Miracle-dz/UniFAR-FTUs huggingface dataset:
Polyphosphate Delays Fibrin Polymerisation and Alters the Mechanical Properties of the Fibrin Network

Summary Polyphosphate (polyP) binds to fibrin(ogen) and alters fibrin structure, generating a heterogeneous network composed of ‘knots’ interspersed by large pores. Here we show platelet-derived polyP elicits similar structural changes in fibrin and examine the mechanism by which polyP alters fibrin structure. Polymerisation of fibrinogen with thrombin and CaCl2 was studied using spinning disk confocal (SDC) microscopy. PolyP delayed fibrin polymerisation generating shorter protofibrils emanating from a nucleus-type structure. Consistent with this, cascade blue-polyP accumulated in fibrin ‘knots’. Protofibril formation was visualized by atomic force microscopy (AFM) ± polyP. In the presence of polyP abundant monomers of longer length were visualised by AFM, suggesting that polyP binds to monomeric fibrin. Shorter oligomers form in the presence of polyP, consistent with the stunted protofibrils visualised by SDC microscopy. We examined whether these structural changes induced by polyP alter fibrin’s viscoelastic properties by rheometry. PolyP reduced the stiffness (G’) and ability of the fibrin network to deform plastically G”, but to different extents. Consequently, the relative plastic component (loss tangent (G”/G’)) was 61 % higher implying that networks containing polyP are less stiff and more plastic. Local rheological measurements, performed using magnetic tweezers, indicate that the fibrin dense knots are stiffer and more plastic, reflecting the heterogeneity of the network. Our data show that polyP impedes fibrin polymerisation, stunting protofibril growth producing ‘knotted’ regions, which are rich in fibrin and polyP. Consequently, the mechanical properties of the fibrin network are altered resulting in clots with overall reduced stiffness and increased ability to deform plastically. Supplementary Material to this article is available online at www.thrombosis-online.com.
Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy

Importance YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. Objectives To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant. Design, Setting, and Participants An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature. Six adults in a well-defined mitochondrial disease cohort and 11 additional cases described in the literature were identified with YARS2 variants between January 1, 2000, and January 31, 2015. Main Outcome and Measures The spectrum of clinical features and disease progression in unreported and reported patients with pathogenic YARS2 variants. Results Seventeen patients (median [interquartile range] age at onset, 1.5 [9.8] years) with YARS2-related mitochondrial myopathy were identified. Fifteen individuals (88%) exhibited an elevated blood lactate level accompanied by generalized myopathy; only 12 patients (71%) manifested with sideroblastic anemia. Hypertrophic cardiomyopathy (9 [53%]) and respiratory insufficiency (8 [47%]) were also prominent clinical features. Central nervous system involvement was rare. Muscle studies showed global cytochrome-c oxidase deficiency in all patients tested and severe, combined respiratory chain complex activity deficiencies. Microsatellite genotyping demonstrated a common founder effect shared between 3 Scottish patients with a p.Leu392Ser variant. Immunoblotting from fibroblasts and myoblasts of an affected Scottish patient showed normal YARS2 protein levels and mild respiratory chain complex defects. Yeast modeling of novel missense YARS2 variants closely correlated with the severity of clinical phenotypes. Conclusions and Relevance The p.Leu392Ser variant is likely a newly identified founder YARS2 mutation. Testing for pathogenic YARS2 variants should be considered in patients presenting with mitochondrial myopathy, characterized by exercise intolerance and muscle weakness even in the absence of sideroblastic anemia irrespective of ethnicity. Regular surveillance and early treatment for cardiomyopathy and respiratory muscle weakness is advocated because early treatment may mitigate the significant morbidity and mortality associated with this genetic disorder.
Formulation and Characterization of Polysaccharide Microparticles for Pulmonary Delivery of Sodium Cromoglycate

Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy; however, many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate, and sodium alginate were selected to co-process SC by spray drying. The influence of these polysaccharides on the spray drying process and powder quality was evaluated (among others, morphology, size, moisture content, hygroscopicity, flowability, densities, liquid sorption, and stability). In vitro aerosolization, drug release, and mucoadhesion performance were also studied. Particularly, a novel method to comparatively evaluate the interaction between formulations and mucin solution (mucoadhesion test) was proposed as a rapid methodology to measure adhesion properties of inhalable particles, being the results as indicative of clearance probability. Among all the studied formulations, the powder based on SC and CMCNa exhibited the best mucoadhesion and aerosolization performance, the highest process yield and adequate moisture content, hygroscopicity, and stability. SC-CMCNa formulation arose as a promising inhalatory system to reduce the daily intakes and to increase the patient compliance.
Microstructure, mechanical properties and corrosion performance of a few TMT rebars

