Miracle-dz/UniFAR-FTUs huggingface dataset:
Shrinking Away from Psychiatry? A Survey of Australian Medical Students' Interest in Psychiatry

Objective: We sought to examine the attitudes of newly recruited medical students towards psychiatry and other specialties to determine what factors influence their career choice options. Method: We surveyed the attitudes of 655 medical students using a 31-item self-report questionnaire. Results: Australian medical students rated the ability to help patients as the most important aspect of a specialty in determining their choice. Attraction to psychiatry was based on the specialty being interesting and intellectually challenging, and providing a career that promised job satisfaction with good prospects and enjoyable work. Females expressed a greater interest in psychiatry and were more likely to consider pursuing it as a career, principally due to a greater interest in the subject matter and a stronger desire for interaction with patients. The least attractive aspects of psychiatry were its lack of prestige among the medical community and a perceived absence of a scientific foundation. Conclusion: The attitudes of medical students can perhaps be modified and recruitment into psychiatry enhanced by presenting the reality of psychiatry today – namely the wide range of available therapeutic processes, the predominantly positive outcomes, the interesting and intellectually challenging nature of the subject and its nurturing and accommodating work environment.
Hot topics in the mechanisms of pulmonary arterial hypertension disease: cancer-like pathobiology, the role of the adventitia, systemic involvement, and right ventricular failure

In order to intervene appropriately and develop disease-modifying therapeutics for pulmonary arterial hypertension, it is crucial to understand the mechanisms of disease pathogenesis and progression. We herein discuss four topics of disease mechanisms that are currently highly debated, yet still unsolved, in the field of pulmonary arterial hypertension. Is pulmonary arterial hypertension a cancer-like disease? Does the adventitia play an important role in the initiation of pulmonary vascular remodeling? Is pulmonary arterial hypertension a systemic disease? Does capillary loss drive right ventricular failure? While pulmonary arterial hypertension does not replicate all features of cancer, anti-proliferative cancer therapeutics might still be beneficial in pulmonary arterial hypertension if monitored for safety and tolerability. It was recognized that the adventitia as a cell-rich compartment is important in the disease pathogenesis of pulmonary arterial hypertension and should be a therapeutic target, albeit the data are inconclusive as to whether the adventitia is involved in the initiation of neointima formation. There was agreement that systemic diseases can lead to pulmonary arterial hypertension and that pulmonary arterial hypertension can have systemic effects related to the advanced lung pathology, yet there was less agreement on whether idiopathic pulmonary arterial hypertension is a systemic disease per se. Despite acknowledging the limitations of exactly assessing vascular density in the right ventricle, it was recognized that the failing right ventricle may show inadequate vascular adaptation resulting in inadequate delivery of oxygen and other metabolites. Although the debate was not meant to result in a definite resolution of the specific arguments, it sparked ideas about how we might resolve the discrepancies by improving our disease modeling (rodent models, large-animal studies, studies of human cells, tissues, and organs) as well as standardization of the models. Novel experimental approaches, such as lineage tracing and better three-dimensional imaging of experimental as well as human lung and heart tissues, might unravel how different cells contribute to the disease pathology.
A Conserved Regulatory Circuit Controls Large Adhesins in Vibrio cholerae

