in individuals with sickle cell anemia.
A hederagenin-type triterpene saponin, sumbulianoside a from Cephalaria sumbuliana and its potent immunomodulatory activity against seasonal flu virus H3N2

Abstract A new hederagenin-type triterpene saponin; hederagenin 28-O-β-D-galactopyranosyl-(1→6)-β-D-glucopyranosyl ester named sumbulianoside A (1), together with twelve known saponins were isolated from the n-butanol extract of Cephalaria sumbuliana (Caprifoliaceae) from which, one known saponin, dipsacus saponin A (2) was isolated, for the first time from Cephalaria species. The structures of the isolated compounds were elucidated by 1 D and 2 D NMR and HRESIMS analyses. Cytotoxic activities were investigated on A549, Hela, PANC1, SHSY5Y cells and non-cancerous cell HEK293 by MTT method and immunomodulatory activities were evaluated against activated H3N2 seasonal virus in whole blood by measuring IL-4, IFN-γ, IL-1β cytokine level with ELISA. According to the cytotoxicity results, compounds 1 and 2 did not possess significant cytotoxicity, while only compound 2 induced significant IL-4 production (** p<.001) against H3N2 showing a possible Th2 response and antibody production. All compounds had no effect on cytokine release (p > 0.5). Graphical Abstract
Aspirin plus ticagrelor or clopidogrel on graft patency one year after coronary bypass grafting: a single-center, randomized, controlled trial

Background Dual antiplatelet therapy (DAPT) improves early post-operative graft patency, but the optimal DAPT strategy for the patients after coronary artery bypass grafting (CABG) has not been confirmed. We sought to evaluate the effect of aspirin plus ticagrelor versus aspirin plus clopidogrel on saphenous vein graft (SVG) patency within 1 year after CABG. Methods Between October 2017 and December 2018, 147 consecutive patients undergoing elective CABG at Changhai Hospital were randomized into two groups: group AT, receiving aspirin 100 mg/d plus ticagrelor 2×90 mg/d; group AC, receiving aspirin 100 mg/d plus clopidogrel 75 mg/d. Both DAPTs should be administered within 24 h when clinical stability was ensured. 64-multislice computed tomography angiography (MSCTA) was used to assess the graft patency at 12 months after CABG.CYP2C19 gene variants were measured to assess the clopidogrel efficacy on graft patency. Results Among the 147 participants who completed the study, one (0.7%) patient from the AC group died at 5 weeks after surgery due to severe infection. All other patients were treated with DAPT for 12 months and underwent 64-MSCTA according to schedule. There were no significant differences in pre-operative characteristics and intraoperative transit-time flow measurement findings between the two groups. Besides, no significant differences in the incidence of major adverse cardiac events (MACEs) and major bleeding were observed. A 64-MSCTA showed that SVG patency was 91.0% (141 of 155) in the AT group and 89.9% (161 of 179) in the AC group (P=0.751). No significant associations were found between different CYP2C19 genotypes and SVG patency (P>0.05). Conclusions Either aspirin plus ticagrelor or aspirin plus clopidogrel can maintain a fairly high graft patency rate in the early phase after CABG, regardless of CYP2C19 genotypes.
Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients

Background Although immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies. Methods A multi-dimensional analysis based on public databases and 2 independent cohorts including 262 patients with lung cancer was performed. Immunohistochemistry (IHC) and fluorescence-based multiplexed staining were used to detect the immune factors. Results PD-L1 was observed to have different expressions and regulatory mechanisms between SCC and ADC. PD-L1 was significantly increased from the messenger RNA (mRNA) to protein levels in the SCC group compared with the ADC group. Also, PD-L1 on tumor cells (TCs) was positively correlated with CD8+ tumor lymphocyte infiltrates in ADC, but not in SCC. More importantly, PD-L1 was considered to be an independent predictor of overall survival (OS) for ADC patients. In contrast, in SCC patients, PD-1+ tumor-infiltrating lymphocytes (TILs) were considered a poor prognostic predictor. Conclusions These findings showed that PD-L1 in ADC and PD-1+ TILs in SCC respectively indicates T-cell function, which plays a crucial role in determining prognosis. The distinct functions of the biomarkers between ADC and SCC might provide potential avenues for guiding anti-PD-1/PD-L1 immunotherapy.
Parenteral prostanoids for severe Group 3 pulmonary hypertension with right ventricular dysfunction