The present work aims to study the evaluation of the microstructure, tensile properties, hardness, corrosion behaviour of the various grades of rebars. The microstructures of all rebar samples comprise an outer tempered martensite ring with an inner core of ferrite-pearlite in between a narrow bainitic transition zone. Maximum hardness is achieved at the periphery which gradually decreases towards the centre. Chinese grade has a similarity with the Fe 600 rebar in terms of strength and % elongation, whereas Fe 500D and Fe 500 have lower strength but higher ductility. The EDS analyses of corrosion products obtained after immersion test in 5% NaCl solution for a period of 7 days apparently indicate the occurrences of iron oxy-hydroxides and iron oxides. X-ray diffraction and FTIR studies of the corrosion products formed on all thermo-mechanically treated (TMT) rebar surfaces after the aforesaid immersion test primarily indicate the presence of Lepidocrocite (γ-FeOOH), Goethite (α-FeOOH), Magnetite (Fe3O4) and Maghemite (γ-Fe2O3). Fe 500 (12 mm) and Chinese rebars have lower corrosion resistance as compared to the other rebars in 5% NaCl solution. Nevertheless, all the TMT rebars are corrosion resistant and can be satisfactorily used for construction purposes.
Vertical Ridge Augmentation With Mandibular Lingual Torus Block Graft.

D ental implant prostheses often provide an ideal restorative option to replace missing teeth. Severe alveolar ridge resorption—resulting from periodontal infections, iatrogenic trauma from extractions, or subsequent bone loss following prolonged edentulism—often preclude proper implant placement and positioning. Under such conditions, ridge augmentation procedures may be required prior to implant therapy. Numerous techniques have been developed for alveolar ridge augmentation. An onlay block graft is one of the procedures designed to correct deficient alveolar ridges. While allografts, xenografts, and synthetic block grafts are viable options, an autogenous block graft may still be considered the gold standard. Autogenous bone grafts harvested from intraoral sources (including mandibular ramus, mandibular symphysis, or maxillary tuberosity) have demonstrated better integration to the recipient site, often with less resorption than bone from extraoral sources. However, the risk of donor site morbidity and postoperative complications have raised concerns about their applications. Tori are benign outgrowths of bone that could function as an alternative source of autogenous bone, concomitantly diminishing complications associated with harvesting. Several case reports have demonstrated successful horizontal ridge and sinus augmentation when utilizing block or particulate form of tori. It is generally accepted that horizontal ridge augmentation and sinus lifting are much more predictable compared to vertical ridge augmentation. Since there is limited literature addressing the feasibility of using tori as an onlay block graft for vertical ridge augmentation, the objective of this case report is to introduce the use of a mandibular lingual torus as an onlay block graft for a vertically deficient alveolar ridge. The successful vertical increase of the deficient mandibular ridge and ultimate implant placement and restoration was demonstrated. CASE PRESENTATION
Life‐stage‐associated remodelling of lipid metabolism regulation in Atlantic salmon

Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. The transition to marine habitats is associated with dramatic changes in the environment, including water salinity, exposure to pathogens and shift in dietary lipid availability. Many changes in physiology and metabolism occur across this life‐stage transition, but little is known about the molecular nature of these changes. Here, we use a long‐term feeding experiment to study transcriptional regulation of lipid metabolism in Atlantic salmon gut and liver in both fresh‐ and saltwater. We find that lipid metabolism becomes significantly less plastic to differences in dietary lipid composition when salmon transitions to saltwater and experiences increased dietary lipid availability. Expression of genes in liver relating to lipogenesis and lipid transport decreases overall and becomes less responsive to diet, while genes for lipid uptake in gut become more highly expressed. Finally, analyses of evolutionary consequences of the salmonid‐specific whole‐genome duplication on lipid metabolism reveal several pathways with significantly different (p < .05) duplicate retention or duplicate regulatory conservation. We also find a limited number of cases where the whole‐genome duplication has resulted in an increased gene dosage. In conclusion, we find variable and pathway‐specific effects of the salmonid genome duplication on lipid metabolism genes. A clear life‐stage‐associated shift in lipid metabolism regulation is evident, and we hypothesize this to be, at least partly, driven by nondietary factors such as the preparatory remodelling of gene regulation and physiology prior to sea migration.
Audiological management of adults with hearing impairment in Malaysia