Vibrio cholerae, the causative agent of the diarrheal disease cholera, benefits from a sessile biofilm lifestyle that enhances survival outside the host but also contributes to host colonization and infectivity. The bacterial second messenger c-di-GMP has been identified as a central regulator of biofilm formation, including in V. cholerae; however, our understanding of the pathways that contribute to this process is incomplete. Here, we define a conserved signaling system that controls the stability of large adhesion proteins at the cell surface of V. cholerae, which are important for cell attachment and biofilm formation. Insight into the regulatory circuit underlying biofilm formation may inform targeted strategies to interfere with a process that renders this bacterium remarkably adaptable to changing environments. ABSTRACT The dinucleotide second messenger c-di-GMP has emerged as a central regulator of reversible cell attachment during bacterial biofilm formation. A prominent cell adhesion mechanism first identified in pseudomonads combines two c-di-GMP-mediated processes: transcription of a large adhesin and its cell surface display via posttranslational proteolytic control. Here, we characterize an orthologous c-di-GMP effector system and show that it is operational in Vibrio cholerae, where it regulates two distinct classes of adhesins. Through structural analyses, we reveal a conserved autoinhibition mechanism of the c-di-GMP receptor that controls adhesin proteolysis and present a structure of a c-di-GMP-bound receptor module. We further establish functionality of the periplasmic protease controlled by the receptor against the two adhesins. Finally, transcription and functional assays identify physiological roles of both c-di-GMP-regulated adhesins in surface attachment and biofilm formation. Together, our studies highlight the conservation of a highly efficient signaling effector circuit for the control of cell surface adhesin expression and its versatility by revealing strain-specific variations. IMPORTANCE Vibrio cholerae, the causative agent of the diarrheal disease cholera, benefits from a sessile biofilm lifestyle that enhances survival outside the host but also contributes to host colonization and infectivity. The bacterial second messenger c-di-GMP has been identified as a central regulator of biofilm formation, including in V. cholerae; however, our understanding of the pathways that contribute to this process is incomplete. Here, we define a conserved signaling system that controls the stability of large adhesion proteins at the cell surface of V. cholerae, which are important for cell attachment and biofilm formation. Insight into the regulatory circuit underlying biofilm formation may inform targeted strategies to interfere with a process that renders this bacterium remarkably adaptable to changing environments.
What's the Use of Worrying? Its Function and Its Dysfunction

Objective: To provide an overview of theory and research regarding the phenomenology and function of worry. Method: A systematic literature search focusing on conceptualizations of worry as a cognitive activity and worry research over the last 20 years was conducted. Results: Worry can be both functional and dysfunctional. Disruption to daily functioning, perceived uncontrollability, pervasiveness and extensive coverage of worry themes (including ‘remote’ events and the presence of meta-worry), all have specificity to more severe and dysfunctional worry. Conclusions: Research investigating both the relationship between worry and anxiety and the attributes of severe worriers, has brought attention to its role in fostering emotional disturbance and has clarified factors relevant to treatment.
Neoplasmas oculares e de anexos em cães e gatos no Rio Grande do Sul: 265 casos (2009 -2014)

Ocular neoplasms cause discomfort, loss of vision or may also reflect systemic diseases. A retrospective study has been performed to identify and analyze ocular and annexes neoplasms obtained by biopsies sent to the Sector of Veterinary Pathology at the Federal University of Rio Grande do Sul (SPV/ UFRGS). 265 diagnoses of ocular and annexes neoplasms, 87.5% in canine species and 12.5% in feline species, were made from January 2009 to December 2014. Neoplasms occurred more in animals over the age of 12 months and animals of old age, dogs (52/232) and cats (21/33) mixed breed were the most affected. The eyelid was most commonly affected in dogs (164/232) and feline (20/33), followed by the third eyelid in dogs (20/232) and eye orbit in cats (5/33). The most common tumor diagnosed was meibomian adenoma in dogs (82/232) and squamous cell carcinoma in cats (10/33) both in the eyelids. Twenty four tumor types have been identified in dogs and 16 in cats. Benign neoplasms in dogs represented the largest number of diagnosis (56%) whereas in cats, there were more cases of malignant neoplasms (75.8%).
Is Being Employed Always Better for Mental Wellbeing Than Being Unemployed? Exploring the Role of Gender and Welfare State Regimes during the Economic Crisis