Background Group 3 pulmonary hypertension (PH) is a common complication in patients with lung diseases but there are currently no FDA-approved therapies. The data is conflicting, but a few small studies suggest potential benefits in using Group 1 PH therapies in these patients, particularly in severe PH with right ventricular (RV) dysfunction. Methods A retrospective cohort study of patients with severe Group 3 PH with RV dysfunction who received parenteral prostanoids from 2007–2018 at our institution was undertaken. Severe PH was defined as mean pulmonary arterial pressure (mPAP) ≥35 mmHg or mPAP 25–34 with cardiac index (CI) <2.4 L/min/m2. Routine prognostic studies including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), WHO Functional Class assessment, oxygen requirement, arterial oxygen saturation, right ventricular systolic pressure (RVSP) and right heart catheterization (RHC) pressures, were obtained before initiation of parenteral therapy and at first clinical follow-up. Results Nine patients were included. Five were female (55.6%) with a median [interquartile range (IQR)] of 69 [54–71] years. Median CI was 1.8 (1.6–2.4) L/min/m2 and median pulmonary vascular resistance (PVR) was 14.7 (10.7–17.1) Wood units (WU). We found no statistically significant improvement in NT-proBNP levels, exercise capacity, or functional class. Resting oxygen requirement worsened from 4 to 6 L/min (P=0.04) and exertional oxygen saturation nadir worsened from 90% to 83% (P=0.01) despite the increase in FiO2 with exertion. Overall results were heterogenous: several patients demonstrated clinical stabilization, with two undergoing lung transplantation and one showing long-term stability with medical therapy. Symptoms remained severe for most: three patients discontinued prostanoid therapy, choosing to pursue hospice care. Conclusions We found no statistically significant improvement in NT-proBNP levels, exercise capacity, or functional class, while oxygen requirement at rest and oxygen saturation during exertion significantly worsened. Our results suggest that parenteral prostanoids should not generally be considered in the treatment of Group 3 PH patients.
Shape accuracy of fiber optic sensing for medical devices characterized in bench experiments

Purpose Fiber Optic RealShape (FORS) is a new technology that visualizes the full three‐dimensional shape of medical devices, such as catheters and guidewires, using an optical fiber embedded in the device. This three‐dimensional shape provides guidance to clinicians during minimally invasive procedures, and enables intuitive navigation. The objective of this paper is to assess the accuracy of the FORS technology, as implemented in the current state‐of‐the‐art Philips FORS system. The FORS system provides the shape of the entire device, including tip location and orientation. We consider all three aspects. Methods In bench experiments, we determined the accuracy of the location and orientation of the tip by displacing and rotating the fiber end, while allowing the rest of the fiber to change shape freely. To test the accuracy of the full shape, we have placed the fiber in a groove, which was accurately machined in a thick, stiff metal “path plate. ” We then compared the reconstructed shape with the known shape of the groove. Results The tip location is found with submillimeter accuracy, and the orientation is sensed with milliradian accuracy. The shape of a fiber in the path plate faithfully follows the known shape of the groove, with typical deviation less than 0.5 mm in the plane of the plate. Out of plane accuracy, perhaps slightly less relevant clinically, is more challenging, due to the influence of twist; yet even out of the plane, the deviation is only submillimeter. Conclusion The technology achieves submillimeter precision and provides full three‐dimensional shape, surpassing the reported precision of other navigation and tracking technologies, and therefore may potentially alleviate the need for fluoroscopy.
Assessing fairness in performance evaluation of publicly available retinal blood vessel segmentation algorithms

Abstract In the literature, various algorithms have been proposed for automatically extracting blood vessels from retinal images. In general, they are developed and evaluated using several publicly available datasets such as the DRIVE and STARE datasets. For performance evaluation, several metrics such as Sensitivity, Specificity, and Accuracy have been widely used. However, not all methods in the literature have been fairly evaluated and compared among their counterparts. In particular, for some publicly available algorithms, the performance is measured only for the area inside the field of view (FOV) of each retinal image while the rest use the complete image for the performance evaluation. Therefore, performing a comparison of the performance of methods in the latter group with those in the former group may lead to a misleading justification. This study aims to assess fairness in the performance evaluation of various publicly available retinal blood vessel segmentation algorithms. The conducted study allows getting several meaningful results: (i) a guideline to assess fairness in performance evaluation of retinal vessel segmentation algorithms, (ii) a more proper performance comparison of retinal vessel segmentation algorithms in the literature, and (iii) a suggestion regarding the use of performance evaluation metrics that will not lead to misleading comparison and justification.
LncRNA lnc_13814 promotes the cells apoptosis in granulosa cells of duck by acting as apla-miR-145-4 sponge

