Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct roles and requirements for Ras pathway signaling in visceral versus somatic muscle founder specification

ABSTRACT Pleiotropic signaling pathways must somehow engender specific cellular responses. In the Drosophila mesoderm, Ras pathway signaling specifies muscle founder cells from among the broader population of myoblasts. For somatic muscles, this is an inductive process mediated by the ETS-domain downstream Ras effectors Pointed and Aop (Yan). We demonstrate here that for the circular visceral muscles, despite superficial similarities, a significantly different specification mechanism is at work. Not only is visceral founder cell specification not dependent on Pointed or Aop, but Ras pathway signaling in its entirety can be bypassed. Our results show that de-repression, not activation, is the predominant role of Ras signaling in the visceral mesoderm and that, accordingly, Ras signaling is not required in the absence of repression. The key repressor acts downstream of the transcription factor Lame duck and is likely a member of the ETS transcription factor family. Our findings fit with a growing body of data that point to a complex interplay between the Ras pathway, ETS transcription factors, and enhancer binding as a crucial mechanism for determining unique responses to Ras signaling. Summary: A fundamentally different mechanism is demonstrated for how Ras signaling governs cell fate specification in the Drosophila somatic versus visceral mesoderms, providing insight into how signaling specificity is achieved.
Round Window Niche Drilling with Intratympanic Steroid Is a Salvage Therapy of Sudden Hearing Loss

Objective: To explore the effectiveness and safety of round window niche drilling combined with intratympanic methylprednisolone injection for the salvage treatment of sudden sensorineural hearing loss (SSNHL) and its associated tinnitus after failed primary treatment. Method: SSNHL patients who showed a less than 10-dB improvement of pure-tone average after receiving standard systemic treatment and intratympanic steroid injection were enrolled. All included patients were randomly divided into two groups (control and study). Patients in the study group received round window niche drilling combined with daily intratympanic methylprednisolone for 7 times; the control group received only daily intratympanic methylprednisolone for 7 times. One month after treatment, the improvements of PTA, speech discrimination score (SDS), tinnitus and the incidence of adverse events were analyzed. Results: 20 patients (10 for each group) were included in this study. The baseline between two groups showed no statistical significance. Patients in the study group experienced an average hearing improvement of 20.38 dB, SDS 19.3 compared with 2.1 dB and SDS 2.0 in the control group. None (0%) in the control group and 4 patients (40%) showed marked recovery, 5 patients (50%) showed slight improvement of hearing in the study group after 1 month. All patients in the study group showed significant recovery of tinnitus. Both tinnitus handicap inventory and a symptom visual analogue scale between two groups revealed statistical differences (p < 0.001, p = 0.002, respectively). None in the control and study groups experienced vertigo, infection and facial paralysis. Conclusion: Round window niche drilling increases the contact area and time of methylprednisolone. It is an effective and safe salvage therapy of idiopathic SSNHL and its induced tinnitus.
Linear Endobronchial Ultrasound: What's New?

Abstract Since its advent more than a decade ago, real-time linear endobronchial ultrasound (EBUS) guided transbronchial needle aspiration has revolutionized the diagnosis and staging of nonsmall cell lung cancer (NSCLC), and has become the standard of care with widespread acceptance. It is also extensively used to diagnose other disease entities such as malignancy besides NSCLC, benign diseases, or infectious processes. Ancillary studies have shown its superior safety profile and cost-effectiveness. In recent years, linear EBUS has been expanding its clinical applications owing to the emerging new tools such as the 19-gauge (19G) needle and miniforceps. Meanwhile, with several ground-breaking discoveries in lung cancer treatment over the past few years, linear EBUS has found its way to fit into this scheme as a safe and effective diagnostic tool. This review summarizes the most recent evidence on evaluating the performance of linear EBUS-guided biopsy in various clinical situations.
Haemostatic Profiles are Similar across All Aetiologies of Cirrhosis