The growth of poor jobs related to economic crisis adds to its increase since the mid-1970s as a result of new forms of flexible employment. In Europe, there is no clear evidence on whether working in a poor-quality job is better for mental wellbeing than being unemployed. The objectives of this study were to compare mental wellbeing between the unemployed and those working in jobs with different quality levels and to examine gender and welfare state differences in Europe. We selected 8324 men and 7496 women from the European Social Survey, 2010. Hierarchical multiple logistic regression models were fitted, separated by sex and country group. No significant differences in mental wellbeing were shown between unemployed-non-active, unemployed-active, and those working in low-quality jobs in either sex. Only men from Conservative countries in low-quality jobs had better mental wellbeing than unemployed (non-active) men. Only having a good-quality job reduced the likelihood of poor mental wellbeing compared with being unemployed (non-active) among men in all countries (except Social-Democratic) and among women in Eastern and Southern European countries. No differences were observed among men or women in Social-Democratic countries, while strong gender differences were found in Conservative and Liberal countries. Our study indicates the need to take job quality into account, in addition to creating jobs during economic crises. The main mechanisms to explain the strong gender and welfare state differences identified could be social protection for unemployed, labor market regulations, and family models.
Effects of tocotrienol supplementation in Friedreich's ataxia: A model of oxidative stress pathology.

Friedreich’s ataxia is an autosomal recessive disorder characterized by impaired mitochondrial function, resulting in oxidative stress. In this study, we aimed at evaluating whether tocotrienol, a phytonutrient that diffuses easily in tissues with saturated fatty layers, could complement the current treatment with idebenone, a quinone analogue with antioxidant properties. Five young Friedreich’s ataxia patients received a low-dose tocotrienol supplementation (5 mg/kg/day), while not discontinuing idebenone treatment. Several oxidative stress markers and biological parameters related to oxidative stress were evaluated at the time of initiation of treatment and 2 and 12 months post-treatment. Some oxidative stress-related parameters and some inflammation indices were altered in Friedreich’s ataxia patients taking idebenone alone and tended to be normal values following tocotrienol supplementation; likewise, a cardiac magnetic resonance study showed some improvement following one-year tocotrienol treatment. The pathway by which tocotrienol affects the Nrf2 modulation of hepcidin gene expression, a peptide involved in iron handling and in inflammatory responses, is viewed in the light of the disruption of the iron intracellular distribution and of the Nrf2 anergy characterizing Friedreich’s ataxia. This research provides a suitable model to analyze the efficacy of therapeutic strategies able to counteract the excess free radicals in Friedreich’s ataxia, and paves the way to long-term clinical studies. Oxidative stress is involved in the pathogenesis of Friedreich's ataxia (FRDA), a genetic disorder causing neurodegeneration due to the dramatic reduction in the expression of frataxin. To date, no cure is available for FRDA patients. In some countries, FRDA patients assume idebenone in order to counteract the effects of frataxin deficiency. We demonstrate that idebenone treatment alone is not able to abrogate oxidative stress in FRDA patients, whereas the combined treatment with tocotrienols might be more efficient and perhaps produce clinical improvement. In fact, a decrease in oxidative stress and inflammation markers can be seen after two months and is more pronounced after one year of treatment. This is, in our opinion, valuable information for clinicians, since idebenone is the treatment of choice for FRDA patients in some countries.
Utilising artificial intelligence to determine patients at risk of a rare disease: idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension is a rare and life-shortening condition often diagnosed at an advanced stage. Despite increased awareness, the delay to diagnosis remains unchanged. This study explores whether a predictive model based on healthcare resource utilisation can be used to screen large populations to identify patients at high risk of idiopathic pulmonary arterial hypertension. Hospital Episode Statistics from the National Health Service in England, providing close to full national coverage, were used as a measure of healthcare resource utilisation. Data for patients with idiopathic pulmonary arterial hypertension from the National Pulmonary Hypertension Service in Sheffield were linked to pre-diagnosis Hospital Episode Statistics records. A non-idiopathic pulmonary arterial hypertension control cohort was selected from the Hospital Episode Statistics population. Patient history was limited to ≤5 years pre-diagnosis. Information on demographics, timing/frequency of diagnoses, medical specialities visited and procedures undertaken was captured. For modelling, a bagged gradient boosting trees algorithm was used to discriminate between cohorts. Between 2008 and 2016, 709 patients with idiopathic pulmonary arterial hypertension were identified and compared with a stratified cohort of 2,812,458 patients classified as non-idiopathic pulmonary arterial hypertension with ≥1 ICD-10 coded diagnosis of relevance to idiopathic pulmonary arterial hypertension. A predictive model was developed and validated using cross-validation. The timing and frequency of the clinical speciality seen, secondary diagnoses and age were key variables driving the algorithm’s performance. To identify the 100 patients at highest risk of idiopathic pulmonary arterial hypertension, 969 patients would need to be screened with a specificity of 99.99% and sensitivity of 14.10% based on a prevalence of 5.5/million. The positive predictive and negative predictive values were 10.32% and 99.99%, respectively. This study highlights the potential application of artificial intelligence to readily available real-world data to screen for rare diseases such as idiopathic pulmonary arterial hypertension. This algorithm could provide low-cost screening at a population level, facilitating earlier diagnosis, improved diagnostic rates and patient outcomes. Studies to further validate this approach are warranted.
Quantitative µMRI and PLM study of rabbit humeral and femoral head cartilage at sub‐10 µm resolutions