ABSTRACT Follicle development is a vital factor which determines the reproductive performance of poultry. Long noncoding RNAs (lncRNAs) have been reported to maintain animal reproductive function and play key roles in ovarian development and hormone secretion. But the regulatory mechanism of lncRNAs in duck follicle development has seldom been reported. In this study, to better explore the molecular mechanism of follicle development in ducks, the follicular lncRNA was sequenced and analyzed. A total of 9,551 lncRNAs were predicted in the duck follicles. Four hundred and forty-five lncRNAs were differentially expressed between the white follicles and yellow follicles. The results of our studies showed that lnc_13814 promoted cell apoptosis in duck GCs. Furthermore, the bioinformatics analysis results demonstrated that lnc_13814 was involved in a lncRNA-miRNA-mRNA coexpression network and it was observed to sponge two follicle-related miRNAs by a luciferase activity assay. Moreover, we found that overexpression of lnc_13814 significantly increased DNA damage inducible transcript 3 (DDIT3) expression and downregulated GCs apoptosis. Finally, we found that lnc_13814 directly binds to and inhibits apla-mir-145-4; then, lnc_13814 increases the expression of DDIT3 and up-regulates GCs apoptosis. Taken together, our findings demonstrate that lncRNAs have potential effects on duck ovarian follicles and lncRNAs may represent a new approach to understand follicular development.
Effect of High-Voltage Electrostatic Field on Inorganic Nitrogen Uptake by Cucumber Plants

We investigated the inorganic nitrogen uptake by cucumber ( L.) plants under high-voltage electrostatic field (HVEF). The maximum uptake rates and affinities significantly changed with increasing field intensity. Ammonium uptake slightly increased when the field intensity increased to 1.0 kV cm -1 and then decreased between 2.0 and 3.0 kV cm -1 . HVEF contributed to the affinity for nitrate in all treatment groups. The affinity of cucumber seedlings for nitrate positively correlated with the intensity of the applied field as the field increased to 1.0 kV cm -1 . HVEF enabled the seedlings to opt to consume when two types of nitrogen were present in the nutrient solution. These results can be attributed to feedback adjustment and electron transportation in nitrogen assimilation.
Integration of cryobiopsies for interstitial lung disease diagnosis is a valid and safe diagnostic strategy—experiences based on 250 biopsy procedures

Background Transbronchial cryobiopsies has become increasingly used in the diagnostic workup in patients suspected of having interstitial lung disease. The procedure is associated with less complications, morbidity and mortality compared to surgical lung biopsies although with a diagnostic yield that is not as high, but close to that of surgical lung biopsies. The aim of the present study was to describe the complications and diagnostic yield and their prognostic factors. Methods All patients undergoing transbronchial cryobiopsies at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational cohort study. Results A total of 250 patients were included [61% male, mean age 66 years (range, 22–81 years)]. Pneumothorax was detected in 70 (28%) of the patients, moderate hemorrhage in 53 (21%) and severe hemorrhage in 2 (1%) of the patients. Hemorrhage was associated with central biopsies, but not with anticoagulant therapy. None of the complications were related to lung function, exercise capacity, biopsy or probe size. Only one patient experienced an acute exacerbation. Three-month mortality was 0.4% (1 patient), caused by cancer and unrelated to the procedure. Cryobiopsies contributed to the final diagnosis in 72% of the patients and after multidisciplinary team discussion, a consensus diagnosis was obtained in 82% of the patients. The gender, the total sum of biopsy sizes, number of biopsies and presence of more than 50% alveolar tissue in biopsies increased the diagnostic yield. Conclusions Our study confirms that using cryobiopsies in the diagnostic setup for interstitial lung diseases is safe with a limited risk of acute exacerbations and mortality. Cryobiopsies contribute to the diagnosis in the majority of patients.