Abstract Objective: This study explored the nature of audiological services for adults with hearing impairment in Malaysia, with an emphasis on whether current services address clients’ overall functioning as described by the World Health Organisation’s International Classification of Functioning, Disability, and Health (ICF) framework. Design: An online survey exploring current practice, skills and confidence of audiologists, and the infrastructure and facilities available in their workplaces, was distributed to audiologists in Malaysia via professional associations and social media. Study sample: A total of 111 audiologists, 84.7% female and 15.3% male (range = 23–44 years), participated in the study. Results: Although audiologists in Malaysia reported addressing all of the ICF domains, less than 26% of them assessed the patients’ speech perception, carried out real-ear measurements, or used outcome measures routinely. The majority of the audiologists reported feeling confident in managing adult patients. However, 83% of the audiologists indicated they wanted to improve their skills related to management of adult patients, particularly in the areas of counselling and auditory training. Conclusions: Inadequate infrastructure, resources and facilities in the workplace may have contributed to the gaps in service provision and influenced the current practice of audiological management for adult patients in Malaysia.
Validation of the New Interpretation of Gerasimov's Nasal Projection Method for Forensic Facial Approximation Using CT Data ,

The most common method to predict nasal projection for forensic facial approximation is Gerasimov's two‐tangent method. Ullrich H, Stephan CN (J Forensic Sci, 2011; 56: 470) argued that the method has not being properly implemented and a revised interpretation was proposed. The aim of this study was to compare the accuracy of both versions using a sample of 66 postmortem cranial CT data. The true nasal tip was defined using pronasale and nasal spine line, as it was not originally specified by Gerasimov. The original guidelines were found to be highly inaccurate with the position of the nasal tip being overestimated by c. 2 cm. Despite the revised interpretation consistently resulting in smaller distance from true nasal tip, the method was not statistically accurate (p > 0.05) in positioning the tip of the nose (absolute distance >5 mm). These results support that Gerasimov's method was not properly performed, and Ullrich H, Stephan CN (J Forensic Sci, 2011; 56: 470) interpretation should be used instead.
Internalization of Heterologous Sugar Transporters by Endogenous α-Arrestins in the Yeast Saccharomyces cerevisiae

ABSTRACT When expressed in Saccharomyces cerevisiae using either of two constitutive yeast promoters (PGK1prom and CCW12prom ), the transporters CDT-1 and CDT-2 from the filamentous fungus Neurospora crassa are able to catalyze, respectively, active transport and facilitated diffusion of cellobiose (and, for CDT-2, also xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed from the plasma membrane by clathrin-mediated endocytosis and are marked for internalization through ubiquitinylation catalyzed by Rsp5, a HECT class ubiquitin:protein ligase (E3). Recruitment of Rsp5 to specific targets is mediated by a 14-member family of endocytic adaptor proteins, termed α-arrestins. Here we demonstrate that CDT-1 and CDT-2 are subject to α-arrestin-mediated endocytosis, that four α-arrestins (Rod1, Rog3, Aly1, and Aly2) are primarily responsible for this internalization, that the presence of the transport substrate promotes transporter endocytosis, and that, at least for CDT-2, residues located in its C-terminal cytosolic domain are necessary for its efficient endocytosis. Both α-arrestin-deficient cells expressing CDT-2 and otherwise wild-type cells expressing CDT-2 mutants unresponsive to α-arrestin-driven internalization exhibit an increased level of plasma membrane-localized transporter compared to that of wild-type cells, and they grow, utilize the transport substrate, and generate ethanol anaerobically better than control cells. IMPORTANCE Ethanolic fermentation of the breakdown products of plant biomass by budding yeast Saccharomyces cerevisiae remains an attractive biofuel source. To achieve this end, genes for heterologous sugar transporters and the requisite enzyme(s) for subsequent metabolism have been successfully expressed in this yeast. For one of the heterologous transporters examined in this study, we found that the amount of this protein residing in the plasma membrane was the rate-limiting factor for utilization of the cognate carbon source (cellobiose) and its conversion to ethanol.
Routine use of Day 6 and Day 7 platelets with rapid testing: two hospitals assess impact 1 year after implementation

In March 2016 the US Food and Drug Administration published a draft guidance to enhance the safety of platelets (PLTs) for transfusion. Options for hospital transfusion services include the use of rapid testing to extend apheresis PLT dating for up to 7 days. This report describes the impact of routine use of Day 6 and Day 7 PLTs at two hospital transfusion services 1 year after implementation of rapid testing for outdate extension.
Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a

Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1 (ISL1), a member of the LIM/Homeobox family of transcription factors, has been identified as a major susceptibility gene for classic bladder exstrophy in humans, a common form of the bladder exstrophy-epispadias complex (BEEC), and is implicated in a role in urinary tract development. We report that deletion of Isl1 from the genital mesenchyme in mice led to hypoplasia of the genital tubercle and prepuce, with an ectopic urethral opening and epispadias-like phenotype. These mice also developed hydroureter and hydronephrosis. Identification of ISL1 transcriptional targets via ChIP-Seq and expression analyses revealed that Isl1 regulates several important signaling pathways during embryonic genital development, including the BMP, WNT, and FGF cascades. An essential function of Isl1 during development of the external genitalia is to induce Bmp4-mediated apoptosis in the genital mesenchyme. Together, these studies demonstrate that Isl1 plays a critical role during development of the external genitalia and forms the basis for a greater understanding of the molecular mechanisms underlying the pathogenesis of BEEC and urinary tract defects in humans.
Solving Large Multicut Problems for Connectomics via Domain Decomposition