This study aimed to establish the baseline characteristics in humeral and femoral cartilage in rabbit, using quantitative magnetic resonance imaging (MRI) relaxation times (T2, T1ρ, and T1) at 9.75 and 70–82 µm pixel resolutions, and quantitative polarized light microscopy (PLM) measures (retardation, angle) at 1.0 and 4.0 µm pixel resolutions. Five intact (i.e., unopened) shoulder joints (the scapula and humeral heads) and three femoral heads of the hip joints from five healthy rabbits were imaged in MRI at 70–82 µm resolution. Thirteen cartilage‐bone specimens were harvested from these joints and imaged in µMRI at 9.75 µm resolution. Subsequently, quantitative PLM study of these specimens enabled the examination of the fibril orientation and organization in both intact joints and individual specimens. Quantitative MRI relaxation data and PLM fibril structural data show distinct features in tissue properties at different depths of cartilage, different in individual histological zones. The thicknesses of the histological zones in µMRI and PLM were successfully obtained. This is the first correlated and quantitative MRI and PLM study of rabbit cartilage at sub‐10 µm resolutions, which benefits future investigation of osteoarthritis using the rabbit model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1052‐1062, 2020
Experimental Evaluation of a UWB-Based Cooperative Positioning System for Pedestrians in GNSS-Denied Environment

Cooperative positioning (CP) utilises information sharing among multiple nodes to enable positioning in Global Navigation Satellite System (GNSS)-denied environments. This paper reports the performance of a CP system for pedestrians using Ultra-Wide Band (UWB) technology in GNSS-denied environments. This data set was collected as part of a benchmarking measurement campaign carried out at the Ohio State University in October 2017. Pedestrians were equipped with a variety of sensors, including two different UWB systems, on a specially designed helmet serving as a mobile multi-sensor platform for CP. Different users were walking in stop-and-go mode along trajectories with predefined checkpoints and under various challenging environments. In the developed CP network, both Peer-to-Infrastructure (P2I) and Peer-to-Peer (P2P) measurements are used for positioning of the pedestrians. It is realised that the proposed system can achieve decimetre-level accuracies (on average, around 20 cm) in the complete absence of GNSS signals, provided that the measurements from infrastructure nodes are available and the network geometry is good. In the absence of these good conditions, the results show that the average accuracy degrades to meter level. Further, it is experimentally demonstrated that inclusion of P2P cooperative range observations further enhances the positioning accuracy and, in extreme cases when only one infrastructure measurement is available, P2P CP may reduce positioning errors by up to 95%. The complete test setup, the methodology for development, and data collection are discussed in this paper. In the next version of this system, additional observations such as the Wi-Fi, camera, and other signals of opportunity will be included.
Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance

Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting inside mammalian striated muscle cells, where it has been implicated in the pathology of ischemia-reperfusion injury. Gelatinase A has no known physiological function in muscle cells, and its localization within mammalian cells appears to be due to inefficient recognition of its N-terminal secretory signal. Here we show that Mmp2 is abundant within the skeletal muscle cells of zebrafish, where it localizes to the M-line of sarcomeres and degrades muscle myosin. The N-terminal secretory signal of zebrafish Mmp2 is also challenging to identify, and this is a conserved characteristic of gelatinase A orthologues, suggesting a selective pressure acting to prevent the efficient secretion of this protease. Furthermore, there are several strongly conserved phosphorylation sites within the catalytic domain of gelatinase A orthologues, some of which are phosphorylated in vivo, and which are known to regulate the activity of this protease. We conclude that gelatinase A likely participates in uncharacterized physiological functions within the striated muscle, possibly in the maintenance of sarcomere proteostasis, that are likely regulated by kinases and phosphatases present in the sarcomere.
Yersinia Phages and Food Safety

One of the human- and animal-pathogenic species in genus Yersinia is Yersinia enterocolitica, a food-borne zoonotic pathogen that causes enteric infections, mesenteric lymphadenitis, and sometimes sequelae such as reactive arthritis and erythema nodosum. Y. enterocolitica is able to proliferate at 4 °C, making it dangerous if contaminated food products are stored under refrigeration. The most common source of Y. enterocolitica is raw pork meat. Microbiological detection of the bacteria from food products is hampered by its slow growth rate as other bacteria overgrow it. Bacteriophages can be exploited in several ways to increase food safety with regards to contamination by Y. enterocolitica. For example, Yersinia phages could be useful in keeping the contamination of food products under control, or, alternatively, the specificity of the phages could be exploited in developing rapid and sensitive diagnostic tools for the identification of the bacteria in food products. In this review, we will discuss the present state of the research on these topics.
Su1051 ANALYSIS OF FACTORS ASSOCIATED WITH LOCAL RECURRENCE AFTER ENDOSCOPIC RESECTION OF GASTRIC EPITHELIAL DYSPLASIA

Background: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used techniques for the treatment of gastric epithelial dysplasia. Previous studies have compared the clinical outcome of endoscopic resection for early gastric cancer, but few studies have focused on gastric dysplasia alone. This study aimed to evaluate the long-term prognosis following endoscopic procedures for gastric epithelial dysplasia, investigate differences in local recurrence rates according to the treatment modality, and identify risk factors associated with local recurrence. Methods: In this retrospective study, local recurrence rates and risk factors associated with local recurrence were compared between 599 patients who underwent EMR and 306 who underwent ESD for gastric epithelial dysplasia from January 2011 to December 2015.Results: The en bloc resection rate (32.2% vs. 100%, p<0.001) and complete resection rate (94.8% vs. 99.0%, p=0.003) were significantly lower in the EMR group than in the ESD group. The local recurrence rate was significantly lower in the ESD group (1.3%) than in the EMR group (4.2%; p=0.026). There was a significantly increased risk of local recurrence, regardless of lesion location or histologic grade, in patients with lesions >2 cm (p=0.002) or red in color (p=0.03). The ESD group had a significantly lower local recurrence rate, with a higher complete resection rate, than that in the EMR group (p<0.05). In the case of recurrence after endoscopic resection, most of the recurred lesions were removed through additional endoscopic procedures; there was no difference between the two groups ( p=0.153). Conclusions: The complete resection rate was significantly higher, and the local recurrence rate was significantly lower, in patients with gastric epithelial dysplasia treated with ESD. Therefore, ESD should be considered the preferred treatment in patients with lesions >2 cm or showing redness due to an increased risk of local recurrence and EMR may be possible for low-grade dysplasia that is less than 2 cm without surface changes such as redness, depression and nodularity.