Abstract Background and Aim Patients with cirrhosis may acquire profound changes in haemostasis. Although haemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed aetiology. As thrombotic events appear more common in some aetiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that haemostatic changes might be different across aetiologies. Patients and Methods We studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease [ALD], 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of haemostasis, thrombin generation assays, fibrin permeability assays and a plasma-based fibrinolytic assay were performed. Results All patients had comparable severity of disease according to their Model for End-Stage Liver Disease score (9 [7–11]). Plasma levels of von Willebrand factor were substantially elevated across all aetiologies, with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels comparable to controls. Thrombin generation capacity was elevated in all aetiologies, most profoundly in ALD. Fibrin permeability was decreased in all aetiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all aetiologies. Conclusion Our in-depth haemostatic profiling of primary, secondary and tertiary haemostasis in a group of patients with Childs–Turcotte–Pugh A/B cirrhosis showed no large differences between aetiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their aetiology.
Evaluation of predictive value of 1H MR spectroscopy for response of neoadjuvant chemotherapy in musculoskeletal tumors.

PURPOSE Bone and soft tissue tumors are rare. There is a variety of types and each one has its own particular behavior, treatment and patient outcome. The assessment of treatment response following the 3rd cycle of chemotherapy is one of the most important aspects of patient care, as therapeutic options and the timing of surgery may vary depending on the achievement of response. Hence, we focused on the advanced imaging technique, proton magnetic resonance spectroscopy (1H MRS), aiming at improving the diagnostic accuracy and the tumor response to therapy, based on the absolute concentration of choline (Cho) as biomarker of malignancy. METHODS Twenty patients were studied. All of them had a pathological diagnosis after biopsy. MRI examinations were performed using a 1.5 T MR scanner (Avanto; Siemens, Erlangen, Germany). Single-voxel 1H MR spectroscopy was performed by using a PRESS with TR/TE 1530/100 ms, before chemotherapy and after the 3rd cycle. 1H MRS was processed in LCmodel. RESULTS Of 20 patients, 7 responded to neoadjuvant chemotherapy and 13 did not. In responders, the mean concentration of tCho before therapy was 4.7±2.5 mmol/kg, which showed statistically significant reduction after therapy. In non-responders, the mean tCho concentration before therapy was 2.9±0.9 mmol/kg which remained the same or increased after the 3rd cycle of neoadjuvant chemotherapy (2.7±2.5 mmol/kg; range from 2.05 to 5.79 with no statistical significance). Compared to reference healthy group, tCho concentrations were increased in all cases. CONCLUSIONS 1H MRS appears to be valuable technique for evaluation of response to neoadjuvant chemotherapy of patients with musculoskeletal tumors (MSK).
Gamma‐aminobutyric acidergic transmission underlies interictal epileptogenicity in pediatric focal cortical dysplasia

Dysregulation of γ‐aminobutyric acidergic (GABAergic) transmission has been reported in lesional acquired epilepsies (gliomas, hippocampal sclerosis). We investigated its involvement in a developmental disorder, human focal cortical dysplasia (FCD), focusing on chloride regulation driving GABAergic signals.
Targeting Antiviral Pathways for Treatment of Allergic Diseases.

Atopic diseases, including atopic eczema, allergic asthma, and allergic rhinitis, are major causes of childhood morbidity. Epidemiologic evidence closely links virus infections to both development and exacerbation of allergic diseases. This is best appreciated in the context of allergic asthma where seasonal increases in exacerbation rates coincide with fall respiratory virus epidemics. Viruses, predominantly rhinoviruses (RVs), can be isolated from respiratory secretions in up to 80% of asthma exacerbations [1], and early infection in children with allergic sensitization increases the risk of asthma development in childhood by 20-fold [2]. These associations are not exclusive to asthma. Early respiratory virus infections are also implicated in the development of allergic rhinitis, with subsequent infections contributing to symptom severity [3]. In a subset of atopic dermatitis patients, infection with deoxyribonucleic acid (DNA) viruses such as herpes simplex virus, also results in increased morbidity [4]. The mechanisms underlying these connections are largely undefined, but a growing body of evidence indicates that the allergic milieu induces deficient antiviral responses in multiple cell types [5], likely contributing to disease pathogenesis.
An Image Classifier Using Deep Learning Concept

Deep Learning has emerged as a new area in machine learning and is applied to a number of signal and image applications. The main purpose of the work presented in this paper, is to apply the concept of a Deep Learning algorithm namely, Convolutional neural networks (CNN) in image classification. The performance of the algorithm is evaluated based on the quality metric known as Mean Squared Error (MSE) and classification accuracy. The graphical representation of the experimental results is given on the basis of MSE against the number of training epochs. The experimental result analysis based on the quality metrics and the graphical representation proves that the algorithm (CNN) gives fairly good classification accuracy for all the tested datasets.
Hellenic Association for the Study of the Liver Clinical Practice Guidelines: Autoimmune hepatitis