In this contribution we demonstrate how a Multicut-based segmentation pipeline can be scaled up to datasets of hundreds of Gigabytes in size. Such datasets are prevalent in connectomics, where neuron segmentation needs to be performed across very large electron microscopy image volumes. We show the advantages of a hierarchical block-wise scheme over local stitching strategies and evaluate the performance of different Multicut solvers for the segmentation of the blocks in the hierarchy. We validate the accuracy of our algorithm on a small fully annotated dataset (5×5×5 μm) and demonstrate no significant loss in segmentation quality compared to solving the Multicut problem globally. We evaluate the scalability of the algorithm on a 95 x 60 x 60 μm image volume and show that solving the Multicut problem is no longer the bottleneck of the segmentation pipeline.
Long-term Outcome of Multiple Small-diameter Drilling Decompression Combined with Hip Arthroscopy versus Drilling Alone for Early Avascular Necrosis of the Femoral Head

Background: Avascular necrosis of femoral head (AVNFH) typically presents in the young adults and progresses quickly without proper treatments. However, the optimum treatments for early stage of AVNFH are still controversial. This study was conducted to evaluate the therapeutic effects of multiple small-diameter drilling decompression combined with hip arthroscopy for early AVNFH compared to drilling alone. Methods: This is a nonrandomized retrospective case series study. Between April 2006 and November 2010, 60 patients (98 hips) with early stage AVNFH participated in this study. The patients underwent multiple small-diameter drilling decompression combined with hip arthroscopy in 26 cases/43 hips (Group A) or drilling decompression alone in 34 cases/55 hips (Group B). Patients were followed up at 6, 12, and 24 weeks, and every 6 months thereafter. Radiographs were taken at every follow-up, Harris scores were recorded at the last follow-up, the paired t-test was used to compare the postoperative Harris scores. Surgery effective rate of the two groups was compared using the Chi-square test. Results: All patients were followed up for an average of 57.6 months (range: 17–108 months). Pain relief and improvement of hip function were assessed in all patients at 6 months after the surgery. At the last follow-up, Group A had better outcome with mean Harris’ scores improved from 68.23 ± 11.37 to 82.07 ± 2.92 (t = −7.21, P = 0.001) than Group B with mean Harris’ scores improved from 69.46 ± 9.71 to 75.79 ± 4.13 (t = –9.47, P = 0.037) (significantly different: t = –2.54, P = 0.017). The total surgery effective rate was also significantly different between Groups A and B (86.0% vs. 74.5%; &khgr;2 = 3.69, P = 0.02). Conclusion: For early stage of AVNFH, multiple small-diameter drilling decompression combined with hip arthroscopy is more effective than drilling decompression alone.
Placental alterations in structure and function in intra‐uterine growth‐retarded horses

BACKGROUND Following embryo transfer (ET), the size and breed of the recipient mare can affect fetal development and subsequent post natal growth rate and insulin sensitivity in foals. OBJECTIVES To investigate placental adaptation in pregnancies where increased or restricted fetal growth was induced through ET between Pony, Saddlebred and Draught horses. STUDY DESIGN In vivo experiment. METHODS Control Pony (P, n = 21) and Saddlebred (S, n = 28) pregnancies were obtained by artificial insemination. Increased pregnancies were obtained by transferring Pony (P-D, n = 6) and Saddlebred (S-D, n = 8) embryos into Draught mares. Restricted pregnancies were obtained by transferring Saddlebred embryos into Pony mares (S-P, n = 6). Placental weight and surface were recorded and samples collected for stereology and analysis of expression of genes involved in placental growth, vascularisation and nutrient transport. Data were analysed by linear model. RESULTS S-P foals were growth retarded when compared with controls despite increased gestational length. Placental weight was reduced but placental surface density and volume fraction were increased. Placental expression of genes involved in growth and development and nutrient transfer was strongly reduced. In contrast, placental size and weight were increased in enhanced growth P-D and S-D foals. The trophoblastic surface density and the allantoic vessels surface density were decreased in P-D and S-D, respectively, both with very few modifications in gene expression. MAIN LIMITATIONS Control embryos were produced by artificial insemination whereas experimental embryos were produced by ET. CONCLUSIONS Placental structure and gene expression are modified after ET into a smaller or larger breed than that of the embryo. These adaptations contribute to the observed phenotype of foal growth restriction or enhanced growth at birth.