Autoimmune hepatitis (AIH) is a relatively rare acute or chronic liver disease of unknown etiology characterized by large heterogeneity. Its distribution is global, covering all ages, both sexes and all ethnic groups. The aim of the present Clinical Practice Guidelines (CPG) of the Hellenic Association for the Study of the Liver was to provide updated guidance and help to gastroenterologists, hepatologists, internists and general practitioners for AIH diagnosis and management. AIH diagnosis is based on clinicopathological characteristics: namely, polyclonal hypergammaglobulinemia, particularly of immunoglobulin G (IgG), circulating autoantibodies, interface hepatitis on liver histology, absence of viral hepatitis, and a favorable response to immunosuppression. Clinical manifestations at disease onset are variable, ranging from asymptomatic to the acute/severe form. Aminotransferase and bilirubin levels vary, while the presence of hepatitis at the histological level is a prerequisite for diagnosis. Autoantibodies are the hallmark for AIH diagnosis; therefore, the CPG describe the appropriate serological algorithm for their detection. AIH therapy should aim to achieve complete biochemical (normalization of IgG and aminotransferases) and histological remission. All patients who have active disease, even those with cirrhosis, should be treated with individualized and response-guided induction therapy using prednisolone in combination with azathioprine or mycophenolate mofetil as first-line therapy. Immunosuppression should be given for at least 3 years and for at least 2 years after the achievement of complete biochemical response, while a liver biopsy should be recommended before treatment discontinuation. Current CPG are also provided for several specific conditions and difficult-to-treat patients.
Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. Glomerular endothelial cells are primary targets of Stx which, after binding to its specific receptor globotriaosylceramide, upregulates proinflammatory proteins involved both in the recruitment and adhesion of leukocytes and thrombus formation at the site of endothelial injury. In this review, we discuss the role of complement activation in promoting glomerular microvascular dysfunction, providing evidence from experimental models and patients with STEC-HUS. Within the glomerulus, an important target for Stx-induced complement activation is the podocyte, a cell type that is in close contact with endothelial cells and participates in maintaining the filtration barrier. Recently, podocyte injury and loss have been indicated as potential risk factors for long-term renal sequelae in patients with STEC-HUS. Therapeutic approaches targeting the complement system, that may be useful options for patients with STEC-HUS, will also be discussed.
Mineralisation of tubular bones is affected differently by low phosphorus supply in growing‐finishing pigs

Abstract BACKGROUND Phosphorus (P) supply is essential for bone mineralisation. Reduced P may result in osteopenia, whereas excessive P may result in environmental impacts. The objective was to study the long‐term effect of three dietary P levels on net bone mineralisation in growing‐finishing pigs. Eighteen female pigs were fed low P (LP (4.1)), medium P (MP (6.2)) or high P (HP (8.9 g P kg−1 DM)) from 39.7 until 110 kg. Trabecular, cortical and overall bone mineral density (BMD), ash, calcium (Ca) and P were determined after slaughter. RESULTS The LP diet generally reduced the BMD, ash, Ca and P in all bones, though all measures were markedly lowered in femur compared with humerus. The trabecular BMD in LP pigs was only different in the distal section compared to the MP‐fed pigs (P < 0.05). In addition, ash, Ca and P were lower in the proximal and distal sections. No significant effect of HP was seen. Conclusively, LP caused lower net bone mineralisation, mainly of femur. The trabecular tissue of the distal bones seems to be most metabolically active. CONCLUSIONS The MP level was sufficient for net bone mineralisation. Femur is recommended for studying bone fragility whereas humerus seems useful to study increased P retention. © 2019 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Pharmacokinetics and bioavailability after intramuscular injection of the 5‐HT1A serotonin agonist R‐8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) in domestic goats (Capra aegagrus hircus)

To determine the bioavailability and pharmacokinetic properties of the serotonin 5-HT1A receptor agonist R-8-OH-DPAT in goats, and 0.1 mg kg-1 R-8-OH-DPAT hydrobromide was administered intramuscularly (i.m.) and intravenously (i.v.) to six goats in a two-phase cross-over design experiment. Venous blood samples were collected from the jugular vein 2, 5, 10, 15, 20, 30, 40 and 60 min following treatment and analysed by liquid chromatography tandem mass spectrometry. Bioavailability and pharmacokinetic parameters were determined by a one-compartment analysis. Mean bioavailability of R-8-OH-DPAT when injected i.m. was 66%. The mean volume of distribution in the central compartment was 1.47 L kg-1 . The mean plasma body clearance was 0.056 L kg-1 min-1 . All goats injected i.v. and two of six goats injected i.m. showed signs of serotonin toxicity. In conclusion, R-8-OH-DPAT is well absorbed following i.m. injection and the observed pharmacokinetics suggest that administration via dart is feasible. Administration of R-8-OH-DPAT hydrobromide, at a dosage of 0.1 mg kg-1 , resulted in the observation of clinical signs of serotonin toxicity in the goats. It is suggested that dosages for the clinical use of the compound should be lower in order to achieve the desired clinical effect without causing serotonin toxicity.
A Meta-Analysis on the Relation Between Fluid Intelligence and Reading/Mathematics: Effects of Tasks, Age, and Social Economics Status

This study aimed to determine the relations between fluid intelligence (Gf) and reading/mathematics and possible moderators. A meta-analysis of 680 studies involving 793 independent samples and more than 370,000 participants found that Gf was moderately related to reading, r = . 38, 95% CI [. 36, . 39], and mathematics, r = . 41, 95% CI [. 39, 44]. Synthesis on the longitudinal correlations showed that Gf and reading/mathematics predicted each other in the development even after controlling for initial performance. Moderation analyses revealed the following findings: (a) Gf showed stronger relations to mathematics than to reading, (b) within reading or mathematics, Gf showed stronger relations to complex skills than to foundational skills, (c) the relations between Gf and reading/mathematics increased with age, and (d) family social economic status (SES) mostly affected the relations between Gf and reading/mathematics in the early development stage. These findings, taken together, are partially in line with the investment theory but are more in line with the intrinsic cognitive load theory, mutualism theory, and the gene–SES interaction hypothesis of cognition and learning. More importantly, these findings imply an integration model of these theories from an educational and developmental perspective: Children may rely on Gf to learn reading and mathematics early on, when high family SES can boost the effects of Gf on reading/mathematics performance. As children receive more formal schooling and gain more learning experiences, their reading and mathematics improvement may promote their Gf development. During development, the negative effects of low family SES on the relations between Gf and reading/mathematics may be offset by education/learning experiences.
Learning the space-time phase diagram of bacterial swarm expansion

Significance Most living systems, from individual cells to tissues and swarms, display collective self-organization on length scales that are much larger than those of the individual units that drive this organization. A fundamental challenge is to understand how properties of microscopic components determine macroscopic, multicellular biological function. Our study connects intracellular physiology to macroscale collective behaviors during multicellular development, spanning five orders of magnitude in length and six orders of magnitude in time, using bacterial swarming as a model system. This work is enabled by a high-throughput adaptive microscopy technique, which we combined with genetics, machine learning, and mathematical modeling to reveal the phase diagram of bacterial swarming and that cell–cell interactions within each swarming phase are dominated by mechanical interactions. Coordinated dynamics of individual components in active matter are an essential aspect of life on all scales. Establishing a comprehensive, causal connection between intracellular, intercellular, and macroscopic behaviors has remained a major challenge due to limitations in data acquisition and analysis techniques suitable for multiscale dynamics. Here, we combine a high-throughput adaptive microscopy approach with machine learning, to identify key biological and physical mechanisms that determine distinct microscopic and macroscopic collective behavior phases which develop as Bacillus subtilis swarms expand over five orders of magnitude in space. Our experiments, continuum modeling, and particle-based simulations reveal that macroscopic swarm expansion is primarily driven by cellular growth kinetics, whereas the microscopic swarming motility phases are dominated by physical cell–cell interactions. These results provide a unified understanding of bacterial multiscale behavioral complexity in swarms.
Synthetic biology for bioengineering virus‐like particle vaccines

Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus‐like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. Several VLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target‐specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described. When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry.